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. 2022 Jun 17;11(12):1599. doi: 10.3390/plants11121599

Therapeutic Potential of Ranunculus Species (Ranunculaceae): A Literature Review on Traditional Medicinal Herbs

Youn-Kyoung Goo 1
Editors: Ivayla Dincheva1, Ilian Badjakov1, Bistra Galunska1
PMCID: PMC9227133  PMID: 35736749

Abstract

The genus Ranunculus includes approximately 600 species and is distributed worldwide. To date, several researchers have investigated the chemical and biological activities of Ranunculus species, and my research team has found them to have antimalarial effects. This review is based on the available information on the traditional uses and pharmacological studies of Ranunculus species. The present paper covers online literature, particularly from 2010 to 2021, and books on the ethnopharmacology and botany of Ranunculus species. Previous studies on the biological activity of crude or purified compounds from Ranunculus species, including R. sceleratus Linn., R. japonicus Thunb., R. muricatus Linn., R. ternatus Thunb., R. arvensis Linn., R. diffusus DC., R. sardous Crantz, R. ficaria Linn., R. hyperboreus Rotlb., and R. pedatus Waldst. & Kit., have provided new insights into their activities, such as antibacterial and antiprotozoal effects as well as antioxidant, immunomodulatory, and anticarcinogenic properties. In addition, the anti-inflammatory and analgesic effects of plants used in traditional medicine applications have been confirmed. Therefore, there is a need for more diverse studies on the chemical and pharmacological activities of highly purified molecules from Ranunculus species extracts to understand the mechanisms underlying their activities and identify novel drug candidates.

Keywords: ethnopharmacologic effect, herbal medicine, Ranunculus species

1. Introduction

The genus Ranunculus includes approximately 600 species globally. Recent taxonomic reports suggest that this genus has a monophyletic origin and is divided into two subgenera and seventeen sections [1]. Owing to its wide distribution, the genus has high genetic diversity. Several Ranunculus species have been used in folk medicine to treat various diseases or symptoms, such as jaundice, nebula, edema, malaria, asthma, pain, gout, rheumatism, inflammatory skin disorders, cancer, and hypertension. In addition, researchers have reported that Ranunculus extracts possess antioxidant, anti-inflammatory, antimutagenic, antimalarial, antibacterial, antitumoral, cardioprotective, and wound-healing properties [2,3,4,5,6,7].

Over the last decade, various studies have investigated the chemical components and pharmacological activities of Ranunculus species [8,9]. However, no recent review has been published detailing the aspects of the plants that have been investigated, including their biology, traditional uses, phytoconstituents, therapeutic activities, and clinical applications, since a previous review article was reported in 2012 [10]. Thus, this article aims to provide an up-to-date survey of the advances in and prospects of the research on the phytochemicals and pharmacological potential of Ranunculus species.

2. Search Strategy

This review article is based on the information available on the phytochemical, toxicological, and pharmacological studies on the traditional uses of Ranunculus species. The present paper covers online literature (Google Scholar, PubMed, ScienceDirect, Scopus, SpringerLink, and Web of Science), particularly from 2010 to 2021, and books on the ethnopharmacology and botany of Ranunculus species. The following words were used as key search terms: (“Ranunculus” OR “Ranunculus species”) AND (“herbal medicine” OR “herb medicine” OR “ethnopharmacological effects” OR “ethnopharmacological activity” OR “phytomedicine” OR “treatment” OR “drug”. The range of the article publication year for the search (from 2010 to 2021) was selected because the previous review by Aslam et al. covered almost all literature data published by 2012 [10].

3. Taxonomy, Distribution, and Morphology

Ranunculaceae Juss., or the buttercup family, has a worldwide distribution, representing a large group comprising more than 2500 species belonging to 59 genera. Its family members live under a wide range of ecological conditions, especially in the Northern Hemisphere [1,11]. Among the family, Ranunculus, comprising 600 species, is distributed across all continents [11]. Ranunculus species are highly genetically diverse; therefore, their classification is challenging. As a result, generic delimitation and infrageneric classification of these species are still under consideration.

Initially, Ranunculus species were classified based on the descriptions of their achenes (e.g., the shape of their body and beak, pericarp structure, and indumentum), flowers (e.g., the number of sepals and honey-leaves, gloss and color of the petals, and shape of the nectaries), roots (e.g., whether they were uniform or dimorphic with fibrous and tuberous roots) [12], and fruit anatomy [13]. Later, Tamura classified the genera into seven subgenera based on the reassessment of the achene structure: Pallasiantha, Coptidium, Ficaria, Batrachium, Crymodes, Gampsoceras, and Ranunculus [1,11]. In this classification, the subgenera of Ranunculus were further subdivided into 20 sections [11].

Subsequently, DNA markers were utilized to delineate the phylogenetic relationships within Ranunculaceae [14,15,16,17,18,19,20,21,22,23]. The sequences of the internal transcribed spacer region of nuclear ribosomal DNA are mostly used as DNA barcode markers for phylogenetic studies at the generic/subgeneric level [24,25]. In combination with data from the chloroplast genome and other external data, this nuclear marker also offers insights into the reticulate patterns caused by hybridization [26,27]. Moreover, a complete study of the taxonomy of the genus using both DNA markers and morphological data suggested the separation of 226 species into two subgenera and 17 sections [20].

4. Phytochemical Investigations of Ranunculus Species

Ranunculus sceleratus Linn., commonly known as the celery-leaved buttercup, is a flowering plant species distributed over the Northern Hemisphere. The main constituents of R. sceleratus L. are flavonoids, steroids such as pyrogallol tannins, and the glycoside ranunculin [28]. Ranunculin is hydrolyzed after the leaves of R. sceleratus L. are dried or crushed and generates protoanemonin associated with the toxic properties of buttercups. Because of its instability, protoanemonin dimerizes to produce anemonin, a nonirritant form [29,30]. In addition, the 70% ethanolic extracts from the aerial parts of R. sceleratus L. have been found to be abundant in myristic acid [31], and sapigenin 4′-O-alpha-rhamnopyranoside, apigenin 7-O-beta-glucopyranosyl-4′-O-alpha-rhamnopyranoside, tricin 7-O-beta-glucopyranoside, tricin, and isoscopoletin have been identified as R. sceleratus-derived compounds in the extract [32].

