# Rivea hypocrateriformis (Desr.) Choisy: An Overview of Its Ethnomedicinal Uses, Phytochemistry, and Biological Activities and Prospective Research Directions

Authors: Mohammad Mukim; Atul Kabra; Christophe Hano; Samantha Drouet; Duangjai Tungmunnithum; Mohit Chaturvedi; Rakesh Patel; Muhammad Ayaz; Daniel M. Shadrack
Journal: Journal of Chemistry
 (2022)

---

## Abstract

Rivea hypocrateriformis (Desr.) Choisy is a robust woody climbing shrub of the genus Rivea which is widely distributed in India, Nepal, Sri Lanka, Pakistan, Bangladesh, Myanmar, and Thailand. R. hypocrateriformis is a promising medicinal herb with a wide range of beneficial and health-promoting properties. Since the ancient times, it has been used as a traditional medicine to treat rheumatic pain, fever, urogenital problems, snake bites, cough, piles, malaria, and skin diseases. Aside from these traditional uses, its leaves and young shoots are also cooked and eaten as a vegetable and used for the preparation of bread with millet flour. This study extensively analyzes the available information on R. hypocrateriformis botanical characterization, distribution, traditional applications, phytochemistry, pharmacology, and toxicological properties. Phytochemical investigations of the plant has revealed the presence of highly valuable secondary metabolites including alkaloids, glycosides, coumarins, flavonoids, xanthones, stilbenes, and other organic compounds. Its crude extracts and isolated compounds have revealed anovulatory, antifertility, antiarthritic, antimicrobial, anticancer, antioxidant hepatoprotective, antilithiatic, and antimitotic potentials. This review of literature clearly identifies R. hypocrateriformis as a potent medicinal plant with remarkable healing and health-promoting properties. Further research directions into the bioactive extracts, clinical, and toxicological evaluations to assess the beneficial health-promoting properties of this promising herb are also discussed.


---

## Body

## 1. Introduction

Medicinal plants are among the vital sources of secondary metabolites used for the management of various diseases since the establishment of the human era [1]. Even today, it is among the most useful sources for the discovery and development of novel drugs against various diseases [2, 3]. Especially, plants which are traditionally used by indigenous people to treat various diseases are more useful as their safety and efficacy are already established [4]. The discovery and clinical approval of numerous drugs using a knowledge-driven ethnomedicinal approach signify the role of medicinal plants and traditional knowledge in the discovery of novel drugs [5, 6]. Further, the development of novel and highly sensitive isolation and identification techniques and the discovery of novel molecules from these plants are easier and more cost-effective. Convolvulaceae is a vast and homogeneous plant family of approximately 50 genera and nearly 1,700 species [7–9]. Rivea hypocrateriformis (Desr.) Choisy is a woody climbing shrub belonging to the Convolvulaceae family and is widely distributed in India, Nepal, Sri Lanka, Pakistan, Bangladesh, Myanmar, and Thailand [9]. Its bark, stems, and leaves are traditionally used to cure a range of ailments including malaria, cancer, mental disorders, and analgesia. For instance, the indigenous people of Pakistan’s Tharparkar region use this plant for the treatment of malaria and to relieve pain. The plant is reported for a wide range of biological potentials including antioxidant, anti-implantation, antimicrobial, pregnancy irruption, anticancer and antiarthritic properties [10, 11]. It is also used as a vital ingredient in the ayurvedic formulation “Rasa panchaka” used for the treatment of asthma [12]. Moreover, similar to other varieties of a related genus, such as Rivea corymbosa Hall and Ipomea violacea L. found in Mexico, this plant is also used as a hallucinogenic drug in India and as a psychoactive medicine in Pakistan [13].Besides, young shoots and leaves of the plant are also cooked and consumed as a vegetable. The leaves are bubbled along with toppings and arranged dishes, for example,bhaji or jowari flour which was then used to prepare bread [14]. It is a rich source of micronutrients, in particular vitamin A [15, 16]. As far as we know, there is no review paper available on R. hypocrateriformis that was accessible in January 2022. The review paper is aimed at providing a more comprehensive analysis of the ethnomedicinal uses, phytochemistry, and biological activities. Furthermore, this review also focuses on filling some of the gaps among the currently performed studies and proposes some areas for future research on potential bioactivities of R. hypocrateriformis.


