Ethnomedicinal, phytochemical, and pharmacological review of asclepiadaceae

Chinedu Enegide; Samuel Ehiabhi Okhale

doi:10.4103/jpdtsm jpdtsm_100_22

REVIEW ARTICLE

Year : 2023 | Volume : 2 | Issue : 1 | Page : 3-18

Ethnomedicinal, phytochemical, and pharmacological review of asclepiadaceae

Chinedu Enegide¹, Samuel Ehiabhi Okhale²
¹ Department of Pharmacology, College of Medical and Health Sciences, Novena University, Ogume, Delta State, Nigeria
² Department of Medicinal Plant Research and Traditional Medicine, National Institute for Pharmaceutical Research and Development, Abuja, Nigeria

Date of Submission	04-Nov-2022
Date of Decision	25-Jan-2023
Date of Acceptance	04-Feb-2023
Date of Web Publication	13-Mar-2023

Correspondence Address:
Chinedu Enegide
FSASS, Department of Pharmacology, College of Medical and Health Sciences, Novena University, Ogume, Delta State
Nigeria

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpdtsm jpdtsm_100_22

Abstract

Asclepiadaceae plant family is among the dominant families, in which plants with medicinal potentials are domiciled. Plants in this family with medicinal claims are widely distributed across the globe. These plants are major components of different forms of traditional medicine globally. They are employed traditionally for the treatment/management of various ailments including pain, skin diseases, worms, hemorrhoids, bronchitis, asthma, leprosy, diabetes, vertigo, and several other ailments. Different phytochemical studies have been carried out on medicinal plants in this family with an important bioactive compound identified in them and isolated, these include giganteol, calotropeol, and β-amyrin from Calotropis gigantea; β-sitosterol and taraxasterol from Calotropis procera; gymnemic acids and Gymnema saponins from Gymnema sylvestre; tylophorine, kaempferol, and stigmasterol from Tylophora indica; and other important bioactive principles. Several pharmacological studies have also been carried out on them which have justified a lot of the ethnomedicinal applications while new possible applications have as well been revealed and proposed from these studies, this makes the plant family a potential source for developing new conventional drugs in the near future. However, due to the fact that the findings from these studies were reported separately most of which are not available on the same platforms, it has become quite difficult to holistically ascertain the scientifically proven therapeutic potentials of this plant family. Hence, the need to chronicle the different scientific findings on the medicinal plants from this plant family in a concise solitary form. This review, therefore, aims at documenting classical information on the phytochemistry, pharmacology, and therapeutic applications of medicinal plants belonging to Asclepiadaceae family. The species reviewed are the predominantly used medicinal plants from the Asclepiadaceae family in traditional medicine and are also the most extensively researched for their therapeutic potential in conventional health-care practice.

Keywords: Asclepiadaceae, ethnomedicine, pharmacological potential, phytomedicine, traditional medicine

How to cite this article:
Enegide C, Okhale SE. Ethnomedicinal, phytochemical, and pharmacological review of asclepiadaceae. J Prev Diagn Treat Strategies Med 2023;2:3-18

How to cite this URL:
Enegide C, Okhale SE. Ethnomedicinal, phytochemical, and pharmacological review of asclepiadaceae. J Prev Diagn Treat Strategies Med [serial online] 2023 [cited 2023 Mar 31];2:3-18. Available from: http://www.jpdtsm.com/text.asp?2023/2/1/3/371628

Introduction

Since ancient times, plants have been a valuable source of drugs; nature has always played a major role in catering for the health of man. A large proportion of the world population depends on herbal medicine for primary health care.^[1] According to a report by Mbali et al., over 80% of the world's population are dependent on plant-based traditional medicines for basic preventive and curative measures for different health challenges.^[2] In the past few years, scientists and researchers have focused mainly on natural products, especially herbal plants in the search for potent and safer agents for curative, prophylactic, and other medicinal purposes.^[3] Scientific investigations of herbal plants are usually initiated due to their claims and use in traditional medicine. Several scientific studies on suspected medicinal plants and other natural products have been carried out, and remarkable success has evolved from such studies. In fact, several pharmacological agents (about 35%) currently in use were developed from medicinal plants as a result of such studies.^[4],[5],[6] Herbal drugs obtained from plants are believed to be much safer than orthodox medicines. Today, several communities, especially in developing countries, meet their basic needs from crude herbal medicines they manufacture and sell based on traditional knowledge.^[7] The past few decades have recorded an increased scientific study on medicinal plants and their medicinal applications in several parts of the world.

