Medicinal Plants Used in the Treatment of Human Immunodeficiency Virus

Abstract

Since the beginning of the epidemic, human immunodeficiency virus (HIV) has infected around 70 million people worldwide, most of whom reside is sub-Saharan Africa. There have been very promising developments in the treatment of HIV with anti-retroviral drug cocktails. However, drug resistance to anti-HIV drugs is emerging, and many people infected with HIV have adverse reactions or do not have ready access to currently available HIV chemotherapies. Thus, there is a need to discover new anti-HIV agents to supplement our current arsenal of anti-HIV drugs and to provide therapeutic options for populations with limited resources or access to currently efficacious chemotherapies. Plant-derived natural products continue to serve as a reservoir for the discovery of new medicines, including anti-HIV agents. This review presents a survey of plants that have shown anti-HIV activity, both in vitro and in vivo.

1. Introduction

The World Health Organisation estimates that over 75 million people globally have been infected with the human immunodeficiency virus (HIV), of which approximately 37 million are still alive and living with the infection [1,2]. It is currently estimated that ~26 million of these patients reside in Africa; 3.3 million in the Americas; 3.5 million in Southeast Asia; 2.4 million in Europe; 360,000 in the eastern Mediterranean; and 1.5 million in the western Pacific [2]. Data from 2016 indicates that there were approximately two million new cases of HIV infections, and as many as one million deaths due to the disease [2]. Importantly, these annual numbers are much reduced, as the numbers of newly infected patients has declined by 35% since 2000, and the mortality rate has also declined by almost 50%. The decline in HIV infections is thought to be due to increased use of condoms, a reduction in the prevalence of sexually transmitted infection, and the increased use of effective therapies, such as the three-drug therapy anti-retroviral therapy (ART). The number of HIV patients now receiving antiretroviral therapy has increased from ~685,000 in 2000 to 20.9 million in 2017 [2].

While HIV is a significant cause of morbidity and mortality worldwide, the sub-Sahara region of Africa is burdened with the largest number of HIV cases [2]. Of the 37 million cases of HIV, the sub-Saharan Africa is home to ~70%, although it has only 21% of the world’s population. In fact, African men and women worldwide are more affected by this disease than any other race [2,3]. Only ten countries in southern and eastern Africa, including South Africa (25%), Nigeria (13%), Mozambique (6%), Uganda (6%), Tanzania (6%), Zambia (4%), Zimbabwe (6%), Kenya (6%), Malawi (4%) and Ethiopia (3%), account for approximately 80% of HIV patients [2,3]; In most countries, the prevalence of HIV is the highest in specific groups including men who have sex with men, intravenous drug users, people in prisons and other confined settings, sex workers and transgender individuals. However, unlike other countries, the primary HIV transmission mode in sub-Saharan Africa is through heterosexual sex, with a concomitant epidemic in children through vertical transmission [3]. As a consequence, African women are disproportionately affected and make up ~58% of the total number of people living with HIV, have the highest number of children living with HIV and the highest number of AIDS related deaths [2].

New data from coding complete genome analyses of US serum samples from 1978 to 1979 revealed that the US HIV-1 epidemic that occurred in the 1970s was extensively genetically diverse [4]. Bayesian phylogentic analyses of HIV-1 genomes suggest that the US epidemic emerged from a preexisting Caribbean epidemic with the place of the ancestral US virus being New York City [4]. The analysis of gag, pol and env RNA sequences placed the US sequences in a monophyletic clade nested within Caribbean subtype B sequences from Haiti, and other Caribbean countries, as well as Haitian immigrants in the US [4]. The data further suggested that the US clade emerged from the early growth phase of the Caribbean epidemic (1969–1973), which began after the introduction of the subtype B lineage from Africa about 1967 [4]. The Centers for Disease Control eventually made the connections between homosexual men with AIDS and Kaposi’s syndrome and sexual transmission of an infectious agent [5,6].

1.1. Pathophysiology

The HIV virus is a retrovirus that is able to integrate a DNA copy of the viral genome into the DNA of the host cells. The virus enters the cell through receptors that are expressed on the surface of T lymphocytes (activated T lymphocytes are preferred targets), monocytes, macrophages and dendritic cells [1,7]. To gain entry to the host cell, HIV-1 binds to the chemokine receptor 5 or the CXC chemokine receptor 4 through interactions with the envelope proteins. After fusion and uncoating, single stranded RNA is reverse transcribed into HIV DNA, and then integrated into the host DNA. HIV DNA is transcribed to viral mRNA and exported to the cytoplasm where it is translated to viral Gag, Gag-Pol, and Nef polyproteins, which are then cleaved later during virion assembly and maturation at the cell surface or after relase of the new viral particles. Current therapies inhibit many of the steps in this process, such as entry inhibitors, reverse transcriptase inhibitors, integrase strand transfer inhibitors and protease inhibitors [1,7].

1.2. Diagnosis

Detection of the HIV virus in the blood is usually measured as viral RNA load and infection is associated with an acute symptomatic period that includes fever, general malaise, lymphadenopathy, rash, myalgias, however serious consequences such as meningitis have also been reported [7,8]. During the period of acute infection, the plasma levels of HIV RNA are at their highest and the severity of symptoms is associated with the level of viral load. It has been suggested that viral characteristics and viral load determine both the replication and pathogenesis. Thus, the clinical outcomes and disease progression are dependent not only on the host, but also on the viral genotype [7]. HIV is difficult to completely eradicate as it establishes a quiescent or latent infection within the memory CD4⁺ T cells, which have a stem-cell-like capacity for self-renewal. Once the HIV DNA is integrated into the host chromatin, the virus can repeatedly initiate replication as long as that cell exists. While ART can prevent new cells from becoming infected, it cannot eliminate infection once the DNA has successfully integrated into the target cell. The lymph nodes harbor the virus because of limited antiretroviral drug penetration, and limited host clearance mechanisms, and serves as a source of virus recrudescence in individuals who stop or interrupt their therapy. It has been suggested that ART therapy may be needed for several decades before the viral reservoir might decay to negligible levels.

1.3. Current Treatments for HIV/AIDS

Although HIV was recognized early in the 1980s, there is still no cure or an effective vaccine for HIV infection, but there have been some significant advances in treatment, control, and prevention [9]. The introduction of anti-retroviral agents and highly active antiretroviral therapy (HAART) in 1996 significantly reduced the morbidity and mortality of HIV/AIDS. Antiretroviral therapy is currently recommended for all adults with HIV. Recommendations for initial regimens include two nucleoside reverse transcriptase inhibitors (NRTIs; abacavir with lamivudine or tenofovir disoproxil fumarate with emtricitabine) and an integrase strand transfer inhibitor, such as dolutegravir, elvitegravir, or raltegravir; a nonnucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine) or a boosted protease inhibitor (darunavir or atazanavir) [10]. Alternative regimens are also available. Protease inhibitor monotherapy is generally not recommended, but NRTI-sparing approaches may be considered. Suspected treatment failure warrants rapid confirmation, performance of resistance testing while the patient is receiving the failing regimen, and evaluation of reasons for failure before consideration of switching therapy. Alterations in therapeutic regimens due to adverse effects, convenience, or to reduce costs should be carefully considered so as not to jeopardize antiretroviral potency. Research continues into HIV vaccines and antimicrobial agents, however other major advances in HIV prevention has been voluntary male medical circumcision [11,12], as well as antiretrovirals for the prevention of mother to child transmission [13,14,15,16].

The reduction in the morbidity and mortality of the disease has changed it from a fatal disease to a chronic, manageable condition [2,3,11,12]. Interestingly, the increased survival rate has resulted in an aging HIV/AIDS population, which has presented a whole new set of issues including a higher prevalence of chronic diseases in this population, such as cardiovascular and pulmonary diseases, malignancies and even a unique set of comorbidities, which are now designated as HIV-associated non-AIDS (HANA) conditions.

Antiretroviral agents remain the cornerstone of HIV treatment and prevention [17]. It is currently recommended that all HIV-infected patients with detectable virus, regardless of their CD4 cell count, should be treated with anti-retroviral therapy (ART) soon after diagnosis to prevent disease progression, improve clinical outcomes including reducing AIDS-associated events, non-AIDS-related events, and all-cause mortality, as well as to decrease transmission [17]. These recommendations are supported by large randomized controlled clinical trials it is recommended that all HIV-infected individuals with detectable plasma virus receive treatment with recommended initial regimens consisting of an integrase strand transfer inhibitors (InSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs). When used effectively, the anti-retroviral agents suppress HIV and prevent new HIV infections. It has been suggested that with these treatment regimens, that survival rates among HIV-infected adults can approach those of uninfected adults [17].

1.4. New Drug Therapies for HIV

A recent review of HIV therapies with new mechanisms of action in phase 2 clinical trials has reported on drugs with new mechanisms of action, including histone deacetylase (HDAC) inhibitors, gene therapies, broadly neutralizing anti-HIV antibodies, immune modulation, and drugs with new mechanisms to block HIV entry [18]. The new therapies are being developed for both as add-on therapy to existing combination antiretroviral therapy and as agents to be used during treatment interruption. The current drugs in development have had varying degrees of success in the early trials. Each of these new drugs may potentially fill a void in current antiretroviral therapy (ART) therapies, which will ultimately lead to improved outcomes in HIV-infected individuals.

1.5. Natural Products and Herbal Medicines for HIV

Although effective, ART is not without serious adverse events, which is especially evident in persons undergoing long-term treatment. In addition, the current therapies are limited by emergence of multidrug resistance [19], and new drugs and novel targets are needed to overcome the issues of HIV reservoirs in the body in order to have the complete eradication of HIV and AIDS. Latently infected cells remain a primary barrier to eradication of HIV-1. Over the last ten years the molecular mechanism by which HIV latency persists has led to the discovery of a number of drugs that are able to selectively reactivate latent proviruses without inducing polyclonal T cell activation [20]. Interestingly, histone deacetylase (HDAC) inhibitors, including vorinostat are able to induce HIV transcription from latently infected cells. Vorinostat has been shown to increase the susceptibility of CD4⁺ T cells to infection by HIV in a dose- and time-dependent manner, does not enhance viral fusion with cells, but increases reverse transcription, nuclear import, and integration, and enhances viral production in a spreading-infection assay. HDAC inhibitors, particularly vorinostat, are currently being investigated clinically as part of a “shock-and-kill” strategy to purge latent reservoirs of HIV [20].

Since new drugs will be needed for the management of HIV, the World Health Organization (WHO) has suggested the that ethnomedicines and other natural products should be systematically tested against HIV as they may yield effective and more affordable therapeutic agents (World Health Organization [21,22]. Interestingly, a significant amount of work in this area was performed in the 1990s, particularly investigations of natural products with activities against HIV-1 reverse transcriptase, HIV-1 and -2 proteases and integrases (extensively reviewed by Kurapati et al. [23]). The natural products calanolides (coumarins), ursolic and betulinic acids (triterpenes), baicalin (flavonoid), polycitone A (alkaloid), lithospermic acid (phenolic compound) have been proposed as promising candidates for anti-HIV agents [23]. However, most of these studies are in vitro, and too few investigations have been performed in vivo or in human studies. In terms of clinical data, a meta-analysis assessed 12 clinical trials involving 881 patients with AIDS to determine the efficacy of traditional Chinese medicines (TCM). The results showed that TCM interventions were associated with significantly reduced plasma viral load compared with placebo. This study further suggested that TCM interventions were significantly more effective than placebo for reducing plasma viral load and increasing CD4⁺ T lymphocyte count in patients with AIDS. However, when compared with conventional Western medicine, TCM interventions were significantly less effective in reducing viral load, but were associated with improved symptoms in a larger number of patients, with fewer adverse events [24]. Thus, there is significant potential for natural products and traditional medicines for the management of HIV infections and symptoms but in vivo and human studies are lacking.

2. Traditional Knowledge on Plants Used against HIV

Medicinal plants can be a promising alternative for various diseases and conditions [25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46]. The 717 species belonging to 151 families are reported in this article. The taxonomy of the plant species plays a significant role in the proper identification. The website, http://www.theplantlist.org and http://www.tropicos.org/Home.aspx were considered as the authentic sources of information in resolving the ambiguity of the names related to plants. A list of plant species with inhibition studies is summarized in Table 1. A majority of the inhibition studies are carried out on the crude extracts of the plant material by various solvents, while limited literature is available on the isolated natural products for different inhibition studies. Table 2 lists all the names which are reported in this article and their synonyms are reported in the literature.

Table 1.

List of plant species exhibiting different human immunodeficiency virus (HIV)-inhibition activities.