## 2. Methods

Publications were retrieved from PubMed, Google Scholar, and ScienceDirect. The strategy was using different combinations of keywords “Traditional medicines, Phytochemistry, Biological activity, Pharmacology” associated with “Rivea hypocrateriformis” and its synonyms. Argyreia bona-nox Sweet, Argyreia uniflora Sweet, Convolvulus hypocrateriformis Desr., Lettsomia uniflora Roxb., Modesta coriacea Rafin., Rivea bona-nox Choisy, and Rivea fragrans Nimmo are the synonyms of R. hypocrateriformis. The detailed research methodology adopted for the selection of articles for this review is stipulated as a flowchart in Figure 1.Figure 1
Flow diagram of research methodology.


## 3. Botanical Description

### 3.1. Taxonomical Classification and Habitat

The taxonomical classification ofR. hypocrateriformis is Kingdom: Plantae; Phylum: Tracheophyta; Class: Magnoliopsida; Subclass: Asteridae; Order: Solanales; Family: Convolvulaceae; Genus: Rivea [9] It is likewise known by a variety of names, such as “Midnapore Creeper” in English, “Thor-ki-bel” or “Phang” in Hindi, “Sanjvel” in Marathi, “Budthi Kiray” or “Musuttai” in Tamil, and “Niruboddi” in Telugu [17]. R. hypocrateriformis is a woody climbing shrub found in subtropical forests of India, Nepal, Sri Lanka, Pakistan, Bangladesh, Myanmar, and Thailand. In India, it is mainly found in Assam, Bihar, Maharashtra, Rajasthan, and Tamil Nadu (Figure 2).Figure 2
Natural distribution ofR. hypocrateriformis in the India. The shaded area represents its natural habitat.R. hypocrateriformis (Desr.) Choisy is a woody climbing shrub belonging to the family Convolvulaceae.


### 3.2. Morphological and Microscopical Characteristics

Morphological characterization ofR. hypocrateriformis plant and its parts are presented in Figures 3(a)–3(d). Its flowers, usually solitary, are creamy white, typical morning glory form, flat-faced, and 6–9 cm long. Sepals unequal, ovate, blunt apically, 10–12 mm long with dense short villoses. Leaves are round-heart-shaped, blunt apically, densely appressed velvet-hairy below. Fruit are indehiscent or tardily dehiscent, dry-baccate of 2 cm long. Seeds are brown, smooth, glabrous, slightly trigonous, and surrounded by a dry white pulp. Transverse sections of the leaf showed that the upper and lower epidermis comprise of single-layered polygonal cells that cover the adhesive fingernail skin [18, 19].Figure 3
R. hypocrateriformis. (a) whole plant; (b) leaf; (c) fruit; (d) flower.
(a)(b)(c)(d)


## 3.1. Taxonomical Classification and Habitat

The taxonomical classification ofR. hypocrateriformis is Kingdom: Plantae; Phylum: Tracheophyta; Class: Magnoliopsida; Subclass: Asteridae; Order: Solanales; Family: Convolvulaceae; Genus: Rivea [9] It is likewise known by a variety of names, such as “Midnapore Creeper” in English, “Thor-ki-bel” or “Phang” in Hindi, “Sanjvel” in Marathi, “Budthi Kiray” or “Musuttai” in Tamil, and “Niruboddi” in Telugu [17]. R. hypocrateriformis is a woody climbing shrub found in subtropical forests of India, Nepal, Sri Lanka, Pakistan, Bangladesh, Myanmar, and Thailand. In India, it is mainly found in Assam, Bihar, Maharashtra, Rajasthan, and Tamil Nadu (Figure 2).Figure 2
Natural distribution ofR. hypocrateriformis in the India. The shaded area represents its natural habitat.R. hypocrateriformis (Desr.) Choisy is a woody climbing shrub belonging to the family Convolvulaceae.