Plants belonging to the Asclepiadaceae family are among the popular plants employed in several parts of the world for an ethnomedicinal purpose and have also attracted the focus of the scientific community leading to several scientific studies that have been carried out on them.^[8] Asclepiadaceae family is among the dominant plant families with several medicinal plants having therapeutic potential against different ailments.^[9] However, of the entire genus stemming from this family, the majority of plant species with medicinal activity are domiciled in a few of them. These include the Calotropis, Caralluma, Ceropegia, Gymnema, Hemidesmus, Leptadenia, and Pergularia genera. Species belonging to these genera have been reported traditionally to possess various medicinal effects. In different parts of the world, people employ plant species from these genera for different medicinal purposes such as antibacterial, antidiabetic, anticancer, anti-ulcer, antiviral, and several other medicinal purposes. Although scientists have carried out studies and reported the phytochemical constituents and pharmacological activities, documents containing these data seem to be disassembled. This is due to the fact that the findings from these scientific studies were reported separately most of which are not available on the same platforms hence, making it difficult to holistically ascertain the scientifically proven therapeutic potentials of this plant family. Hence, the need to chronicle the different scientific findings on the medicinal plants from this plant family in a concise one-stop-shop document. This review, therefore, aims at documenting classical information on the ethnomedicinal uses, phytochemistry, pharmacology, and therapeutic applications of medicinal plants belonging to Asclepiadaceae family. The species reviewed are the predominantly used medicinal plants from the Asclepiadaceae family in traditional medicine and are also the most extensively researched for their therapeutic potential in conventional health-care practice.

Methodology

In carrying out this review, the literature search was performed through relevant databases which include Web of Science, PubMed, Embase, Springer, Science Direct, SciFinder, Scopus, and Google Scholar. The keywords applied for the search are Asclepiadaceae, Asclepiadaceae family, ethnomedicinal uses, phytochemistry, phytochemical, and pharmacological evaluation, and pharmacological activity of extracts, fractions, or isolated principles from Asclepiadaceae. Selection and inclusion criteria were based on articles published in the English language only. All included manuscripts were scrutinized for relevance to the topic and plant species and evaluated pharmacological activities, phytochemistry, and isolated chemical compounds.

Phytogeographic Distribution

Plants belonging to Asclepiadaceae family are widely distributed in several countries globally including Afghanistan, Algeria, Burkina Faso, Cameroon, Chad, China, Cote d'Ivoire, Democratic Republic of Congo, Egypt, Eritrea, Ethiopia, Gambia, Ghana, Guinea-Bissau, India, Iran, Iraq, Israel, Kenya, Kuwait, Lebanon, Libyan, Malaysia, Mali, Mauritania, morocco, Mozambique, Myanmar, Nepal, Niger, Nigeria, Oman, Pakistan, Saudi Arabia, Senegal, sierra Leone, Somalia, Sudan, Syrian Arab Republic, Tanzania, Thailand, Uganda, United Arab emirates, Vietnam, Yemen, Republic of Zimbabwe, Argentina, Australia, Bahmas, Barbados, Bolivia, Brazil, Chile, Colombia, Cuba, Dominica, Dominican Republic, Ecuador, Grenada, Guadeloupe, Guatemala, Guyana, Haiti, Honduras, Jamaica, Martinique, Mexico, Montserrat, Netherlands Antilles, Nicaragua, Panama, Paraguay, Peru, Puerto Rico, St Kitts and Nevis, St Lucia, St Vincent, and the Grenadines, Surinam, Trinidad and Tobago, Uruguay, Venezuela, and Virgin Islands.^{[10],[11],[12]}

Ethnomedicinal Uses

Asclepiadaceae family is among the dominant families, in which plants with medicinal potentials are domiciled. Plants in this family with medicinal claims are widely distributed globally.^[11],[12] They are employed traditionally for the treatment/management of several ailments including pain, skin diseases, worms, hemorrhoids, bronchitis, asthma, leprosy, tooth ache, vertigo, and several other ailments.^[13] Some of the extensively used species in Asclepiadaceae family includes Calotropis gigantea, Calotropis procera, Caralluma umbellate, Gymnema sylvestre, Hemidesmus indicus, Leptadenia pyrotechnica, Pergularia daemia, and Tylophora indica.

