Plant‐Based Therapeutics Against Communicable Diseases: A Review of Ethnopharmacology and Medicinal Chemistry Approaches

ABSTRACT

Infectious diseases are traditionally managed using medicinal herbs in traditional Chinese medicine, Ayurveda and Unani. These conventional therapies are an essential source of new anti‐infective drugs considering antimicrobial resistance threatens global public health. The present review critically appraises the use of medicinal plants against bacterial, viral, fungal and parasitic infections in combination with medicinal chemistry and ethnopharmacology. A comprehensive review of ethnobotanical data, phytochemistry and pharmacological studies was performed on the basis of WHO classification of infectious diseases in order to identify repeating medicinal plants and their active ingredients. Over 150 medicinal plants have been discovered by major ethnomedical systems in the course of history and have been used as the remedy of infectious diseases. Essential phytochemicals such as alkaloids, terpenoids, flavonoids, phenolics and saponins showed broad‐spectrum anti‐infective activity via mechanisms including membrane damage, enzyme inhibition, oxidative stress regulation and interference with nucleic acid synthesis. Some examples of such successful combination of ethnopharmacology with pharmacology include artemisinin, berberine, andrographolide and glycyrrhizin. Nevertheless, the lack of standardization, poor bioavailability and insufficient clinical trials are still problematic.

Traditional medicine–derived bioactive phytomolecules targeting communicable diseases.

Abbreviations

3D

three‐dimensional

ADMET

absorption, distribution, metabolism, excretion and toxicity

AMR

antimicrobial resistance

API

ayurvedic pharmacopoeia of India

CNS

central nervous system

COVID‐19

coronavirus disease 2019

DNA

deoxyribonucleic acid

EGCG

epigallocatechin‐3‐gallate

GI

gastrointestinal

HBV

hepatitis B virus

HCV

hepatitis C virus

HIV

human immunodeficiency virus

HSV

herpes simplex virus

IF

impact factor

LD₅₀

median lethal dose

MDR

multidrug resistance

MPNS

medicinal plant names services

MT

medicinal therapy / multitarget (depending on usage context)

PCP

pneumocystis pneumonia

PCR

polymerase chain reaction

PK

pharmacokinetics

QSAR

quantitative structure–activity relationship

ROS

reactive oxygen species

SAR

structure–activity relationship

SARS‐CoV‐2

severe acute respiratory syndrome coronavirus 2

TCM

traditional Chinese medicine

URTI

upper respiratory tract infection

WFO

world flora online

WHO

world health organization

1. Introduction

Globally, infectious diseases brought on by bacterial, viral, fungal and parasitic pathogens remain a major public health concern [1]. Despite substantial advancements in antimicrobial medication research, properly controlling infectious illnesses remains a challenge. Long‐term utility of many conventional pharmaceuticals has been diminished by the rising incidence of antimicrobial resistance, the limited effectiveness of current treatments in some infections, adverse drug reactions and treatment failures [2]. Scientific interest in supplemental and alternative therapeutic sources has increased as a result of these limitations. Medicinal herbs, which have long been essential in the treatment of infectious diseases, are still widely used in traditional medical systems such as Ayurveda, Traditional Chinese Medicine, Unani and other indigenous healthcare traditions [3]. Plant‐based treatments are frequently used to cure symptoms associated with communicable diseases, including fever, lung infections, gastrointestinal issues, skin infections and parasitic infestations [4]. Crucially, these conventional methods have often served as the foundation for the discovery of bioactive molecules with antibacterial, antiviral, anti‐parasitic and antifungal effects [5]. Natural products made from plants are recognized as a valuable source of chemically diverse bioactive chemicals. The structural diversity and complexity of phytochemicals set them apart from many synthetic substances and contribute to their biological relevance [6].

Numerous studies highlight how this kind of chemical diversity makes it possible to interact with a variety of biological targets, which could be helpful in addressing intricate pathways of infectious diseases. However, traditional use or initial biological activity alone cannot establish therapeutic efficacy, highlighting the need for thorough scientific validation. Figure 1 Although ethnopharmacology is a useful method for selecting therapeutic plants for further investigation, it needs to be combined with current pharmacological and phytochemical research [7]. Plant‐derived drugs show encouraging in vitro and in vivo action against infectious pathogens, their direct therapeutic translation is frequently limited [8]. Poor water solubility, limited oral bioavailability, chemical instability, phytochemical composition fluctuation and a lack of safety and toxicity data are common problems [9].

FIGURE 1.

Integrated framework linking ethnopharmacology, phytochemicals, mechanisms and drug development.

Medicinal chemistry provides crucial ways to get over these limitations by enabling the optimization of natural product leads [10]. The research covered in this analysis suggests that plant‐derived chemicals are better evaluated as lead structures than as surefire medicinal prospects. Semi‐synthetic modification, rational derivatization and structure‐activity relationship studies are frequently employed to improve potency, selectivity and pharmacokinetic properties. Several clinically relevant anti‐infective medicines generated from or inspired by natural products have been successfully developed thanks to such approaches [11]. Chemicals originating from plants have a variety of mechanisms of action against pathogens that cause communicable diseases [12]. These include altering host–pathogen interactions, modifying oxidative stress, disrupting microbial membranes, inhibiting essential enzymes and interfering with nucleic acid synthesis [13]. In this regard, the current work uses ethnopharmacological data and medicinal chemistry techniques to investigate plant‐based treatments for infectious disorders [14]. The review concentrates on bioactive compounds, their chemical properties, modes of action and lead optimization techniques rather than offering a comprehensive list of medicinal plants [15, 16]. A interdisciplinary strategy that combines developments in medicinal chemistry, pharmacology and pharmaceutical sciences with ethnopharmacological knowledge is needed to address these issues [17]. In this sense, the current study examines plant‐based remedies for infectious diseases by combining medicinal chemistry methods with ethnopharmacological data. Instead of providing an exhaustive list of medicinal plants, the review focuses on bioactive chemicals, their chemical characteristics, modes of action and lead optimization strategies [16]. This balanced perspective aims to emphasize both the potential and limitations of medicinal plants as sources of anti‐infective medications in order to support their logical appraisal and future development [18].

Standardized reporting and tracking of worldwide health trends are made possible by the WHO's classification of communicable diseases [19]. Comparing disease burden, identifying new zoonoses and prioritising diseases that can be prevented by vaccination are made easier by classifying infections by pathogen family [20]. Bacterial and viral diseases continue to be the most common causes of epidemic outbreaks worldwide, although fungal and parasitic illnesses continue to cause significant morbidity among immunocompromised and resource‐constrained individuals. Recent WHO research show that the death rate from vaccine‐preventable diseases has decreased, although vector‐borne parasitic infections and antibiotic resistance still present challenges or are resurfacing. Consequently, this comprehensive list provides a single point of reference for understanding the origins of infectious diseases, the affected organ systems and the current WHO framework for global health management. The disease classification in Table 1 forms the basis of the disease classification adopted in this paper and underscores the wide range of communicable diseases whose therapy has been documented in traditional medicinal practices. The spread of diseases into bacteria, virus, fungi and parasites groups shows the variety of pathogens against which herbal medicines have been studied in Ayurveda, Traditional Chinese Medicine and Unani medicine. It also helps in comparing the results of ethnopharmacology with those of modern pharmacology studies in terms of disease groups that have been extensively studied in modern science, including malaria, tuberculosis, viral respiratory infections, and gastrointestinal infections. Thus, Table 1 forms the basis for assessment of the ethnomedical importance of bioactive molecules from plant sources to be discussed in later parts of the paper [1, 21, 22].

TABLE 1.

List of communicable disease caused by bacteria, fungus, parasites, and virus.