Ranunculus ficaria Linn. is known as lesser celandine. The compositions found in R. ficaria L. were ranunculin and its enzymatic reaction products, flavonoids such as quercetin and rutoside, saponosides with hederagenin, oleanolic acid aglyca, macerate, and tinctures [33,34,35].

The components of R. japonicus Thunb. revealed by a Waters Acquity Ultra Performance liquid chromatography system were lactone glycosides, flavonoid glycosides, and aglycones including ranunculin, tricin, adonivernite, orientin, isorientin, vitexin, 6-C-β-D-glucosyl-8-C-α-L-arabinosylapigenin, and tricin-7-O-β-D-glucopyranoside [36].

Ranunculus muricatus Linn. is also known as spiny fruit buttercup. Phytochemical analysis of R. muricatus L. revealed the presence of saponins, tannins, phenols, flavonoids, alkaloids, cardiac glycosides, anthocyanins, carbohydrates, coumarins, and phytosterols [8,37,38]. The major constituents by HPLC were stigmast-4-ene-3,6-dione, stigmasterol, anemonin, β-sitosterol, protocatechuic aldehyde, protocatechuic acid, lutein, flavonoid glycosides, ranunculoside A, ranunculoside B, and ranunculone C, in addition to two potent antioxidants, caffeoyl-β-D-glucopyranoside, and 1,3-dihydroxy-2-tetracosanoylamino-4-(E)-nonadecene [9,39,40,41]. Moreover, four compounds, muriolide, muricazine, chalcone 4-benzyloxylonchocarpin, and new-to-nature anthraquinone muracatanes B, were recently isolated [42,43].

Phytochemical analyses of R. ternatus Thunb. reported that the plant contains flavonoids, glycosides, benzine, organic acids, sterols, esters, amino acids, and constant and trace elements [44]. Furthermore, R. ternatus ethyl acetate extract constitutes contain sternbin, methylparaben, 3-[(4-O-d-glucopyranosyl)-phenyl]-2-propenoic acid, linocaffein, β-d-glucose, robustaflavone-4′-methylether, kayaflavone, podocarpus flavone A, bilobetin, isoginkgetin, amentoflavone, ternatoside A, ternatoside B, and 4-O-d-glucopyranosyl-p-coumaric acid [45,46,47]. Furthermore, methyl (R)-3-[2-(3,4-dihydroxybenzoyl)-4,5-dihydroxyphenyl]-2-hydroxypropanoate was isolated from R. ternatus roots [48].

Ranunculus arvensis Linn. is commonly known as field buttercup. Phytochemical analysis indicated that R. arvensis L. possesses rutin, caffeic acids, and classes of flavonoids and phenolics, including flavonol glycosides of quercetin, kaempferol, isorhamnetin, and their aglycons [49].

In Ranunculus species, several bioactive compounds and Ranunculus-specific constituents have been identified, such as ranunculosides, muricazine, and muracatanes. Although many other species related to Ranunculus have also been studied to evaluate their pharmacological activities, the novel bioactive compounds found in Ranunculus species with high pharmacological effects show nutraceutical and pharmaceutical potential. Pharmacological properties and molecular formula of Ranunculus species compounds reported in articles published from 2010 to 2021 are summarized in Table 1.

Table 1.

Pharmacological properties and molecular formula of Ranunculus species compounds reported in articles published from 2010 to 2021.

Ranunculus Species Molecule Molecular Formula Pharmacological Activity Ref
Ranunculus japonicus Thunb. berberine C20H18NO4+ inhibited the migration capacity of RA-FLSs
in a dose-dependent manner
[50]
yangonin C15H14O4
Ranunculus muricatus
Linn.
muricazine C16H10N2O4 antioxidant effect, lipoxygenase, and
urease inhibitory activities.
[42]
4-benzyloxylonchocarpin C27H24O4 acetylcholinesterase inhibitory effect [43]
muracatane B C14H8O5 alpha-glucosidase inhibitory effect [43]
4-methoxylonchocarpin C21H20O4 moderate cytotoxic effects towards
ovarian carcinoma, colorectal
adenocarcinoma, breast cancer,
and thyroid carcinoma
[43]
muriolide C15H15O8 antioxidant and
lipoxygenase inhibitory activities
[42]
caffeoyl-beta-D-glucopyranoside C14H18O9 antioxidant effect [41]
1,3-dihydroxy-2-tetracosanoylamino
-4-(E)-nonadecene
C43H80NO3 antioxidant effect [41]
ranuncoside C22H11O7 antioxidant effect [42]
Ranunculus ternatus
Thunb.
n-butyl-β-D-fructofuranoside C10H20O6 inhibitory effect of
multidrug-resistant tuberculosis
[48]