Family	Plant	Plant Part	HIV-RT	HIV-PR	HIV-IN	Anti-HIV
Acanthaceae	Andrographis paniculata (Burm. f.) Wall. ex Nees	Aerial part				Crude [51,52]
Acanthaceae	Avicennia marina var. rumphiana (Hallier f.) Bakh.	Seed				Iridoid glycoside [53]
Acanthaceae	Avicennia officinalis L.	Leaf	Crude [54]	Crude [55]
Acanthaceae	Justicia adhatoda L.					Crude [56]
Acanthaceae	Justicia gendarussa Burm.f.	Aerial part	Crude [57]
Acanthaceae	Rhinacanthus nasutus (L.) Kurz	Aerial part	Crude [58]			Crude [59]
Acanthaceae	Strobilanthes cusia (Nees) Kuntze					Crude [60]
Acoraceae	Acorus calamus L.	Rhizome	Crude [58]
Adoxaceae	Sambucus ebulus L.	Whole plant				Crude [61]
Adoxaceae	Sambucus nigra L.	Whole plant	Crude [62]			Crude [61,63]
Adoxaceae	Sambucus racemosa L.	Leaf, Fruit	Crude [62,64]
Adoxaceae	Sambucus williamsii Hance	Roots , Fruits				Crude [65,66]
Adoxaceae	Viburnum opulus L.	Leaf, Fruit	Crude [62]
Aizoaceae	Sceletium tortuosum (L.) N.E. Br.		Crude [67]	Crude [67]	Crude [67]
Alismataceae	Alisma plantago-aquatica L.	Rhizome		Crude [68]
Amaranthaceae	Achyranthes bidentata Blume					Crude [66,69]
Amaranthaceae	Achyranthes japonica (Miq.) Nakai	Root				Crude [66]
Amaranthaceae	Aerva lanata (L.) Juss. ex Schult.	Root	Phytotesrols [70]
Amaranthaceae	Alternanthera brasiliana (L.) Kuntze					Crude [71]
Amaranthaceae	Alternanthera philoxeroides (Mart.) Griseb.	Aerial part				Crude [72,73]
Amaryllidaceae	Allium sativum L.	Bulb	Crude [58]			Crude [56]
Amaryllidaceae	Crinum amabile Donn ex Ker Gawl.	Bulb	Crude [74]
Amaryllidaceae	Crinum macowanii Baker	Bulb	Crude [75]	Crude [75]
Amaryllidaceae	Haemanthus albiflos Jacq.					Crude [76]
Amaryllidaceae	Leucojum vernum L.	Bulb	Alkaloids [77]
Amaryllidaceae	Pamianthe peruviana Anonymous	Bulb	Crude [74]
Amaryllidaceae	Tulbaghia alliacea L. f.	Bulb				Crude [78]
Amaryllidaceae	Tulbaghia violacea Harv.	Bulb	Crude [75]	Crude [75]
Anacardiaceae	Lannea edulis (Sond.) Engl.	Bulb				Crude [79]
Anacardiaceae	Mangifera indica L.	Stem bark				Crude [80]
Anacardiaceae	Rhus chinensis Mill.	Leaf, Root, Stem, Bark, Fruit				Read phyto [81]
Anacardiaceae	Schinus molle L.	Leaf				Crude [82]
Anacardiaceae	Spondias pinnata (L. f.) Kurz	Fruit	Crude [58]
Anacardiaceae	Toxicodendron acuminatum (DC.) C.Y. Wu & T.L. Ming	Gall		Crude [83]
Ancistrocladaceae	Ancistrocladus korupensis D.W. Thomas & Gereau	Root	Naphthylisoquinoline alkaloids [84]			Crude [85] Naphthylisoquinoline alkaloids [86]
Annonaceae	Annona glabra L.	Fruit				Alkaloids [87]
Annonaceae	Annona senegalensis Pers.	Leaf				Crude [80]
Annonaceae	Annona squamosa L.	Fruit				Diterpenoids [88]
Annonaceae	Dasymaschalon rostratum Merr. & Chun	Stem	Phenylpropanoid derivatives [89]
Annonaceae	Dasymaschalon sootepense Craib	Leaf	Alkaloids, Flavonoid [90]
Annonaceae	Polyalthia suberosa (Roxb.) Thwaites	Stem bark	Crude [57]			Triterpene [91] and 2-substituted furans [92]
Annonaceae	Xylopia frutescens Aubl.	Bark		Crude [93]
Apiaceae	Alepidea amatymbica Eckl. & Zeyh.					Rosmarinic acid [94]
Apiaceae	Ammi visnaga (L.) Lam.	Fruit		Crude [95]
Apiaceae	Anethum graveolens L.	Seed		Crude [83]
Apiaceae	Angelica dahurica (Fisch.) Benth. & Hook. f.	Root				Crude [66]
Apiaceae	Angelica grosseserrata Maxim.	Aerial part		Crude [96]
Apiaceae	Apium graveolens L.	Fruit		Crude [83]
Apiaceae	Cryptotaenia japonica Hassk.	Aerial part		Crude [96]
Apiaceae	Foeniculum vulgare Mill.	Fruit				Crude [66]
Apiaceae	Lomatium suksdorfii (S. Watson) J.M. Coult. & Rose	Fruit				Coumarin [97]
Apiaceae	Mulinum ulicinum Gillet & Hook.	Leaf, Stem				Crude [82]
Apiaceae	Ridolfia segetum (L.) Moris		Essential oils [98]
Apiaceae	Saposhnikovia divaricate (Turcz.) Schischk.			Crude [60,68]		Crude [66]
Apiaceae	Torilis japonica (Houtt.) DC.	Seed		Crude [96]
Apocynaceae	Alstonia scholaris (L.) R. Br.	Stem bark				Crude [56]
Apocynaceae	Carissa bispinosa Desf. ex Brenan	Roots				Crude [99]
Apocynaceae	Catharanthus roseus (L.) G. Don	Leaf				Crude [56]
Apocynaceae	Cynanchum atratum Bunge	Root				Crude [66]
Apocynaceae	Cynanchum paniculatum (Bunge) Kitag.	Root				Crude [66]
Apocynaceae	Gymnema sylvestre (Retz.) R. Br. ex Schult.			Crude [99]
Apocynaceae	Hemidesmus indicus (L.) R. Br. ex Schult.		Crude [100]
Apocynaceae	Hoodia gordonii (Masson) Sweet ex Decne.		Crude [101]	Crude [101]	Crude [101]
Apocynaceae	Parameria laevigata (Juss.) Moldenke	Bark		Crude [68]
Apocynaceae	Rauvolfia serpentine (L.) Benth. ex Kurz					Crude [56]
Apocynaceae	Solenostemma argel (Delile) Hayne	Root		Crude [95]
Apocynaceae	Tabernaemontana stapfiana Britten		Crude [102]
Araceae	Alocasia odora (Roxb.) K. Koch	Rhizome		Crude [68]
Araliaceae	Acanthopanax koreanum Nakai	Stem bark		Crude [96]		Crude [96]
Araliaceae	Eleutherococcus sessiliflorus (Rupr. & Maxim.) S.Y. Hu					Crude [66]
Araliaceae	Kalopanax pictus (Thunb.) Nakai	Stem bark				Crude [66]
Araliaceae	Panax ginseng C.A. Mey.	Root		Triterpenoids [103]		Saponin [104]
Araliaceae	Panax notoginseng (Burkill) F.H. Chen ex C.H. Chow			Crude [60]	Crude [105]
Araliaceae	Panax zingiberensis C.Y. Wu & K.M. Feng	Rhizome				Zingibroside [106]
Arecaceae	Areca catechu L.	Seed		Crude [60,83]
Arecaceae	Attalea tessmannii Burret	Seed				Crude [82]
Aristolochiaceae	Aristolochia bracteolate Lam.	Fruit	Crude [74]	Crude [95]
Aristolochiaceae	Aristolochia contorta Bunge	Fruit				Crude [66]
Aristolochiaceae	Aristolochia manshuriensis Kom.	Stem				Oxoperezinone [107]
Aristolochiaceae	Asarum sieboldii Miq.	Root				Crude [66]
Asparagaceae	Anemarrhena asphodeloides Bunge	Rhizome		Crude [68]
Asparagaceae	Asparagus cochinchinensis (Lour.) Merr.	Root				Crude [66]
Asparagaceae	Asparagus racemosus Willd.	Root				Crude [56]
Asparagaceae	Dracaena cochinchinensis (Lour.) S.C. Chen		Crude [58]
Asteraceae	Acanthospermum hispidum DC.	Aerial part	Crude [74]
Asteraceae	Achyrocline alata (Kunth) DC.	Flower, Stem				Crude [82]
Asteraceae	Achyrocline flaccida (Weinm.) DC.					Crude [108]
Asteraceae	Achyrocline satureioides (Lam.) DC.	Flower				Crude [82]
Asteraceae	Ainsliaea acerifolia Sch. Bip.	Whole plant		Crude [96]
Asteraceae	Ambrosia artemisiifolia L.	Whole plant		Crude [96]
Asteraceae	Ambrosia maritima L.	Aerial part		Crude [95]
Asteraceae	Ambrosia peruviana All.	Leaf, stem				Crude [82]
Asteraceae	Anvillea garcinii (Burm. f.) DC.	Aerial part				Germacranolides [109]
Asteraceae	Arctium lappa L.	Aerial part		Crude [60]	Crude [105]	Crude [51,66,72]
Asteraceae	Artemisia absinthium L.	Leaf				Crude [82]
Asteraceae	Artemisia annua L.	Aerial part				Crude [66]
Asteraceae	Artemisia capillaris Thunb.	Aerial part, Seed		Crude [68]		Crude [66]
Asteraceae	Artemisia princeps Pamp.	Leaf		Crude [68,96]
Asteraceae	Artemisia verlotorum Lamotte					Crude [110]
Asteraceae	Aspilia pluriseta Schweinf. ex Schweinf.					Crude [111]
Asteraceae	Aster tataricus L. f.	Root		Crude [68]
Asteraceae	Atractylodes japonica Koidz.	Root		Crude [96]		Crude [66]
Asteraceae	Atractylodes lancea (Thunb.) DC.	Rhizome		Crude [68]		Crude [112]
Asteraceae	Atractylodes ovate (Thunb.) DC.	Rhizome		Crude [68]
Asteraceae	Baccharis genistelloides (Lam.) Pers.	Leaf, stem				Crude [82]
Asteraceae	Baccharis latifolia (Ruiz & Pav.) Pers.	Leaf, stem				Crude [82]
Asteraceae	Baccharis trimera (Less.) DC.	Leaf, stem				Crude [82]
Asteraceae	Baccharis trinervis Pers.	Aerial part				Crude [93]
Asteraceae	Bidens pilosa L.	Aerial part				Crude [93]
Asteraceae	Blumea balsamifera (L.) DC.				Crude [113]	Crude [113]
Asteraceae	Breea segeta (Bunge) Kitam.	Aerial part				Crude [66]
Asteraceae	Calea jamaicensis (L.) L.	Root				Crude [93]
Asteraceae	Calendula officinalis L.	Leaf	Crude [114]			Crude [115]
Asteraceae	Carlina acaulis L.	Leaf	Crude [62]
Asteraceae	Carpesium abrotanoides L.			Crude [96]
Asteraceae	Carthamus tinctorius L.	Flower				Crude [66]
Asteraceae	Centratherum punctatum Cass.	Leaf	Crude [114]
Asteraceae	Chrysanthemum indicum L.	Capitulum		Crude [60]	Crude [105]
Asteraceae	Chrysanthemum morifolium Ramat.	Capitulum	Flavonoids [116]	Crude [60,68]	Crude [105] Flavonoid [117]	Crude [117,118]
Asteraceae	Cirsium japonicum DC.			Crude [96]
Asteraceae	Eclipta prostrate (L.) L.	Whole plant		Lactone [119]	Crude [120] Lactone [119]
Asteraceae	Elephantopus scaber L.	Leaf		Crude [68]
Asteraceae	Eupatorium lindleyanum DC.	Aerial part		Crude [96]
Asteraceae	Francoeuria crispa (Forssk.) Cass.					Crude [121]
Asteraceae	Franseria artemisioides Willd.	Leaf, stem				Crude [82]
Asteraceae	Gamochaeta simplicicaulis (Willd. ex Spreng.) Cabrera		Crude [122]			Crude [108]
Asteraceae	Geigeria alata (DC.) Oliv. & Hiern					Crude [121]
Asteraceae	Gnaphalium sylvaticum L.	Leaf	Crude [62]
Asteraceae	Gynura pseudochina (L.) DC.	Leaf	Crude [57]
Asteraceae	Helianthus tuberosus L.	Whole plant		Crude [96]
Asteraceae	Helichrysum acutatum DC.	Aerial part				Crude [123]
Asteraceae	Helichrysum allioides Less.	Aerial part				Crude [123]
Asteraceae	Helichrysum anomalum Less.	Aerial part				Crude [123]
Asteraceae	Helichrysum appendiculatum (L. f.) Less.	Aerial part				Crude [123]
Asteraceae	Helichrysum auronitens Sch. Bip.	Aerial part				Crude [123]
Asteraceae	Helichrysum cephaloideum DC.	Aerial part				Crude [123]
Asteraceae	Helichrysum chionosphaerum DC.	Aerial part				Crude [123]
Asteraceae	Helichrysum confertum N.E. Br.	Aerial part				Crude [123]
Asteraceae	Helichrysum cymosum (L.) D. Don ex G. Don	Aerial part				Crude [123]
Asteraceae	Helichrysum difficile Hilliard	Aerial part				Crude [123]
Asteraceae	Helichrysum drakensbergense Killick	Aerial part				Crude [123]
Asteraceae	Helichrysum herbaceum (Andrews) Sweet	Aerial part				Crude [123]
Asteraceae	Helichrysum melanacme DC.	Aerial part				Crude [123]
Asteraceae	Helichrysum miconiifolium DC.	Aerial part				Crude [123]
Asteraceae	Helichrysum natalitium DC.	Aerial part				Crude [123]
Asteraceae	Helichrysum nudifolium (L.) Less.	Aerial part				Crude [123]
Asteraceae	Helichrysum odoratissimum (L.) Sweet	Aerial part				Crude [123]
Asteraceae	Helichrysum oreophilum Dinter	Aerial part				Crude [123]
Asteraceae	Helichrysum oxyphyllum DC.	Aerial part				Crude [123]
Asteraceae	Helichrysum pallidum DC.	Aerial part				Crude [123]
Asteraceae	Helichrysum panduratum O. Hoffm.	Aerial part				Crude [123]
Asteraceae	Helichrysum pannosum DC.	Aerial part				Crude [123]
Asteraceae	Helichrysum pilosellum (L. f.) Less.	Aerial part				Crude [123]
Asteraceae	Helichrysum populifolium DC.	Aerial part				Crude [123]
Asteraceae	Helichrysum rugulosum Less.	Aerial part				Crude [123]
Asteraceae	Helichrysum splendidum (Thunb.) Less.	Aerial part				Crude [123]
Asteraceae	Helichrysum subluteum Burtt Davy	Aerial part				Crude [123]
Asteraceae	Helichrysum sutherlandii Harv.	Aerial part				Crude [123]
Asteraceae	Helichrysum umbraculigerum Less.	Aerial part				Crude [123]
Asteraceae	Helichrysum vernum Hilliard	Aerial part				Crude [123]
Asteraceae	Hieracium pilosella L.	Whole plant				Crude [61]
Asteraceae	Hieracium umbellatum L.	Whole plant		Crude [96]
Asteraceae	Inula britannica L.	Flower				Crude [66]
Asteraceae	Inula helenium L.	Root				Crude [66]
Asteraceae	Ixeris tamagawaensis (Makino) Kitam.	Aerial part				Crude [124]
Asteraceae	Lactuca raddeana Maxim.	Whole plant		Crude [96]
Asteraceae	Miyamayomena koraiensis (Nakai) Kitam.	Root		Crude [96]
Asteraceae	Mutisia acuminata Ruiz & Pav.	Leaf				Crude [82]
Asteraceae	Perezia multiflora (Bonpl.) Less.	Leaf				Crude [82]
Asteraceae	Pilosella officinarum F.W. Schultz & Sch. Bip.	Whole plant				Crude [61]
Asteraceae	Psiadia dentata (Cass.) DC.					Coumarin [125]
Asteraceae	Santolina oblongifolia Boiss.	Whole plant				Crude [61]
Asteraceae	Saussurea seoulensis Nakai	Whole plant		Crude [96]
Asteraceae	Schkuhria pinnata (Lam.) Kuntze ex Thell.	Leaf				Crude [82]
Asteraceae	Senecio comosus Sch. Bip.	Leaf				Crude [82]
Asteraceae	Senecio mathewsii Wedd.	Leaf				Crude [82]
Asteraceae	Senecio rhizomatus Rusby	Leaf				Crude [82]
Asteraceae	Senecio scandens Buch.-Ham. ex D. Don	Whole plant		Crude [60]	Crude [105]	Crude [72]
Asteraceae	Serratula coronate L.	Aerial part		Crude [96]
Asteraceae	Sigesbeckia glabrescens (Makino) Makino	Whole plant				Crude [66]
Asteraceae	Sonchus oleraceus L.	Leaf				Crude [82]
Asteraceae	Symphyotrichum undulatum (L.) G.L.Nesom	Aerial part			Quinic acid [126]
Asteraceae	Tagetes riojana M. Ferraro	Leaf				Crude [82]
Asteraceae	Tanacetum microphyllum DC.	Whole plant				Crude [61]
Asteraceae	Taraxacum mongolicum Hand.-Mazz.	Whole plant		Crude [68]
Asteraceae	Xanthium spinosum L.	Flower				Crude [82]
Berberidaceae	Berberis holstii Engl.	Root and Leaf				Crude [127]
Berberidaceae	Epimedium grandiflorum C. Morren	Aerial part				Crude [21,72]
Berberidaceae	Epimedium sagittatum (Siebold & Zucc.) Maxim.	Leaf		Crude [68]