Category	Disease name	Causative agent	Pathogen family	Principal organ affected
Bacterial diseases	Tuberculosis	Mycobacterium tuberculosis	Mycobacteriaceae	Lungs (pulmonary TB)
	Leprosy (Hansen's disease)	Mycobacterium leprae	Mycobacteriaceae	Skin, peripheral nerves
	Cholera	Vibrio cholera	Vibrionaceae	Intestine (acute watery diarrhea)
	Typhoid & Paratyphoid fevers	Salmonella enterica, S. Typhi	Enterobacteriaceae	Intestine, systemic
	Plague	Yersinia pestis	Enterobacteriaceae	Lymph nodes, lungs
	Diphtheria	Corynebacterium diphtheriae	Corynebacteriaceae	Throat, heart
	Tetanus	Clostridium tetani	Clostridiaceae	Nervous system (spasms)
	Pertussis (Whooping cough)	Bordetella pertussis	Alcaligenaceae	Respiratory tract
	Meningococcal meningitis	Neisseria meningitidis	Neisseriaceae	Brain meninges
	Gonorrhea	Neisseria gonorrhoeae	Neisseriaceae	Genital tract
	Syphilis	Treponema pallidum	Spirochaetaceae	Genitals, skin, CNS
	Trachoma	Chlamydia trachomatis	Chlamydiaceae	Eye (conjunctiva, cornea)
	Q fever	Coxiella burnetii	Coxiellaceae	Lungs, liver
	Brucellosis	Brucella spp.	Brucellaceae	Liver, spleen
	Leptospirosis	Leptospira interrogans	Leptospiraceae	Kidneys, liver
Fungal diseases	Candidiasis	Candida albicans	Saccharomycetaceae	Mouth, vagina, bloodstream
	Aspergillosis	Aspergillus fumigatus	Trichocomaceae	Lungs, sinuses
	Cryptococcosis	Cryptococcus neoformans	Tremellaceae	Brain, lungs
	Histoplasmosis	Histoplasma capsulatum	Ajellomycetaceae	Lungs, liver
	Blastomycosis	Blastomyces dermatitidis	Ajellomycetaceae	Lungs, skin
	Coccidioidomycosis	Coccidioides immitis	Onygenaceae	Lungs
	Pneumocystis pneumonia (PCP)	Pneumocystis jirovecii	Pneumocystidaceae	Lungs (especially in HIV/AIDS)
	Sporotrichosis	Sporothrix schenckii	Ophiostomataceae	Skin, lymphatics
	Dermatophytosis (Ringworm)	Trichophyton rubrum	Arthrodermataceae	Skin, nails
Parasitic diseases	Malaria	Plasmodium falciparum, vivax, ovale, malariae	Plasmodiidae	Blood, liver
	Leishmaniasis (Visceral/Cutaneous)	Leishmania donovani, tropica	Trypanosomatidae	Skin, liver, spleen
	Trypanosomiasis (African sleeping sickness)	Trypanosoma brucei	Trypanosomatidae	CNS, blood
	Chagas disease	Trypanosoma cruzi	Trypanosomatidae	Heart, GI tract
	Schistosomiasis	Schistosoma haematobium, Mansoni, japonicum	Schistosomatidae	Urinary tract, intestines
	Filariasis (Lymphatic)	Wuchereria bancrofti	Onchocercidae	Lymphatic system
	Onchocerciasis (River blindness)	Onchocerca volvulus	Onchocercidae	Skin, eyes
	Ascariasis	Ascaris lumbricoides	Ascarididae	Intestine
	Hookworm disease	Ancylostoma duodenale	Ancylostomatidae	Intestine, blood
	Trichuriasis	Trichuris trichiura	Trichuridae	Colon
	Taeniasis/Cysticercosis	Taenia solium, saginata	Taeniidae	Intestine, muscle, brain
	Echinococcosis	Echinococcus granulosus	Taeniidae	Liver, lungs
	Amoebiasis	Entamoeba histolytica	Entamoebidae	Colon, liver
	Giardiasis	Giardia lamblia	Hexamitidae	Intestine
	Toxoplasmosis	Toxoplasma gondii	Sarcocystidae	Brain, eyes
	Cryptosporidiosis	Cryptosporidium parvum	Cryptosporidiidae	Intestine
	Trichomoniasis	Trichomonas vaginalis	Trichomonadidae	Genital tract
	Dracunculiasis	Dracunculus medinensis	Dracunculidae	Skin, subcutaneous tissue
	Fascioliasis	Fasciola hepatica	Fasciolidae	Liver
	Clonorchiasis	Clonorchis sinensis	Opisthorchiidae	Liver, bile ducts
Viral diseases	COVID‐19	SARS‐CoV‐2	Coronaviridae	Respiratory tract, systemic
	Influenza (Seasonal)	Influenza A/B virus	Orthomyxoviridae	Respiratory tract
	Measles	Measles morbillivirus	Paramyxoviridae	Skin, respiratory system
	Mumps	Mumps orthorubulavirus	Paramyxoviridae	Salivary glands
	Rubella	Rubella virus	Matonaviridae	Skin, fetus (congenital defects)
	Hepatitis A	Hepatitis A virus	Picornaviridae	Liver
	Hepatitis B	Hepatitis B virus	Hepadnaviridae	Liver (cirrhosis, cancer)
	Hepatitis C	Hepatitis C virus	Flaviviridae	Liver
	HIV/AIDS	Human immunodeficiency virus 1/2	Retroviridae	Immune system
	Dengue	Dengue virus	Flaviviridae	Blood vessels (hemorrhagic fever)
	Zika virus disease	Zika virus	Flaviviridae	Brain (microcephaly in fetus)
	Yellow fever	Yellow fever virus	Flaviviridae	Liver, vascular system
	Poliomyelitis	Poliovirus	Picornaviridae	CNS (motor neurons)
	Rabies	Rabies lyssavirus	Rhabdoviridae	Brain (encephalitis)
	Ebola virus disease	Ebolavirus	Filoviridae	Blood, liver
	Marburg virus disease	Marburg marburgvirus	Filoviridae	Blood, liver
	Lassa fever	Lassa mammarenavirus	Arenaviridae	Vascular system
	Human papillomavirus infection	Human papillomavirus (HPV)	Papillomaviridae	Skin, genitals (cancer risk)
	Smallpox (eradicated)	Variola virus	Poxviridae	Skin, systemic
	Monkeypox (Mpox)	Mpox virus	Poxviridae	Skin, lymph nodes

2. Ethnopharmacological Foundations of Plant‐Based Anti‐Infective Therapy

An essential beginning point for the development of plant‐based therapeutic medicines is ethnopharmacology, which studies the traditional usage of medicinal plants within particular cultural and historical contexts [23]. Plant‐based remedies have long been used in traditional medical systems and indigenous healing practices to treat infectious disease symptoms as fever, inflammation, diarrhoea, respiratory distress and skin lesions. Figure 2 Numerous geographical areas and medical traditions, such as Ayurveda, Traditional Chinese Medicine, Unani and indigenous healthcare systems, have documented these practices Tables 2, 3, and 4. The potential of ethnopharmacological knowledge to direct the selection of therapeutic plants for additional scientific study is the main source of its usefulness. The presence of biologically active components may be shown by the repeated use of a specific plant species in several cultures or historical eras. knowledge on plant parts used, preparation techniques and administration routes is frequently documented in ethnobotanical surveys and old pharmacopoeias. This knowledge can help guide experimental design in contemporary pharmacological research. However, rather than being a confirmation of therapeutic efficacy, such traditional use should be seen as suggestive. Numerous studies highlight how ethnopharmacology has made a significant contribution to the discovery of chemicals derived from plants that have anti‐infective properties. By reducing the enormous botanical diversity to a manageable number of candidates for phytochemical and biological investigation, this method has historically aided in the discovery of significant medicinal medicines. In contemporary research, bioassay‐guided fractionation and molecular screening techniques are still used to enhance ethnopharmacological data. Ethnopharmacological evidence has limits despite its significance. It might be challenging to assign biological effects to individual components of traditional treatments because they are occasionally created as complex combinations. Significant variations in chemical composition and biological activity can also arise from variations in plant species, geographic origin, harvesting conditions and preparation techniques. These elements show how crucial consistency and repeatability are in converting ethnopharmacological findings into experimentally validated results. Importantly, ethnopharmacological use may not always suggest safety or efficacy. Some widely used herbs may be hazardous at certain quantities or interact with prescription drugs. Therefore, in order to establish scientific credibility, ethnopharmacological knowledge needs to be combined with phytochemical characterization, pharmacological evaluation and toxicological assessment. In the context of finding anti‐infective drugs, ethnopharmacology should be seen as a field that produces hypotheses rather than a definitive source of therapeutic validation [24]. When combined with medicinal chemistry and mechanistic research, ethnopharmacological expertise can greatly benefit in the identification of lead compounds produced from plants. By maintaining scientific integrity and minimizing the likelihood of overstated assertions, this integrated approach allows historical information to influence current research.

FIGURE 2.

Conceptual framework illustrating the integration of traditional knowledge, bioactive phytochemicals and medicinal chemistry approaches in developing plant‐based therapeutics against communicable diseases.

TABLE 2.

Ayurveda Medicinal plants ^a traditionally reported for the management of communicable diseases and their ethnopharmacological relevance.