5. Pharmacological Activities of Ranunculus Species

5.1. Ranunculus sceleratus Linn.

All parts of Ranunculus sceleratus Linn. are poisonous when fresh; however, the plant is used in folk medicine to treat various diseases after heating or drying [7]. In recent decades, ethnopharmacological effects have been experimentally proven by several studies (Table 2). The two ranunculins, protoanemonin and anemonin, have shown fungicidal, antimicrobial, antimutanenic, and antipyretic properties [29,30,51], and have been used for ethnopharmacological purposes in many countries [52,53]. Sharif et al. performed an in vivo study to evaluate the effects of hypertension treatment using normotensive and fructose-induced hypertensive rats, in which the aqueous fraction produced the most interesting effects. Furthermore, mechanistic studies with various pharmacological antagonists have demonstrated that the hypotensive response induced by R. sceleratus L. is caused by the involvement of a muscarinic receptor, angiotensin-converting enzyme inhibition, ganglionic block, and nitric oxide release [54]. In addition, the 70% ethanolic extracts from the aerial parts of R. sceleratus L. revealed that abundant myristic acid in the extract inhibited nitrite concentration in LPS-stimulated RAW 264.7 macrophage cell line [31]. Moreover, R. sceleratus-derived compounds, sapigenin 4′-O-alpha-rhamnopyranoside, apigenin 7-O-beta-glucopyranosyl-4′-O-alpha-rhamnopyranoside, tricin 7-O-beta-glucopyranoside, tricin, and isoscopoletin, showed inhibitory activity against the hepatitis B virus [32]. In addition to the treatment effect of R. sceleratus extract, fresh R. sceleratus for TianJiu therapy, which involves adding Chinese medicinal herbal paste on designated acupoints, showed good therapeutic effect on intrahepatic cholestasis in rats, although the fresh form of R. sceleratus L. is known as an irritant [55]. Specific mechanisms by which the extract induces irritant or nonirritant responses have not been revealed. To eluciate this phenomenon, a methanolic extract of R. sceleratus L. was used to demonstrate the mechanism of both irritant and non-irritant properties induced by the extract in topical inflammation. When arachidonic acid elicited the inflammatory process, the effect of the extract was generally proinflammatory or neutral. However, if the response was caused by the application of an irritant, such as etradecanoylphorbol acetate, the extract mainly resulted in anti-inflammatory effects. This effect was mentioned as a counter-irritant, and the extract itself could be an irritant in physiological conditions but could also counteract the action of previously applied irritants [7].

Table 2.

Therapeutic activity of Ranunculus species.

Ranunculus Species Therapeutic Activity Therapeutic Indications Source Ref.
Ranunculus sceleratus
Linn.
Anti-inflammatory Inhibits nitrite accumulation in macrophage ethanolic extract of whole plant [7,31]
Hepatoprotective
(treatment of
cholestasis hepatitis)
Improves serum hepatic enzyme activity and hepatic pathologic changes in cholestatic rats fresh R. sceleratus of whole plant [55]
Antihypertensive Inhibits angiotensin converting enzyme (ACE) Involes muscarinic receptor, ganglionic block, and NO aqueous fraction of aerial parts and roots [28,54]
Antiviral Inhibits hepatitis B virus replication isolated compounds of whole plant [32]
Ranunculus japonicus
Thunb.
Antirheumatoid arthritis Inhibits migration capacity of
rheumatoid arthritis fibroblast-like synoviocytes
methanolic extract of whole plant [50]
Antimalarial Inhibits parasite growth in Plasmodium falciparum and P. berghei improve hepatic and renal parameters ethanolic extract of whole plant [56]
Antihypertrophic Suppresses elevated expression of the ANP, BNP, and beta-MHC inhibits up-regulation of [Ca2+] i total glycosides of whole plant [57]
Protective effect of
myocardial ischemic-
reperfusion injury
Improves heart function indexes
Reduces the area of myocardial infarction
total glycosides of whole plant [58]
Antihypertensive Decreases blood pressure and reduces calcium ions level in cells total glycosides of whole plant [36]
Ranunculus muricatus
Linn.
Antioxidant Scavenges the DPPH free radical
Inhibits lipoxygenase and urease enzyme activity
methanolic extract of whole plant
ethyl acetate fraction of whole plant
[41,42]
Anticarcinogenic Shows cytotoxic activity to cancer cells
Inhibits acetylcholinesterase and alpha glucosidase
ethanolic extract of whole plant [43]
Anti-inflammatory
Analgesic
Inhibits paw edema, paw licking and abdominal constrictions/stretching of hind limbs methanolic extract of whole plant [59]
Cardiotonic
(cardiovascular)
Increases perfusion pression and force of contraction
Increases heart rate
methanolic extract of whole plant [60]
Ranunculus ternatus
Thunb.
Anticarcinogenic Induces cell death depending on caspase-7 ethyl acetate extract of whole plant [61]
Antibacterial Shows inhibitory activity against Mycobacterium tuberculosis
Inhibits multidrug-resistant tuberculosis
ethanolic extract of roots [48]
Ranunculus arvensis
Linn.
Antioxidant Shows antioxidant activity in DPPH free radical scavenging assay methanolic extract of whole plant [49]
Anticarcinogenic Induces cell death aqueous and methanolic extract of whole plant [62]
Ranunculus diffusus DC. Anti-inflammatory Suppresses NF-kB signaling targeting Src and Syk methanolic extract of aerial parts [63,64]
Ranunculus sardous Crantz. Anti-inflammatory Inhibits nitrite accumulation in macrophage ethanolic extract
from aerial and
root parts
[35]
Ranunculus ficaria Linn. Anti-inflammatory Inhibits nitrite accumulation in macrophage ethanolic extract
from aerial and
root parts
[33,35]
Ranunculus hyperboreus Rotlb. Anti-inflammatory Decreases the elevated nitrate amount
Regulates the expression and protein levels
of inflammation-related enzymes,
iNOS and COX-2, and proinflammatory cytokines, TNF-α, IL-1β, and IL-6
Suppresses activation of MAPK pathway
aqueous and
methanolic extract
of whole plant
[65]
Ranunculus pedatus Waldst. & Kitt. Anti-inflammatory Inhibits increased capillary permeability induced by acetic-acid methanolic extract of whole plant [66]
Wound healing Shows fast dermal remodeling and re-epithelization in epidermis
Enhances hydroxyproline content
methanolic and
aqueous extract
of whole plant
Ranunculus constantinapolitanus (DC.) d’Urv Anti-inflammatory Inhibits increased capillary permeability induced by acetic-acid methanolic extract of whole plant [66]
Wound healing Enhances hydroxyproline content methanolic extract
of whole plant

5.2. Ranunculus ficaria Linn.

Ranunculus ficaria Linn. is an herbal astringent commonly used to treat hemorrhoids internally or externally [67]. Various methods have been applied for ethnopharmacological use. Infusion or decoction of the leaves and roots of R. ficaria was known to have trophic and anti-inflammatory effects in varicose veins, hemorrhoids, and skin disorders in Romania. The macerate and tinctures obtained from this plant are used to treat hemorrhoids by stimulating blood circulation as a traditional medication [67]. The compositions found in R. ficaria could inhibit nitrite accumulation, and thus may be useful for preventing inflammatory diseases mediated by the excessive production of nitric oxide, according to an in vitro macrophage study. However, a previous report suggested that clinicians should consider using lesser celandine (pilewort, R. ficaria) as a causative agent owing to its hepatotoxicity [35,68].