C. gigantea is employed traditionally for the treatment of different ailments in several countries including India and China. All parts of the plant are employed in the treatment/management of bronchitis and asthma. Its milky juice is used as a purgative.^[14] The use of the root part in traditional medicine for the treatment/management of leprosy, lupus, tuberculosis, syphilis, elephantiasis, scabies, boils, earache, tooth decay, ringworm, body ache, mumps, headache, joints pain, ulceration, and also as antidote for scorpion venom has been documented.^[14] The leaf juice is used for the treatment of edema, while the preparation of leaves and roots in different forms such as balms, powder, and enemas is employed for the management of tumors, dysentery, and diarrhea. Its root powder and fumes are inhaled as an effective cough relief agent.^{[15],[16],[17]}

C. procera is a common medicinal plant with high relevance in traditional medicine. The plant is mostly found in West Africa and other tropical regions of the world.^[18] The root bark is used in traditional medicine for the treatment of cough, skin diseases, ascites, anasarca, and intestinal worms. It is also used in cases of enlargement of abdominal viscera. The milky juice is used as a purgative agent, while the flowers are used to promote digestion, increase appetite, treatment of asthma and catarrh, and as well for induction of abortion. The root bark is used for the treatment of elephantiasis, while the latex is used for toothache. The plant is also used in the treatment of leprosy and enlargement of the liver and spleen. The boiled leaves and oily preparations are used in ethnomedicine for the treatment of paralysis, while the powdered leaf is used as a wound-healing agent.^[19],[20] The fruit and latex are also used for various medicinal purposes. The powdered root mixed with goat milk is used in the management of epilepsy, while the tender leaves are used to treat migraine.^[21]

Caralluma umbellate belongs to the Caralluma genus, its medicinal property has been utilized in traditional medicine in several countries including Sri Lanka, Nepal, and India. The stem juice mixed with turmeric powder is used in the treatment of diabetes, obesity, abdominal pain, and other stomach disorders. The burnt stem of the plant is used for the treatment of ulcers. The plant is also used in folkloric medicine as an analgesic and anti-inflammatory agent.^[22]

G. sylvestre is a known ethnomedicinal plant used in the remedy of glycosuria and other urinary disorders in India and other Asian regions.^[23] It is also used in the treatment of malaria, diabetes, diseases caused by phlegm, dyspepsia, constipation, jaundice, piles, hemorrhoids, renal and vesicle calculi, cardiopathy, asthma, diabetes, Parkinsonism ^{More Details}, bronchitis, amenorrhea, leukoderma, asthma, eye, urinary and gastric disorders, and as antidote for snake venom.^{[24],[25],[26],[27]} Different parts of the plant such as the roots, stem, and leaves are used as laxatives, digestants, cardiotonics, diuretics, stimulants, and uterine tonic agents in ethnomedicine.^{[28],[29],[30],[31]}

Hemidesmus indicus is a widely used plant in the traditional medicine of several countries including India, Sri Lanka, Iran, Pakistan, and Bangladesh. The root is used as an antidiarrheal and antipyretic agent and as a blood purifier as well. The plant is also used for the treatment of dysentery, blood-related diseases, bronchitis, asthma and other respiratory disorders, biliousness, diarrhea, rheumatism, leprosy, leukoderma, leukorrhoea, itching, syphilis, epilepsy in children, lack of appetite, burning sensation, urinary, and kidney disorders.^{[29],[30],[31]}

Leptadenia pyrotechnica is employed traditionally in Pakistan, Saudi Arabia–Senegal, and several other countries for the treatment of dysmenorrheal, fever, jaundice, hepatitis, constipation, obesity, smallpox, disorders of the upper gastrointestinal tract, and impotency.^[32],[33] The seeds and whole plant are used in the treatment of flu and as an expectorant, while the juice is used for the treatment of cold, cough, ringworm, and other skin diseases. The plant is also used as a laxative for infants.^{[34],[35],[36]}

Pergularia daemia is also an ethnomedicinal plant of Asclepiadaceae family. The aerial parts are used as antiseptic and antihelminthic agents. It is also used for treating ulcers, uterine, and menstrual disorders. The plant leaves are used in ethnomedicine for the treatment of several ailments including leprosy, arthritis, anemia, hemorrhoids, asthma, amenorrhea, infantile diarrhea, dysmenorrheal, pain, whooping cough, and bronchitis.^[37] The stem is used for the treatment of cold, malarial fever, and pyrexia, while the plant latex is used for the treatment of boils and sores.^[38] Furthermore, the root extract is used in the treatment of constipation, asthma, and gonorrhea as well as an abortifacient and emetic agent. Its fresh leaf extract mixed with lime or ginger is used in the treatment of rheumatic welling.^[39]

Tylophora indica is employed traditionally for the treatment of jaundice, bronchial asthma, dermatitis, hypertension, rheumatism, cancer, liver disorder, jaundice, dysentery, and inflammation.^[40],[41] It is used also as antitumor, immunomodulatory, antioxidant, and antiasthmatic agents.^[42]

Phytochemistry

Different parts of medicinal plants belonging to Asclepiadaceae family have been reported to contain various bioactive chemicals, the diversity of these bioactive chemicals in the Asclepiadaceae family largely accounts for its numerous therapeutic applications and reported pharmacological activities.^[43] Several compounds have been identified and isolated from plants belonging to this family; they are listed in [Table 1].