S. No.	Botanical name	Accepted name (WFO/MPNS)	Author citation	Family	Ayurvedic name	API category	Communicable disease	Ethnopharmacological use
1	Abrus precatorius	Abrus precatorius	L.	Fabaceae	Gunja	Krimi‐ghna	Parasitic infection	Antimicrobial; used externally for lice, ringworm
2	Abutilon indicum	Abutilon indicum	(L.) Sweet	Malvaceae	Atibala	Shothahara	Fever, infection	Antipyretic, wound healing
3	Adhatoda vasica	Justicia adhatoda	L.	Acanthaceae	Vasaka	Swasahara	Cough, TB	Expectorant, bronchodilator; used for asthma, bronchitis
4	Aegle marmelos	Aegle marmelos	(L.) Corrêa	Rutaceae	Bilva	Atisara‐nashaka	Dysentery, fever	Antibacterial, antiamoebic; used for diarrhea and cholera
5	Aloe barbadensis	Aloe vera	(L.) Burm.f.	Asphodelaceae	Kumari	Vrana‐roghahara	Skin, wounds	Antifungal, wound healing, antiviral
6	Argyreia speciose	Argyreia speciosa	(L.f.) Sweet	Convolvulaceae	Vriddhadaru	Rasayana	Chronic infection	Immunostimulant
7	Asparagus racemosus	Asparagus racemosus	Willd.	Asparagaceae	Shatavari	Rasayana	Immunodeficiency	Immunostimulant; adjuvant in infection recovery
8	Bacopa monnieri	Bacopa monnieri	(L.) Wettst.	Plantaginaceae	Brahmi	Rasayana	Chronic infections	Immunomodulatory, antiviral
9	Boerhavia diffusa	Boerhavia diffusa	L.	Nyctaginaceae	Punarnava	Shothahara	Fever, edema	Antimicrobial, hepatoprotective; used in jaundice
10	Calotropis gigantea	Calotropis gigantea	(L.) Dryand.	Apocynaceae	Arka	Kustha‐ghna	Skin infections	Antibacterial, antifungal
11	Carum carvi	Carum carvi	L.	Apiaceae	Krishnajiraka	Deepaniya	GI infections	Antimicrobial, antispasmodic
12	Cassia alata	Senna alata	(L.) Roxb.	Fabaceae	Dadamari	Kustha‐ghna	Fungal infections	Antifungal; ringworm remedy
13	Centella asiatica	Centella asiatica	(L.) Urb.	Apiaceae	Mandukaparni	Rasayana	Wound infections	Antibacterial, wound‐healing; topical and oral use
14	Cinnamomum tamala	Cinnamomum tamala	(Buch.‐Ham.) T.Nees & Eberm.	Lauraceae	Tamalapatra	Krimi‐ghna	Cold, cough	Antimicrobial, anti‐inflammatory
15	Cissampelos pareira	Cissampelos pareira	L.	Menispermaceae	Patha	Jwara‐hara	Fever, malaria	Antipyretic, antimalarial
16	Cissus quadrangularis	Cissus quadrangularis	L.	Vitaceae	Asthisamhara	Shothahara	Inflammation, fever	Antibacterial, antioxidant; promotes healing
17	Citrus limon	Citrus limon	(L.) Osbeck	Rutaceae	Nimbuka	Deepaniya	Fever, sore throat	Antiseptic, antiviral
18	Citrus medica	Citrus medica	L.	Rutaceae	Matulunga	Deepaniya	Fever, cough	Antimicrobial, anti‐inflammatory
19	Clerodendrum serratum	Clerodendrum serratum	(L.) Moon	Lamiaceae	Bharangi	Swasahara	Cough, cold	Expectorant, antimicrobial; used for bronchitis
20	Coleus forskohlii	Plectranthus barbatus	Andrews	Lamiaceae	Pashanbheda	Mutrakrichha	Urinary infections	Antibacterial
21	Curcuma longa	Curcuma longa	L.	Zingiberaceae	Haridra	Kustha‐ghna	Skin, wound infections	Antibacterial, antifungal, wound‐healing; topical paste for ulcers
22	Curcuma zedoaria	Curcuma zedoaria	(Christm.) Roscoe	Zingiberaceae	Kachura	Kustha‐ghna	Skin infections	Antifungal, antiseptic
23	Cynodon dactylon	Cynodon dactylon	(L.) Pers.	Poaceae	Durva	Shothahara	Fever, wounds	Antipyretic, antiseptic
24	Desmodium gangeticum	Desmodium gangeticum	(L.) DC.	Fabaceae	Shalaparni	Jwara‐hara	Fever, infection	Antipyretic, tonic
25	Desmodium triflorum	Desmodium triflorum	(L.) DC.	Fabaceae	Tripatra	Jwara‐hara	Fever	Antipyretic
26	Elettaria cardamomum	Elettaria cardamomum	(L.) Maton	Zingiberaceae	Ela	Deepaniya	Respiratory infections	Antibacterial, expectorant
27	Embelia ribes	Embelia ribes	Burm.f.	Primulaceae	Vidanga	Krimi‐ghna	Intestinal worms	Anthelmintic, antibacterial; classical Krimighna drug
28	Ficus benghalensis	Ficus benghalensis	L.	Moraceae	Nyagrodha	Kustha‐ghna	Skin infections	Antibacterial, healing
29	Garcinia indica	Garcinia indica	(Thouars) Choisy	Clusiaceae	Kokam	Deepaniya	Fever, diarrhea	Antioxidant, antimicrobial
30	Gmelina arborea	Gmelina arborea	Roxb.	Lamiaceae	Gambhari	Jwara‐hara	Fever, viral infections	Antimicrobial, antioxidant
31	Hemidesmus indicus	Hemidesmus indicus	(L.) R.Br.	Apocynaceae	Anantamul	Rasayana	Fevers, skin infection	Antimicrobial, blood purifier
32	Holarrhena antidysenterica	Holarrhena antidysenterica	(L.) Wall. ex A.DC.	Apocynaceae	Kutaja	Atisara‐nashaka	Dysentery, diarrhea	Antibacterial, antiprotozoal; used in amoebiasis
33	Justicia adhatoda	Justicia adhatoda	L.	Acanthaceae	Vasaka	Swasahara	Bronchitis	Antitussive, expectorant
34	Justicia gendarussa	Justicia gendarussa	Burm.f.	Acanthaceae	Nilambari	Jwara‐hara	Fever, malaria	Antipyretic, anti‐inflammatory
35	Mangifera indica	Mangifera indica	L.	Anacardiaceae	Amra	Jwara‐hara	Fever, wound healing	Antibacterial, anti‐inflammatory
36	Melia azedarach	Melia azedarach	L.	Meliaceae	Bakain	Krimi‐ghna	Skin, intestinal infections	Antimicrobial, antiparasitic
37	Mentha piperita	Mentha × piperita	L.	Lamiaceae	Pudina	Deepaniya	Cold, cough	Antiviral, antiseptic
38	Moringa oleifera	Moringa oleifera	Lam.	Moringaceae	Shigru	Deepaniya	Bacterial, viral infections	Antimicrobial, antioxidant
39	Myristica fragrans	Myristica fragrans	Houtt.	Myristicaceae	Jatiphala	Deepaniya	Cough, cold	Antibacterial, expectorant
40	Nelumbo nucifera	Nelumbo nucifera	Gaertn.	Nelumbonaceae	Kamala	Jwara‐hara	Fever, infections	Antioxidant, antipyretic
41	Nyctanthes arbor‐tristis	Nyctanthes arbor‐tristis	L.	Oleaceae	Parijata	Jwara‐hara	Chronic fever, malaria	Antimalarial, febrifuge; used in Assam and Bengal for fevers
42	Ocimum sanctum	Ocimum tenuiflorum	L.	Lamiaceae	Tulasi	Swasahara	Cold, cough, flu	Antiviral, immunomodulatory; decoction used for influenza and bronchitis
43	Phyllanthus niruri	Phyllanthus niruri	L.	Phyllanthaceae	Bhumyamalaki	Yakrit‐vikara	Viral hepatitis	Antiviral (HBV), hepatoprotective; used in liver infections
44	Picrorhiza kurroa	Picrorhiza kurroa	Royle ex Benth.	Plantaginaceae	Katuki	Yakrit‐vikara	Fever, jaundice	Antimicrobial, hepatoprotective; used for malaria and hepatitis
45	Piper betle	Piper betle	L.	Piperaceae	Tambula	Krimi‐ghna	Oral, skin infections	Antifungal, antibacterial
46	Piper cubeba	Piper cubeba	L.f.	Piperaceae	Kababchini	Swasahara	Bronchitis	Antibacterial, expectorant
47	Plumbago zeylanica	Plumbago zeylanica	L.	Plumbaginaceae	Chitraka	Krimi‐ghna	Fever, infection	Antibacterial, stimulant; used in chronic fever
48	Rauvolfia serpentina	Rauvolfia serpentina	(L.) Benth. ex Kurz	Apocynaceae	Sarpagandha	Jwara‐hara	Fevers	Antipyretic, antibacterial
49	Ricinus communis	Ricinus communis	L.	Euphorbiaceae	Eranda	Shothahara	Fever, inflammation	Anti‐inflammatory, antipyretic
50	Saussurea lappa	Saussurea costus	(Falc.) Lipsch.	Asteraceae	Kushtha	Kustha‐ghna	Skin, inflammation	Antibacterial, antifungal; used in eczema and leprosy
51	Sida cordifolia	Sida cordifolia	L.	Malvaceae	Bala	Shothahara	Fever, inflammation	Antiviral, antipyretic
52	Solanum xanthocarpum	Solanum virginianum	L.	Solanaceae	Kantakari	Swasahara	Asthma, bronchitis	Antibacterial, bronchodilator; used for cough
53	Syzygium cumini	Syzygium cumini	(L.) Skeels	Myrtaceae	Jambu	Krimi‐ghna	Oral infections	Antibacterial, antioxidant
54	Tamarindus indica	Tamarindus indica	L.	Fabaceae	Amlika	Deepaniya	Diarrhea	Antibacterial, cooling
55	Tephrosia purpurea	Tephrosia purpurea	(L.) Pers.	Fabaceae	Sharapunkha	Kustha‐ghna	Liver disorders	Antimicrobial, hepatoprotective
56	Terminalia arjuna	Terminalia arjuna	(Roxb.) Wight & Arn.	Combretaceae	Arjuna	Rasayana	Fever, infections	Antioxidant, antimicrobial
57	Tinospora cordifolia	Tinospora cordifolia	(Willd.) Miers	Menispermaceae	Guduchi	Rasayana	Fevers, infections	Immunostimulant; used for dengue, malariaand chronic fevers
58	Tribulus terrestris	Tribulus terrestris	L.	Zygophyllaceae	Gokshura	Mutrakrichha	Urinary infections	Antimicrobial, anti‐inflammatory
59	Tridax procumbens	Tridax procumbens	L.	Asteraceae	Jayanti	Vrana‐roghahara	Wound infections	Antibacterial, wound‐healing
60	Uraria picta	Uraria picta	(Jacq.) DC.	Fabaceae	Prishniparni	Jwara‐hara	Fever, inflammation	Antipyretic, immunostimulant
61	Vetiveria zizanioides	Chrysopogon zizanioides	(L.) Roberty	Poaceae	Ushira	Jwara‐hara	Fever	Antipyretic, cooling; used for seasonal fevers
62	Wrightia tinctoria	Wrightia tinctoria	(Roxb.) R.Br.	Apocynaceae	Indra	Kustha‐ghna	Psoriasis, leprosy	Antifungal, antibacterial

^a Plants listed in Table 2 are documented in authoritative Ayurvedic classical texts including Charaka Saṃhitā, Suśruta Saṃhitā, Aṣṭāṅga Hṛdayaand the Ayurvedic Pharmacopoeia of India, Government of India, Ministry of AYUSH. These texts record therapeutic uses for communicable.

TABLE 3.

Traditional Chinese medicinal plants ^** traditionally reported for the management of communicable diseases and their ethnopharmacological relevance.