5.3. Ranunculus japonicus Thunb.

Ranunculus japonicus Thunb. has been used to treat malaria, jaundice, migraines, stomachaches, arthralgia, crane-like arthropathy, ulcers, toothaches, and eye inflammation since Zhou Hou Bei Ji Fang was first recorded more than 1800 years ago [69]. Since then, studies have demonstrated various phytomedicinal activities, such as the protective effect on heart diseases including myocardial ischemic-reperfusion injury, hypertrophy in cardiomyocytes, and high blood pressure by alleviating chronic [Ca2+] i overload, as well as therapeutic effects on rheumatoid arthritis and decreasing intracellular [Ca2+] i in vascular smooth muscle cells [50,57,58]. In addition, R. japonicus extracts showed antimalarial effects in in vitro culture of Plasmodium falciparum and in vivo rodent malaria experimental systems of Plasmodium berghei [56].

5.4. Ranunculus muricatus Linn.

Ranunculus muricatus Linn. has tremendous medicinal potentials [70]. It is used by the local population as a folk medicine for cough, asthma, heart disease, jaundice, diarrhea, dysentery, urinary infection, eczema, lymphatic tuberculosis, dental diseases, ringworm infection, and leprosy [71,72]. In addition, it exhibits antioxidant, anti-inflammatory, antibacterial, antifungal, analgesic, and cytotoxic activities [37,59,60,73]. Therefore, among Ranunculus species, R. muricatus L. is the most extensively studied. Several constituents identified in R. muricatus L. exhibit phytochemical activities. For example, the major isolated constituents are stigmast-4-ene-3,6-dione, stigmasterol, anemonin, β-sitosterol, protocatechuic aldehyde, protocatechuic acid, lutein, flavonoid glycosides, ranunculoside A, ranunculoside B, and ranunculone C, in addition to the two potent antioxidants, caffeoyl-β-D-glucopyranoside and 1,3-dihydroxy-2-tetracosanoylamino-4-(E)-nonadecene [9,39,40,41]. Moreover, two recently isolated compounds, muriolide, a new lactone, and muricazine, a new hydrazine derivative, exhibited robust free radical scavenging properties and exerted an inhibitory effect on lipoxygenase [42]. Finally, chalcone 4-benzyloxylonchocarpin, which inhibits AcheE, and the new-to-nature anthraquinone muracatanes B, which inhibits α-glucosidase, were isolated from R. muricatus L. [43].

5.5. Ranunculus diffusus DC.

The phytomedicinal effects of Ranunculus diffusus DC. have recently been reported. The methanol extract of R. diffusus showed photoaging protective effects on ultraviolet B radiation-induced skin by inhibiting the p38-AP-1 signal cascade. In addition, the extract exerted anti-inflammatory effects without toxicity by suppressing Src and Syk, which are targets of NF-κB signaling [63,64].

5.6. Ranunculus ternatus Thunb.

Ranunculus ternatus Thunb. has been used in traditional Chinese medicine [74] because of its effects on malignant lymphoma, leukemia, pulmonary tuberculosis, breast tumors, goiters, esophageal tumors, lung disease, gastric problems, and other health conditions [75,76,77]. Constituents of R. ternatus, such as amentoflavone and podocarpus flavone A, induce apoptosis [78,79]; however, their mechanisms have not been evaluated. Furthermore, n-butyl-β-D-fructofuranoside, isolated from R. ternatus roots, demonstrated significant therapeutic activity against tuberculosis [48]. Finally, the ethyl acetate extract of R. ternatus exerts caspase-7-dependent apoptosis in a cancer model [61].

5.7. Ranunculus arvensis Linn.

Ranunculus arvensis Linn. has been widely used to treat arthritis, asthma, hay fever, rheumatism, psoriasis, gut diseases, and rheumatic diseases [49]. Moreover, R. arvensis extracts showed antioxidant and anticarcinogenic activities [49,62]. However, topical use of the plant may cause contact dermatitis, such as skin inflammation, skin burns, and injury of mucous membranes [80,81,82].

5.8. Ranunculus hyperboreus Rotlb.

Ranunculus hyperboreus Rotlb. is a subarctic and subalpine plant that lives in extreme environmental conditions. R. hyperboreus extract induces anti-inflammatory activity by regulating the gene expression and protein levels of inflammation-related enzymes, such as iNOS and COX-2, and proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6 [65].

5.9. Ranunculus pedatus Waldst. & Kit.

The wound healing activity of Ranunculus pedatus Waldst. & Kitt. was evaluated using its methanolic extract and was found to exert significant effects on wound healing with robust anti-inflammatory activity in both incision and excision wound animal models [66].

6. Conclusions

The chemical and biological activities of Ranunculus species have been investigated using plant extracts. Contemporary research on the biological activity of the extracts of the species mentioned above has uncovered many activities, including antibacterial, antiviral, and antiprotozoal effects, as well as antioxidant and anticarcinogenic properties. In addition, these studies have demonstrated that herbal extracts exert hepatoprotective, hypoglycemic, and thyroid regulatory effects. Moreover, the anti-inflammatory and analgesic effects of the plants, known from the application of traditional medicine, have been confirmed. Furthermore, the molecules isolated from Ranunculus species showed promising pharmacological activity. Therefore, it is expected that effective purified molecules could be discovered from Ranunculus species to develop novel drugs through intensive research.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The author declares no conflict of interest.

Funding Statement

This research was financially supported by the Basic Science Research Program (NRF-2019R1C1C1002170) through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT and Future Planning.