Table 1: Compounds isolated from species of the Asclepiadaceae family

Click here to view

Pharmacological Studies

Different studies have been performed on various parts of plants belonging to the Asclepiadaceae family these include their roots, latex, stem bark, leaf, and flower. These studies have reported several pharmacological activities by plants of Asclepiadaceae family including antioxidant, anticoagulant, antidiarrheal, anti-inflammatory, analgesic, anticancer, antiulcer, cough-expectorant, hepatoprotective, wound healing, smooth muscle-contracting, neuromuscular blocking, spermicidal activities, and several other pharmacological activities.

Calotropis gigantean

Anticancer activity

A study by Habib and Karim on the effect of anhydrosophoradiol-3-acetate (A3A) isolated from C. gigantea showed a decrease in viable tumor cells in mice induced with Ehrlich's ascites carcinoma (EAC). There was an increase in bodyweight and improved hematological indices (hemoglobin, red blood cell, and white blood cell), while the biochemical parameters were unchanged. It increased the survival period of the experimental mice. The result led to the inference that A3A from C. gigantean has potent anticancer activity against EAC in mice.^[67]

Wound healing activity

C. gigantea latex in a study by Nalwaya et al.^[68] using excision and incision wound animal models had a potent wound-healing effect in experimental rats. C. gigantea latex elicited an 83.42% reduction in the wound area, this was better than the standard (framycetin sulfate cream 1% w/w) which had 76.22%. The latex also caused a faster epithelization compared to the control. Similarly, another study in streptozotocin-induced diabetic rats using an excision wound animal model revealed that C. gigantean latex extract ointment (2%) increased the rate of wound contraction and decreased the time of epithelization in rats significantly (P < 0.05). This study revealed that C. gigantean by collagen synthesis stimulation and promotion of histological processes essential for wound healing improves diabetic wound healing.^[69]

Antiasthmatic activity

C. gigantea in a study in rats had potent antiasthmatic activity against ova albumin-induced asthma. In the study, C. gigantea significantly (P < 0.05) inhibited neutrophils, eosinophils, and lymphocytes as well as total leukocyte counts in the bronchoalveolar lavage fluid. The study result thus reveals that C. gigantea may serve as a potent antiasthmatic agent.^[70]

Antidiarrheal activity

C. gigantea aerial part hydroalcoholic extract elicited potent antidiarrheal effect in castor oil-induced diarrheal animal model. In the study, the extract inhibited the volume and weight of intestinal content in a similar way as atropine (a cholinergic receptor blocker). Furthermore, fecal output and frequency of droppings were as well decreased by the extract.^[71] A separate study on C. gigantea aqueous root bark extract using castor oil-induced enteropooling test revealed that the aqueous extract had a significant antidiarrheal effect.^[72] In another study carried out on C. gigantea aqueous extract using the charcoal-induced gut motility model, the extract significantly reduced the distance traveled by charcoal. The study result thus revealed that C. gigantea aqueous extract had significant antidiarrheal activity.^[73]

Analgesic and anti-inflammatory activity

In a study to evaluate the analgesic activity of C. gigantea flower alcoholic extract using chemical and thermal models in mice, the extract had a notable analgesic effect in both test models.^[74] Furthermore, in another study, C. gigantea showed a potent anti-inflammatory effect in albumin-induced inflammation in mice. The highest anti-inflammatory effect demonstrated by the extract was similar to that elicited by the standard drug ibuprofen which was 85.71%.^[75]

Sedative and anxiolytic activity

In a study on C. gigantea ethanolic extract in Swiss albino mice using hole cross test elevated plus maze (EPM) test, open field test, and thiopental sodium-induced sleeping time test, the extract elicited a significant decrease of movement, decreased the time needed for sleep onset, and increased the duration of sleep (i.e., sleeping time) in test animals when compared with control. It also reduced the percentage of mice entries into the open arms and the time spent in open arms of the EPM.^[76]

Hypoglycemic/antidiabetic activity

The result from a study aimed at evaluating the hypoglycemic activity of C. gigantea leaf and flower chloroform extracts in streptozotocin-induced diabetic rat model revealed that the extracts effectively decreased serum glucose levels in rats, while oral glucose tolerance was also improved. This thus suggests that C. gigantea may serve as a potent antidiabetic agent.^[77]

Hepatoprotective activity

The hepatoprotective activity of C. gigantea leaf chloroform and methanolic extracts showed significant (P < 0.05) hepatoprotective activity against acetaminophen-induced hepatotoxicity in rats. In the study, the extracts caused a decrease in the liver enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels, respectively.^[78]