## 3.2. Morphological and Microscopical Characteristics

Morphological characterization ofR. hypocrateriformis plant and its parts are presented in Figures 3(a)–3(d). Its flowers, usually solitary, are creamy white, typical morning glory form, flat-faced, and 6–9 cm long. Sepals unequal, ovate, blunt apically, 10–12 mm long with dense short villoses. Leaves are round-heart-shaped, blunt apically, densely appressed velvet-hairy below. Fruit are indehiscent or tardily dehiscent, dry-baccate of 2 cm long. Seeds are brown, smooth, glabrous, slightly trigonous, and surrounded by a dry white pulp. Transverse sections of the leaf showed that the upper and lower epidermis comprise of single-layered polygonal cells that cover the adhesive fingernail skin [18, 19].Figure 3
R. hypocrateriformis. (a) whole plant; (b) leaf; (c) fruit; (d) flower.
(a)(b)(c)(d)


## 4. Ethnomedicinal Uses

R. hypocrateriformis is a common ayurvedic herb, used in different ways by various local population groups due to the various beneficial uses of its bark, roots, leaves, and blossoms. Ayurvedic physicians traditionally use R. hypocrateriformis preparations to prevent fertility in women [20, 21]. The various ethnomedicinal usages of this herbal medicine are summarized in Table 1.Table 1
Ethnomedicinal uses ofR. hypocrateriformis.
Plant part usedMethod of administrationUsageReferencesWhole plant and rootThe plant juice/paste is orally takenTreatment of snake bite[22–24]Whole plantPowderPiles and heart disease[25]LeavesCookedIndigestion[26]Whole plantPowderConstipation[27]LeavesPasteDiarrhoea[28,29]Whole plantPowderDiuretic[30]Whole plantPowderLaxative[30]StemPowderCough and headache[26]LeavesJuice with cow’s milkRheumatic pain[31]LeavesJuiceSkin disease of hair scalp[31]Whole plant and rootPlant juice/paste taken orallySnake bite treatment[23,24,32]RootDecoctionFever[33]LeavesPowderUrogenital problem (hematuria)[34]LeavesPowderBlood purifier[35]RootPasteCough, swelling and headache, poisonous animals bite[22–24]LeavesInternal useStomach wounds[36]LeavesInternal use (cooked)Stomach upset and indigestion[37,38]RootPowderAfter parturition[16]


## 5. Phytochemistry

R. hypocrateriformis is extensively reported for the presence of important metabolites. For instance, Loganayaki et al. reported the extractive value of leaf, stem, and flower parts of the plant using polarity-directed solvent systems including chloroform, methanol, and acetone. Flowers exhibited a higher extractive value of 13.3%, followed by the flower-methanol extract 12.5%, flower-chloroform extract 11.5%, leaf-methanol extract 8.6%, stem-methanol extract 7.43%, leaf-acetone extract 5.9%, leaf-chloroform extract 2.9%, stem-acetone extract 1.87%, and stem-chloroform extract 0.7%. The same group of researchers also reported R. hypocrateriformis as a rich source of phenolic compounds as observed in the different extracts from leaves, stems, and flowers obtained using organic solvents. The highest total phenolic content was quantified in the flower-acetone extract and flower-methanolic extracts [39] as summarized in Table 2. These quantitative results are in agreement with recent the study [40] (Table 2). Furthermore, qualitative phytochemical screening of different parts of R. hypocrateriformis revealed the presence of alkaloids, flavonoids, tannins, saponins, glycosides, steroids, carbohydrates, phytosterols, and amino acid derivatives.Table 2
Quantitative phytochemical content inR. hypocrateriformis.
Plant partExtract/fractionTotal phenolic contentTotal flavonoid contentExtractive value (%w/w)ReferencesAerialPolyphenolic0.170μg TAE/mg fraction0.193μg QAE/mg fraction—[40]LeavesChloroform1.1 g GAE/100 g—2.9Acetone2.1 g GAE/100 g—5.9Methanolic1.1 g GAE/100 g—8.6StemChloroform0.9 g GAE/100 g—0.7[39]Acetone1.5 g GAE/100 g—1.87Methanolic1.2 g GAE/100 g—7.43FlowerChloroform1.6 g GAE/100 g—11.5Acetone4.2 g GAE/100 g—Methanolic3.5 g GAE/100 g—12.5TAE: tannic acid equivalent; QAE: quercetin equivalent; GAE: gallic acid equivalent.