Footnotes

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  • 1.Tamura M. Ranunculaceae. In: Kubitzki K., Rohwer J.G., Bittrich V., editors. Flowering Plants Dicotyledons. The Families and Genera of Vascular Plants. Volume 2 Springer; Berlin/Heidelberg, Germany: 1993. [Google Scholar]
  • 2.Gürhan G., Ezer N. Plants used in the treatment of hemorrhoids in folk medicine-1. J. Hacetterpe Univ. Fac. Pharm. 2004;24:37–55. [Google Scholar]
  • 3.Zou Y.P., Tan C.H., Wang B.D., Jiang S.H., Zhu D.Y. Flavonoid glycosides from Ranunculus chinensis Bge. Helv. Chim. Acta. 2007;90:1940–1945. doi: 10.1002/hlca.200790202. [DOI] [Google Scholar]
  • 4.Sezik E., Yeşilada E., Honda G., Takaishi Y., Takeda Y., Tanaka T. Traditional medicine in Turkey, X. Folk medicine in Central Anatolia. J. Ethnopharmacol. 2001;75:95–115. doi: 10.1016/S0378-8741(00)00399-8. [DOI] [PubMed] [Google Scholar]
  • 5.Newall D.R., Beedles K.E. The stem-cell test: An in vitro assay for teratogenic potential. Results of a blind trial with 25 compounds. Toxicol. In Vitro. 1996;10:229–240. doi: 10.1016/0887-2333(95)00110-7. [DOI] [PubMed] [Google Scholar]
  • 6.Barbour E.K., Al Sharif M., Sagherian V.K., Habre A.N., Talhouk R.S., Talhouk S.N. Screening of selected indigenous plants of Lebanon for antimicrobial activity. J. Ethnopharmacol. 2004;93:1–7. doi: 10.1016/j.jep.2004.02.027. [DOI] [PubMed] [Google Scholar]
  • 7.Prieto J.M., Recio M.C., Giner R.M., Máñez S., Ríos J.L. Pharmacological approach to the pro- and anti-inflammatory effects of Ranunculus sceleratus L. J. Ethnopharmacol. 2003;89:131–137. doi: 10.1016/S0378-8741(03)00271-X. [DOI] [PubMed] [Google Scholar]
  • 8.Khan F.A., Zahoor M., Khan E. Chemical and biological evaluation of Ranunculus muricatus. Pak. J. Pharm. Sci. 2016;29:503–510. [PubMed] [Google Scholar]
  • 9.Wu B.L., Zou H.L., Qin F.M., Li H.Y., Zhou G.X. New ent-kaurane-type diterpene glycosides and benzophenone from Ranunculus muricatus Linn. Molecules. 2015;20:22445–22453. doi: 10.3390/molecules201219801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Aslam M.S., Choudhary B.A., Uzair M., Ijaz A.S. The genus Ranunculus: A phytochemical and ethnopharmacological review. Int. J. Pharm. Pharm. Sci. 2012;4:15–22. [Google Scholar]
  • 11.Tamura M. Angiospermae. Ordnung Ranunculales. Fam. Ranunculaceae. II. Systematic Part. In: Hiepko P., editor. Natürliche Pflanzenfamilien. 2nd ed. Duncker & Humblot; Berlin, Germany: 1995. pp. 223–519. [Google Scholar]
  • 12.Candolle A.P.D. Prodromus Systematis Naturalis Regni Vegetabilis. Treuttel & Wurz; Paris, France: 1838. [Google Scholar]
  • 13.Prantl K. Beiträge zur Morphologie und Systematik der Ranunculaceen. Volume 9. Engelmann; Leipzig, Germany: 1887. pp. 225–273. [Google Scholar]
  • 14.Johansson J.T. Chloroplast DNA restriction site mapping and the phylogeny of Ranunculus (Ranunculaceae) Plant Syst. Evol. 1998;213:1–19. doi: 10.1007/BF00988905. [DOI] [Google Scholar]
  • 15.Hörandl E., Paun O., Johansson J.T., Lehnebach C., Armstrong T., Chen L., Lockhart P. Phylogenetic relationships and evolutionary traits in Ranunculus s.l. (Ranunculaceae) inferred from ITS sequence analysis. Mol. Phylogenet. Evol. 2005;36:305–327. doi: 10.1016/j.ympev.2005.02.009. [DOI] [PubMed] [Google Scholar]
  • 16.Paun O., Greilhuber J., Temsch E.M., Hörandl E. Patterns, sources and ecological implications of clonal diversity in apomictic Ranunculus carpaticola (Ranunculus auricomus complex, Ranunculaceae) Mol. Ecol. 2006;15:897–910. doi: 10.1111/j.1365-294X.2006.02800.x. [DOI] [PubMed] [Google Scholar]
  • 17.Hoffmann M.H., von Hagen K.B., Hörandl E., Röser M., Tkach N.V. Sources of the arctic flora: Origins of arctic species in Ranunculus and related genera. Int. J. Plant Sci. 2010;171:90–106. doi: 10.1086/647918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Emadzade K., Lehnebach C., Lockhart P., Hörandl E. A molecular phylogeny, morphology and classification of genera of Ranunculeae (Ranunculaceae) Taxon. 2010;59:809–828. doi: 10.1002/tax.593011. [DOI] [Google Scholar]
  • 19.Emadzade K., Gehrke B., Linder H.P., Hörandl E. The biogeographical history of the cosmopolitan genus Ranunculus L. (Ranunculaceae) in the temperate to meridional zones. Mol. Phylogenet. Evol. 2011;58:4–21. doi: 10.1016/j.ympev.2010.11.002. [DOI] [PubMed] [Google Scholar]
  • 20.Hörandl E., Emadzade K. Evolutionary classification: A case study on the diverse plant genus Ranunculus L. (Ranunculaceae), Perspectives in Plant Ecology. Evol. Syst. 2012;14:310–324. [Google Scholar]
  • 21.Emadzade K., Lebmann M.J., Hoffmann M.H., Tkach N., Lone F.A., Hörandl E. Phylogenetic Relationships and Evolution of High Mountain Buttercups (Ranunculus) in North America and Central Asia, Perspectives in Plant Ecology. Evol. Syst. 2015;17:131–141. [Google Scholar]