Other pharmacological activities

Report from several other studies carried out on different parts of C. gigantea revealed that the plant also possesses several other important pharmacological activities including antibacterial activity against both Gram-positive and Gram-negative bacteria, antioxidant, cytotoxic, vasodilatation, hair growth, ovicidal, antihelminthic, antiviral, and antivenom activities.^{[79],[80],[81],[82],[83],[84],[85]}

Toxicity

Oral doses of C. gigantea higher than the therapeutic dose have been reported to elicit gastrointestinal upset such as diarrhea, nausea, and vomiting. Burning micturition and headache have also been reported with chronic use. Furthermore, it has been postulated that use in pregnant women especially at the early stages may cause abortion, as well as liver and lung injuries.^[86]

Calotropis procera

Anticonvulsant activity

The anticonvulsant activity of C. procera root aqueous and chloroform extracts have been demonstrated in rats using the maximal electroshock seizures (MESs), lithium-pilocarpine, pentylenetetrazol (PTZ), and electrical kindling seizures animal models. Both extracts inhibited lithium-pilocarpine and electrical kindling-induced convulsion/seizure, however, the chloroform extract had a better effect in PTZ and MES tests.^[50]

Antimalarial activity

The ethanolic extract of C. procera in an in vitro antimalarial study had IC₅₀ value of 0.52 mg/ml against MRC 76 CQ-resistant strain and 0.11 mg/ml against Plasmodium falciparum MRC20 CQ-sensitive strain. The bud and flower parts were reported to have the best antimalarial effect compared to other parts of the plant.^[87]

Analgesic and antinociceptive activity

Report from a study on the analgesic activity of C. procera latex test showed that the plant had a significant analgesic effect in acetic acid-induced writhing test and tail flick animal models. Its activity was similar to that elicited by the standard analgesic agent used for the study (aspirin).^[48],[88]

In a study reported by Gupta et al., proteins isolated from C. procera latex had a remarkable antinociceptive effect in three different experimental mice models, namely formalin-induced abdominal constrictions, acetic acid, and hot plate tests. The effect was dose-dependent, however, the highest activity was recorded at 50 mg/kg. This was nondependent on the opioid system.^[89]

Immunomodulatory activity

C. procera root bark ethanolic extract in a study to ascertain its immunomodulatory potential in mice elicited a significant effect. The plant extract stimulated the mice immunity by modulation of various immunological parameters.^[48],[88] The immunomodulatory activities of C. procera latex extract protein have also been reported by Nascimento et al. They stated that the protein had a protective effect against Listeria monocytogenes

nes infections in their experiment.^[90]

Wound healing and antiulcer activities

The wound healing activity of C. procera in guinea pigs has also been reported. In the study, a dose of 20 μl of 1.0% sterile solution of C. procera latex was administered topically to the animals. The result revealed that there was a significant augmentation of the healing process and epithelization.^[91] According to Parihar and Balekar, the mechanism for eliciting this effect is by increasing the synthesis of collagen, DNA, and protein in animals.^[48] Tsala et al. also reported the antioxidant activity and the healing effect of C. procera bark ethanol extract against surgical wounds.^[91]

Similarly, results from a study aimed at evaluating the antiulcer activity of C. procera using different in vivo ulcer animal models showed that the plant had a significant antiulcer effect in the different models, namely alcohol, aspirin, reserpine, and serotonin-induced gastric ulcer in rats. The plant had a protective effect on the gastric mucosa against aspirin-induced ulceration in experimental pyloric-ligated rats, and as well had a protective effect in histamine-induced duodenal ulcer model.^[50]

Dermatophytic activity

C. procera fresh latex in a study to demonstrate its effect against dermatophytes had a potent effect against dermatophytes such as Trichophyton spp., Microsporum spp., and Epidermophyton spp. In the study, C. procera fresh latex dermatophytic activity was highest against Trichophyton spp., while Epidermophyton spp. was list susceptible to its activity.^[49]

Antifertility activity

The antifertility activity of C. procera root ethanolic extract has been demonstrated in albino rats. Results from the study showed potent anti-implantation and heterotrophic activities. The best effect was at 250 mg/kg, however, no antiestrogenic activity was observed.^[92]

Other pharmacological activities and toxicity

Several other scientifically proven pharmacological activities of C. procera have also been reported, these include anthelmintic activity of C. procera flowers, antioxidant and antidiabetic activity of the dried latex, potent protective effect against isoproterenol-induced myocardial infarction (MI) in albino rats, anticancer and cytotoxic effects in transgenic mouse model of hepatocellular carcinoma, antibacterial activity against Candida albicans, Pseudomonas pseudomallei, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia ^{More Details} coli, Staphylococcus aureus, Staphylococcus albus, Streptococcus pyogenes and Streptococcus pneumonia, antifungal effect against Aspergillus niger, Aspergillus flavus, and Microsporum boulardii. The anti-inflammatory, larvacidal, and anti-diarrheal activities of C. procera have been documented as well. Reports have also shown that C. procera roots ethanolic and aqueous extracts in a study in rats interrupted the normal estrous cycle.^{[93],[94],[95],[96]}