Berberidaceae	Nandina domestica Thunb.	Leaf		Crude [68]
Betulaceae	Alnus firma Siebold & Zucc.	Leaf	Triterpenoids [128]
Betulaceae	Alnus incana (L.) Moench	Leaf	Crude [62]
Bignoniaceae	Kigelia Africana (Lam.) Benth.	Fruit	Crude [102]
Bignoniaceae	Spathodea campanulata P. Beauv.	Stem bark				Crude [129]
Bignoniaceae	Tecomella undulata (Sm.) Seem.	Aerial part				Crude [130]
Blechnaceae	Blechnum spicant (L.) Sm.	Leaf	Crude [62]
Blechnaceae	Brainea insignis (Hook.) J. Sm.	Rhizome		Crude [68]
Blechnaceae	Woodwardia orientalis Sw.	Rhizome		Crude [68]
Blechnaceae	Woodwardia unigemmata (Makino) Nakai	Rhizome		Crude [60]	Crude [105]	Crude [72]
Boraginaceae	Brachybotrys paridiformis Maxim. ex Oliv.	Leaf		Crude [96]
Boraginaceae	Cordia spinescens L.	Leaf		Crude [93]	Crude [93]
Boraginaceae	Lithospermum erythrorhizon Siebold & Zucc.	Root		Crude [60,68]	Crude [105]	Crude [72,131]
Boraginaceae	Lobostemon trigonus H. Buek		Crude [132]
Brassicaceae	Brassica juncea (L.) Czern.	Semen	Crude [133]			Crude [66]
Brassicaceae	Brassica oleracea L.		Crude [134]
Brassicaceae	Brassica rapa L.		Crude [134]
Brassicaceae	Capsella bursa-pastoris (L.) Medik.	Whole plant				Crude [82]
Brassicaceae	Lepidium abrotanifolium Turcz.	Leaf				Crude [82]
Brassicaceae	Raphanus raphanistrum L.					Crude Inhibition [66]
Cactaceae	Pereskia bleo (Kunth) DC.	Whole plant				Crude [93]
Calophyllaceae	Marila pluricostata Standl. & L.O. Williams					Phenylcoumarins [135]
Campanulaceae	Adenophora triphylla (Thunb.) A. DC.	Root				Crude [66]
Campanulaceae	Platycodon grandiflorus (Jacq.) A. DC.	Root		Crude [68]
Cannabinaceae	Cannabis sativa L.	Fruit		Crude [68]
Cannabinaceae	Humulus lupulus L.					Flavonoid [136]
Cannaceae	Canna indica L.	Rhizome	Crude [57]
Canellaceae	Warburgia ugandensis Sprague		Crude [102]
Capparaceae	Boscia senegalensis (Pers.) Lam. ex Poir.	Leaf	Crude [74]
Capparaceae	Capparis decidua (Forssk.) Edgew.	Stem	Crude [74]
Capparaceae	Crateva religiosa G. Forst.	Bark		Crude [83]
Caprifoliaceae	Lonicera japonica Thunb.	Flower bud	Crude [137]	Crude [60,68]	Crude [105]	Crude [66,72]
Caprifoliaceae	Patrinia scabiosifolia Link	Root		Crude [96]		Crude [66]
Caprifoliaceae	Patrinia villosa (Thunb.) Dufr.	Root		Crude [68,96]
Caprifoliaceae	Valeriana coarctata Ruiz & Pav.	Leaf				Crude [82]
Caprifoliaceae	Valeriana micropterina Wedd.					Crude [82]
Caprifoliaceae	Valeriana thalictroides Graebn.	Root				Crude [82]
Caprifoliaceae	Weigela subsessilis L.H. Bailey	Stem		Crude [96]
Caryophyllaceae	Drymaria cordata (L.) Willd. ex Schult.	Leaf				Crude [138]
Caryophyllaceae	Drymaria diandra Blume					Alkaloid [139]
Caryophyllaceae	Silene seoulensis Nakai	Aerial part		Crude [96]
Celastraceae	Cassine crocea (Thunb.) C.Presl					Glycoside [140]
Celastraceae	Cassine schlechteriana Loes.					Crude [141]
Celastraceae	Celastrus hindsii Benth.					triterpene [142]
Celastraceae	Celastrus orbiculatus Thunb.	Root		Crude [96]		Crude [143]
Celastraceae	Euonymus alatus (Thunb.) Siebold	Leaf		Crude [96]
Celastraceae	Gymnosporia buchananii Loes.		Crude [102]
Celastraceae	Gymnosporia senegalensis (Lam.) Loes.		Crude [102]
Celastraceae	Maytenus buchananii (Loes.) R. Wilczek	Root, bark	Crude [102]
Celastraceae	Maytenus macrocarpa (Ruiz & Pav.) Briq.					Triterpenes [144]
Celastraceae	Maytenus senegalensis (Lam.) Exell	Stem	Crude [102]	Crude [95]
Celastraceae	Salacia chinensis L.	Stem	Crude [58]
Celastraceae	Tripterygium wilfordii Hook. f.	Root	Salaspermic acid [145]			Crude [146,147] Diterpene [146,148] Sesquiterpene pyridine Alkaloids [147]
Chenopodiaceae	Chenopodium ambrosioides L.	Leaf				Crude [82]
Chloranthaceae	Chloranthus japonicas Siebold	Whole plant	Disesquiterpenoids [149]	Crude [96]		Crude [150]
Cistaceae	Whole plant	Whole plant				Crude [61]
Cistaceae	Tuberaria lignose Samp.	Whole plant				Crude [61]
Cleomaceae	Cleome viscosa L.	Seed	Nevirapine [151]	Crude [83]
Clusiaceae	Allanblackia stuhlmannii (Engl.) Engl.					Benzophenone [152]
Clusiaceae	Calophyllum brasiliense Cambess.	Leaf	Crude [153] Dipyranocoumarins [154] Coumrains [155]
Clusiaceae	Calophyllum cerasiferum Vesque		Coumarins [156]
Clusiaceae	Calophyllum cordato-oblongum Thwaites		Cordatolide [157]
Clusiaceae	Calophyllum inophyllum L.	Bark	Crude [158]	Crude [158]	Crude [158]	Dipyranocoumarins [159] Inophyllum [160]
Clusiaceae	Calophyllum lanigerum Miq.		Calanolide [161]			Calanolide [162] Coumarin [163] Pyranocoumarins [164]
Clusiaceae	Calophyllum rubiginosum M.R. Hend. & Wyatt-Sm.	Stem bark				Crude [165]
Clusiaceae	Calophyllum teysmannii Miq.					Pyranocoumarins [141]
Clusiaceae	Clusia quadrangular Bartlett		Crude [153]
Clusiaceae	Garcinia buchneri Engl.	Stem bark		Crude [166]
Clusiaceae	Garcinia gummi-gutta Roxb.	Leaf	Crude [158]	Crude [158]	Crude [158]
Clusiaceae	Garcinia hanburyi Hook. f.	Root				Xanthone [167]
Clusiaceae	Garcinia indica Choisy	Leaf	Crude [158]	Crude [158]	Crude [158]
Clusiaceae	Garcinia kingaensis Engl.	Stem bark		Crude [166]
Clusiaceae	Garcinia livingstonei T. Anderson	Fruit				Crude [168]
Clusiaceae	Garcinia mangostana L.	Fruit bark	Crude [58]	Crude [169]
Clusiaceae	Garcinia semseii Verdc.	Stem bark		Crude [166]		Crude [168]
Clusiaceae	Garcinia smeathmanii (Planch. & Triana) Oliv.	Stem bark		Crude [166]
Colchicaceae	Colchicum luteum Baker	Bulb				Crude [56]
Combretaceae	Anogeissus acuminata (Roxb. ex DC.) Guill., Perr. & A. Rich.		Lignans [170]			Crude [170]
Combretaceae	Combretum adenogonium Steud. ex A. Rich.	Root, Leaf and Stem bark		Crude [171]
Combretaceae	Combretum hartmannianum C. Schweinf.	Stem	Crude [74]
Combretaceae	Combretum molle R. Br. ex G. Don	Root	Crude [172]			Crude [173]
Combretaceae	Combretum paniculatum Vent.	Leaf				Crude [174]
Combretaceae	Terminalia arjuna (Roxb. ex DC.) Wight & Arn.	Stem bark		Crude [68,83]		Crude [56]
Combretaceae	Terminalia bellirica (Gaertn.) Roxb.	Fruit	Crude [58,175]	Crude [68]		Crude [176]
Combretaceae	Terminalia chebula Retz.	Fruit	Crude [58,175]	Crude [68,83]	Galloyl glycosides [177]	Crude [175]
Combretaceae	Terminalia sericea Burch. ex DC.		Crude [178]			Crude [179]
Convolvulaceae	Argyreia nervosa (Burm. f.) Bojer	Aerial part	Crude [57]
Convolvulaceae	Calystegia soldanella (L.) R. Br.	Leaf, Stem		Crude [96]
Convolvulaceae	Cuscuta chinensis Lam.	Fruit, Stem		Crude [96]
Convolvulaceae	Cuscuta japonica Choisy	Semen		Crude [96]		Crude [66]
Convolvulaceae	Ipomoea aquatic Forssk.	Whole plant	Crude [57]
Convolvulaceae	Ipomoea cairica (L.) Sweet	Whole plant	Crude [57]			Lignans [180]
Convolvulaceae	Ipomoea carnea Jacq.	Aerial part	Crude [57]
Convolvulaceae	Merremia peltata (L.) Merr.					Crude [181]
Cornaceae	Cornus walteri Wangerin	Aerial part		Crude [96]
Cornaceae	Camptotheca acuminata Decne		Rubitecan [182]
Crassulaceae	Orostachys japonica A. Berger	Aerial part		Crude [183]
Crassulaceae	Sedum album L.	Whole plant				Crude [61]
Crassulaceae	Sedum maximum Hoffm.	Leaf	Crude [62]
Crassulaceae	Sedum polytrichoides Hemsl.	Whole plant		Crude [96]
Crassulaceae	Sedum roseum Scop.			Crude [96]
Cucurbitaceae	Citrullus colocynthis (L.) Schrad.	Fruit peel	Crude [74]
Cucurbitaceae	Gynostemma pentaphyllum (Thunb.) Makino					Crude [184]
Cucurbitaceae	Hemsleya endecaphylla C.Y. Wu	Tuber				Crude [185]
Cucurbitaceae	Momordica balsamina L.	Leaf				Crude [186]
Cucurbitaceae	Momordica charantia L.	Seed, Fruit				Crude [187]
Cucurbitaceae	Momordica cochinchinensis (Lour.) Spreng.	Semen		Crude [96]		Crude [66]
Cucurbitaceae	Trichosanthes kirilowii Maxim.	Semen				Crude [66,188]
Cupressaceae	Cupressus sempervirens L.					Crude [189]
Cupressaceae	Platycladus orientalis (L.) Franco					Crude [66]
Cupressaceae	Thuja occidentalis L.					Crude [190]
Cyperaceae	Bolboschoenus maritimus (L.) Palla					Crude [66]
Cyperaceae	Cyperus rotundus L.	Rhizome		Crude [68]
Davalliaceae	Davallia mariesii T. Moore ex Baker	Root				Crude [66]
Dioscoreaceae	Dioscorea bulbifera L.				Flavonoid [191]
Dioscoreaceae	Dioscorea hispida Dennst.	Rhizome		Crude Protease [68]
Dioscoreaceae	Dioscorea polystachya Turcz.					Crude inhibition [66]
Dioscoreaceae	Dioscorea tokoro Makino	Root				Crude inhibition [66]
Dipterocarpaceae	Monotes africana A. DC.					Crude [192]
Dryopteridaceae	Cyrtomium fortune J. Sm.	Rhizome		Crude Protease [68]
Dryopteridaceae	Dryopteris crassirhizoma Nakai	Rhizome	Flavonoid [193]	Triterpenes [194]
Ebenaceae	Euclea natalensis A. DC.		Naphthoquinone [195]
Ebenaceae	Diospyros mollis Griff.	Stem	Crude [58]
Elaeocarpaceae	Elaeocarpus grandiflorus Sm.	Fruit		Crude [68]
Ephedraceae	Ephedra americana Humb. & Bonpl. ex Willd.	Stem				Crude [82]
Ephedraceae	Ephedra sinica Stapf	Stem	Crude [196]	Crude [68]		Crude [196]
Equisetaceae	Equisetum arvense L.	Stem				Crude [82]
Equisetaceae	Equisetum giganteum L.	Stem				Crude [82]
Equisetaceae	Equisetum hyemale L.	Aerial part				Crude [66]
Erythroxylaceae	Erythroxylum citrifolium A. St.-Hil.	Trunk		Crude [93]
Eucommiaceae	Eucommia ulmoides Oliv.	Stem bark				Crude [66]
Euphorbiaceae	Acalypha macrostachya Jacq.	Leaf				Crude [93]
Euphorbiaceae	Alchornea cordifolia (Schumach. & Thonn.) Müll. Arg.	Leaf				Crude [80]
Euphorbiaceae	Baliospermum solanifolium (Geiseler) Suresh			Crude [99]
Euphorbiaceae	Chamaesyce hyssopifolia (L.) Small	Whole plant	Crude [93]	Crude [93]
Euphorbiaceae	Croton billbergianus Müll. Arg.	Trunk				Crude [93]
Euphorbiaceae	Croton gratissimus Burch.		Crude [74]
Euphorbiaceae	Croton tiglium L.	Seed				Crude [197]
Euphorbiaceae	Croton zambesicus Müll. Arg.	Seed	Crude [74]	Crude [95]
Euphorbiaceae	Euphorbia erythradenia Boiss.	Aerial part				Triterpene [198]
Euphorbiaceae	Euphorbia granulate Forssk.	Leaf		Crude [95]
Euphorbiaceae	Euphorbia hirta L.	Whole plant	Crude [58]
Euphorbiaceae	Euphorbia hyssopifolia L.	Whole plant	Crude [93]	Crude [93]
Euphorbiaceae	Euphorbia kansui T.N. Liou ex S.B. Ho					Crude [199]
Euphorbiaceae	Euphorbia neriifolia L.	Stem bark				Diterpenoids [200,201]
Euphorbiaceae	Euphorbia polyacantha Boiss.		Crude [74]
Euphorbiaceae	Euphorbia prostrate Aiton			Crude [95]
Euphorbiaceae	Euphorbia thi Schweinf.	Aerial part	Crude [74]
Euphorbiaceae	Homalanthus nutans (G. Forst.) Guill.					Prostratin [202]
Euphorbiaceae	Jatropha curcas L.	Leaf	Crude [93]	Crude [93]		Crude [80,93]
Euphorbiaceae	Mallotus japonicus (L.f.) Müll.Arg.		Tannins [203]
Euphorbiaceae	Mallotus philippensis (Lam.) Müll. Arg.	Flower	Crude [58]
Euphorbiaceae	Maprounea africana Müll. Arg.	Leaf	Xanthone [204] Triterpene [205]			Crude [80] Triterpene [205]
Euphorbiaceae	Neoshirakia japonica (Siebold & Zucc.) Esser	Leaf		Crude [96]
Euphorbiaceae	Ricinus communis L.	Leaf	Lectins [206]	Crude [83]		Crude [207]
Euphorbiaceae	Sapium indicum Willd.	Fruit	Crude [58]
Euphorbiaceae	Shirakiopsis indica (Willd.) Esser		Crude [58]
Euphorbiaceae	Trigonostemon thyrsoideus Stapf	Stem				Diterpenoid [208,209]
Fabaceae	Abrus precatorius L.	Seed		Saponins [210]		Crude [211]
Fabaceae	Acacia catechu (L. f.) Willd.	Resin	Crude [58]			Crude [212]
Fabaceae	Acacia mellifera (Vahl) Benth.	Stem bark	Crude [102]
Fabaceae	Acacia nilotica (L.) Willd. ex Delile	Bark		Crude [95]
Fabaceae	Albizia gummifera (J.F. Gmel.) C.A. Sm.	Stem bark	Crude [102]
Fabaceae	Albizia procera (Roxb.) Benth.				Crude [113]	Crude [113]
Fabaceae	Astragalus propinquus Schischk.	Aerial part		Crude [68]		Crude [51]
Fabaceae	Astragalus spinosus Muschl.	Aerial part				Triterpene [213]
Fabaceae	Bauhinia strychnifolia Craib				Crude [113]
Fabaceae	Bauhinia variegata L.		Crude [134]
Fabaceae	Butea monosperma (Lam.) Taub.	Root				Crude [56]
Fabaceae	Caesalpinia bonduc (L.) Roxb.	Seed		Crude [83]
Fabaceae	Caesalpinia sappan L.	Stem	Crude [58]		Crude [113]	Crude [66]
Fabaceae	Canavalia gladiate (Jacq.) DC.		Crude [134]
Fabaceae	Cassia fistula L.	Bark		Crude [68,83]
Fabaceae	Castanospermum austral A. Cunn. & C. Fraser					Alkaloid [214]
Fabaceae	Cullen corylifolium (L.) Medik.					Crude [66]
Fabaceae	Detarium microcarpum Guill. & Perr.					Flavonoids [215]
Fabaceae	Elephantorrhiza elephantine (Burch.) Skeels	Bulb				Crude [79]
Fabaceae	Erythrina abyssinica Lam.	Bark	Crude [74] [102]			Alkaloids [216]
Fabaceae	Erythrina senegalensis DC.				Flavonoids [217]
Fabaceae	Euchresta formosana (Hayata) Ohwi					Crude [218]
Fabaceae	Gleditsia japonica Miq.	Fruit				Saponin [219]
Fabaceae	Glycine max (L.) Merr.		Crude [134]
Fabaceae	Glycyrrhiza glabra L.			Crude [220]		Crude [56,221]
Fabaceae	Glycyrrhiza uralensis Fisch. ex DC.					Crude [222]
Fabaceae	Gymnocladus chinensis Baill.	Fruit				Saponin [219]
Fabaceae	Hylodendron gabunense Taub.					Crude [223]
Fabaceae	Lespedeza juncea (L. f.) Pers.	Whole plant		Crude [96]
Fabaceae	Lespedeza tomentosa (Thunb.) Siebold ex Maxim.	Leaf		Crude [96]