  • 22.Li Z., Yang L., Lu W., Guo W., Gong X., Xu J., Yu D. Spatial patterns of leaf carbon, nitrogen stoichiometry and stable carbon isotope composition of Ranunculus natans C.A. Mey. (Ranunculaceae) in the arid zone of northwest China. Ecol. Eng. 2015;77:9–17. doi: 10.1016/j.ecoleng.2015.01.010. [DOI] [Google Scholar]
  • 23.Almerekova S., Shchegoleva N., Abugalieva S., Turuspekov Y. The molecular taxonomy of three endemic Central Asian species of Ranunculus (Ranunculaceae) PLoS ONE. 2020;15:e0240121. doi: 10.1371/journal.pone.0240121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Lockhart P.J., McLenachan P.A., Havell D., Glenny D., Huson D., Jensen U. Phylogeny, radiation, and transoceanic dispersal of New Zealand alpine buttercups: Molecular evidence under split decomposition. Ann. Mo. Bot. Gard. 2001;88:458–477. doi: 10.2307/3298586. [DOI] [Google Scholar]
  • 25.Winkworth R.C., Wagstaff S.J., Glenny D., Lockhart P.J. Evolution of the New Zealand mountain flora: Origins, diversification and dispersal. Org. Divers. Evol. 2005;5:237–247. doi: 10.1016/j.ode.2004.12.001. [DOI] [Google Scholar]
  • 26.Suh Y.J., Lee S., Lee S.H., Lee N.S. Molecular evidence for the taxonomic identity of Korean Adonis (Ranunculaceae) J. Plant Res. 2002;115:217–223. doi: 10.1007/s102650200027. [DOI] [PubMed] [Google Scholar]
  • 27.Li T., Fu X., Deng H., Han X., Wen F., Xu L. The complete chloroplast genome of Ranunculus Cantoniensis. Mitochondrial DNA B. 2019;4:1095–1096. doi: 10.1080/23802359.2019.1586483. [DOI] [Google Scholar]
  • 28.Mahran G.H., Saber A.H., el-Alfy T. Spectrophotometric determination of protoanemonin, anemonin and ranunculin in Ranunculus sceleratus L. Planta Med. 1968;16:323–328. doi: 10.1055/s-0028-1099915. [DOI] [PubMed] [Google Scholar]
  • 29.Martín M.L., San Román L., Domínguez A. In vitro activity of protoanemonin, an antifungal agent. Planta Med. 1990;56:66–69. doi: 10.1055/s-2006-960886. [DOI] [PubMed] [Google Scholar]
  • 30.Minakata H., Komura H., Nakanishi K., Kada T. Protoanemonin, an antimutagen isolated from plants. Mutat. Res. 1983;116:317–322. doi: 10.1016/0165-1218(83)90069-1. [DOI] [PubMed] [Google Scholar]
  • 31.Marrelli M., De Marco C.T., Statti G., Neag T.A., Toma C.C., Conforti F. Ranunculus species suppress nitric oxide production in LPS-stimulated RAW 264.7 macrophages. Nat. Prod. Res. 2021;6:1–5. doi: 10.1080/14786419.2021.1920018. [DOI] [PubMed] [Google Scholar]
  • 32.Li H., Zhou C., Pan Y., Gao X., Wu X., Bai H., Zhou L., Chen Z., Zhang S., Shi S., et al. Evaluation of antiviral activity of compounds isolated from Ranunculus sieboldii and Ranunculus sceleratus. Planta Med. 2005;71:1128–1133. doi: 10.1055/s-2005-873169. [DOI] [PubMed] [Google Scholar]
  • 33.Bonora A., Botta B., Menziani-Andreoli E., Bruni A. Organ-specific distribution and accumulation of protoanemonin in Ranunculus fiscaria L. Biochem. Physiol. Pflanz. 1988;183:443–447. doi: 10.1016/S0015-3796(88)80059-3. [DOI] [Google Scholar]
  • 34.Tomczyk M., Gudej J., Sochacki M. Flavonoids from Ficaria verna Huds. Z. Nat. C. 2002;57:440–444. doi: 10.1515/znc-2002-5-606. [DOI] [PubMed] [Google Scholar]
  • 35.Neag T., Olah N.K., Hanganu D., Benedec D., Pripon F.F., Ardelean A., Toma C.C. The anemonin content of four different Ranunculus species. Pak. J. Pharm. Sci. 2018;31:2027–2032. [PubMed] [Google Scholar]
  • 36.Rui W., Chen H., Tan Y., Zhong Y., Feng Y. Rapid analysis of the main components of the total glycosides of Ranunculus japonicus by UPLC/Q-TOF-MS. Nat. Prod. Commun. 2010;5:783–788. doi: 10.1177/1934578X1000500521. [DOI] [PubMed] [Google Scholar]
  • 37.Ibrar M., Samreen U. Phytochemical screening and evaluation of cytotoxic and phytotoxic effects of Ranunculus muricatus L. Pak. J. Plant. Sci. 2012;18:35–45. [Google Scholar]
  • 38.Aslam M.S., Choudhary B.A., Uzair M., Ijaz A.S. Phytochemical study of Ariel parts of Ranunculus muricatus for the pharmacological active compounds. J. Appl. Pharm. 2013;5:827–832. [Google Scholar]
  • 39.Wang L.J., Gao X.Z. Studies on the chemical constituents in Ranunculus muricatus L. Chin. JMAP. 2009;26:460–462. [Google Scholar]
  • 40.Wu B., Qin F., Zhou G. Studies on chemical constituents of Ranunculus muricatus Linn. Nat. Prod. Res. Dev. 2013;25:736–741. [Google Scholar]
  • 41.Azam F., Chaudhry B.A., Ijaz H., Qadir M.I. Caffeoyl-β-d-glucopyranoside and 1,3-dihydroxy-2-tetracosanoylamino-4-(E)-nonadecene isolated from Ranunculus muricatus exhibit antioxidant activity. Sci. Rep. 2019;9:15613. doi: 10.1038/s41598-019-52166-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Raziq N., Saeed M., Ali M.S., Zafar S., Shahid M., Lateef M. A new glycosidic antioxidant from Ranunculus muricatus L. (Ranunculaceae) exhibited lipoxygenasae and xanthine oxidase inhibition properties. Nat. Prod. Res. 2017;31:1251–1257. doi: 10.1080/14786419.2016.1236098. [DOI] [PubMed] [Google Scholar]