S. No.	Botanical name	Accepted name (WFO/MPNS)	Author citation	Family	Chinese name (Pinyin)	API category	Communicable disease	Ethnopharmacological Use
1	Lonicera japonica	Lonicera japonica	Thunb.	Caprifoliaceae	金银花 (Jin Yin Hua)	TCM Herb	Viral URTIs, epidemic fever	Heat‐clearing, antiviral, antibacterial
2	Forsythia suspense	Forsythia suspensa	(Thunb.) Vahl	Oleaceae	连翘 (Lian Qiao)	TCM Herb	Febrile infections	Detoxifying, antimicrobial
3	Scutellaria baicalensis	Scutellaria baicalensis	Georgi	Lamiaceae	黄芩 (Huang Qin)	TCM Herb	Respiratory & GI infections	Antiviral, anti‐inflammatory
4	Isatis indigotica (root)	Isatis indigotica	Fortune ex Lindl.	Brassicaceae	板蓝根 (Ban Lan Gen)	TCM Herb	Epidemic viral diseases	Antiviral, immune‐modulating
5	Isatis indigotica (leaf)	Isatis indigotica	Fortune ex Lindl.	Brassicaceae	大青叶 (Da Qing Ye)	TCM Herb	Febrile viral infections	Heat‐clearing
6	Glycyrrhiza uralensis	Glycyrrhiza uralensis	Fisch. ex DC.	Fabaceae	甘草 (Gan Cao)	TCM Herb	Cough, sore throat	Antimicrobial, harmonizing
7	Ephedra sinica	Ephedra sinica	Stapf	Ephedraceae	麻黄 (Ma Huang)	TCM Herb	Influenza, cold syndromes	Diaphoretic, bronchodilator
8	Houttuynia cordata	Houttuynia cordata	Thunb.	Saururaceae	鱼腥草 (Yu Xing Cao)	TCM Herb	Pneumonia, lung infections	Antiviral, antibacterial
9	Artemisia annua	Artemisia annua	L.	Asteraceae	青蒿 (Qing Hao)	TCM Herb	Malarial & febrile diseases	Antipyretic
10	Coptis chinensis	Coptis chinensis	Franch.	Ranunculaceae	黄连 (Huang Lian)	TCM Herb	Dysentery, GI infections	Strong antibacterial
11	Phellodendron amurense	Phellodendron amurense	Rupr.	Rutaceae	黄柏 (Huang Bai)	TCM Herb	Damp‐heat infections	Antimicrobial
12	Gardenia jasminoides	Gardenia jasminoides	J.Ellis	Rubiaceae	栀子 (Zhi Zi)	TCM Herb	Febrile inflammation	Anti‐inflammatory
13	Platycodon grandifloras	Platycodon grandiflorus	(Jacq.) A.DC.	Campanulaceae	桔梗 (Jie Geng)	TCM Herb	Respiratory infections	Expectorant
14	Fritillaria cirrhosa	Fritillaria cirrhosa	D.Don	Liliaceae	川贝母 (Chuan Bei Mu)	TCM Herb	Chronic cough	Antitussive
15	Pinellia ternate	Pinellia ternata	(Thunb.) Makino	Araceae	半夏 (Ban Xia)	TCM Herb	Phlegm‐related infections	Expectorant
16	Bupleurum chinense	Bupleurum chinense	DC.	Apiaceae	柴胡 (Chai Hu)	TCM Herb	Fever, chills	Antipyretic
17	Magnolia officinalis	Magnolia officinalis	Rehder & E.H.Wilson	Magnoliaceae	厚朴 (Hou Po)	TCM Herb	GI infections	Anti‐inflammatory
18	Atractylodes lancea	Atractylodes lancea	(Thunb.) DC.	Asteraceae	苍术 (Cang Zhu)	TCM Herb	Dampness‐related infections	Antimicrobial
19	Pueraria lobate	Pueraria lobata	(Willd.) Ohwi	Fabaceae	葛根 (Ge Gen)	TCM Herb	Fever, diarrhea	Antipyretic
20	Patrinia scabiosifolia	Patrinia scabiosifolia	Fisch. ex Trevir.	Caprifoliaceae	败酱草 (Bai Jiang Cao)	TCM Herb	Intestinal abscess	Antibacterial
21	Sophora flavescens	Sophora flavescens	Aiton	Fabaceae	苦参 (Ku Shen)	TCM Herb	Parasitic & skin infections	Antimicrobial
22	Chrysanthemum indicum	Chrysanthemum indicum	L.	Asteraceae	野菊花 (Ye Ju Hua)	TCM Herb	Respiratory infections	Anti‐inflammatory
23	Viola yedoensis	Viola yedoensis	Makino	Violaceae	紫花地丁 (Zi Hua Di Ding)	TCM Herb	Abscess, infections	Detoxifying
24	Taraxacum mongolicum	Taraxacum mongolicum	Hand.‐Mazz.	Asteraceae	蒲公英 (Pu Gong Ying)	TCM Herb	URTIs, mastitis	Antibacterial
25	Scrophularia ningpoensis	Scrophularia ningpoensis	Hemsl.	Scrophulariaceae	玄参 (Xuan Shen)	TCM Herb	Throat infections	Anti‐inflammatory
26	Gentiana scabra	Gentiana scabra	Bunge	Gentianaceae	龙胆草 (Long Dan Cao)	TCM Herb	Damp‐heat infections	Antimicrobial
27	Verbena officinalis	Verbena officinalis	L.	Verbenaceae	马鞭草 (Ma Bian Cao)	TCM Herb	Fever, malaria	Antipyretic
28	Andrographis paniculata	Andrographis paniculata	(Burm.f.) Nees	Acanthaceae	穿心莲 (Chuan Xin Lian)	TCM Herb	Viral URTIs	Antiviral
29	Lobelia chinensis	Lobelia chinensis	Lour.	Campanulaceae	半边莲 (Ban Bian Lian)	TCM Herb	Skin infections	Antibacterial
30	Eupatorium fortune	Eupatorium fortunei	Turcz.	Asteraceae	佩兰 (Pei Lan)	TCM Herb	Summer infections	Aromatic antimicrobial
31	Zingiber officinale	Zingiber officinale	Roscoe	Zingiberaceae	生姜 (Sheng Jiang)	TCM Herb	Cold infections	Antimicrobial
32	Mentha haplocalyx	Mentha canadensis	L.	Lamiaceae	薄荷 (Bo He)	TCM Herb	Cold & flu	Antiviral
33	Perilla frutescens	Perilla frutescens	(L.) Britton	Lamiaceae	紫苏叶 (Zi Su Ye)	TCM Herb	Respiratory infections	Antimicrobial
34	Cinnamomum cassia	Cinnamomum cassia	(L.) J.Presl	Lauraceae	桂枝 (Gui Zhi)	TCM Herb	Cold syndromes	Circulatory stimulant
35	Acorus tatarinowii	Acorus tatarinowii	Schott	Acoraceae	石菖蒲 (Shi Chang Pu)	TCM Herb	Infection‐related delirium	Antimicrobial
36	Angelica dahurica	Angelica dahurica	(Hoffm.) Benth. & Hook.f.	Apiaceae	白芷 (Bai Zhi)	TCM Herb	Sinus infections	Antibacterial
37	Schizonepeta tenuifolia	Nepeta tenuifolia	Benth.	Lamiaceae	荆芥 (Jing Jie)	TCM Herb	Early infections	Diaphoretic
38	Elsholtzia ciliate	Elsholtzia ciliata	(Thunb.) Hyl.	Lamiaceae	香薷 (Xiang Ru)	TCM Herb	Summer flu	Antipyretic
39	Lycopus lucidus	Lycopus lucidus	Turcz. ex Benth.	Lamiaceae	泽兰 (Ze Lan)	TCM Herb	Febrile diseases	Antibacterial
40	Eclipta prostrata	Eclipta prostrata	(L.) L.	Asteraceae	旱莲草 (Han Lian Cao)	TCM Herb	Viral fevers	Immunomodulatory
41	Sanguisorba officinalis	Sanguisorba officinalis	L.	Rosaceae	地榆 (Di Yu)	TCM Herb	Dysentery	Antibacterial
42	Cirsium japonicum	Cirsium japonicum	DC.	Asteraceae	大蓟 (Da Ji)	TCM Herb	Inflammatory infections	Anti‐inflammatory
43	Oldenlandia diffusa	Hedyotis diffusa	Willd.	Rubiaceae	白花蛇舌草 (Bai Hua She She Cao)	TCM Herb	Viral & tumor‐related infections	Detoxifying
44	Lysimachia christinae	Lysimachia christinae	Hance	Primulaceae	金钱草 (Jin Qian Cao)	TCM Herb	UTIs	Antimicrobial
45	Polygonum cuspidatum	Reynoutria japonica	Houtt.	Polygonaceae	虎杖 (Hu Zhang)	TCM Herb	Viral infections	Antiviral
46	Hedyotis corymbosa	Hedyotis corymbosa	(L.) Lam.	Rubiaceae	白花蛇草	TCM Herb	Epidemic infections	Antimicrobial
47	Imperata cylindrical	Imperata cylindrica	(L.) Raeusch.	Poaceae	白茅根 (Bai Mao Gen)	TCM Herb	Febrile bleeding	Heat‐clearing
48	Pogostemon cablin	Pogostemon cablin	(Blanco) Benth.	Lamiaceae	广藿香 (Guang Huo Xiang)	TCM Herb	GI infections	Antimicrobial
49	Coix lacryma‐jobi	Coix lacryma‐jobi	L.	Poaceae	薏苡仁 (Yi Yi Ren)	TCM Herb	Damp‐heat infections	Immune support

^**Medicinal species listed in Table 3 are referenced in traditional Chinese medical formularies, including Shénnóng Běncǎo Jīng (Divine Farmer's Classic of Materia Medica), Běncǎo Gāngmù (Compendium of Materia Medica) by Li Shizhen and the Pharmacopoeia of the People's Republic of China. These authoritative sources describe applications of the listed herbs in febrile, respiratory, gastrointestinal, parasitic and epidemic infectious disorders (Wēn bìng, Shī rèand related categories).

TABLE 4.

Unani medicinal plants ^*** for communicable diseases.