Fabaceae	Melilotus suaveolens Ledeb.	Whole plant		Crude [96]
Fabaceae	Millettia erythrocalyx Gagnep.	Leaf				Flavonoid [224]
Fabaceae	Peltophorum africanum Sond.	Stem bark	Crude [172]		Crude [172]	Betulinic acid [225]
Fabaceae	Phaseolus vulgaris L.	Seed	Lectin [226]			[223]
Fabaceae	Pongamia pinnata (L.) Pierre	Bark	Flavonoids [227]	Crude [83]
Fabaceae	Prosopis glandulosa Torr.	Leaf				Oleanolic acid [228]
Fabaceae	Psoralea glandulosa L.	Leaf				Crude [82]
Fabaceae	Pterocarpus marsupium Roxb.		Crude [229]
Fabaceae	Pueraria montana (Lour.) Merr.			Crude [60]		Crude [66]
Fabaceae	Saraca indica L.	Bark		Crude [83]
Fabaceae	Securigera securidaca (L.) Degen & Dorfl.		Kaempferol [230]
Fabaceae	Senna alata Roxb.	Aerial part	Crude [57]
Fabaceae	Senna garrettiana (Craib) H.S.Irwin & Barneby				Crude [113]
Fabaceae	Senna obtusifolia (L.) H.S. Irwin & Barneby	Aerial part		Crude [95]		Crude [231]
Fabaceae	Senna occidentalis (L.) Link	Leaf				Crude [56]
Fabaceae	Sophora flavescens Aiton	Root	Crude [196]	Crude [60,96]	Crude [105]	Crude [196]
Fabaceae	Sophora japonica L.	Flower				Crude [66]
Fabaceae	Sophora tonkinensis Gagnep.	Root		Crude [60,68]
Fabaceae	Spatholobus suberectus Dunn	Rhizome		Crude [60,68]	Crude [105]
Fabaceae	Styphnolobium japonicum (L.) Schott	Flower bud		Crude [68]		Crude [66]
Fabaceae	Sutherlandia frutescens (L.) R. Br.		Crude [132]
Fabaceae	Tephrosia purpurea (L.) Pers.	Root		Crude [83]
Fabaceae	Vigna unguiculata (L.) Walp.	Seed		Crude [83]
Fagaceae	Quercus infectoria Olivier	Fruit	Crude [58]
Fagaceae	Quercus robur L.		Crude [175]
Flacourtiaceae	Hydnocarpus anthelminthicus Pierre ex Laness.	Semen				Crude [66]
Gentianaceae	Gentiana asclepiadea L.	Leaf	Crude [62]
Gentianaceae	Gentiana macrophylla Pall.	Root		Crude [68]
Gentianaceae	Gentiana scabra Bunge	Root		Crude [68]
Gentianaceae	Swertia bimaculata (Siebold & Zucc.) Hook. f. & Thomson ex C.B. Clarke					Sesterterpenoid [232]
Gentianaceae	Swertia franchetiana Harry Sm.	Root	Xanthone [204]			Xanthone [233]
Gentianaceae	Swertia punicea Hemsl.					Xanthone [234]
Gentianaceae	Tripterospermum lanceolatum (Hayata) H. Hara ex Satake		Crude [235]
Gesneriaceae	Drymonia serrulata (Jacq.) Mart.	Leaf				Crude [93]
Ginkgoaceae	Ginkgo biloba L.	Semen	Crude [236]	Crude [236] Ginkgolic acid [237]		Crude [66]
Gunneraceae	Gunnera magellanica Lam.	Stem				Crude [82]
Hydrangeaceae	Philadelphus schrenkii Rupr.	Stem		Crude [96]
Hydrocharitaceae	Thalassia testudunum Banks & Sol. ex K.D. Koenig					Crude [238]
Hypericaceae	Cratoxylum arborescens Blume	Leaf				Xanthones [239]
Hypericaceae	Hypericum capitatum Choisy					Crude [240]
Hypericaceae	Hypericum hircinum L.		Crude [241]
Hypericaceae	Hypericum perforatum L.					Crude [242]
Hypericaceae	Vismia baccifera (L.) Triana & Planch.		Crude [155]
Hypericaceae	Vismia cayennensis (Jacq.) Pers.	Leaf				Crude [243]
Hypoxidaceae	Hypoxis hemerocallidea Fisch., C.A. Mey. & Avé-Lall.					Crude [244]
Hypoxidaceae	Hypoxis sobolifera Jacq.	Corm	Crude [75]	Crude [75]
Iridaceae	Aristea ecklonii Baker
Iridaceae	Eleutherine bulbosa (Mill.) Urb.	Bulb				Naphthoquinone [245]
Iridaceae	Iris domestica (L.) Goldblatt & Mabb.			Crude [68]
Juglandaceae	Juglans mandshurica Maxim.	Bark		Crude [96]		Glycosides [246]
Lamiaceae	Aegiphila anomala Pittier	Leaf	Crude [93]
Lamiaceae	Agastache rugosa (Fisch. & C.A. Mey.) Kuntze	Whole plant		Crude [60,96]	Crude [247]	Crude [248]
Lamiaceae	Ajuga decumbens Thunb.		Crude [249]
Lamiaceae	Anisomeles indica (L.) Kuntze					Diterpenoid [250]
Lamiaceae	Clinopodium bolivianum (Benth.) Kuntze	Leaf				Crude [82]
Lamiaceae	Clinopodium chinense (Benth.) Kuntze	Whole plant		Crude [96]
Lamiaceae	Coleus forskohlii (Willd.) Briq.	Aerial part				Crude [56,251]
Lamiaceae	Cornutia grandifolia (Schltdl. & Cham.) Schauer	Trunk				Crude [93]
Lamiaceae	Cornutia pyramidata L.					Crude [93]
Lamiaceae	Hyptis capitata Jacq.	Whole plant				Oleanolic acid [228]
Lamiaceae	Hyptis lantanifolia Poit.	Aerial part	Crude [93]	Crude [93]
Lamiaceae	Hyssopus officinalis L.	Leaf	Crude [252]
Lamiaceae	Isodon excisus (Maxim.) Kudô	Whole plant		Crude [96]
Lamiaceae	Isodon inflexus (Thunb.) Kudô			Crude [96]
Lamiaceae	Leonotis leonurus (L.) R. Br.	Leaf	Crude [75]	Crude [75]
Lamiaceae	Leonurus japonicas Houtt.	Semen				Crude [66]
Lamiaceae	Leonurus sibiricus L.	Aerial part		Crude [96]
Lamiaceae	Lycopus lucidus Turcz. ex Benth.	Whole plant		Crude [68]
Lamiaceae	Marrubium vulgare L.	Leaf				Crude [82]
Lamiaceae	Meehania urticifolia (Miq.) Makino	Whole plant		Crude [96]
Lamiaceae	Melissa officinalis L.	Whole plant				Crude [253]
Lamiaceae	Mentha arvensis L.	Leaf				Crude [66]
Lamiaceae	Mentha canadensis L.	Whole plant		Crude [60,68]
Lamiaceae	Mentha longifolia (L.) Huds.					Crude [254]
Lamiaceae	Minthostachys mollis Griseb.	Leaf				Crude [82]
Lamiaceae	Mosla scabra (Thunb.) C.Y. Wu & H.W. Li	Whole plant		Crude [96]
Lamiaceae	Ocimum basilicum L.	Leaf	Crude [58]			Crude [255]
Lamiaceae	Ocimum kilimandscharicum Baker ex Gürke		Crude [255]
Lamiaceae	Ocimum labiatum (N.E. Br.) A.J. Paton					Triterpenoid [256]
Lamiaceae	Ocimum tenuiflorum L.	Leaf	Crude [54,58]
Lamiaceae	Perilla frutescens (L.) Britton	Leaf		Crude [60]		Crude [66]
Lamiaceae	Plectranthus amboinicus (Lour.) Spreng.	Leaf	Crude [229]	Crude [83,99]
Lamiaceae	Plectranthus barbatus Andrews					Crude [257]
Lamiaceae	Pogostemon heyneanus Benth.	Leaf		Crude [83]
Lamiaceae	Prunella vulgaris L.	Whole plant		Crude [60]	Crude [105]	Crude [51,72,258]
Lamiaceae	Rosmarinus officinalis L.			Crude [259]
Lamiaceae	Salvia haenkei Benth.					Crude [82]
Lamiaceae	Salvia miltiorrhiza Bunge	Root	Crude [260]	Crude Protease [68]	Crude [261]
Lamiaceae	Salvia officinalis L.	Leaf	Crude [262]		Coumarin [263]	Crude [264]
Lamiaceae	Salvia punctate Ruiz & Pav.					Crude [82]
Lamiaceae	Salvia revolute Ruiz & Pav.					Crude [82]
Lamiaceae	Salvia yunnanensis C.H. Wright	Root				Polyphenol [265]
Lamiaceae	Satureja cuneifolia Ten.	Whole plant				Crude [61]
Lamiaceae	Satureja obovate Lag.	Whole plant				Crude [61]
Lamiaceae	Scutellaria baicalensis Georgi	Root		Crude [60,68]		Flavonoid [266]
Lamiaceae	Teucrium buxifolium Schreb.	Whole plant				Crude [61]
Lamiaceae	Vitex glabrata R. Br.	Branche	Crude [57]
Lamiaceae	Vitex negundo L.	Aerial part	Crude [57]
Lamiaceae	Vitex trifolia L.	Aerial part	Crude [57]			Crude [66]
Lardizabalaceae	Akebia quinata (Houtt.) Decne.	Lignum				Crude [66]
Lardizabalaceae	Stauntonia obovatifoliola Hayata			Triterpenoid [267]
Lauraceae	Cinnamomum loureiroi Nees	Stem bark	Crude [58]
Lauraceae	Cinnamomum verum J. Presl	Leaf		Crude [83]
Lauraceae	Lindera aggregate (Sims) Kosterm.	Stem		Crude [60]	Crude [268]	Crude [66]
Lauraceae	Lindera chunii Merr.				Sesquiterpenoid [269]
Lauraceae	Lindera erythrocarpa Makino	Leaf		Crude [270]
Lauraceae	Lindera obtusiloba Blume	Leaf, Stem		Crude [96]
Lauraceae	Litsea glutinosa (Lour.) C.B. Rob.	Bark		Crude [83]
Lauraceae	Litsea verticillata Hance	Leaf	Crude [58]			Crude [271]
Liliaceae	Amana edulis (Miq.) Honda		Crude [196]	Crude [96]		Crude [196]
Liliaceae	Fritillaria cirrhosa D. Don	Rhizome		Crude [60]	Crude [105]
Liliaceae	Fritillaria thunbergii Miq.	Rhizome		Crude [68]
Loasaceae	Caiophora pentlandii (Paxton ex Graham) G. Don ex Loudon	Leaf				Crude [82]
Loganiaceae	Strychnos ignatii P.J. Bergius	Semen				Crude [66]
Loganiaceae	Strychnos nuxvomica L.	Seed	Crude [58]
Loganiaceae	Strychnos potatorum L. f.	Seed		Crude [83]
Loranthaceae	Scurrula parasitica L.	Aerial part		Crude [68]
Lycopodiaceae	Lycopodium japonicum Thunb.					Alkaloids [272]
Lythraceae	Lawsonia inermis L.	Aerial part	Crude [58]
Lythraceae	Lythrum salicaria L.	Leaf	Crude [62]
Lythraceae	Punica granatum L.	Fruit bark	Crude [58]	Crude [68,83]
Lythraceae	Woodfordia fruticosa (L.) Kurz	Flower		Crude [68]
Magnoliaceae	Magnolia biondii Pamp.	Flower bud		Crude [68]
Magnoliaceae	Magnolia denudate Desr.	Flower		Crude [96]
Magnoliaceae	Magnolia obovate Thunb.	Bark		Crude [68]
Magnoliaceae	Magnolia officinalis Rehder & E.H. Wilson	Bark		Crude [68]
Malpighiaceae	Tetrapterys goudotiana Triana & Planch.		Crude [93]	Crude [93]
Malvaceae	Adansonia digitata L.	Leaf	Crude [273]	Crude [273]
Malvaceae	Corchoropsis tomentosa (Thunb.) Makino	Aerial part		Crude [96]
Malvaceae	Grewia mollis Juss.	Root	Crude [102]
Malvaceae	Hibiscus sabdariffa L.	Flower	Crude [58]
Malvaceae	Pavonia schiedeana Steud.	Aerial part	Crude [93]
Malvaceae	Sida cordata (Burm. f.) Borss. Waalk.	Root		Crude [83]		Polyphenols [274]
Malvaceae	Sida mysorensis Wight & Arn.	Seed		Crude [68]		Polyphenols [274]
Malvaceae	Sida rhombifolia L.	Leaf				Crude [80] Polyphenols [274]
Malvaceae	Thespesia populnea (L.) Sol. ex Corrêa					Crude [275]
Malvaceae	Tilia amurensis Rupr.	Leaf, Stem		Crude [96]
Malvaceae	Waltheria indica	Branch		Crude [93]
Meliaceae	Aglaia lawii (Wight) C.J. Saldanha	Leaf			Crude [276]
Meliaceae	Azadirachta indica A. Juss.	Leaf	Crude [58,102]	Crude [83,95]
Meliaceae	Khaya senegalensis (Desr.) A. Juss.			Crude [95]
Meliaceae	Melia azedarach L.	Fruit	Crude [102]			Crude [66]
Meliaceae	Swietenia macrophylla King					Crude [277]
Meliaceae	Swietenia mahagoni (L.) Jacq.	Bark		Crude [278]
Meliaceae	Trichilia emetic Vahl			Crude [95]
Melianthaceae	Bersama abyssinica Fresen.	Root			Crude [174]
Menispermaceae	Coscinium fenestratum Colebr.	Gall	Crude [158]	Crude [83,158]	Crude [158]
Menispermaceae	Pericampylus glaucus (Lam.) Merr.	Aerial part				Alkaloids [279]
Menispermaceae	Sinomenium acutum (Thunb.) Rehder & E.H. Wilson	Root		Crude [96]
Menispermaceae	Stephania cephalantha Hayata	Root				Crude [280]
Menispermaceae	Tinospora crispa (L.) Hook. f. & Thomson	Vine	Crude [57]		Crude [281]
Menispermaceae	Tinospora sinensis (Lour.) Merr.	Stem bark	Crude [54]			Crude [56]
Menyanthaceae	Nymphoides peltata (S.G. Gmel.) Kuntze	Whole plant				Crude [66]
Monimiaceae	Boldea fragrans Endl.					Crude [82]
Moraceae	Artocarpus heterophyllus Lam.	Seed	Crude [58]
Moraceae	Ficus carica L.	Leaf				Crude [124]
Moraceae	Ficus edelfeltii King	Bark		Crude [68]
Moraceae	Ficus racemosa L.	Bark			Crude [282]
Moraceae	Ficus religiosa L.	Bark		Crude [83]
Moraceae	Maclura cochinchinensis (Lour.) Corner	Stem	Crude [58]
Moraceae	Maclura tinctoria (L.) D. Don ex Steud.					Xanthones [283]
Moraceae	Morus alba L.	Stem bark				Crude [66]
Moringaceae	Moringa oleifera Lam.	Seed	Crude [58,74]
Musaceae	Musa acuminata Colla	Fruit				Lectin [284]
Myricaceae	Morella salicifolia (Hochst. ex A. Rich.) Verdc. & Polhill	Root bark	Crude [102]
Myricaceae	Myrica salicifolia Hochst. ex A. Rich.	Root bark	Crude [102]
Myristicaceae	Myristica fragrans Houtt.	Stem	Crude [58]	Crude [83]
Myrothamnaceae	Myrothamnus flabellifolius Welw.	Leaf	Polyphenol [285]
Myrtaceae	Corymbia citriodora (Hook.) K.D. Hill & L.A.S. Johnson					Crude [80]
Myrtaceae	Eucalyptus citriodora Hook.	Leaf				Crude [80]
Myrtaceae	Eugenia hiemalis Cambess.					Glycosides [286]
Myrtaceae	Psidium guajava L.					Saponin [287]
Myrtaceae	Syzygium aromaticum (L.) Merr. & L.M. Perry					Crude [288]
Myrtaceae	Syzygium claviflorum (Roxb.) Wall. ex A.M. Cowan & Cowan	Leaf				Oleanolic acid [228]
Myrtaceae	Syzygium cumini (L.) Skeels	Bark		Crude [83]
Nelumbonaceae	Nelumbo nucifera Gaertn.	Leaf				Crude [289]
Nyctaginaceae	Boerhavia caribaea Jacq.	Root				Crude [82]
Nyctaginaceae	Boerhavia diffusa L.					Crude [290]
Nyctaginaceae	Boerhavia erecta L.				Glycosides [291]
Ochnaceae	Ochna integerrima (Lour.) Merr.	Leaf				Flavonoids [292]
Olacaceae	Heisteria spruceana Engl.	Bark				Crude [82]
Olacaceae	Ximenia americana L.	Stem bark				Crude [174]
Olacaceae	Ximenia caffra Sond.		Crude [293]
Oleaceae	Chionanthus retusus Lindl. & Paxton			Crude [96]
Oleaceae	Ligustrum lucidum W.T. Aiton	Fruit		Crude [60]	Crude [105]
Onagraceae	Epilobium angustifolium L.	Leaf	Crude [62]
Onagraceae	Oenothera erythrosepala (Borbás) Borbás	Leaf				Oenothein [294]
Onocleaceae	Matteuccia struthiopteris (L.) Tod.	Rhizome		Crude [68]
Orchidaceae	Arundina graminifolia (D. Don) Hochr.	Whole plant				Crude [295]
Orchidaceae	Bletilla striata (Thunb.) Rchb. f.	Root				Crude [66]
Orchidaceae	Dendrobium moniliforme (L.) Sw.	Whole plant				Crude [66]
Orobanchaceae	Melampyrum roseum Maxim.	Whole plant		Crude [96]
Orobanchaceae	Pedicularis resupinata L.	Whole plant		Crude [96]
Orobanchaceae	Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey.	Root				Crude [66]
Paeoniaceae	Paeonia lactiflora Pall.					Crude [66]
Paeoniaceae	Paeonia suffruticosa Andrews	Root		Crude [60,68]	Crude [105]
Papaveraceae	Argemone mexicana L.	Leaf				Crude [56]
Papaveraceae	Papaver somniferum L.	Seed				Crude [56]
Parmeliaceae	Usnea florida (L.) Weber ex F.H. Wigg.	Whole plant				Crude [82]
Pentaphylacaceae	Ternstroemia gymnanthera (Wight & Arn.) Sprague	Aerial part				Oleanolic acid [228]