  • 43.Hussain H., Ali I., Wang D., Mamadalieva N.Z., Hussain W., Csuk R., Loesche A., Fischer L., Staerk D., Anam S., et al. 4-Benzyloxylonchocarpin and Muracatanes A-C from Ranunculus muricatus L. and Their Biological Effects. Biomolecules. 2020;10:1562. doi: 10.3390/biom10111562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Miao Y.D., Li X.J., Jia Y.J. Research progress on chemical constituents of Ranunculi Ternati Radix and their pharmacological effects. Chin. Tradit. Herb. Drugs. 2014;45:1651–1654. [Google Scholar]
  • 45.Zhang X.G., Tian J.K. Studies on chemical constituents of Ranunculus ternatus (III) Chin. Pharmacol. J. 2006;41:1460–1461. [Google Scholar]
  • 46.Xiong Y., Deng K.Z., Guo Y.Q., Gao W.Y. Studies on Toxiological chemical constituents of flavonoids and glycosides in Ranunculus ternatus. Chin. Tradit. Herb. Drugs. 2008;39:1449–1452. [Google Scholar]
  • 47.Tian J.K., Sun F., Cheng Y.Y. Chemical constituents from the roots of Ranunculus ternatus. J. Asian Nat. Prod. Res. 2006;8:35–39. doi: 10.1080/10286020500385663. [DOI] [PubMed] [Google Scholar]
  • 48.Deng K.Z., Xiong Y., Zhou B., Guan Y.M., Luo Y.M. Chemical constituents from the roots of Ranunculus ternatus and their inhibitory effects on Mycobacterium tuberculosis. Molecules. 2013;18:11859–11865. doi: 10.3390/molecules181011859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Bhatti M.Z., Ali A., Saeed A., Saeed A., Malik S.A. Antimicrobial, antitumor and brine shrimp lethality assay of Ranunculus arvensis L. extracts. Pak. J. Pharm. Sci. 2015;28:945–949. [PubMed] [Google Scholar]
  • 50.Wang Z.Y., Chu F.H., Gu N.N., Wang Y., Feng D., Zhao X., Meng X.D., Zhang W.T., Li C.F., Chen Y., et al. Integrated strategy of LC-MS and network pharmacology for predicting active constituents and pharmacological mechanisms of Ranunculus japonicus Thunb. for treating rheumatoid arthritis. J. Ethnopharmacol. 2021;271:113818. doi: 10.1016/j.jep.2021.113818. [DOI] [PubMed] [Google Scholar]
  • 51.Misra S.B., Dixit S.N. Antifungal principle of Ranunculus sceleratus. Econ. Bot. 1980;34:362–367. doi: 10.1007/BF02858312. [DOI] [Google Scholar]
  • 52.Cappelletti E.M., Trevisan R., Caniato R. External antirheumatic and antineuralgic herbal remedies in the traditional medicine of north-eastern Italy. J. Ethnopharmacol. 1982;6:161–190. doi: 10.1016/0378-8741(82)90003-4. [DOI] [PubMed] [Google Scholar]
  • 53.Turner N.J. Counter-irritant and other medicinal uses of plants in Ranunculaceae by native peoples in British Columbia and neighbouring areas. J. Ethnopharmacol. 1984;11:181–201. doi: 10.1016/0378-8741(84)90038-2. [DOI] [PubMed] [Google Scholar]
  • 54.Sharif A., Saleem M., Alotaibi N.H., Alharbi K.S., Bukhari S.N.A., Irfan H.M., Younis W. Blood pressure lowering effects of Ranunculus scleratus Linn. in normal and fructose induced hypertensive rats and estimation of underlying mechanisms. Pak. J. Pharm. Sci. 2020;33:2243–2247. [PubMed] [Google Scholar]
  • 55.Zhang Z., Miao Y., Xu M., Cheng W., Yang C., She X., Geng Q., Zhang Q. TianJiu therapy for α-naphthyl isothiocyanate-induced intrahepatic cholestasis in rats treated with fresh Ranunculus sceleratus L. J. Ethnopharmacol. 2020;248:112310. doi: 10.1016/j.jep.2019.112310. [DOI] [PubMed] [Google Scholar]
  • 56.Yun H.S., Dinzouna-Boutamba S.D., Lee S., Moon Z., Kwak D., Rhee M.H., Chung D.I., Hong Y., Goo Y.K. Antimalarial Effect of the Total Glycosides of the Medicinal Plant, Ranunculus japonicus. Pathogens. 2021;10:532. doi: 10.3390/pathogens10050532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Dai H.L., Jia G.Z., Zhao S. Total glycosides of Ranunculus japonicus prevent hypertrophy in cardiomyocytes via alleviating chronic Ca(2+) overload. Chin. Med. Sci. J. 2015;30:37–43. doi: 10.1016/S1001-9294(15)30007-9. [DOI] [PubMed] [Google Scholar]
  • 58.Gao X.W., Liu Y., Yang Z.C., Tan Y.Z. Protective effect of total glycosides of Ranunculus japonicus on myocardial ischemic-reperfusion injury in isolated rat hearts. Zhong Yao Cai. 2014;37:1429–1433. [PubMed] [Google Scholar]
  • 59.Nasreen P., Uttra A.M., Asif H., Younis W., Hasan U.H., Irfan H.M., Sharif A. Evaluation of anti-inflammatory and analgesic activities of aqueous methanolic extract of Ranunculus muricatus in albino mice. Pak. J. Pharm. Sci. 2020;33:1121–1126. [PubMed] [Google Scholar]
  • 60.Khan A.Q., Ahmad T., Mushtaq M.N., Malik M.N.H., Naz H., Ahsan H., Asif H., Noor N., Rahman M.S.U., Dar U., et al. Phytochemical analysis and cardiotonic activity of methanolic extract of Ranunculus muricatus Linn. in isolated rabbit heart. Acta Pol. Pharm. 2016;73:949–954. [PubMed] [Google Scholar]