### 5.1. Alkaloids

Three pyrrolizidine alkaloids, namely, macrophylline (1), meteloidine (2), and symlandine (3) as well as four tropane alkaloids, namely, cochlearine (4), darlingine (5), tigloidine (6), and serratanidine (7) were found in the root ofR. hypocrateriformis [41]. Two other alkaloids were quantified in the aerial parts of the plant, namely, hypocretine 1(8i) and hypocretine 2 (8ii) [40]. The presence of aminopyrimidine pyrimethanil (9) was also reported from the roots of R. hypocrateriformis [41].


### 5.2. Glycosides

Four glycosides, namely, bergenin (10), norbergenin (11), rivebergenin A (12i), and rivebergenin B (12ii) are reported from the stem ofR. hypocrateriformis. An aromatic glycoside lucuminic acid (13) and a cardiac glycoside oleandrose (14) were reported from the roots of R. hypocrateriformis [41].


### 5.3. Flavonoids

Godipurge et al. reported the presence of multifunctional compound quercetin (15) in a polyphenolic fraction of the aerial part [40]. Flavonoids including C-glycosides 3′-deoxymaysin (16), 6-C-glucopyranosylpilloin (17), O-glycoside peruvianoside II (18), and a prenylated flavonoid morusin (19) were identified in the roots of R. hypocrateriformis [41].


### 5.4. Xanthones

Several xanthone derivatives including dulciol B (20) and mangostenone B (21) are also reported from the roots ofR. hypocrateriformis [41].


### 5.5. Stilbenes

The occurrence of blestriarene B (22) andα-viniferin (23) was reported from the roots of R. hypocrateriformis [41].


### 5.6. Coumarins

Various coumarins including tomentolide A (24) and calophyllolide (25) were reported from the root extract of the plant. Likewise, desmethylbergenin hemihydrate (26) was reported from the whole plant ofR. hypocrateriformis [41].


### 5.7. Sterols and Fatty Acid Derivatives

Sterols and fatty acids including sphingosine (27) and 3S, 7S-dimethyl-tridecan-2S-ol (28) were found in the root ofR. hypocrateriformis [41]. A long-chain fatty aldehyde pentadecanal (29), two fatty acids, namely, 2-hexyl-decanoic acid (30) and 1-palmitoyl lysophosphatidic acid (31), and 2,4-undecadienal (32) were reported from the roots of R. hypocrateriformis [41].


### 5.8. Miscellaneous Compounds

Various other compounds are also reported from the plant. Among these,N-acetylmuramoyl-alanine (33) belongs to the class of organic compounds known as acylamino sugars. These are organic compounds containing a sugar linked to a chain through N-acyl group. Two tripeptides His-His-Lys (34) and Asp-Arg-Asp (35), one bipeptide Glu-His (36) and an amino cyclitol streptidine (37), and a volatile compound methyl jasmonate (38) were reported from the roots of R. hypocrateriformis [41]. Structures of these bioactive phytoconstituents reported in the R. hypocrateriformis plant are presented in Figure 4.Figure 4
(a) Structure of some isolated alkaloids and glycosides from different parts ofR. hypocrateriformis. (1) Macrophylline, (2) meteloidine, (3) symlandine, (4) cochlearine, (5) darlingine, (6) tigloidine, (7) serratanidine, (8) (i) hypocretine 1 and (ii) hypocretine 2, (9) pyrimethanil, (10) bergenin, (11) norbergenin, (12) (i) rivebergenin A and (ii) rivebergenin B, (13) lucuminic acid, (14) oleandrose. (b) Structure of some isolated flavonoids, xanthones, and stilbenes from different parts of R. hypocrateriformis. (15) Quercetin, (16) 3′-deoxymaysin, (17) 6-C-glucopyranosylpilloin, (18) peruvianoside II, (19) morusin, (20) dulciol B, (21) mangostenone B, (22) blestriarene B, and (23) α-viniferin. (c) Structure of some coumarins, fatty acids, and sterols from different parts of R. hypocrateriformis. (24) Tomentolide A, (25) calophyllolide, (26) desmethylbergenin hemihydrate, (27) sphingosine, (28) 3S, 7S-dimethyl-tridecan-2S-ol, (29) pentadecanal, (30) 2-hexyl-decanoic acid, (31) 1-palmitoyl lysophosphatidic acid, and (32) 2, 4-undecadienal. (d) Structure of some isolated other organic compounds from different parts of R. hypocrateriformis. (33) N-acetylmuramoyl-alanine, (34) his-his-lys, (35) asp-arg-asp, (36) glu-his, (37) streptidine, and (38) jasmonate.
(a)(b)(c)(d)