S. No.	Botanical Name	Accepted Name (WFO/MPNS)	Author Citation	Family	Unani Name	API Category	Communicable Disease	Ethnopharmacological Use
1	Piper longum	Piper longum	L.	Piperaceae	Filfil Daraz	Unani Medicinal Plant	Cough, bronchitis, respiratory infections	Expectorant, antibacterial
2	Piper nigrum	Piper nigrum	L.	Piperaceae	Filfil Siyah	Unani Medicinal Plant	Respiratory & GI infections	Antimicrobial, stimulant
3	Zingiber officinale	Zingiber officinale	Roscoe	Zingiberaceae	Zanjabeel	Unani Medicinal Plant	Cold, flu, GI infections	Antiviral, anti‐inflammatory
4	Trachyspermum ammi	Trachyspermum ammi	(L.) Sprague	Apiaceae	Ajwain	Unani Medicinal Plant	GI & respiratory infections	Antibacterial, carminative
5	Allium sativum	Allium sativum	L.	Amaryllidaceae	Lehsun	Unani Medicinal Plant	Bacterial & viral infections	Broad‐spectrum antimicrobial
6	Nigella sativa	Nigella sativa	L.	Ranunculaceae	Kalonji	Unani Medicinal Plant	Respiratory, GI infections	Immunomodulatory, antibacterial
7	Cordia myxa	Cordia myxa	L.	Boraginaceae	Sapistan	Unani Medicinal Plant	Cough, sore throat, URTIs	Antitussive, antiviral
8	Ziziphus jujube	Ziziphus jujuba	Mill.	Rhamnaceae	Unnab	Unani Medicinal Plant	Influenza‐like illness	Immunonutritional, soothing
9	Cydonia oblonga	Cydonia oblonga	Mill.	Rosaceae	Behidana	Unani Medicinal Plant	Cold, flu, pharyngitis	Demulcent, anti‐inflammatory
10	Viola odorata	Viola odorata	L.	Violaceae	Banafsha	Unani Medicinal Plant	Bronchitis, fever	Expectorant, antipyretic
11	Matricaria chamomilla	Matricaria chamomilla	L.	Asteraceae	Babuna	Unani Medicinal Plant	Viral URTIs	Anti‐inflammatory, antimicrobial
12	Pistacia integerrima	Pistacia integerrima	J.L.Stewart ex Brandis	Anacardiaceae	Kakra Singhi	Unani Medicinal Plant	Bronchitis, pneumonia	Expectorant, antibacterial
13	Glycyrrhiza glabra	Glycyrrhiza glabra	L.	Fabaceae	Asl‐us‐Soos	Unani Medicinal Plant	Throat & respiratory infections	Antiviral, soothing
14	Acorus calamus	Acorus calamus	L.	Acoraceae	Bach	Unani Medicinal Plant	GI & respiratory infections	Antibacterial
15	Cyperus rotundus	Cyperus rotundus	L.	Cyperaceae	Nagarmotha	Unani Medicinal Plant	Dysentery, fever	Antimicrobial
16	Operculina turpethum	Operculina turpethum	(L.) Silva Manso	Convolvulaceae	Turbud	Unani Medicinal Plant	Bacterial infections	Antimicrobial, purgative
17	Curcuma longa	Curcuma longa	L.	Zingiberaceae	Haldi	Unani Medicinal Plant	Wound & skin infections	Antibacterial, anti‐inflammatory
18	Withania somnifera	Withania somnifera	(L.) Dunal	Solanaceae	Asgand	Unani Medicinal Plant	Recurrent infections	Immunomodulatory
19	Ocimum basilicum	Ocimum basilicum	L.	Lamiaceae	Rehan	Unani Medicinal Plant	Respiratory infections	Antimicrobial
20	Trigonella foenum‐graecum	Trigonella foenum‐graecum	L.	Fabaceae	Hulba	Unani Medicinal Plant	Respiratory & GI infections	Anti‐inflammatory
21	Cinnamomum verum	Cinnamomum verum	J.Presl	Lauraceae	Darchini	Unani Medicinal Plant	Cold, flu, GI infections	Antibacterial
22	Foeniculum vulgare	Foeniculum vulgare	Mill.	Apiaceae	Badiyan	Unani Medicinal Plant	GI infections	Antimicrobial, carminative
23	Cuminum cyminum	Cuminum cyminum	L.	Apiaceae	Zeera	Unani Medicinal Plant	Diarrhea, dysentery	Antibacterial
24	Ficus religiosa	Ficus religiosa	L.	Moraceae	Peepal	Unani Medicinal Plant	Throat & respiratory infections	Antimicrobial
25	Emblica officinalis	Phyllanthus emblica	L.	Phyllanthaceae	Amla	Unani Medicinal Plant	Viral & bacterial infections	Immunomodulatory
26	Psoralea corylifolia	Cullen corylifolium	(L.) Medik.	Fabaceae	Babchi	Unani Medicinal Plant	Skin infections	Antibacterial
27	Smilax china	Smilax china	L.	Smilacaceae	Chob‐e‐Chini	Unani Medicinal Plant	Chronic infections	Antimicrobial
28	Sphaeranthus indicus	Sphaeranthus indicus	L.	Asteraceae	Mundi	Unani Medicinal Plant	Fever & infections	Antipyretic
29	Ruta graveolens	Ruta graveolens	L.	Rutaceae	Suddab	Unani Medicinal Plant	Bacterial infections	Antimicrobial
30	Malva sylvestris	Malva sylvestris	L.	Malvaceae	Khubazi	Unani Medicinal Plant	Respiratory infections	Demulcent
31	Linum usitatissimum	Linum usitatissimum	L.	Linaceae	Alsi	Unani Medicinal Plant	Throat infections	Anti‐inflammatory
32	Hordeum vulgare	Hordeum vulgare	L.	Poaceae	Jau	Unani Medicinal Plant	Febrile illness	Cooling, nutritive
33	Plantago ovata	Plantago ovata	Forssk.	Plantaginaceae	Ispaghula	Unani Medicinal Plant	GI infections	Soothing
34	Cassia fistula	Cassia fistula	L.	Fabaceae	Amaltas	Unani Medicinal Plant	Intestinal infections	Mild antimicrobial
35	Azadirachta indica	Azadirachta indica	A.Juss.	Meliaceae	Neem	Unani Medicinal Plant	Skin & systemic infections	Broad antimicrobial
36	Berberis aristata	Berberis aristata	DC.	Berberidaceae	Rasaut	Unani Medicinal Plant	Eye & GI infections	Antibacterial
37	Terminalia chebula	Terminalia chebula	Retz.	Combretaceae	Halela	Unani Medicinal Plant	GI infections	Antimicrobial
38	Terminalia bellirica	Terminalia bellirica	(Gaertn.) Roxb.	Combretaceae	Balela	Unani Medicinal Plant	Respiratory & GI infections	Antibacterial
39	Rosa damascene	Rosa × damascena	Mill.	Rosaceae	Gulab	Unani Medicinal Plant	Throat & febrile illness	Anti‐inflammatory
40	Mentha arvensis	Mentha arvensis	L.	Lamiaceae	Podina	Unani Medicinal Plant	GI & respiratory infections	Antimicrobial
41	Syzygium aromaticum	Syzygium aromaticum	(L.) Merr. & L.M.Perry	Myrtaceae	Laung	Unani Medicinal Plant	Dental & throat infections	Antibacterial
42	Punica granatum	Punica granatum	L.	Lythraceae	Anar	Unani Medicinal Plant	Diarrhea, dysentery	Antimicrobial
43	Lawsonia inermis	Lawsonia inermis	L.	Lythraceae	Hina	Unani Medicinal Plant	Skin infections	Antifungal
44	Althaea officinalis	Althaea officinalis	L.	Malvaceae	Khatmi	Unani Medicinal Plant	Respiratory infections	Demulcent
45	Coriandrum sativum	Coriandrum sativum	L.	Apiaceae	Kishneez	Unani Medicinal Plant	GI infections	Antibacterial
46	Anethum graveolens	Anethum graveolens	L.	Apiaceae	Soya	Unani Medicinal Plant	Digestive infections	Antimicrobial
47	Morus alba	Morus alba	L.	Moraceae	Toot	Unani Medicinal Plant	Respiratory infections	Antibacterial
48	Eucalyptus globulus	Eucalyptus globulus	Labill.	Myrtaceae	Nilgiri	Unani Medicinal Plant	Respiratory infections	Antiseptic
49	Hibiscus rosa‐sinensis	Hibiscus rosa‐sinensis	L.	Malvaceae	Gudhal	Unani Medicinal Plant	Fever & infections	Anti‐inflammatory

^***Plants included in Table 4 are recognized in established Unani literature and formularies such as Al‐Qānūn fī’l‐Ṭibb, Kitāb al‐Hāwī, Makhzan‐ul‐Advia and the National Formulary of Unani Medicine, Ministry of AYUSH, Government of India. These works describe therapeutic use of the listed botanicals in communicable diseases.

3. Major Classes of Plant‐Derived Bioactive Compounds

Medicinal plants produce a wide array of secondary metabolites that contribute to their reported biological activities [8]. These compounds are not directly involved in primary metabolic processes but play important ecological roles, such as defense against pathogens and environmental stress [9, 10]. Secondary metabolites originating from plants are a valuable source of chemically varied scaffolds that have been studied for their possible effectiveness against pathogens that cause communicable diseases [12]. Alkaloids, terpenoids, phenolic compounds, flavonoids and glycosides are the main types of phytochemicals that are frequently reported in anti‐infective research; each is distinguished by unique chemical characteristics and biological profiles [2, 25].

3.1. Alkaloids

Alkaloids are chemical substances that include nitrogen and frequently have strong biological effects [20]. They are found in many medicinal plants and have been well investigated for their antiviral, antibacterial and anti‐parasitic qualities [23]. From simple heterocyclic systems to complex polycyclic frameworks, alkaloids display a broad variety of structural diversity [3, 26]. Numerous alkaloids have been demonstrated to hinder the growth of microbes by mechanisms such as enzyme inhibition, disruption of nucleic acid synthesis and change of membrane function [25]. However, the same structural features that produce biological activity can also cause cytotoxicity, underscoring the significance of meticulous dose optimization and safety evaluation [20]. Alkaloids are often studied as lead compounds in medicinal chemistry; structural changes are used to improve selectivity and lower toxicity [26]. Alkaloids have become significant bioactive substances that can disrupt the molecular mechanisms necessary for viral survival and reproduction [4, 27]. Antiviral effect is mainly mediated by suppressing a number of crucial phases of the viral life cycle, such as transcription, protein synthesis and DNA and RNA replication [28]. Other processes reported in the literature include DNA intercalation, enzyme inhibition and disruption of ribonucleoprotein complex translocation, all of which contribute to impaired viral genome assembly and expression. Certain alkaloids have also been shown to alter the host's immune system by increasing humoral immune responses, which fortifies immunological defense and viral resistance in addition to these direct antiviral effects [29] Figure 3.

FIGURE 3.

Schematic representation of the antiviral effects of plant‐derived alkaloids.

3.2. Terpenoids

One of the biggest and most structurally varied groups of secondary metabolites found in plants are terpenoids [23]. These are made up of isoprene units that are biosynthesized into mono‐, sesqui‐, di‐and triterpenes [4, 5]. Terpenoids are found in many medicinal herbs that have long been used to treat infectious diseases. Terpenoids' ability to interact with biological membranes through lipophilia may account for some of their antibacterial or anti‐parasitic effects. Furthermore, certain terpenoid drugs have been found to target particular redox systems or enzymatic pathways in infections [6, 28]. Despite their intriguing biological activity, terpenoids cannot be directly utilized in medicine due to issues with solubility and metabolic stability. Medicinal chemistry methods, such as semi‐synthetic modification and formulation approaches, are often studied to get over these limitations [11].

Terpenoids, which include hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes and tetraterpenoids, are one of the most structurally varied classes of natural products [7, 8]. All plant parts contain these substances, which are produced by primary and secondary metabolism. However, they are most abundant in the leaves and fruits, where they contribute to ecological protection, aroma and color. Their wide antibacterial and antiviral characteristics have made them appealing scaffolds in medicinal chemistry due to their pharmacological relevance [18]. Notable examples include glycyrrhizin from Glycyrrhiza glabra, which is known for its antiviral, anti‐inflammatory and immunomodulatory properties against hepatitis and corona viruses and monoterpenes such as isoborneol, β‐pineneand limonene, which have strong action against the herpes simplex virus [30]. Triterpenoids like celastrol and carotenoid derivatives like fucoxanthin have also been demonstrated to inhibit the replication of dengue, HIV, hepatitis viruses and SARS‐CoV‐2 by disrupting viral polymerases and entry channels Figure 4 [31].

FIGURE 4.

Schematic representation of the antiviral effects of plant‐derived terpenoids.