  • 61.Fang M., Shinomiya T., Nagahara Y. Cell death induction by Ranunculus ternatus extract is independent of mitochondria and dependent on Caspase-7. 3 Biotech. 2020;10:123. doi: 10.1007/s13205-020-2111-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Bhatti M.Z., Ali A., Ahmad A., Saeed A., Malik S.A. Antioxidant and phytochemical analysis of Ranunculus arvensis L. extracts. BMC Res. Notes. 2015;8:279. doi: 10.1186/s13104-015-1228-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Hong Y.H., Kim J.H., Cho J.Y. Photoaging Protective Effects of Ranunculus bulumei Methanol Extract. Evid.-Based Complement. Alternat. Med. 2020;2020:1761785. doi: 10.1155/2020/1761785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Hong Y.H., Kim J.H., Cho J.Y. Ranunculus bulumei Methanol Extract Exerts Anti-Inflammatory Activity by Targeting Src/Syk in NF-κB Signaling. Biomolecules. 2020;10:546. doi: 10.3390/biom10040546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Kong C.S., Lee J.I., Karadeniz F., Kim H., Seo Y. Effect of the Arctic terrestrial plant Ranunculus hyperboreus on LPS-induced inflammatory response via MAPK pathways. Z. Nat. C J. Biosci. 2018;73:273–279. doi: 10.1515/znc-2017-0173. [DOI] [PubMed] [Google Scholar]
  • 66.Akkol E.K., Süntar I., Erdoğan T.F., Keleş H., Gonenç T.M., Kıvçak B. Wound healing and anti-inflammatory properties of Ranunculus pedatus and Ranunculus constantinapolitanus: A comparative study. J. Ethnopharmacol. 2012;139:478–484. doi: 10.1016/j.jep.2011.11.037. [DOI] [PubMed] [Google Scholar]
  • 67.Tita I., Mongosanu G.D., Tita M.G. Ethnobotanical inventory of medicinal plants from the South-West of Romania. Farmacia. 2009;57:141–156. [Google Scholar]
  • 68.Yilmaz B., Yilmaz B., Aktaş B., Unlu O., Roach E.C. Lesser celandine (pilewort) induced acute toxic liver injury: The first case report worldwide. World J. Hepatol. 2015;7:285–288. doi: 10.4254/wjh.v7.i2.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69.Fawen K. A comprehensive Chinese-Latin-English dictionary of the names of Chinese Herbal Medicines. World Publishing Corporation; Shanghai, China: 1998. pp. 671–682. [Google Scholar]
  • 70.Ullah M., Khan M.U., Mahmood A., Malik R.N., Hussain M., Wazir S.M., Daud M., Shinwari Z.K. An ethnobotanical survey of indigenous medicinal plants in Wana district South Waziristan agency. Pak. J. Ethnopharmacol. 2013;150:918–924. doi: 10.1016/j.jep.2013.09.032. [DOI] [PubMed] [Google Scholar]
  • 71.Iqbal H., Sher Z., Khan Z.U. Medicinal plants from salt range Pind Dadan Khan, district Jhelum, Punjab, Pakistan. J. Med. Plant Res. 2011;5:2157–2168. [Google Scholar]
  • 72.Rahman I.U., Ijaz F., Iqbal Z., Afzal A., Ali N., Afzal M., Khan M.A., Muhammad S., Qadir G., Asif M. A novel survey of the ethno medicinal knowledge of dental problems in Manoor Valley (Northern Himalaya) Pak. J. Ethnopharmacol. 2016;194:877–894. doi: 10.1016/j.jep.2016.10.068. [DOI] [PubMed] [Google Scholar]
  • 73.Nazir S., Tahir K., Naz R., Khan Z., Khan A., Islam R., Rehman A.U. In vitro screening of Ranunculus muricatus for potential cytotoxic and antimicrobial activities. J. Pharmacol. 2014;8:427–431. [Google Scholar]
  • 74.Pan Z.H., Sun Y.X. Observation on the antibacterial effect of Artemisia annua and Ranunculus ternatus on mycobacterium tuberculosis drug resistant. Inf. Tradit. Chin. Med. 1986;5:28. [Google Scholar]
  • 75.Zhang J.H., Wan M.R. Toxic effect of Rannuculin on leukemic cells in vitro. Chin. J. Clin. Oncol. 1993;12:941–943. [Google Scholar]
  • 76.Chen B.C., Hang Y.Y., Chen B.R. Advances in medicinal plant Ranunculus ternatus. Chin. Wild Plant. Res. 2002;1:7–9. [Google Scholar]
  • 77.Tong Y.L., Yang F., Dai G.H., Ren Z.M., Wang B.B. Study on activity in vitro of radix Ranunculus ternati saponins on cell A549 of non-small cell lung cancer. Chin. Arch. Tradit. Chin. Med. 2013;31:2181–2184. [Google Scholar]
  • 78.Pei J.S., Liu C.C., Hsu Y.N., Lin L.L., Wang S.C., Chung J.G., Bau D.T., Lin S.S. Amentoflavone induces cell-cycle arrest and apoptosis in MCF-7 human breast cancer cells via mitochondria-dependent pathway. In Vivo. 2012;26:963–970. [PubMed] [Google Scholar]
  • 79.Yeh P.H., Shieh Y.D., Hsu L.C., Kuo L.M., Lin J.H., Liaw C.C., Kuo Y.H. Naturally occurring cytotoxic [3′→8″]-biflavonoids from Podocarpus nakaii. J. Tradit. Med. 2012;2:220–226. doi: 10.1016/S2225-4110(16)30103-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80.An I., Ucmak D., Esen M., Gevher O.D. Phytocontact dermatitis due to Ranunculus arvensis: Report of three cases. North. Clin. Istanb. 2018;6:81–84. doi: 10.14744/nci.2018.93695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81.Kocak A.O., Saritemur M., Atac K., Guclu S., Ozlu I. A rare chemical burn due to Ranunculus arvensis: Three case reports. Ann. Saudi Med. 2016;36:89–91. doi: 10.5144/0256-4947.2016.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 82.Polat M. A case of phytodermatitis due to Ranunculus arvensis used as an herbal remedy. Int. J. Dermatol. 2016;55:e37–e38. doi: 10.1111/ijd.13123. [DOI] [PubMed] [Google Scholar]

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