Phrymaceae	Phryma leptostachya L.	Whole plant		Crude [96]
Phyllanthaceae	Aporosa cardiosperma (Gaertn.) Merr.			Crude [99]
Phyllanthaceae	Bridelia ferruginea Benth.	Stem bark				Crude [80]
Phyllanthaceae	Bridelia micrantha (Hochst.) Baill.	Root	Crude [296]
Phyllanthaceae	Hymenocardia acida Tul.	Leaf				Crude [80]
Phyllanthaceae	Phyllanthus amarus Schumach. & Thonn.		Crude [297]
Phyllanthaceae	Phyllanthus emblica L.	Fruit	Crude [83]			Crude [175]
Phyllanthaceae	Phyllanthus myrtifolius Moon ex Hook. f.		Lignans [137]
Phyllanthaceae	Phyllanthus niruri L.		Crude [298]
Phyllanthaceae	Phyllanthus sellowianus (Klotzsch) Müll. Arg.		Crude [122]			Crude [108]
Pinaceae	Pinus nigra J.F. Arnold	Seed				Crude [299]
Pinaceae	Pinus parviflora Siebold & Zucc.	Cone				Crude [300]
Piperaceae	Piper aduncum L.					Crude [82]
Piperaceae	Piper elongatum Vahl	Leaf				Crude [82]
Piperaceae	Piper longum L.	Fruit				Crude c
Plantaginaceae	Digitalis purpurea L.	Leaf				Crude [82]
Plantaginaceae	Scoparia dulcis L.	Leaf	Crude [301]
Plumbaginaceae	Plumbago indica L.	Root	Crude [58]
Poaceae	Chrysopogon zizanioides (L.) Roberty	Root		Crude [83]
Poaceae	Coix lacryma L.	Seed		Crude [68]
Poaceae	Cortaderia rudiuscula Stapf	Leaf				Crude [82]
Poaceae	Saccharum officinarum L.	Stem	Crude [58]
Poaceae	Sasa borealis (Hack.) Makino & Shibata	Whole plant		Crude [96]
Polemoniaceae	Cantua hibrida Herrera	Leaf				Crude [82]
Polygalaceae	Polygala tenuifolia Willd.	Root				Crude [66]
Polygonaceae	Muehlenbeckia fruticulosa (Walp.) Standl.	Leaf				Crude [82]
Polygonaceae	Persicaria tinctoria (Aiton) H. Gross	Whole plant		Crude [96]
Polygonaceae	Polygonum aviculare L.	Aerial part				Crude [66]
Polygonaceae	Polygonum senticosum (Meisn.) Franch. & Sav.	Whole plant		Crude [96]
Polygonaceae	Reynoutria japonica Houtt.	Root		Crude [68]
Polygonaceae	Reynoutria multiflora (Thunb.) Moldenke			Crude [60]	Crude [105]
Polygonaceae	Rheum palmatum L.	Rhizome	Sennoside [302]	Crude [68] Sennoside [302]	Sennoside [302]
Polygonaceae	Rheum tanguticum Maxim. ex Balf.					Glycosides [303]
Polygonaceae	Rumex crispus L.	Root				Crude [82]
Polygonaceae	Rumex cyprius Murb.		Crude [175]
Polygonaceae	Rumex frutescens Thouars	Root				Crude [82]
Polygonaceae	Rumex nepalensis Spreng.					Crude [111]
Polygonaceae	Rumex peruanus Rech. f.	Leaf				Crude [82]
Polypodiaceae	Drynaria roosii Nakaike	Rhisome		Crude [68]
Polypodiaceae	Pleopeltis pycnocarpa (C. Chr.) A.R. Sm.					Crude [82]
Polypodiaceae	Polypodium pycnocarpum C. Chr.	Root				Crude [82]
Polypodiaceae	Pyrrosia lingua (Thunb.) Farw.	Aerial part				Crude [66]
Polypodiaceae	Polytrichum commune Hedw.		Crude [62]
Portulacaceae	Portulaca oleracea L.	Aerial part		Crude [68]
Primulaceae	Ardisia japonica (Thunb.) Blume	Aerial part				Crude [304]
Primulaceae	Embelia ribes Burm. f.	Fruit				Crude [56]
Proteaceae	Conospermum incurvum Lindl.					Crude [305]
Ranunculaceae	Aconitum ferox Wall. ex Ser.	Tuber		Crude [83]
Ranunculaceae	Aconitum jaluense Kom.	Root				Crude [66]
Ranunculaceae	Aconitum uchiyamai Nakai	Root		Crude [96]
Ranunculaceae	Actaea heracleifolia (Kom.) J. Compton	Rhizome		Crude [68]
Ranunculaceae	Anemone chinensis Bunge	Root		Crude [68]
Ranunculaceae	Clematis chinensis Osbeck	Root		Crude [60,68]
Ranunculaceae	Clematis mandschurica Max.			Crude [96]
Ranunculaceae	Coptis chinensis Franch.	Rhizome		Crude [60,68]	Crude [105]	Crude [72]
Ranunculaceae	Nigella sativa L.	Seed		Crude [83]
Ranunculaceae	Pulsatilla cernua (Thunb.) Bercht. ex J. Presl	Root				Crude [66]
Resedaceae	Reseda lutea L.	Whole plant				Crude [61]
Resedaceae	Reseda suffruticosa Loefl.	Whole plant				Crude [61]
Rhamnaceae	Berchemia berchemiifolia (Makino) Koidz.	Bark		Crude [96,270]
Rhamnaceae	Rhamnus staddo A. Rich.		Crude [102]
Rhamnaceae	Ziziphus spina-christi (L.) Desf.	Fruit	Crude [74]
Rhizophoraceae	Rhizophora mucronata Lam.	Leaf	Crude [54]	Crude [55]
Rosaceae	Agrimonia pilosa Ledeb.	Whole plant		Crude [96]
Rosaceae	Alchemilla andina (L.M. Perry) J.F. Macbr.	Stem				Crude [82]
Rosaceae	Chaenomeles sinensis (Thouin) Koehne	Fruit				Crude [66]
Rosaceae	Crataegus pinnatifida Bunge	Leaf		Crude [96] Triterpenes [306]
Rosaceae	Eriobotrya japonica (Thunb.) Lindl.	Leaf		Crude [96]		Crude [66]
Rosaceae	Geum macrophyllum Willd.	Whole plant		Crude [68]
Rosaceae	Malus baccata (L.) Borkh.	Stem		Crude [96]
Rosaceae	Malus sieboldii (Regel) Rehder	Stem		Crude [96]
Rosaceae	Prunus africana (Hook. f.) Kalkman	Stem bark	Crude [102]
Rosaceae	Prunus armeniaca L.	Seed		Crude [68]
Rosaceae	Prunus mume (Siebold) Siebold & Zucc.	Fruit		Crude [68]
Rosaceae	Prunus persica (L.) Batsch	Semen				Crude [66]
Rosaceae	Prunus yedoensis Matsum.	Stem bark				Crude [66]
Rosaceae	Rosa damascena Mill.					Crude [307]
Rosaceae	Rosa davurica Pall.			Crude [308]
Rosaceae	Rosa laevigata Michx.	Fruit				Crude [66]
Rosaceae	Rosa woodsii Lindl.	Leaf				Oleanolic acid [228]
Rosaceae	Sanguisorba minor Scop.	Whole plant				Crude [61]
Rosaceae	Sanguisorba officinalis L.	Root		Crude [96]		Crude [309]
Rosaceae	Sorbus commixta Hedl.	Stem		Crude [96]
Rosaceae	Stephanandra incise (Thunb.) Siebold & Zucc. ex Zabel			Crude [96]
Rubiaceae	Canthium coromandelicum (Burm.f.) Alston	Leaf	Crude [310]
Rubiaceae	Cinchona pubescens Vahl	Bark				Crude [82]
Rubiaceae	Cruciata glabra Ehrend.		Crude [62]
Rubiaceae	Galium aparine L.	Leaf	Crude [62]
Rubiaceae	Galium mollugo L.	Leaf	Crude [62]
Rubiaceae	Galium verum L.	Whole plant		Crude [96]
Rubiaceae	Gardenia ternifolia Schumach. & Thonn.		Crude [74]
Rubiaceae	Gardenia tubifera Wall. ex Roxb.	Leaf	Cycloartanes [311]
Rubiaceae	Hedyotis corymbosa (L.) Lam.			Crude [99]
Rubiaceae	Hedyotis diffusa Willd.	Aerial part				Crude [66]
Rubiaceae	Morinda citrifolia L.	Leaf	Crude [158]	Crude [158]	Crude [158]
Rubiaceae	Oldenlandia diffusa (Willd.) Roxb.	Whole plant		Crude [60,68]	Crude [105]
Rubiaceae	Oldenlandia herbacea (L.) Roxb.	Root		Crude [83]
Rubiaceae	Rubia cordifolia L.	Root	Crude [229]			Crude [56]
Rubiaceae	Sarcocephalus latifolius (Sm.) Bruce			Crude [95]		Crude [312]
Rutaceae	Aegle marmelos (L.) Corrêa	Leaf		Crude [83]		Crude [56]
Rutaceae	Citrus hystrix DC.	Fruit bark	Crude [58]
Rutaceae	Clausena anisata	root	Crude [102]			Crude [313]
Rutaceae	Clausena excavate (Willd.) Hook. f. ex Benth.	Aerial part	Crude [57]			Limonoid [314]
Rutaceae	Dictamnus albus L.	Root bark		Crude [68]
Rutaceae	Murraya koenigii (L.) Spreng.	Aerial part	Crude [57]
Rutaceae	Phellodendron amurense Rupr.	Bark		Crude [68]
Rutaceae	Tetradium ruticarpum (A. Juss.) T.G. Hartley			Crude [68]
Rutaceae	Toddalia asiatica (L.) Lam.	Root	Crude [102]			Alkaloid [315]
Rutaceae	Vepris simplicifolia (Engl.) Mziray		Crude [102]
Rutaceae	Zanthoxylum bungeanum Maxim.	Fruit peel		Crude [68]		Crude [66]
Rutaceae	Zanthoxylum chalybeum Engl.	Root bark	Crude [102]			Crude [211]
Rutaceae	Zanthoxylum schinifolium Siebold & Zucc.	Fruit peel		Crude [68,96]
Salvadoraceae	Salvadora persica L.	Stem	Crude [74]	Crude [95]
Santalaceae	Phoradendron juniperinum Engelm. ex A. Gray	Whole plant				Oleanolic acid [228]
Santalaceae	Viscum album L.	Flower				Crude [118]
Sapindaceae	Acer okamotoanum Nakai	Leaf			Flavonoid [316]
Sapindaceae	Acer pictum Thunb.	Stem		Crude [96]
Sapindaceae	Aesculus chinensis Bunge	Seed				Triterpenoid [317]
Sapindaceae	Aesculus turbinate Blume	Fruit		Crude [96]
Sapindaceae	Allophylus cobbe (L.) Raeusch.	Leaf			Crude [318]
Sapindaceae	Dodonaea viscosa Jacq.	Leaf				Crude [82,174]
Sapindaceae	Koelreuteria paniculata Laxm.	Stem		Crude [96]
Sapindaceae	Nephelium lappaceum L.	Seed	Crude [319]
Sapindaceae	Serjania mexicana (L.) Willd.	Whole plant		Crude [93]
Sapotaceae	Madhuca longifolia (J. Koenig ex L.) J.F. Macbr.	Bark				Crude [56]
Sapotaceae	Mimusops elengi L.	Bark	Crude [320]	Crude [83]		Saponin [321]
Sapotaceae	Tieghemella heckelii Pierre ex A. Chev.	Leaf				Crude [318]
Sauruaceae	Houttuynia cordata Thunb.	Aerial part				Crude [66,322]
Sauruaceae	Saururus chinensis (Lour.) Baill.	Rhizome				Lignans [323]
Saxifragaceae	Astilbe grandis Stapf ex E.H. Wilson	Aerial part		Crude [96]
Saxifragaceae	Astilbe rubra Hook. f. & Thomson ex Hook.	Whole plant		Crude [96]
Schisandraceae	Illicium verum Hook. f.	Root				Phytochemicals [324]
Schisandraceae	Kadsura angustifolia A.C. Sm.					Lignans [325]
Schisandraceae	Kadsura heteroclite (Roxb.) Craib			Triterpenoid [326]		Crude [327]
Schisandraceae	Kadsura longipedunculata Finet & Gagnep.			Lignans [328]
Schisandraceae	Schisandra chinensis (Turcz.) Baill.	Fruit		Protease [68]
Schisandraceae	Schisandra lancifolia (Rehder & E.H. Wilson) A.C. Sm.	Leaf, Stem				Triterpenoid [329] Nortriterpenoid [330]
Schisandraceae	Schisandra propinqua Hook. f. & Thomson	Aerial part				Lignans [331]
Schisandraceae	Schisandra rubriflora (Franch.) Rehder & E.H. Wilson					Lignans [332]
Schisandraceae	Schisandra sphaerandra Stapf	Stem	Triterpenoid [333]			Triterpenoid [333]
Schisandraceae	Schisandra sphenanthera Rehder & E.H. Wilson	Leaf, Stem				Nortriterpenoid [334] Triterpenoids [335]
Schisandraceae	Schisandra wilsoniana A.C. Sm.	Fruit				Lignans [336]
Scrophulariaceae	Buddleja officinalis Maxim.	Flower				Crude [66]
Scrophulariaceae	Scrophularia buergeriana Miq.	Root		Crude [96]
Scrophulariaceae	Scrophularia kakudensis Franch.	Aerial part		Crude [96]
Scrophulariaceae	Verbascum densiflorum Bertol.		Crude [62]
Scrophulariaceae	Verbascum thapsiforme Schrad.		Crude [62]
Selaginellaceae	Selaginella tamariscina (P. Beauv.) Spring	Aerial part				Crude [66]
Simaroubaceae	Ailanthus altissima (Mill.) Swingle	Stem bark				Crude [66]
Simaroubaceae	Brucea javanica (L.) Merr.	Seed	Crude [58]	Crude [68]
Simaroubaceae	Leitneria floridana Chapm.					Crude [337]
Simaroubaceae	Quassia amara L.	Bark				Crude [82]
Smilacacea	Smilax campestris Griseb.	Root				Crude [82]
Smilacacea	Smilax china L.	Fruit		Crude [96]		Crude [338]
Solanaceae	Cestrum parqui L’Hér.	Leaf				Crude [82]
Solanaceae	Lycium chinense Mill.	Fruit				Crude [66]
Solanaceae	Physaliastrum japonicum (Franch. & Sav.) Honda	Aerial part		Crude [96]
Solanaceae	Solanum incanum L.					Betulinic acid [339]
Solanaceae	Solanum tomentosum L.		Crude [340]
Solanaceae	Solanum virginianum L.					Crude [341]
Solanaceae	Withania somnifera (L.) Dunal	Root	Crude [54]	Crude [342]
Staphyleaceae	Staphylea bumalda DC.	Whole plant		Crude [96]
Styracaceae	Styrax japonicas Siebold & Zucc.	Stem				Lignins [343]
Styracaceae	Styrax obassis Siebold & Zucc.	Stem		Crude [96]
Tamaricaceae	Tamarix senegalensis DC.		Crude [74]
Taxaceae	Taxus caespitosa Nakai	Stem		Crude [96]
Taxaceae	Taxus cuspidate Siebold & Zucc.			Crude [96]
Theaceae	Camellia japonica L.	Leaf		Crude [344]
Theaceae	Stewartia koreana Nakai ex Rehder	Leaf		Crude [96]
Thymelaeaceae	Daphne acutiloba Rehder					Diterpene [345]
Thymelaeaceae	Daphne feddei H.Lév.	Leaf, Stem				Lignans [346]
Thymelaeaceae	Wikstroemia indica (L.) C.A. Mey.					Crude [347]
Typhaceae	Typha domingensis Pers.		Crude [102]
Ulmaceae	Ulmus davidiana Planch.	Leaf, Stem		Crude [96]
Ulmaceae	Ulmus pumila L.	Bark				Crude [66]
Urticaceae	Myrianthus holstii Engl.					Lectin [348]
Urticaceae	Phenax angustifolius (Kunth) Wedd.	Leaf				Lignans [349]
Urticaceae	Urtica dioica L.	Rhizome	Crude [62]			Crude [350]
Urticaceae	Urtica magellanica Juss. ex Poir.	Leaf				Crude [82]
Urticaceae	Urtica urens L.	Leaf				Crude [82]
Verbenaceae	Lampaya medicinalis Phil.	Leaf				Crude [82]
Verbenaceae	Lippia javanica (Burm f.) Spreng.		Phytochemicals [351]
Verbenaceae	Stachytarpheta jamaicensis (L.) Vahl	Whole plant	Crude [57]
Violaceae	Viola yedoensis Makino	Whole plant		Crude [60]	Crude [105]	Crude [72]
Vitaceae	Cissus quadrangularis L.	Stem	Crude [74]
Vitaceae	Vitis vinifera L.				Phytochemicals [352]
Xanthorrhoeaceae	Aloe ferox Mill.					Crude [353]
Xanthorrhoeaceae	Aloe vera (L.) Burm. f.					Crude [354]
Xanthorrhoeaceae	Asphodelus ramosus L.	Whole plant				Crude [61]
Xanthorrhoeaceae	Bulbine alooides Willd.	Roots	Crude [75]	Crude [75]
Zingiberaceae	Alpinia galangal (L.) Willd.			Crude [355]		Crude [356]
Zingiberaceae	Alpinia officinarum Hance	Root		Crude [68]		Crude [66]
Zingiberaceae	Boesenbergia rotunda (L.) Mansf.			Phytochemicals [357]		Flavonoid [358]
Zingiberaceae	Curcuma longa L.	Rhizome	Crude [58]	Crude [83]	Crude [359]	Crude [66]
Zingiberaceae	Curcuma zanthorrhiza Roxb.		Crude [58]
Zingiberaceae	Elettaria cardamomum (L.) Maton	Fruit		Crude [83]
Zingiberaceae	Kaempferia parviflora Wall. ex Baker			Crude [355]
Zygophyllaceae	Balanites aegyptiacus (L.) Delile	Bark		Crude [95]
Zygophyllaceae	Larrea tridentata (Sessé & Moc. ex DC.) Coville					Lignan [360]
Zygophyllaceae	Tribulus terrestris L.	Fruit		Crude [95]		Crude [66]