The plant has been reported to posses some levels of toxicity and this may be a major reason why it is not eaten by grazing animals. In fact, history shows that latex was used to make arrow poison used by animal hunters. Latex causes ocular toxicity and loss of vision with photophobia in man. Toxic effects such as iridocyclitis, corneal endothelial cytotoxicity, keratoconjunctivitis, and keratitis have also been documented with the plant latex. Dose-dependent cytotoxic effect was also reported in an in vitro study on the leaves and flowers of C. procera.^[97],[98]

Caralluma umbellate

Nephroprotective and antioxidant activities

Bharathi et al.^[99] in the report from a study aimed at evaluating C. umbellate methanolic extract nephroprotective and antioxidant activities revealed that the extract exhibited potent nephroprotective and antioxidant effects. C. umbellate hexane, benzene, diethyl ether, chloroform, acetone, and methanol extracts in a study to determine their antibacterial activity also had significant antibacterial effects against B. subtilis, E. coli, and B. cereus.^[100] Kumar and Sandhya^[101] carried out in vitro antioxidant study on C. umbellate aqueous alcoholic extract. Result from the study showed that the extract gave a potent antioxidant effect. The high phenolic content was, however, implicated as the major reason for the potent antioxidant activity of the extract. The antioxidant effects of both methanolic and aqueous extracts of C. umbellate have also been reported by Kalyani and Anuradha.^[102] Significant scavenging activity and lipid peroxidation effects were elicited by the extracts in the study.

Hepatoprotective and anti-inflammatory effects

C. umbellate hepatoprotective activity in acetaminophen-induced hepatic damage in rats was estimated by Shanmugam et al. and reported that it elicited significant hepatoprotective activity.^[103] Carumbelloside-II and III (isolated from C. umbellata) have been reported to posses significant anti-inflammatory effects by Ray et al. from their study on anti-inflammation. This gives credence to the ethnomedicinal use of C. umbellate as a painkiller and inflammation agent.^[104],[105]

Gymnema sylvestre

Antidiabetic activity

The most popular ethnomedicinal use of G. sylvestre is for the treatment of diabetes. Reports from different studies to evaluate its antidiabetic activity showed that the ethanol and aqueous extract of G. sylvestre reduced blood glucose levels by 46% and 26%, respectively, while the methanol extract elicited a 12% decrease.^{[106],[107],[108],[109]} In streptozotocin-induced diabetes rat model, it was reported that G. sylvestre significantly (P < 0.05) reduced the elevated blood glucose, AST, ALT, triglycerides, low-density lipoprotein (LDL)-cholesterol, total cholesterol, and malondialdehyde, while insulin, high-density lipoprotein (HDL)-cholesterol, and erythrocyte superoxide dismutase levels were increased in the diabetic rats.^{[110],[111],[112]} Gymnemic acid isolated from G. sylvestre, at a dose of 3.4/13.4 mg/kg administered for 6 h caused a 14.0%–60.0% decrease in blood glucose level. Gymnemic acid also caused an increase in plasma insulin levels in STZ-diabetic mice at a dose of 13.4 mg/kg.^[113]

Anticancer activity

The outcome of several studies on G. sylvestre has shown that it has potent anticancer activity. Gymnemagenol, a bioactive constituent of G. sylvestre, elicited a significant anticancer effect against HeLa cells in a study carried out by Khanna.^[114] Results from a study aim at evaluating G. sylvestre chloroform, ethyl, and ethanolic extracts for anticancer activity against human lung adenocarcinoma (A549) and human breast carcinoma (MCF7) cell lines revealed a potent anticancer activity, however, chloroform and ethyl extracts had better anticancer activity than the ethanol extract.^[115] Flavonoids isolated from G. sylvestre were also found to inhibit BCRP and improve multidrug resistance of BCRP substrates induced by it.^[116] Hence, this may indicate that inhibition of this protein by G. sylvestre flavanoid may help enhance the activity of BCRP substrates such as daunorubicin, methotrexate, epirubicin, and topotecan through increased absorption and systemic bioavailability.^[117]