3.3. Phenolic Compounds and Phenolic Acids

Plant metabolites with one or more hydroxylated aromatic rings are known as phenolic compounds. Tannins, phenolic acids, simple phenols and associated substances are all members of this class [6, 8]. In experiments, phenolics have shown antiviral, antifungal and antibacterial properties [25]. The capacity of phenolic compounds to interact with metal ions, proteins and enzymes is a widely accepted explanation for their biological effects [26]. These interactions may cause membrane instability, interfere with microbe adherence, or inhibit enzymes in microbial systems but the quick metabolism of phenolic compounds is another well‐known characteristic [27]. Therefore, rather than acting as direct therapeutic agents, their involvement in drug development is frequently concentrated on acting as pharmacophoric templates. Through a variety of mechanisms that interfere with the viral life cycle, phenolic substances demonstrate wide antiviral action [31]. They have the ability to weaken viral envelopes, prevent binding to receptors on host cells and stop vital viral enzymes and protein functions [32]. Among these, green tea's epigallocatechin‐3‐gallate has been demonstrated to inhibit HIV‐1 gp120 binding to CD4 receptors and limit influenza A virus replication through modification of the p38 MAPK–IFN‐λ2 pathway [8, 9]. Other phenolics, such sodium ferulate and chicoric acid, prevent nucleic acid production and integration by interfering with viral polymerases and integrases [33]. By inducing cytokines and chemokines, substances like gallic acid and salicylic acid activate host immunological defences while further impeding viral attachment, replication and intercellular transmission [34]. When used together, phenolic chemicals limit the spread of infection, improve host antiviral responses and prevent viral reproduction Figure 5.

FIGURE 5.

Schematically summarizes the anti‐infective mechanisms of plant‐derived flavonoids.

3.4. Flavonoids

A category of polyphenolic chemicals found in many therapeutic plants are flavonoids [35]. They are frequently mentioned in ethnopharmacological research concerning the management of inflammatory and infectious diseases [9, 36]. Flavonoids have a distinctive C6–C3–C6 backbone that permits a great deal of structural diversity through methylation, glycosylation and hydroxylation [37]. Flavonoids may have anti‐infective effects via a variety of mechanisms, including as interference with viral replication processes, modification of oxidative stress and inhibition of microbial enzymes [8, 9, 38]. Although flavonoids' multi target nature has drawn attention, it also makes exact target identification more difficult [38, 39]. Furthermore, low oral bioavailability continues to be a major obstacle, which has sparked interest in prodrug and chemical modification techniques Figure 6.

FIGURE 6.

Schematic representation of antiviral, antibacterial and immunomodulatory mechanisms of plant‐derived flavonoids.

3.5. Glycosides and Saponins

Glycosides are substances that have a sugar moiety attached to a non‐sugar aglycone [20]. The amphiphilic nature of saponins, a subclass of glycosides, enables them to interact with lipid membranes [9, 10]. These compounds are frequently present in medicinal plants that are used to treat infectious and inflammatory illnesses [23]. Saponins are said to increase membrane permeability and facilitate the absorption of other bioactive chemicals. On occasion, their immunomodulatory properties have also been investigated [25]. However, at higher doses, their membrane‐active behaviour might have cytotoxic or haemolytic effects. Medicinal chemistry efforts often focus on changing the sugar or aglycone components to improve safety and selectivity [11, 28].

3.6. Relevance to Anti‐Infective Drug Discovery

Relatively few plant‐derived drugs make it to clinical use without significant modification, despite the fact that many show encouraging biological activity in experimental settings [40, 41]. Regarding chemical stability, bioavailability, selectivity and safety, each class of phytochemicals has unique benefits and drawbacks [12, 29]. Understanding these characteristics is essential for the rational evaluation of plant‐based compounds as potential anti‐infective medications [42, 43]. Phytochemicals are no longer seen as finished medications in modern research, but rather as helpful starting points for lead discovery and optimization [13, 15]. Combining knowledge of ethnopharmacology with medicinal chemistry and mechanistic research offers a more balanced and scientifically rigorous approach to studying plant‐based remedies against infectious diseases Table 5 [44, 45, 46, 47, 48].

TABLE 5.

Isolated plant‐derived bioactive compounds reported with anti‐infective activity against communicable diseases.

Compound	Plant source	Chemical class	Key chemical structure features	Communicable disease category	Mechanistic relevance	References
Artemisinin	Artemisia annua	Sesquiterpene lactone	Tricyclic sesquiterpene with endoperoxide bridge	Parasitic (malaria)	Endoperoxide cleavage → parasite oxidative stress	[49]
Quinine	Cinchona spp.	Quinoline alkaloid	Quinoline ring linked to quinuclidine moiety	Parasitic (malaria)	Inhibits heme detoxification	[50]
Berberine	Berberis spp.	Isoquinoline alkaloid	Planar tetracyclic isoquinoline scaffold	Bacterial	DNA intercalation; enzyme inhibition	[51]
Curcumin	Curcuma longa	Polyphenolic diarylheptanoid	Two phenolic rings linked by α,β‐unsaturated diketone	Bacterial, viral	Enzyme inhibition; redox modulation	[33]
Andrographolide	Andrographis paniculata	Diterpenoid lactone	Bicyclic diterpene with lactone ring	Viral, bacterial	Interference with viral replication	[52]
Glycyrrhizin	Glycyrrhiza glabra	Triterpenoid saponin	Oleanane‐type triterpene with sugar residues	Viral	Inhibits viral entry and replication	[34]
Quercetin	Multiple plants	Flavonol	C6–C3–C6 flavonoid backbone with hydroxyl groups	Bacterial, viral	Enzyme inhibition; antioxidant activity	[36]
Baicalein	Scutellaria baicalensis	Flavone	Trihydroxyflavone with planar aromatic rings	Viral	Inhibits viral proteases	[53]
Epigallocatechin gallate	Camellia sinensis	Catechin	Polyhydroxylated flavanol with gallate ester	Viral, bacterial	Membrane interaction; enzyme inhibition	[54]
Allicin	Allium sativum	Organosulfur compound	Thiosulfinate functional group	Bacterial, fungal	Reacts with thiol‐containing enzymes	[55]
Thymol	Thymus vulgaris	Monoterpene phenol	Phenolic ring with isopropyl substituent	Bacterial, fungal	Disrupts membrane integrity	[56]
Carvacrol	Origanum spp.	Monoterpene phenol	Isomer of thymol with phenolic OH	Bacterial	Alters membrane permeability	[57]
Sanguinarine	Sanguinaria Canadensis	Benzophenanthridine alkaloid	Planar polycyclic aromatic system	Bacterial	DNA and enzyme interaction	[58]
Limonene	Citrus spp.	Monoterpene	Cyclic monoterpene hydrocarbon	Fungal, bacterial	Membrane perturbation	[59]
Piperine	Piper nigrum	Alkaloid	Piperidine ring linked to methylenedioxy phenyl	Bacterial	Efflux pump inhibition	[60]
Capsaicin	Capsicum spp.	Vanilloid alkaloid	Vanillyl group linked to long alkyl chain	Bacterial	Membrane disruption; enzyme interference	[61]
Resveratrol	Polygonum cuspidatum	Stilbene polyphenol	Two phenyl rings linked by ethylene bridge	Viral	Inhibits viral replication pathways	[62]
Luteolin	Ocimum, Celery	Flavone	Tetrahydroxyflavone structure	Viral, bacterial	Enzyme inhibition; anti‐inflammatory modulation	[63]
Ellagic acid	Punica granatum	Polyphenolic dilactone	Biphenyl with lactone rings	Viral	Protein binding; antioxidant activity	[64]
Tannic acid	Multiple plants	Hydrolysable tannin	Polygallic acid esterified to glucose	Bacterial	Protein precipitation; enzyme inhibition	[65]

The aforementioned substances are isolated, chemically characterized molecules produced from plants that have been shown to have anti‐infective properties in experimental studies. Although their inclusion in this table does not imply clinical efficacy or curative potential, their chemical structures offer mechanistic justification for biological activity. The majority of drugs need additional clinical validation, pharmacokinetic analysis and medicinal chemistry optimization.

4. Mechanistic Relevance of Isolated Plant‐Derived Bioactive Compounds Reported With Anti‐Infective Activity Against Communicable Diseases

Experimental and mechanistic research, rather than clinical evidence, is the main source of support for the anti‐infective potential of isolated plant‐derived bioactive chemicals Figure 7 [30, 66]. These substances have a variety of chemical scaffolds that interact through various metabolic routes with microbial or parasite systems [67]. Assessing translational potential and directing medicinal chemistry optimization require an understanding of their mechanistic significance [68, 69].

FIGURE 7.

Type of mechanistic relevance of isolated plant‐derived bioactive compounds.

5. Disruption of Pathogen Cellular Integrity

The membrane perturbing effect of natural plant extracts is greatly determined by their physiochemical properties, especially lipophility, molecular weight and functional group distribution [70, 71]. Phenolic monoterpenes like thymol and carvacrol have hydrophobic aromatic rings and hydrophilic hydroxyl functional groups, which allow them to penetrate the phospholipid membrane structure of the microorganisms. Once they enter the membrane structure, they cause changes in the fluidity and packing of lipids and increased ion permeability [72, 73]. Leakage of potassium ions, depletion of ATP and proton motive force has been shown experimentally to occur after treatment with these extracts [33]. These changes have a negative impact on metabolism and eventually cause cell death. Membrane alteration in fungal pathogens also disrupts the ergosterol‐dependent arrangement of membranes and hence increases sensitivity to these drugs [31, 39]. But since mammalian membranes have some structural similarities to microbial membranes, increased membrane activity can lower selectivity and cause cell toxicity [74]. As a result, medicinal chemists tend to develop compounds that optimize membrane binding and pathogen selectivity [53, 54].

5.1. Inhibition of Enzymatic Pathways Essential for Pathogen Survival

Among the most studied anti‐infective mechanisms of the phyto‐compounds is the inhibition of the enzymes necessary for the infection reproduction and development [54, 75]. This is possible only because of the capability of the phytochemicals to interact specifically with certain sites of the enzyme structure due to the hydrogen bonding, hydrophobic and π‐π‐stacking interactions and electrostatic interactions [76]. Such flavonoids as baicalein, quercetin, and luteolin inhibit various viruses' and bacteria's enzymes [38, 77]. Molecular docking and enzymatic assays demonstrated that these compounds interact with the amino acid residues responsible for catalysis of proteases, which leads to the inhibition of proteolytic processing of viral polyproteins and thus prevents virus reproduction [78]. In the case of coronavirus, flavonoids were found to be capable to interact with the catalytic site of 3CLpro and PLpro proteases which are important for viral maturation [79, 80]. Hydroxyl group of the flavonoid structure plays an important role in the interaction with catalytic residues through hydrogen bonding. Another example of such action is alkaloids [81]. Berberine is known to target the bacterial DNA gyrase and topoisomerase enzymes that play an important role in super‐coiling and replication of DNA. The planar nature of the cationic berberine molecule makes it possible for the drug to interact with negatively charged nucleic acid–protein complexes and inhibit bacterial growth [81, 82]. The polyphenolic molecules like EGCG inhibit viral polymerases, neuraminidases, and proteases by targeting multiple targets [82]. This implies that plant derived molecules may target highly specific molecular sites in addition to being generally antimicrobial.