Table 2.

Plant names which are having synonyms found in theplantlist.org.

Reported Name	Accepted Name
Aglaia andamanica Hiern	Aglaia lawii (Wight) C.J. Saldanha
Andropogon muricatus Retz.	Chrysopogon zizanioides (L.) Roberty
Angelica koreana Maxim.	Angelica grosseserrata Maxim.
Aporosa lindleyana (Wight) Baill.	Aporosa cardiosperma (Gaertn.) Merr.
Aster koraiensis Nakai	Miyamayomena koraiensis (Nakai) Kitam.
Aster scaber Elliott	Symphyotrichum undulatum (L.) G.L. Nesom
Astilbe chinensis (Maxim.) Franch. & Sav.	Astilbe rubra Hook. f. & Thomson ex Hook.
Astilbe koreana (Kom.) Nakai	Astilbe grandis Stapf ex E.H. Wilson
Astragalus membranaceus Moench	Astragalus propinquus Schischk.
Baliospermum montanum (Willd.) Müll. Arg.	Baliospermum solanifolium (Geiseler) Suresh
Baphicacanthus cusia (Nees) Bremek.	Strobilanthes cusia (Nees) Kuntze
Belamcanda chinensis (L.) Redouté	Saposhnikovia divaricate (Turcz.) Schischk.
Boesenbergia pandurata (Roxb.) Schltr.	Boesenbergia rotunda (L.) Mansf.
Brassica alboglabra L.H. Bailey	Brassica oleracea L.
Brassica campestris L.	Brassica rapa L.
Caesalpinia bonducella (L.) Fleming	Caesalpinia bonduc (L.) Roxb.
Carissa edulis (Forssk.) Vahl	Carissa spinarum L.
Cassia garrettiana Craib	Senna garrettiana (Craib) H.S. Irwin & Barneby
Cassia occidentalis L.	Senna occidentalis (L.) Link
Chamaesyce hyssopifolia (L.) Small	Euphorbia hyssopifolia L.
Cimicifuga heracleifolia Kom.	Actaea heracleifolia (Kom.) J. Compton
Clerodendrum inerme (L.) Gaertn.	Volkameria inermis L.
Coleus amboinicus Lour.	Plectranthus amboinicus (Lour.) Spreng.
Curcuma domestica Valeton	Curcuma longa L.
Cydonia vulgaris Pers.	Chaenomeles sinensis (Thouin) Koehne
Dictamnus dasycarpus Turcz.	Dictamnus albus L.
Dodonaea angustifolia L. f.	Dodonaea viscosa Jacq.
Dolichos biflorus L.	Vigna unguiculata (L.) Walp.
Drymaria diandra Blume	Drymaria cordata (L.) Willd. ex Schult.
Drynaria fortunei (Kunze ex Mett.) J. Sm.	Drynaria roosii Nakaike
Elaeodendron croceum (Thunb.) DC.	Cassine crocea (Thunb.) C. Presl
Eleutherine americana (Aubl.) Merr. ex K. Heyne	Eleutherine bulbosa (Mill.) Urb.
Enantia chlorantha Oliv.	Annickia chlorantha (Oliv.) Setten & Maas
Epinetrum villosum Troupin	Albertisia villosa Forman
Erythroxylum lucidum Kunth	Erythroxylum macrophyllum Cav.
Eugenia caryophyllata Thunb.	Syzygium aromaticum (L.) Merr. & L.M. Perry
Eugenia jambolana Lam.	Syzygium cumini (L.) Skeels
Eupatorium buniifolium Hook. ex Arn.	Acanthostyles buniifolius (Hook. ex Arn.) R.M. King & H. Rob.
Euodia ruticarpa (A. Juss.) Benth.	Tetradium ruticarpum (A. Juss.) T.G. Hartley
Ferula sumbul (Kauffm.) Hook. f.	Ferula moschata (H. Reinsch) Koso-Pol.
Garcinia cambogia Roxb.	Garcinia gummi-gutta Roxb.
Garcinia edulis Exell	Garcinia buchneri Engl.
Garcinia polyantha Oliv.	Garcinia smeathmannii (Planch. & Triana) Oliv.
Geum japonicum Thunb.	Geum macrophyllum Willd.
Ginkgo biloba L.	Salisburia ginkgo (L.) Rich.
Glycosmis montana Pierre	Glycosmis lanceolata (Blume) Teijsm. & Binn. ex Kurz
Kadsura interior A.C. Sm.	Kadsura heteroclite (Roxb.) Craib
Kalopanax pictus (Thunb.) Nakai	Acer pictum Thunb.
Ledebouriella divaricate (Turcz.) Hiroë	Saposhnikovia divaricate (Turcz.) Schischk.
Lespedeza cuneata (Dum. Cours.) G. Don	Lespedeza juncea (L. f.) Pers.
Lindera glauca (Siebold & Zucc.) Blume	Lindera communis Hemsl.
Litsea sebifera Pers.	Litsea glutinosa (Lour.) C.B. Rob.
Loranthus parasiticus (L.) Merr.	Scurrula parasitica L.
Madhuca indica J.F. Gmel.	Madhuca longifolia (J. Koenig ex L.) J.F. Macbr.
Magnolia fargesii (Finet & Gagnep.) W.C. Cheng	Magnolia biondii Pamp.
Margyricarpus setosus Ruiz & Pav.	Margyricarpus pinnatus (Lam.) Kuntze
Maytenus heterophylla (Eckl. & Zeyh.) N. Robson	Gymnosporia heterophylla (Eckl. & Zeyh.) Loes.
Maytenus senegalensis (Lam.) Exell	Gymnosporia senegalensis (Lam.) Loes.
Melandrium seoulense (Nakai) Nakai	Silene seoulensis Nakai
Mentha haplocalyx Briq.	Mentha canadensis L.
Mosla punctulata (J.F. Gmel.) Nakai	Mosla scabra (Thunb.) C.Y. Wu & H.W. Li
Mutisia viciifolia fo. intermedia Cuatrec.	Mutisia acuminata Ruiz & Pav.
Orthosiphon labiatus N.E. Br.	Ocimum labiatum (N.E. Br.) A.J. Paton
Persicaria senticosa (Meisn.) H. Gross ex Nakai	Polygonum senticosum (Meisn.) Franch. & Sav.
Peucedanum graveolens (L.) Hiern	Anethum graveolens L.
Phoradendron juniperinum Engelm. ex A. Gray	Phoradendron ligatum Trel.
Polanisia icosandra (L.) Wight & Arn.	Cleome viscosa L.
Polygonum cuspidatum Sieb. et Zucc.	Reynoutria japonica Houtt.
Polygonum multiflorum (Meisn.) H. Gross ex Nakai	Reynoutria multiflora (Thunb.) Moldenke
Pongamia glabra Vent.	Pongamia pinnata (L.) Pierre
Pulsatilla chinensis (Bunge) Regel	Anemone chinensis Bunge
Quercus pedunculata Hoffm.	Quercus robur L.
Rhodiola rosea L.	Sedum rosea (L.) Scop.
Rhus acuminata DC.	Toxicodendron acuminatum (DC.) C.Y. Wu & T.L. Ming
Rhus javanica L.	Brucea javanica (L.) Merr.
Rhodiola rosea L.	Sedum rosea (L.) Scop.
Rumex bequaertii De Wild.	Rumex nepalensis Spreng.
Rumex cuneifolius Campd.	Rumex frutescens Thouars
Sapium japonicum (Siebold & Zucc.) Pax & K. Hoffm.	Neoshirakia japonica (Siebold & Zucc.) Esser
Satureja boliviana (Benth.) Briq.	Clinopodium bolivianum (Benth.) Kuntze
Scrophularia koraiensis Nakai	Scrophularia kakudensis Franch.
Senecio culcitioides Sch. Bip.	Senecio comosus Sch. Bip.
Scutellaria baicalensis Georgi	Scutellaria macrantha Fisch. ex Rchb.
Sophora angustifolia Siebold & Zucc.	Sophora flavescens Aiton
Sophora japonica L.	Styphnolobium japonicum (L.) Schott
Sophora subprostrata Chun & T.C. Chen	Sophora tonkinensis Gagnep.
Syringa dilatata Nakai	Syringa oblata var. dilatata (Nakai) Rehder
Teclea simplicifolia (Engl.) I. Verd.	Vepris simplicifolia (Engl.) Mziray
Tinospora cordifolia (Willd.) Miers ex Hook. f. & Thomson	Tinospora sinensis (Lour.) Merr.
Trigonostemon lii Y.T. Chang	Trigonostemon bonianus Gagnep.
Tripterygium hypoglaucum (H. Lév.) Hutch.	Tripterygium wilfordii Hook. f.
Tulipa edulis (Miq.) Baker	Amana edulis (Miq.) Honda
Veronica linariifolia Pall. ex Link	Pseudolysimachion linariifolium (Pall. ex Link) Holub
Wedelia chinensis (Osbeck) Merr.	Sphagneticola calendulacea (L.) Pruski
Werneria ciliolate A. Gray	Xenophyllum ciliolatum (A. Gray) V.A. Funk
Werneria dactylophylla Sch. Bip.	Xenophyllum dactylophyllum (Sch. Bip.) V.A. Funk
Woodfordia floribunda Salisb.	Woodfordia fruticosa (L.) Kurz