## 5.1. Alkaloids

Three pyrrolizidine alkaloids, namely, macrophylline (1), meteloidine (2), and symlandine (3) as well as four tropane alkaloids, namely, cochlearine (4), darlingine (5), tigloidine (6), and serratanidine (7) were found in the root ofR. hypocrateriformis [41]. Two other alkaloids were quantified in the aerial parts of the plant, namely, hypocretine 1(8i) and hypocretine 2 (8ii) [40]. The presence of aminopyrimidine pyrimethanil (9) was also reported from the roots of R. hypocrateriformis [41].


## 5.2. Glycosides

Four glycosides, namely, bergenin (10), norbergenin (11), rivebergenin A (12i), and rivebergenin B (12ii) are reported from the stem ofR. hypocrateriformis. An aromatic glycoside lucuminic acid (13) and a cardiac glycoside oleandrose (14) were reported from the roots of R. hypocrateriformis [41].


## 5.3. Flavonoids

Godipurge et al. reported the presence of multifunctional compound quercetin (15) in a polyphenolic fraction of the aerial part [40]. Flavonoids including C-glycosides 3′-deoxymaysin (16), 6-C-glucopyranosylpilloin (17), O-glycoside peruvianoside II (18), and a prenylated flavonoid morusin (19) were identified in the roots of R. hypocrateriformis [41].


## 5.4. Xanthones

Several xanthone derivatives including dulciol B (20) and mangostenone B (21) are also reported from the roots ofR. hypocrateriformis [41].


## 5.5. Stilbenes

The occurrence of blestriarene B (22) andα-viniferin (23) was reported from the roots of R. hypocrateriformis [41].


## 5.6. Coumarins

Various coumarins including tomentolide A (24) and calophyllolide (25) were reported from the root extract of the plant. Likewise, desmethylbergenin hemihydrate (26) was reported from the whole plant ofR. hypocrateriformis [41].


## 5.7. Sterols and Fatty Acid Derivatives

Sterols and fatty acids including sphingosine (27) and 3S, 7S-dimethyl-tridecan-2S-ol (28) were found in the root ofR. hypocrateriformis [41]. A long-chain fatty aldehyde pentadecanal (29), two fatty acids, namely, 2-hexyl-decanoic acid (30) and 1-palmitoyl lysophosphatidic acid (31), and 2,4-undecadienal (32) were reported from the roots of R. hypocrateriformis [41].


## 5.8. Miscellaneous Compounds

Various other compounds are also reported from the plant. Among these,N-acetylmuramoyl-alanine (33) belongs to the class of organic compounds known as acylamino sugars. These are organic compounds containing a sugar linked to a chain through N-acyl group. Two tripeptides His-His-Lys (34) and Asp-Arg-Asp (35), one bipeptide Glu-His (36) and an amino cyclitol streptidine (37), and a volatile compound methyl jasmonate (38) were reported from the roots of R. hypocrateriformis [41]. Structures of these bioactive phytoconstituents reported in the R. hypocrateriformis plant are presented in Figure 4.Figure 4
(a) Structure of some isolated alkaloids and glycosides from different parts ofR. hypocrateriformis. (1) Macrophylline, (2) meteloidine, (3) symlandine, (4) cochlearine, (5) darlingine, (6) tigloidine, (7) serratanidine, (8) (i) hypocretine 1 and (ii) hypocretine 2, (9) pyrimethanil, (10) bergenin, (11) norbergenin, (12) (i) rivebergenin A and (ii) rivebergenin B, (13) lucuminic acid, (14) oleandrose. (b) Structure of some isolated flavonoids, xanthones, and stilbenes from different parts of R. hypocrateriformis. (15) Quercetin, (16) 3′-deoxymaysin, (17) 6-C-glucopyranosylpilloin, (18) peruvianoside II, (19) morusin, (20) dulciol B, (21) mangostenone B, (22) blestriarene B, and (23) α-viniferin. (c) Structure of some coumarins, fatty acids, and sterols from different parts of R. hypocrateriformis. (24) Tomentolide A, (25) calophyllolide, (26) desmethylbergenin hemihydrate, (27) sphingosine, (28) 3S, 7S-dimethyl-tridecan-2S-ol, (29) pentadecanal, (30) 2-hexyl-decanoic acid, (31) 1-palmitoyl lysophosphatidic acid, and (32) 2, 4-undecadienal. (d) Structure of some isolated other organic compounds from different parts of R. hypocrateriformis. (33) N-acetylmuramoyl-alanine, (34) his-his-lys, (35) asp-arg-asp, (36) glu-his, (37) streptidine, and (38) jasmonate.
(a)(b)(c)(d)