5.2. Modulation of Oxidative Stress and Redox Balance

Numerous plant‐derived chemicals have been shown to have anti‐infective properties by regulating pathogens' oxidative stress [83]. In parasite‐specific settings, artemisinin, a sesquiterpene lactone containing an endoperoxide bridge, is activated to produce reactive oxygen species [49, 50]. Important parasite proteins and membranes are oxidatively damaged by these reactive intermediates. Redox signalling pathways are also impacted by polyphenolic substances like resveratrol and curcumin [84]. Despite their well‐established antioxidant qualities, experimental evidence indicates that they might cause oxidative imbalance in microbial systems, which would obliquely contribute to antimicrobial actions [85]. The modulation of oxidative stress is a complex mechanism since, in different biological systems, phytochemicals can act as either antioxidants or pro‐oxidants [86]. Artemisinin serves as an example of a redox‐activated anti‐infective compound. In malaria parasites, iron generated during the process of haemoglobin degradation reacts with the endoperoxide bridge of artemisinin and induces the formation of reactive oxygen species and carbon‐centered radicals [49]. These reactive molecules attack macromolecules, which leads to the death of the parasite. On the other hand, polyphenolic substances, such as curcumin, quercetin and resveratrol [87]. Although they are capable of scavenging ROS at physiological conditions, they might cause an imbalance in the redox status in microbes by interfering with redox balance and mitochondrial functions [88]. This might lead to disruption in ATP synthesis, enzyme functioning, and membrane stability. The link between redox modification and biofilm formation, virulence factors expression, which implies that oxidative strategies not only kill the pathogens but also affect their adaptability and persistence [70].

5.3. Interference With Nucleic Acid Function and Replication

It has been demonstrated that a variety of polyphenols and alkaloids exhibit activity through interactions with nucleic acids or processes associated with them [63, 65]. Sanguinarine and berberine can intercalate into DNA and disrupt transcription and replication due to their planar aromatic properties [37]. Although these techniques are effective against infections in vitro, they also necessitate a careful evaluation of host damage [89]. It has been demonstrated that compounds such as EGCG and baicalein restrict viral genome processing and decrease viral replication in viral systems by interfering with viral proteases or polymerases [40]. Nucleic acid synthesis interference is among the most straightforward approaches in the inhibition of pathogen reproduction by plant compounds [74]. Berberine and sanguinarine alkaloids share planar aromatic molecular configurations that facilitate intercalation into DNA bases. These effects lead to changes in DNA configuration, inhibit transcription activities and disrupt replication machinery. Apart from direct interactions with DNA, a few phytochemicals have been shown to block enzymatic reactions associated with the synthesis of nucleic acids such as DNA polymerase, reverse transcriptase and helicase [69]. The viral pathogens appear to be highly sensitive to these processes since their replication depends on the use of a small number of conserved enzymes. Polyphenolic EGCG, baicalein and some tannins exhibit inhibitory effects toward viral polymerases and replication complexes. By disrupting the formation of viral genomes, these substances are able to decrease viral loads and infection development [90]. However, owing to the similar pathway used by host cells, the selectivity of the inhibition becomes an important issue in lead optimization.

5.4. Modulation of Host–Pathogen Interactions

Certain bioactive substances originating from plants may affect host‐mediated pathways related to infection in addition to their direct antibacterial effect [70]. It has been observed that the triterpenoid saponin glycyrrhizin both modulates inflammatory responses and prevents viral entry and replication [18, 41]. Although conclusive therapeutic implications have not yet been proven, such dual action may help alleviate symptoms and lower the burden of pathogens [31, 77]. It is now increasingly clear that there are more than just direct antibacterial properties to the therapeutic actions of bioactive agents found in plants, and that immune modulation is often a key mechanism of action [34]. In the case of infection, hyperactivation of the inflammatory response is one of the main causes of tissue injury and disease development. For this reason, agents that can effectively inhibit the growth of pathogens as well as regulate the immune system might be considered highly advantageous in terms of treatment options. Glycyrrhizin, which is a triterpenoid saponin obtained from Glycyrrhiza glabra, has been shown to affect several host signaling pathways responsible for inflammation and the antiviral response [34]. Glycyrrhizin modulates NF‐κB signalling and reduces pro‐inflammatory cytokine production [91]. Flavonoids, including quercetin and luteolin, are known to influence MAPK and Nrf2 signaling pathways that regulate oxidative stress and inflammation [34, 91]. In addition to their mode of action based on pathogen destruction, these molecules might act by reducing tissue damage, regulating the immune response, and aiding recovery. On the other hand, excess immunomodulation will interfere with the protective immune reaction [92]. It is thus important to have an in‐depth knowledge of dose and pathway selectivity.

5.5. Multitarget Activity and Implications for Resistance

Compounds originating from plants frequently exhibit a multitarget mode of action. Numerous phytochemicals interact with several cellular pathways at once, in contrast to manufactured medicines that only target one [39, 42, 72]. This characteristic makes mechanistic interpretation and medicinal chemistry optimization more difficult, but it may also lessen the chance of rapid resistance development [43]. Multi‐target action should be well described from the standpoint of drug development in order to differentiate advantageous polypharmacology from nonspecific toxicity [44, 45].

5.5.1. Structure–Mechanism Relationships

Biological activity of natural bioactive compounds derived from plants is strongly linked with chemical structure because the smallest changes in the molecule can strongly affect interactions with biological targets, membrane permeability, stability of the molecule and its biological activity [45]. In case of flavonoids, presence and position of hydroxyl group are of particular importance for antimicrobial and antiviral activity of flavonoids because hydrogen bonds that can be formed between hydroxyl group of the compound and amino acid residues present in enzyme active site and viral protease provide strong interactions with target [93]. However, too much hydroxylation may decrease lipophilicity of the molecule and its ability to penetrate into cells. Methoxylation increases lipophilicity, which improves membrane permeability and metabolic stability of the molecule, but weakens interactions with biological targets. Planar structure of flavonoids and many alkaloids contributes to biological activity due to π‐π stacking with proteins and nucleic acids. For example, planar structure of berberine and sanguinarine provides interaction with nucleic acids [94]. The terpenoid compounds have an altogether distinct structure‐mechanism relation. The lipophilic nature of the hydrocarbon skeleton of terpenoids promotes their ability to distribute within biological membranes; hence, leading to the destabilization of the membranes, changes in permeability and pathogen imbalance. In like manner, the structural properties of the saponins due to the hydrophobicity of the aglycone part attached to the hydrophilic sugar units promote their interaction with membrane sterols and lead to membrane permeabilization [93, 94]. The pharmacokinetics of the compounds include aspects such as absorption, distribution, metabolism and excretion. Knowledge of the structure‐mechanism relations is thus vital for medicinal chemistry purposes since modifications of the hydroxyl groups, aromatic substitutions, stereoselectivity and lipophilicity of the compounds can increase potency and minimize toxicity [94].

5.6. Translational Considerations

Although experimental data supports the mechanistic importance of isolated plant‐derived bioactive chemicals, it is crucial to note that the majority of the evidence is still preclinical [45, 46, 47, 48, 67, 95, 96, 97]. Variations in tissue distribution, metabolic stability and attainable concentrations can have a big impact on in vivo relevance. Therefore, rather than confirming therapeutic efficacy, molecular insights should be seen as a basis for lead optimization [44]. The aforementioned molecular pathways offer biological justification for observed anti‐infective efficacy and are developed from experimental research [85, 97].

6. Medicinal Chemistry Perspectives

The conversion of bioactive chemicals originating from plants into promising anti‐infective medication prospects is largely dependent on medicinal chemistry [41, 78]. Although many phytochemicals with documented activity against pathogens that cause communicable diseases have been found through ethnopharmacological and experimental research, the majority of these compounds do not have the best drug‐like qualities in their native forms [42, 79]. Medicinal chemistry techniques are therefore crucial for enhancing pharmacokinetic behavior, potency, selectivity and stability while reducing toxicity and adverse effects [43, 44] Figure 8.

FIGURE 8.

Various stages of the drug discovery process from natural products (1‐Plant collection, 2‐Extraction, 3‐Isolation and purification, 4‐Bioassays, 5‐Structural characterization, 6‐Lead optimization).

6.1. Natural Products as Lead Structures Rather Than Finished Drugs

Rather than being final therapeutic agents, plant‐derived compounds are increasingly recognized as lead structures [44, 48]. Although their varied and intricate chemical frameworks offer useful beginning points for drug discovery, they frequently don't meet standard drug‐likeness standards like solubility, permeability and metabolic stability [67]. This paradigm has historically produced a number of potent anti‐infective drugs by structural simplification or semi‐synthetic alteration, proving that medicinal chemistry concepts can be used to optimize natural products [95]. Eliminating compounds that do not fit into the traditional chemical space is less important in modern medicinal chemistry than understanding which structural features are crucial for biological activity and which contribute to undesirable attributes [46]. This distinction preserves pharmacological importance while allowing for logical correction [96].

6.2. Structure‐Activity Relationship Considerations

Studies of structure‐activity relationships are essential for improving chemicals obtained from plants [97]. Biological activity and selectivity can be significantly impacted by small modifications to functional groups, stereochemistry, or ring substitution patterns [47]. For instance, changes to alkaloid nitrogen atoms can change target affinity and toxicity profiles, whereas flavonoid hydroxylation patterns are known to impact enzyme binding and antioxidant activity [48]. The multitarget nature of phytochemicals frequently makes SAR analysis more difficult [67]. Target specificity and dose optimization are challenged, even though this may provide therapeutic benefits in complex infectious illnesses. Because of this, efforts in medicinal chemistry usually try to strike a balance between enhanced selectivity and multitarget activity [95].

Structure–activity relationship studies help immensely in understanding how to optimize anti‐infective drugs obtained from plants. For instance, in case of flavonoids, presence of more numbers of hydroxyl groups influences the biological activity [95]. The addition of hydroxyl groups at C‐3 and C‐5 of quercetin helps increase hydrogen bonding with the viral protease or bacteria enzymes; however, too many hydroxyl groups decrease membrane permeability. Methylation of hydroxyl group of flavonoids improves lipophilicity and penetration into cells but reduces binding affinity towards the targets. In case of baicalein and similar flavones, the presence of trihydroxyl groups at positions 5, 6 and 7 increases the inhibition of viral proteases. Moreover, the modification of berberine at C‐9 improves antimicrobial activity and DNA binding specificity [96].