The Food and Drug Administration (FDA or USFDA) classifies antiretroviral drugs for HIV infection into the following categories:

• (1)Multi-class Combination Products,
• (2)Nucleoside Reverse Transcriptase Inhibitors (NRTIs),
• (3)Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs),
• (4)Protease Inhibitors (PIs),
• (5)Fusion Inhibitors,
• (6)Entry Inhibitors—CCR5 co-receptor antagonist and
• (7)HIV integrase strand transfer inhibitors.

For better understanding, 1st, 5th and 6th types are not explicitely mentioned in this article. 2nd and 3rd classes are categorized into HIV-reverse transcription (HIV-RT), 4th type as HIV-protease (HIV-PR) and 7th type as HIV-integrase (HIV-IN). Painter et al. [47] Konvalinka et al. [48] and Blanco et al. [49] have reviewed the roles of HIV-RT, HIV-PR and HIV-IN, respectively. Also, Matthée et al. [50] have discussed the natural inhibitors of HIV-RT.

Of these 717 species, HIV-RT, HIV-PR, and HIV-IN are reported for 206, 254 and 43 species, respectively. Apart from these three inhibitor studies, researchers have also evaluated 390 species for other enzyme inhibition studies which are grouped under anti-HIV activities.

3. Plant Extracts and Some Secondary Metabolites with Anti-HIV Activity

Most of the world’s cultures have centuries of tradition in the use of plant materials in order to control diseases. With recent advancement in pharmacognosy and technology along with the current trends of a more health-conscious general public, natural products are becoming a popular resource for researchers to discover novel and more effective antiviral drugs, considering the relatively reduced adverse effects and cost effectiveness of natural products in commercial scale [361]. Plants, as evolutionary responses to infections by fungi, nematodes, and other organisms, to avoid herbivory, and to comptete for light and space, produce numerous secondary metabolites such as phenolics, glycosides, alkaloids, coumarins, terpenoids, essential oils and peptides. These metabolites have been identified with different biological activities. Some of them play an important role in immune system enhancement, exhibiting antiviral potential [362], including viral infections associated with Human Immunodeficiency Virus type 1 (HIV-1) and 2 (HIV-2) as genetic variabilities. An increasing number of patients with HIV infection cannot use the currently approved anti-HIV drugs including the reverse transcriptase and protease inhibitors, due to the adverse reactions, particularly liver diseases, that have been reported for antiretroviral drugs. The best antiretroviral therapy (HAART) has also fallen short of completely suppressing HIV replication [363]. Therefore, the discovery and development of new anti-HIV agents or new mechanisms of activity from medicinal plants are required to reduce toxicity in drug application and to minimize side effects when compared with current synthetic drugs [364]. The potential utilization of plant extracts and their secondary metabolites to combat the development of anti-HIV agents is considered to be one of the most important approaches toward effective therapy for AIDS [365]. Bioassay-guided fractionation and isolation of secondary metabolites from medicinal plants according to their preliminary high throughput screenings provide systematic source to the novel compounds. The in vitro and in vivo evaluation affirmed the therapeutic potentials in these chemical compounds. Thus, traditional medicines can serve as sources of potential new drug candidates and initial research has focused on the isolation of bioactive lead compounds [366].

Many compounds with anti-HIV-1 effects have been screened and isolated from natural sources and discovered to inhibit HIV at nearly all stages of the viral life cycle. They include alkaloids, sulfated polysaccharides, polyphenolics, flavonoids, coumarins, phenolics, tannins, triterpenes, lectins, phloroglucinols, lactones, iridoids, depsidones, O-caffeoyl derivatives, lignans, ribosome inactivating proteins, saponins, xanthones, naphthodianthrones, photosensitisers, phosholipids, quinones and peptides [367]. Natural products provide a large reservoir for screening of anti-HIV agents with novel structures and anti-viral mechanisms because of their structural diversity. A variety of natural products have been found to inhibit unique enzymes and proteins crucial to the life cycle of HIV including efficient intervention with the reverse transcription process, virus entry, and integrase and protease inhibition [368]. However the mechanism of anti-HIV activities of many natural products is still unknown. Some of the plant extracts have significantly inhibited the enzyme activity of HIV-1 replication and protected cells infected with HIV-1. These extracts with anti-HIV activity are also active against other retroviruses such as Herpes Simplex Virus (HSV). Most studies have used in vitro test systems for anti-HIV-1 enzyme assays such as HIV-1 reverse transcriptase colorimetric assay, HIV-1 integrase assay, and HIV-1 protease fluorogenic assay, but a few in vivo studies have been carried out using compounds isolated from natural sources [369]. The anti-HIV activities of extracts from some medicinal plants have been reviewed.

3.1. Artemisia annua L. (Asteraceae)

The anti-HIV activity of the tea infusion prepared from the Chinese medicinal plant identified as Artemisia annua L. by using the validated cellular systems were examined. The tea infusion of Artemisia annua was found to be highly active with IC₅₀ values as low as 2.0 μg/mL. In addition, artemisinin was found as inactive at 25 μg/mL and the related species Artemisia afra (not containing artemisinin) has also shown a similar level of activity [370].

3.2. Astragalus membranaceus Bunge (Fabaceae)

Astragalus membranaceus is well-known Chinese traditional medicine as an immunostimulant. Studies in immune-suppressed and immune-competent human patients have demonstrated restoration or augmentation of local graft versus host rejection using Astragalus extracts. These extracts have improved symptomology in HIV-infected patients. These results are suggested that the extracts of Astragalus to be safe, however mutagenecity has yet to be examined [115].

3.3. Calendula officinalis L. (Asteraceae)

In India, the flowers of Calendula officinalis are used in ointments for treating wounds, herpes, ulcers, frostbite, skin damage, scars and blood purification. The infusions prepared from the leaves have been used for treating varicose veins in traditional use. Dichloromethane-methanol (1:1) extract of Calendula officinalis flowers exhibited potent anti-HIV activity in in vitro (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide)(MTT)/tetrazolium-based assay. This activity was attributed to inhibition of HIV1-RT at a concentration of 1000 μg/mL as well as suppression of the HIV mediated fusion at 500 μg/mL [371]. The organic and aqueous extracts of dried flowers from Calendula officinalis were examined for their ability to inhibit the human immunodeficiency virus type 1 (HIV-l) replication. Both extracts were relatively nontoxic to human lymphocytic Molt-4 cells, but only the organic one exhibited potent anti-HIV activity in an in vitro MTT ketrazolium-based assay. In addition, in the presence of the organic extract (500 pg/mL), the uninfected Molt-4 cells were completely protected for up to 24 h from fusion and subsequent death, caused by cocultivation with persistently infected U-937/HIV-1 cells. It was also found that the organic extract from Calendula officinalis flowers caused a significant dose- and time-dependent reduction of HIV-l reverse transcription (RT) activity. An 85% RT inhibition was achieved after a 30 min treatment of partially purified enzyme in a cell-free system. These results suggested that organic extract of flowers from Calendula oflicinalis are possessed anti-HIV properties of therapeutic interest [163].

3.4. Calophyllum lanigerum Miq. var. austrocoriaceum (T.C. Whitmore) P.F. Stevens (Clusiaceae)

Calophyllum lanigerum var. austrocoriaceum has been found to inhibit the cytopathic effects of in vitro HIV infection. Bioassay-guided fractionation of the extract and the chemical along with biological characterization of active constituents as coumarine derivatives have been reported [372]. The latex of Calophyllum teysmanni L. has shown to be active against HIV-1 reverse transcriptase mediated by soulattrolide, a coumarin isolated from the latex of Calophyllum teysmanni [373].

3.5. Cassia abbreviata Oliv. Oliv., C. sieberiana D.C. (Fabaceae)

Cassia abbreviata growing in Botswana used by traditional healers to manage HIV/AIDS, was tested for their inhibitory effects on HIV replication against a clone of HIV-1c (MJ4) measuring cytopathic effect protection and levels of viral p24 antigen in infected PBMCs. Cassia sieberiana and Cassia abbreviata extracts have shown significant inhibition of HIV-1c (MJ4) replication. Anti-HIV activity of Cassia sieberiana root and bark extracts, and Cassia abbreviata root extracts were occurred in a concentration-dependent manner with an effective concentration (EC₅₀) of 65.1 μg/mL, 85.3 μg/mL and 102.8 μg/mL, respectively [374].

3.6. Chelidonium majus L. (Papaveraceae)

The anti-retroviral activity of the freshly prepared crude extract of Chelidonium majus L. was examined and a low-sulfated poly-glycosaminoglycan moiety with molecular weight of ~3800 Da. was isolated from the extract [173]. The substance prevented infection of human CD4⁺ T-cell lines AA2 and H9 with HIV-1 at concentration of 25 μg/mL as well as the cell-to-cell virus spread in H9 cells continuously infected with HIV-1 were determined by the measurement of reverse transcriptase activity and p24 content in cell cultures. In addition, in a murine AIDS model that the treatment with purified substance significantly prevented splenomegaly and the enlargement of cervical lymph nodes in C57Bl/6 mice chronically infected with the pool of murine leukemia retroviruses were also reported [173].

3.7. Combretum molle (R. Br. ex. G. Don.) Engl & Diels (Combretaceae)

In vitro anti-HIV activity of various extracts prepared from the stem bark of Combretum molle widely used in Ethiopian traditional medicine for the treatment of liver diseases, malaria and tuberculosis has been assessed against human imnmuunodeficiencvy virus type 1 (HIV-1) and type 2 (HIV-2). The extracts were prepared by percolation with petroleum ether, chloroform, acetone and the methanol extract was obtained by successive hot extraction using Soxhlet apparatus. Selective inhibition of viral growth was assessed by the simultaneous determination of the in vitro cytotoxicity of each of the extracts against MT-4 cells [375]. The results obtained in this study indicate that the acetone fraction possessed the highest selective inhibition of HIV-1 replication. Phytochemical investigation of the acetone fraction has resulted in the isolation of two tannins and two oleanane-type pentacyclic triterpene glycosides. One of the tannins was identified as punicalagin (an ellagitannin), while the structure of the other (CM-A) has not yet been fully elucidated. On the other hand, both punicalagin and CM-A had displayed selective inhibition of HIV-1 replication with selectivity indices (ratio of 50% cytotoxic concentration to 50% effective antiviral concentration) of 16 and 25, respectively and afforded cell protection of viral induced cytopathic effect of 100% when compared with control samples.

3.8. Diospyros lotus L. (Ebenaceae)

Methanol extract of the fruits of Diospyros lotus were tested for anti-HIV-1 activity. Gallic acid was found the most active compound against HIV-1 with Therapeutic Index (TI) value of >32.84 and the other compounds were less potent active. Diospyros lotus fruits could provide a chemical reservoir of anti-HIV agents. All identified compounds were tested for their cytotoxicity and anti-HIV-1 activities. For positive control, the marketed drug azido-thymidine (AZT) was also tested as a reference according to the same methods. The activity data were described as 50% cytotoxicity concentration (CC₅₀), 50% effective concentration (EC₅₀%), and therapeutic index (TI), the ratio of CC₅₀/EC₅₀). Seven isolated phenolic compounds (CC₅₀ > 200 μg/mL) have shown less toxicity to C8166 cells compared to ellagic acid (CC₅₀ = 35.84 μg/mL). Gallic acid inhibited HIV-1 replication with EC₅₀ value of 6.09 μg/mL and TI value of > 32.84, higher than any other compounds. The anti-HIV-1 activity assay was performed by syncytia formation. The seven phenolic compounds showed a good anti-HIV-1 activity and compound gallic acid, a simple tannin compound was the most active and its TI value was the highest [376].

3.9. Dittrichia viscosa (L.) Greuter (Asteraceae)

The aqueous extract of Dittrichia viscosa was tested for its ability to inhibit the HIV replication. HIV infection of MT-2 cells was used for evaluating antiviral test as rapid and sensitive assay system for the detection of potential antiviral drugs effective against AIDS. The aqueous extract of Dittrichia viscosa has showed inhibitory effects against HIV-1 induced infections in MT-2 cells at concentrations ranging from 25 to 400 μg/mL of therapeutic interest [377].

3.10. Galanthus nivalis L. (Amaryllidaceae)

Agglutinin isolated from Galanthus nivalis (GNA) is a member of a superfamily of strictly mannose-binding specific lectins widespread among monocotyledonous plants, and is well-known to possess a broad range of biological functions such as anti-tumor, anti-viral and anti-fungal activities [378]. The molecular mechanisms of GNA exerting anti-viral activities by blocking the entry of the virus into its target cells, preventing transmission of the virus as well as forcing virus to delete glycan in its envelope protein and triggering neutralizing antibody were discussed. These findings may provide a new perspective of GNA-related lectins as potential drugs for virus therapeutics in the future.

3.11. Garcinia edulis Exell (Clusiaceae)

The isoprenylated xanthone derivative determined as 1,4,6-trihydroxy-3-methoxy-2-(3-methyl-2-butenyl)-5-(1,1-dimethyl-prop-2-enyl)xanthone was isolated from the ethanolic extract of the root bark of Garcinia edulis. It exhibited anti-HIV-1 protease activity with IC₅₀ value of 11.3 μg/mL in vitro while acetyl pepstatin was used as a positive control possessing an anti-HIV-1 PR activity of IC₅₀ value of 2.2 μg/mL [379]. However, this compound has also showed potent lethality with LC₅₀ value of 2.36 μg/mL against brine shrimp larvae in vitro.