Antioxidant activity

G. sylvestre antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical have also been reported from separate investigations by Rupanar et al. and Rahman et al.^[118],[119] The plant was observed to elicit better DPPH radical scavenging activity than butylated hydroxyltoluene (BHT), while the report from another study showed it reduce LDL oxidation.^[118],[120] Furthermore, a separate study showed it had significant hydroxyl-free radical scavenging activity and antioxidative potential against DPPH where DPPH inhibition and hydroxyl-free radical inhibitions were 87.3% and 59.8%, respectively.^[121] It was also found to have significant radical scavenging activity against ferric, super oxide, and also against hydrogen peroxide.^[122] Arun et al., Kishore and Singh, Chakrapani and Periandavan, also reported that G. sylvestre elicited antioxidant activity in various conditions such as against high-fat diets, nitric oxide, hydrogen peroxide, and superoxide radically induced oxidative stress in animal models.^{[123],[124],[125]}

Anti-inflammatory and antiarthritic activities

G. sylvestre methanolic extract had potent anti-inflammatory activity in Wistar rats in a study reported by Kumar et al., where a carrageenan-induced inflammatory model was used. The methanolic extract significantly reduced rat paw edema in the study.^[126] Similarly, in another study, its aqueous extract had a potent inhibitory effect against carrageenan-induced rat paw edema as well as against mice model peritoneal ascites.^[127] Its ethanolic extract also showed potent inhibitory effects against TPA-induced inflammation in mice.^[128]

G. sylvestre petroleum and aqueous extracts in a study documented by Malik et al. had significant antiarthritic activity. This effect was attributed to the fact that G.sylvestre may have inhibited the release of inflammatory mediators which in turn may have led to a reduction in bone destruction in arthritis.^[129]

Hepatoprotective activity

G.sylvestre hydroalcoholic extract in an in vitro study exhibited a significant antihepatotoxic effect in isolated rat hepatocytes in a dose-dependent manner where hepatotoxicity was induced using D–galactosamine. A significant increase in liver enzymes level including ALT, AST, ALP, direct bilirubin, and total bilirubin were also observed in the study.^[130] Its methanolic extract has also been reported to decrease both creatinine and urea levels in Wistar rats after acute and chronic administration.^[131] Report from another study on a methanolic polyherbal preparation containing G. sylvestre showed that the preparation has the potential to reverse paraffin and carbon tetrachloride-induced hepatotoxicity in rats.^[132]

Other pharmacological activities and toxicity

Other studies carried out on G. sylvestre have as well reported several other pharmacological activities associated with G. sylvestre. The plant lowered cholesterol, LDL, and triglyceride levels while an increase in HDL level was observed in studies by Singh et al., Rachh et al., Dholi and Raparla.^{[131],[133],[134]} These effects have been attributed to the presence of bioactive constituents such as flavonoids, tannins, and saponins.

Various G. sylvestre extracts and isolated compounds have been chronicled to elicit potent antimicrobial activity against a broad range of pathogenic microorganisms including B. cereus, E. coli, C. albicans, C. kefyr, C. krusei, S. aureus, C. perfringens type-A, S. aureus, B. cereus, S. enterica, H. paragallinarum, Salmonella ^{More Details} species ( S.typhi , S. Typhimurium, and S. paratyphi), P. vulgaris, E. coli, P. aeroginosa, K. pneumoniae, S. aureus, E. Coli, K. pneumonia and P. aeruginosa, S. dysenteriae, P. aeruginosa, and P. vulgaris.^{[135],[136],[137],[138],[139]} Furthermore, the immunomodulating, anti-ulcer, and anti-caries activities of G. sylvestre have been documented.^[140]

Aside divers, preclinical studies on G.sylvestre, several clinical studies have also been carried out to evaluate its therapeutic efficacy in man. Report from clinical investigations on G.sylvestre showed its efficacy in decreasing blood glucose, LDL-c, triglyceride, and total cholesterol levels, while elevated C-peptide and insulin were observed. Report on a clinical study carried out on type 2 diabetes mellitus patients showed that G.sylvestre reduced both fasting and postprandial blood glucose levels and triglyceride.^[126] Similarly, another study on type 1 diabetes patients treated with G. sylvestre leaf extract showed that the extract caused a decrease in plasma glucose, external insulin dose, and HbA1c.^[141] Furthermore, in a study by Li et al., G. sylvestre caused a reduction in blood glucose, triglyceride, cholesterol, and LDL levels in type 2 diabetes patients.^[142]

Chattopadhyay (1999) reported the oral LD₅₀of G. sylvestre to be 3990 mg/kg while the safety index was found to be between 11.08 and 16.03. Neurologic, behavioral, and autonomic adverse effects were not observed in this study. Report from another study showed the intraperitoneal LD₅₀ of G. sylvestre ethanol and aqueous extracts to be 375mg/kg in mice.^[143] A case of drug-induced liver injury was reported in a diabetic patient treated with G. sylvestre.^[144] The hypoglycemic effect of the plant in both diabetic and nondiabetic patients has also been documented.^[145]