## 6. Pharmacological Studies

Crude extracts from medicinal plants are extensively studied for various pharmacological properties [3, 42–44]. R. hypocrateriformis is also reported for various pharmacological potentials which might be attributed to the presence of various phytochemicals (Table 3). Many studies have shown that the presence of phenolic acids and flavonoids may be linked to cancer-prevention action [2, 48–51]. The identified phytochemicals offer protection against oxidative stress by scavenging radicals [52, 53].Table 3
Biological activities ofR. hypocrateriformis.
Part usedExtract/fractionDose tested/route of administrationStudy modelExperimental modelsResultsReferencesAntiarthritic activityLeavesMethanolic250 and 500 mg/kg, p.o.Albino Wistar ratsComplete Freund’s adjuvant (CFA)-induced arthritisExtract showed significant anti-arthritic activity[45]Antimicrobial activityAerial partAu, Ag, and Au–Ag alloy NPs25–100µg/mLKP, SA, BS, PA, EC, CA, TR, and CIAgar well diffusion methodGreen-synthesized AgNPs displayed very good antimicrobial potential compared to AuNPs[40]Aerial partPet. ether, chloroform, ethanol, and aqueous extract10000, 5000, 2500, 1250 and 0.625μg/mLSA, BS, EC, PA, PV, AN, CA, and AFAgar disk diffusion methodEthanolic and aqueous extract showed higher antimicrobial potential than other extracts[46]Anticancer activityAerial partAu, Ag, and Au–Ag alloy NPs1–100µg/mLMCF7, Sf9, VeroMTT assaySignificant cytotoxicity on tested cancer cells in a concentration-dependent manner[40]Aerial partPet. ether, chloroform, ethanol, and aqueous4 × 103 cells/mlMCF-7, MCF-15, MOLT-4, HOP-62, prOSRB assayChloroform and ethanolic extracts exhibited strong anticancer activity[46]Anovulatory effectAerial partEthanol200 and 400 mg/kgWistar albino ratIn vivo (effect on duration of different phases of the oestrous cycle)Significant decrease in number of Graafian follicles and corpora lutea and significant increase in number of atretic follicles[20]Antioxidant activityAerial partPolyphenolic fraction—In vitroHydroxyl radical scavenging assayExtracted demonstrated significant antioxidant activity[40]Aerial partAu, Ag, and Au–Ag alloy NPs10–100μg/mlIn vitroDPPH assayNPs were capable of scavenging DPPH radicals[40]LeafAqueous15.51, 62.5, 250 and 1000μg/mlIn vitroDPPH assayAqueous extract showed highest DPPH radical scavenging activity[15]Leaf, stem, and fruitChloroform, acetone, and methanolIn vitroDPPH, ABTS, and FRAP assayAntioxidant activity was the highest in MeAA extracts, while it was intermediate in MeAM and MeA extracts.[39]Antifertility activityAerial partPet. ether, chloroform, ethanol, and aqueous200 and 400 mg/kgAlbino Wistar ratsIn vivo (anti-implantation effect)Ethanol extract found significant anti-implantation and interruption of early pregnancy[20]Whole plant95% ethanolic extract200 and 400 mg/kgAlbino Wistar ratsIn vivo (anti-implantation effect)Extract dose 400 mg/kg showed significant anti-implantation potential[47]Hepatoprotective activityAerial partPolyphenolic fraction300 and 600 mg/kgAlbino Wistar ratsParacetamol-induced hepatotoxicityDecreased ALT, AST, ALP, and TB[40]Antimitotic activityAerial partPet. ether, chloroform, ethanol, and aqueous10 mg/mlIn vitroAllium cepa root inhibitionChloroform and ethanol extracts showed significant antimitotic activity[46]Antiproliferative activityAerial partPet. ether, chloroform, ethanol, and aqueous—In vitroYeastSaccharomyces cerevisiae modelChloroform and ethanol extracts showed significant antiproliferative activity[46]Antilithiatic activityLeavesEthanolic2.5 ml of 0.2 g/ml solutionIn vitro—Extract showed significant inhibition of calcium and phosphate accumulation[35]Anti-inflammatory activityLeavesEthanolic200 and 400 mg/kgAlbino Wistar ratsCarrageenan-induced paw edemaEthanol extracts showed significant anti-inflammatory activity[31]Analgesic activityLeavesEthanolic200 and 400 mg/kgAlbino Wistar ratsRadiant heat tail flick methodEthanol extracts showed significant analgesic activity[31]Various identified phytochemicals from the plant might be implicated in the therapeutic properties of the crude extracts as they are reported for protective properties in various diseases [54, 55]. For instance, bergenin is reported to exhibit hepatoprotective, antiarrhythmic, neuroprotective, antifungal, anti-inflammatory, immunomodulatory, anti-HIV, antifungal, antihepatotoxic, wound, and ulcer healing potentials [56, 57]. Norbergenin, an O-methyl derivative of bergenin, is also reported to have antioxidant [58, 59] and gastroprotective [60] potentials. Likewise, calophyllolide has been reported to exhibit some biological activities including anti-inflammatory, vasodilatory, anticancer, antimicrobial, and anticoagulant properties [61]. Further, stilbene trimers including α-viniferin are reported to exhibit AChE potentials in a dose-dependent manner [62].These findings suggest that clinical studies into the pharmacological potentials ofR. hypocrateriformis and its derivatives could be warranted for the discovery of new potential therapeutic entities. Simultaneous in vitro and in vivo experiments on the pharmacological profile of R. hypocrateriformis and its derivatives might help evaluate their modes of action.