3.12. Helichrysum populifolium (Asteraceae)

The methanol:water (1:1) extract of the aerial parts of Helichrysum populifolium growing in South Africa was tested for the anti-HIV test by using HeLa-SXR5 expressed the CD4 receptor and the CXCR4/CCR5 chemokine receptors and the extract was found to be active (IC₅₀ value of 12 μg/mL) [123]. The anti-HIV compounds identified from H. populifolium were three dicaffeoylquinic acid derivatives, i.e., 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid as well as two tricaffeoylquinic acid derivatives, i.e., 1,3,5-tricaffeoylquinic acid and either 5-malonyl-1,3,4-tricaffeoylquinic or 3-malonyl-1,4,5-tricaffeoylquinic acid.

3.13. Hoodia gordonii (Masson) Sweet ex Decne (Apocynaceae)

The in vitro anti-HIV potential of the ethanol and ethylacetate extracts of Hoodia gordonii was examined. Both extracts had shown good inhibition in a dose-dependent manner against HIV-1 reverse transcriptase (RT) with IC₅₀ values of 73.55 ± 0.04 and 69.81 ± 9.45 μg/mL, respectively. Doxorubicin, a known RT inhibitor was used as a positive control and inhibited HIV RT by 68% at 25 μg/mL (IC₅₀ < 25 μg/mL). Both extracts also demonstrated inhibitory activity against HIV protease (PR) with IC₅₀ values of 97.29 ± 0.01 and 63.76 ± 9.01 μg/mL for ethanol and ethyl acetate extracts, respectively. Acetyl pepstatin was used as a known PR inhibitor and inhibited HIV PR by as much as 82% at 50 μg/mL (IC₅₀ < 50 μg/mL). In addition, both ethanol and ethyl acetate extracts had weak inhibition against HIV-1 integrase (IN) with <50% inhibition at the highest concentration tested of 400 μg/mL. Sodium azide was used as a positive control compound for IN inhibition [101]. In the same study, phytochemical screening of Hoodia gordonii was revealed the presence of phenolics, alkaloids, terpenes, steroids, cardiac glycosides and tannins in the ethanolic extract, while the ethyl acetate extract only showed the presence of phenolics, cardiac glycosides and steroids.

3.14. Hypericum perforatum L. (Hypericaceae)

Hypericum perforatum, known as St. John’s Wort, has been used for medicinal purposes, particularly wound healing, since the Middle Ages. It was also used in treatment of AIDS [380]. In a clinical trial, hypericin and pseudohypericin isolated from this plant have shown antiretroviral activity in HIV-infected patients [381].

3.15. Hyssopus officinalis L. (Lamiaceae)

Hyssopus officinalis has been used as herbal medicine and the extracts of this species have demonstrated strong activity against HIV-1 due to the content of polysaccharide-type compounds [252]. The 50% hydroalcoholic extract of Hysoppus officinalis was examined for its ability to inhibit HIV replication. Among the variety of assays for evaluating antiviral tests, HIV infection of MT-2 cells was used as a rapid and sensitive assay system for the detection of potential antiviral drugs effective against AIDS. This extract had shown inhibitory effects against HIV-1 induced infections in MT-2 cells at concentrations ranging from 50 to 100 μg/mL.

3.16. Justicia gendarussa Burm. f. (syn: Gendarussa vulgaris Nees) (Acanthaceae)

Justicia gendarussa was identified as a potent anti-HIV-1 active lead from the evaluation of over 4500 plant species growing in Vietnam and Laos by showing complete inhibition against HIV replication at a concentration 20 μg/mL. The methanol extract of the stems and barks of the plant have led to the isolation of justiprocumins A and B as new arylnaphthalide lignan glycosides by using bioassay-guided isolation. Justiprocumin B has shown potent activity against a broad spectrum of HIV strains with IC₅₀ values in the range of 15–21 nM (AZT, IC₅₀ 77–95 nM, as positive control). Justiprocumin B also displayed potent inhibitory activity against the NRTI (nucleoside reverse transcriptase inhibitor)-resistant isolate (HIV-1_1617-1) of the analogue (AZT) as well as the NNRTI (non-nucleoside reverse transcriptase inhibitor)-resistant isolate (HIV-1_N119) of the analogue (nevaripine) [382]. The dichloromethane plant extract has shown complete inhibition of HIV replication at a concentration of 20 μg/mL. This bioactivity was confirmed by the evaluation of the MeOH extract prepared from a re-collected sample of the same plant, with HIV-1 replication inhibition at an IC₅₀ value of 40 ng/mL. Bioassay-guided separation of the extracts of the stems and roots of this plant led to the isolation of an anti-HIV arylnaphthalene lignan (ANL) glycoside, patentiflorin A. Evaluation of the compound against both the M- and T-tropic HIV-1 isolates showed it to possess a significantly higher inhibition effect than the clinically used anti-HIV drugs known as the nucleotide analogue (AZT) and non-nucleotide analogue (nevaripine). Thus, patentiflorin A has the potential to be developed as a novel anti-HIV drug [382]. Patentiflorin A showed anti-HIV-1 activity with an IC₅₀ value of 26.9 nM in the defective HIV-based pseudotyped assay. The results clearly showed that patentiflorin A has broad-spectrum activity against both M-tropic and T-tropic HIV-1 isolates with IC₅₀ values lower than that of AZT, the first anti-HIV drug developed and still used in the treatment of HIV/AIDS. Like AZT, it inhibited the particle production of all four HIV-1 isolates effectively in a dose-dependent manner. Patentiflorin A gave an IC₅₀ value of 24–37 nM, compared to 77–95 nM for AZT.

3.17. Momordica charantia L. (Cucurbitacae)

Momordica charantia, known as bitter melon and widely exploited in folkloric medicine, has been shown to inhibit HIV-1 reverse transcriptase due to its protein coded as MRK29 [383]. The efficacies and molecular mechanisms of bitter gourd-induced anti-diabetic, anti-HIV, and antitumor activities contributed by over twenty active components were determined. Therefore, bitter gourd is a cornucopia of health and it has been deserved in-depth investigations for clinical application in the future.

Anti-HIV properties of the fruit pulp extract of Momordica balsamina, commonly used in the northern part of Nigeria for its anti-viral efficacy in poultry, was studied in vitro and was found as a potent inhibitor of HIV-1 replication; further research on fruit pulp extract should be pursued for its potential in the prophylaxis and therapy of retroviral infections in humans [384].

3.18. Pachyma hoelen Rumph (Polyporaceae)

The hexane extract of Pachyma hoelen Rumph used in folk medicine in Korea was shown to have the best anti-HIV-1 activity compared to the other extracts tested. This extract had 37.3 μg/mL (EC₅₀) on the p24 antigen assay as the highest value, 36.8% on the RT activity test (at 200 μg/mL). In addition, this extract had shown protective effects on infected MT-4 cells; the protection was the highest observed at 58.2%. The 50% cytotoxic concentration (CC₅₀) of the hexane extract of this plant species was found 100.6 μg/mL [196].

3.19. Phyllanthus pulcher (Euphorbiaceae)

The methanol extract of Phyllanthus species growing in Malaysia was evaluated for anti-HIV-1 reverse transcriptase (RT) activity using the HIV-RT assay by inhibition of the HIV-1 RT enzyme based on their IC₅₀ values. Azido-deoxythymidine-triphosphate (AZT151TP) was used as a positive control. The inhibition of HIV-RT for P. pulcher was IC₅₀ of 5.9 μg/mL [385].

3.20. Rhus chinensis Mill (Anacardiaceae)

The anti-HIV-1 activities of the petroleum ether, ethyl acetate, butanol and aqueous extracts of Rhus chinensis growing in China and Japan where it is known as Chinese Sumac were examined. The petroleum ether extract had significantly suppressed HIV-1 activity in vitro and was found to inhibit syncytium formation and HIV-1 p24 antigen at non-cytotoxic concentrations, the EC₅₀ were 0.71 and 0.93 μg/mL respectively. The petroleum ether extract had no activity on inhibiting HIV-1 recombinant RT or HIV-1 entry into host cells cycle. R. chinensis would be a useful medicinal plant for the chemotherapy of HIV-1 infection. The petroleum ether extract of this plant likely inhibit the post entry steps or target the new sites of HIV-1 replication [386].

3.21. Sceletium tortuosum (L.) N.E. Brown (Aizoaceae)

The ethanolic and ethyl acetate extracts prepared from the whole part of Sceletium tortuosum, distributed throughout southern Africa, were investigated for their inhibitory activity against HIV-1 enzymes including protease (PR), reverse transcriptase (RT) and integrase (IN) [172]. The HIV-1 RT inhibition testing had IC₅₀ values of <50 and 121.7 ± 2.5 μg/mL for ethanol and ethyl acetate extracts, respectively. In addition, both extracts had also inhibited HIV-1 PR with IC₅₀ values < 100 μg/mL. Sceletium tortuosum might be a potential source of new lead compounds in the development of new anti-HIV compounds [67].

3.22. Smilax corbularia Kunth (Smilaceae)

The ethanolic and aqueous extracts were tested for their inhibitory effects against HIV-1 protease (HIV-PR) and HIV-1 integrase (HIV-1 IN). The results indicated that the ethanolic extract of S. corbularia exhibited anti-HIV-1 IN activity with an IC₅₀ value of 1.9 μg/mL, approximately two-fold lower than that of suramin (IC₅₀ = 3.4 μg/mL) as the positive control. The value of IC₅₀ = 5.4 μg/mL was determined for the water extract of Smilax corbularia [120].

3.23. Terminalia paniculata (Combretaceae)

The in vitro anti-HIV1 activity of acetone and methanol extracts prepared from the fruits of Terminalia paniculata was examined. The EC₅₀ values of the acetone and methanol extracts of T. paniculata were ≤10.3 μg/mL. The enzymatic assays were performed to determine the mechanism of action and indicated that the anti-HIV1 activity might be due to inhibition of reverse transcriptase (≥77.7% inhibition) and protease (≥69.9% inhibition) enzymes [387].

3.24. Tuberaria lignosa (Sweet) Sampaio (Asteraceae)

Tuberaria lignosa was widely used in the folk medicine to treat diseases of viral origin of the Iberian Peninsula and the ethanolic and aqueous extracts were evaluated for its anti-HIV activity by inhibiting HIV replication. The toxicity of the extracts to MT-2 cells was also investigated. The ethanolic extract was especially toxic, which prevented the evaluation of their potential antiviral effects at higher concentrations. However, the aqueous extract of T. lignosa tested was relatively nontoxic to human lymphocytic MT-2 cells, but did show anti-HIV activity at concentrations ranging from 12.5 to 50 μg/mL [61].

In conclusion, terrestrial plants produce secondary metabolites for their chemical defense, which possess unique chemical structures and have played pivotal roles in human health. There is continuous need to introduce new drug candidates to treat diseases and the drug discovery process can be realized using both ancient and modern research methodologies in a complementary manner. Some medicinal plants are still unexplored; therefore there are numerous avenues of research for the determination of their biological activities. In this review, the anti-HIV activity of some plant extracts and their potential utilization for anti-HIV agents have been summarized. Among them Calendula officinalis, Justicia gendarussa and Sceletium tortuosum might be useful potential sources for new lead compounds in the development of new candidates with anti-HIV properties of therapeutic interest. These studies are considered to be one of the most important approaches toward effective therapy for AIDS.

4. Human Clinical Trials

There are few reports about using the herbal medicine in clinical studies and treatment for HIV/AIDS. This area is not well researched. But, in Africa, where HIV, AIDS and HIV related diseases are the most widespread problems, herbal medicines are used as primary treatment for them. Highly active antiretroviral therapy is also applied in China and implies three types of treatment systems. One of them is traditional Chinese medicine provided by trained Chinese herbalists. There are several randomized studies related to beneficial effects of traditional medical plants on patients with HIV or AIDS which were compared with control group (without treatment and placebo). The effects in promoting CD4⁺ cells were followed. Based on selected, different, studies approximately eleven different Chinese traditional medical plants such as Panax ginseng, Astragalus membranaceus, Lycium barbarum, Trichosanthis kirilowii, and Viola mandshurica were tested in about 1000 patients within different studies. Compared with placebo, treatment with traditional medical plants showed positive effect, increasing CD4 cells, but studies need to be improved [388].

Some Chinese herbal preparation which consists of 14 plants (Coptis chinensis, Jasminum officinale, Wolfiporia extensa, Sparganium stoloniferum, Polygonatum odoratum, and Scrophularia buergeriana was investigated during 24 weeks and observed to have increased plasma CD4 count and also showed inhibition of HIV growth [389]. According to one US study, 26% of HIV-infected people use herbal medicine as part of their treatment. A European study showed that herbal medicines are used by approximately 25% of HIV infected people [390].

The study, which included 366 HIV-positive African-American women who were enrolled in herbal medicine therapy, showed that in these patients experienced 1.69 time stronger anti-retroviral effect compered to women not using the therapy based on medical plants [391]. Thirty-three HIV-positive volunteers (7 men and 26 women between 22 and 43 years of age) who used Calendula officinalis or Agastache rugosa were evaluated in South Africa. There was a significant decrease in viral loads and in CD4 T-cell counts [392].

The Ministry of Health of South Africa is actively promoting the use of traditional medicines with antiretroviral treatments and recommended two plants remedies which have been used for HIV/AIDS treatment: Hypoxis hemerocallidea and Sutherlandia frutescens [393]. Also, in Romania it was noticed that children with AIDS who were treated with natural herbal remedies showed a decrease in mortality rate [393]. Furthermore, in blood samples of 30 adults who used an extract of Alternanthera pungens, a significant increase of CD4 and CD8 lymphocytes was observed [394].

The study which was conducted to demonstrate using medical plants in different districts in Uganda, where this disease first described and one million habitants are infected, 25 traditional medicine practitioners were interviewed. The practitioners received on average 29 (range, 2–250) patients each year. They mentioned 145 belong to families Asteraceae, Fabaceae and Euphorbiaceae. It was also noted that the most used plants were Aloe spp., Erythrina abyssinica, Sarcocephalus latifolius, Psorospermum febrifugum, Mangifera indica, and Warburgia salutaris. In patients involved in herbal medicine treatment progressive loss of CD4 positive T-cell lymphocytes in the blood was observed [311].

5. Conclusions

Focusing on phytochemicals that have reached clinical trials, if there are any; highlighting medicinal plants where high level of scientific evidence has been reached; future perspectives.

Although there have been major accomplishments in HIV chemotherapy, there remains a need for new anti-HIV drug discovery, and medicinal plants can play an important role in this endeavor. Several plant species have shown remarkable anti-HIV activity, especially Artemisia annua, Garcinia edulis, Justicia gendarussa, Phyllanthus pulcher, Rhus chinensis, Smilax corbularia, Terminalia paniculata, and Tuberaria lignosa. These plant species are worthy of further study for the development of new anti-HIV chemotherapeutic options. In particular, in vivo testing and, ultimately, human clinical trials need to be carried out on key lead plants and phytochemical isolates. In addition, continuous evaluation of medicinal plants for anti-HIV activity should be pursued.

Author Contributions

All authors contributed equally in the preparation of the manuscript.

Conflicts of Interest

The authors declare no conflict of interest.