6.3. Optimization of Pharmacokinetic Properties

Poor pharmacokinetic performance is a significant drawback of many bioactive chemicals originating from plants. Low oral bioavailability, fast metabolism, restricted membrane permeability and low water solubility are common problems [95]. Reduction of molecular flexibility, prodrug design and functional group modification is medicinal chemistry approaches to these problems [96].

6.4. Semi‐Synthetic Derivatization and Molecular Simplification

One of the most effective methods for enhancing plant‐derived anti‐infective drugs is still semi‐synthetic modification [97]. Medicinal chemists can improve drug‐like characteristics while maintaining important pharmacophores by carefully altering functional groups or streamlining intricate scaffolds [85]. For extremely complicated natural compounds that are challenging to synthesize or scale, molecular simplification is especially helpful. Simplified equivalents could provide better manufacturing and consistency while maintaining biological activity, which is crucial for clinical development [98].

6.5. Addressing Toxicity and Selectivity

A major consideration in the creation of chemicals derived from plants is toxicity. Cytotoxicity may also result from structural characteristics that provide antibacterial activity, such as DNA intercalation or membrane‐disruptive qualities [98]. By increasing pathogen selectivity and decreasing interactions with host targets, medicinal chemistry optimization seeks to improve therapeutic indices [99, 100]. Reducing late‐stage failures and guiding structural refinement can be achieved through the early integration of predictive computational methods and toxicity screening [78].

6.6. Multitarget Activity and Resistance Considerations

Numerous phytochemicals' multitarget activity has been suggested as a possible benefit in the fight against antibiotic resistance [101, 102]. These substances may lessen the chance of resistance development by concurrently altering several biological pathways [100]. However, multitarget behavior needs to be precisely described from the standpoint of medicinal chemistry in order to prevent unwanted pharmacological consequences. An emerging technique to improve efficacy while reducing resistance is the rational mixing of plant‐derived scaffolds with known pharmacophores or current medications [78]. To guarantee compatibility and safety, such methods need to be carefully optimized [103].

6.7. Translational Challenges and Future Directions

The conversion of plant‐derived molecules into clinically authorized anti‐infective medicines is still limited, despite advancements in medicinal chemistry [79]. Chemical complexity, natural source diversity and mechanistic knowledge gaps are among the difficulties [80].

Medicinal chemistry, pharmacology, computational modelling and standardized phytochemical supply will all need to be combined in order to address these problems [104].

7. Safety, Toxicity, and Pharmacokinetics

Safety, toxicity and pharmacokinetic behavior must be carefully assessed when developing bioactive molecules derived from plants as anti‐infective medicines [105]. Many phytochemicals can show dose‐dependent toxicity, restricted selectivity or unfavorable pharmacokinetic profiles, despite the fact that medicinal plants are typically thought to be intrinsically harmless due to their traditional use [103, 106]. As a result, medicinal chemistry optimization and translational success depend heavily on safety and pharmacokinetic factors [102].

7.1. Safety Considerations and Dose‐Dependent Toxicity

A limited therapeutic window is exhibited by a number of drugs produced from plants, especially when their actions entail membrane disruption or contact with nucleic acids [101]. Because of its planar shape and capacity to intercalate DNA, the isoquinoline alkaloid berberine, for instance, has been linked to lethal effects at higher concentrations despite exhibiting antibacterial activity [103]. In order to increase selectivity toward bacterial targets while lowering host toxicity, medicinal chemistry efforts have thus concentrated on structural modification. Similar to this, the benzophenanthridine alkaloid sanguinarine has demonstrated antibacterial activity in vitro, but it also interacts with cellular proteins and nucleic acids, which raises safety concerns [102].

7.2. Pharmacokinetic Limitations of Plant‐Derived Compounds

Poor pharmacokinetic performance is a recurring issue in the development of anti‐infective medications derived from plants [103]. Many phytochemicals have weak water solubility, rapid metabolism and limited oral absorption [107]. For example, curcumin has a very poor systemic bioavailability due to its restricted solubility and quick first‐pass metabolism [108]. With differing degrees of success, medicinal chemistry techniques like conjugation, structural modification and prodrug design have been investigated to improve its pharmacokinetic characteristics [109]. Due to its quick metabolism through glucuronidation and sulfation, quercetin and similar flavonoids have little exposure to the parent molecule in plasma [110].

7.3. Semi‐Synthetic Derivatives and Pharmacokinetic Improvement

Artemisinin is among the most effective instances of pharmacokinetic optimization of a substance obtained from plants [111]. Sustained therapeutic exposure is limited by the parent compound's comparatively short plasma half‐life. Artesunate and artemether are examples of semi‐synthetic derivatives that were created to improve pharmacokinetic behavior and solubility, greatly increasing therapeutic value [19]. This example shows how the inherent limits of natural goods can be overcome by medicinal chemistry [112].

7.4. Herb–Drug Interactions and Metabolic Considerations

Herb‐drug interactions could result from plant‐derived chemicals interacting with drug‐metabolizing enzymes and transporters [74, 108]. For instance, piperine has been shown to affect drug metabolism by modifying efflux transporters and cytochrome P450 enzymes [113]. These characteristics raise questions about unanticipated pharmacokinetic interactions even if they may increase the bioavailability of medications taken together [110]. Comprehending these interactions is crucial, especially when drugs derived from plants are being evaluated as lead structures for future research or adjuvant medicines [89].

8. Limitations and Future Perspectives

8.1. Limitations

Despite a plethora of ethnopharmacological knowledge and growing experimental evidence, several obstacles remain in the way of turning plant‐based remedies into clinically effective anti‐infective medications [89, 114]. One major drawback is the use of preclinical and in vitro research, which typically falls short in forecasting in vivo safety or efficacy in humans [115]. While many plant‐based bioactive compounds exhibit promising antibacterial activity in laboratory conditions, they may not always exhibit therapeutic effects in complex biological systems [93, 116].Another significant limitation is the biological and chemical variety of plant materials. Significant differences in phytochemical composition resulting from species, geographic origin, growing conditions and extraction methods might make reproducibility and standardization challenging [35, 117, 118]. Many phytochemicals have less‐than‐ideal drug‐like characteristics from the standpoint of medicinal chemistry, such as poor solubility, low bioavailability, quick metabolism and restricted target selectivity [119]. Furthermore, some substances have structural characteristics linked to cytotoxicity, such DNA intercalation or membrane rupture, which limit their therapeutic window. These problems emphasize the necessity of early safety evaluation and the significance of interpreting potency data cautiously [120]. Additionally, mechanistic knowledge of many chemicals originating from plants is still lacking. Although multitarget action may be advantageous, it makes target validation and dose optimization more difficult [121]. Moreover, medicinal chemistry optimization is slowed and rational structure‐based drug design is hampered by the absence of well‐defined molecular targets [32].

9. Conclusion

In the worldwide hunt for new anti‐infective drugs, plant‐based treatments remain a vital resource. Numerous bioactive compounds with broad‐spectrum antibacterial, antiviral, anti‐fungal and anti‐parasitic properties have been produced by the ethnopharmacological legacy of systems like Ayurveda, Traditional Chinese Medicine and Unani. These conventional ideas offer a reasonable framework for locating and improving plant‐derived molecules with therapeutically relevant potential when paired with developments in medicinal chemistry and pharmacological evaluation. Nevertheless, there has been little conversion of these discoveries into authorized treatments, despite considerable preclinical promise. Poor bioavailabilities, structural complexity and a dearth of standardized pharmacokinetic and toxicological data are major obstacles. Future studies should focus on combining ethnopharmacological data with pharmacokinetic profiling, in silico modelling and medicinal chemistry optimization in order to close this gap. This approach can improve selectivity, potency and safety while maintaining the overall advantages of natural products by expediting lead identification and optimization procedures. Multi‐omics and network pharmacology techniques should be applied to better understand the complex, multitarget interactions of phytochemicals within host‐pathogen systems. To ensure regulatory approval and reproducibility, standardized extraction techniques and comprehensive clinical validation would also be required. The collaboration of ethnobotanists, chemists, pharmacologists and computational biologists will ultimately determine whether or not the next generation of antimicrobial medications can successfully emerge from traditional medicinal knowledge.

Author Contributions

Conceptualization writing work by Manish Pathak, Supervision by Akanchha dwivedi & Sokindra Kumar, Garima verma & Vivek Pal. All authors have read and agreed to the published version of the manuscript.

Funding

This review work received no external funding.

Conflicts of Interest

The authors declare no conflicts of interest.

Ethics Statement

Not applicable

Use of Generative AI and AI‐Assisted Technologies in the Writing Process

During the preparation of this manuscript, the author(s) used ChatGPT for language refinement, grammar correction. After its use, the author(s) thoroughly reviewed, verified and revised all AI‐assisted content to ensure accuracy and originality. The author(s) take full responsibility for the integrity and final content of the published article.

Biographies

Dr. Manish Pathak is a Professor in the Faculty of Pharmacy at Swami Vivekanand Subharti University, Meerut, India. His research interests include natural product chemistry, ethnopharmacology, phytochemical profiling, and the development of plant‐based therapeutics for inflammatory and chronic diseases.

Ms. Akanchha dwivedi is a Research Scholar at Bhilai Mahila Mahavidyalaya, Pt. Ravishankar Shukla University, Raipur, India. Her research focuses on medicinal plants, phytochemistry, traditional medicine systems, and their pharmacological evaluation in inflammatory disorders.

Dr. Sokindra Kumar is a faculty member in the field of Pharmacy with research interests in pharmacology, herbal drug technology, and evaluation of medicinal plants for antimicrobial and anti‐inflammatory activities. He is actively involved in research on natural products and traditional medicine.

Dr. Garima Verma is Associate Professor in the Professor in the Faculty of Pharmacy at Swami Vivekanand Subharti University, Meerut, India. Her research interests include Pharmaceutics, spectral interpretation, drug characterization techniques and quality assurance of herbal pharmaceutical formulations.

Mr. Vivek Pal is a Associate Professor in the Smt. Vidyawati College of Pharmacy, AKT University, Lucknow, India. His research interests include Pharmaceutical Chemistry, Phytochemistry, Natural Product and quality assurance of herbal pharmaceutical formulations.

Data Availability Statement

Data has been made available for other Reseachers availability.