## 7. Toxicological Studies

The toxicological properties of the plant were reported in various studies. In a toxicological study performed on the polyphenolic fraction ofR. hypocrateriformis, no adverse effects or mortality were observed in the Swiss albino mice and Wistar albino rats at 4,000 mg kg−1 p/o dose. This was observed during 24 h period, and the extract was found to be safe at the given dose [40]. However, further detailed studies are required on different fractions and/or extracts for their toxicological effects on individual organs. Here, it should also be emphasized that the nature of R. hypocrateriformis can be affected by the environment and the picking time [19]. It is critical to implement authentication methods to monitor the nature and quality of the collected materials, remove the contaminated material, and ensure the biological activity associated with the resulting extracts for safety purposes, but also to ensure the reproducibility of the experiments [63, 64]. It is important to note that if the material authentication has not been done or is not sufficiently clear, its therapeutic significance is therefore meaningless. This critical prior authentication work is still conducted too infrequently and should be systematized for R. hypocrateriformis but also other medicinal herbs.


## 8. Conclusion

Based on the findings of the current study that sum up the traditional usages and pharmacological activities of its extracts and constituents,R. hypocrateriformis clearly appears as a promising medicinal herb with a wide range of beneficial and health-promoting properties. Nevertheless, it also appears that additional evidence from clinical studies as well as toxicological examinations are required. A particular effort should be made to put in place an adequate authentication method. Along these lines, the deliberate examinations on R. hypocrateriformis ought to be attempted to rationalize its ethnomedicinal uses and consider future pharmacological applications to take advantage of the properties of this herbal medicine.



---

*Source: 9099672-2022-06-22.xml*