Hemidesmus indicus

Antiangiogenic activity

Results from in vitro study to evaluate H. indicus root decoction antiangiogenic effect using human umbilical vein endothelial cells showed that it had several interactions with several crucial steps in angiogenic cascade targeting vesicular endothelial growth factor expression (VEGF) triggered by hypoxia-inducible factor 1-alpha (HIF-1α) and as well migration and differentiation of endothelial cells.^[146]

Antiarthritic activity

H. indicus hydroalcohol root extract and ethyl acetate fraction demonstrated significant protective activity against arthritis in a study by Mehta et al.^[147] This effect was attributed to the presence of sterols, terpenes, and phenolic compounds in the extract and fraction. These fractions showed higher antiarthritic activity than chloroform and residual fraction. Similarly, the activity of H. indicus root ethanolic extract against osteoporosis was evaluated in ovariectomized rats and the result showed that it prevented bone loss in dorsal ovariectomy-induced osteoporosis this was, however, without the common estrogen-like side effects.^[148]

Anti-cancerous activity

H. indicus roots have been reported to elicit protective activity against hepatocarcinogenesis and other cancers.^[149] In vitro chemopreventive study on the effect of H. indicus extract on acute lymphoblastic leukemia (ALL) cell line had cytotoxic effects by both intrinsic and extrinsic apoptotic pathways. It inhibited the cell cycle in the S phase and prevented DNA damage.^[146] H. indicus root decoction cytostatic, cytotoxic, and cytodifferentiation activities have also been reported from a study carried out using the human promyelocytic leukemia cell line (HL-60).^[150]

Antidiabetic and anti-cataractous activities

Result from a study aimed at evaluating the antidiabetic activity of 2-hydroxy-4-methoxy benzoic acid a bioactive compound isolated from H. indicus roots showed that it elevated the activity of Na/K⁺ ATPase, total ATPases, Ca²⁺ ATPase, and Mg²⁺-ATPase; caused a decrease in superoxide dismutase, glutathione peroxidase, catalase, glutathione-S-transferase in erythrocytes; improved vitamin E; decreased levels of vitamin C and glutathione in blood plasma and erythrocytes in streptozotocin-induced diabetic rats.^[151] Similarly, β-amyrin palmitate an active principle from H. indicus root extract was reported to exhibit antidiabetic activity both in alloxan and streptozotocin-induced diabetes in rats.^[152]

Furthermore, in a study to evaluate anticataract activity of H. indicus in streptozotocin-induced diabetic cataract in rodents, H. indicus methanol root extract elicited decreased blood glucose, reductase activity on aldose, delay in progression of cataract, prevention of loss of antioxidants, and reduced osmotic stress.^[153]

Antivenom and antiretroviral activities

H. indicus root extract has been reported to elicit antivenom activity against viper venom-induced inflammation. The mechanism for this effect has been speculated to be by reduction in reactive oxygen species and inflammatory cytokines by the extract. Reports also show that H. indicus root extract neutralizes viper venom-induced coagulant activity.^[154]

H. indicus has also been reported to elicit potent antiretroviral activity against HIV-1. This activity has been attributed to the inhibition of RT-associated RNase H function, HIV-1 RT-associated RNA-dependent DNA polymerase activity, and cellular α-glucosidase.^[155]

Other pharmacological activities

Several other studies carried out on H. indicus reveal that the plant also has other pharmacological effects including anti-inflammatory, antioxidant, anti-hepatocarcinogenic, monophenolase, diuretic, acetylcholinesterase, and butyrylcholinesterase inhibitory activities.^{[156],[157],[158],[159]}

Leptadenia pyrotechnica

Antifungal activity

Rekha et al. carried out a study on L. pyrotechnica leaves antifungal activity against A. flavus, A. niger, F. moniliformis, and F. oxysporium. In the study, L. Pyrotechnica leaves methanol extract had significant activity against A. flavus, while its aqueous extract gave a better effect against F. moniliformis. Hexane and ethyl acetate extracts had more activity against A. niger.^[160] Its antifungal activity has been speculated to be as a result of the presence of alkaloids.^{[161],[162],[163]}

Antibacterial activity

Al-Fatimi et al. evaluated L. pyrotechnica whole plant methanolic, aqueous, and dichloromethane extracts antimicrobial activities against B. subtilis, S. aureus, E. coli, M. flavus, and P. aeruginosa using DPPH agar and diffusion methods. In this study, the various extracts had different degrees of activity.^[164] Similarly, in another study, L. Pyrotechnica root and fruit extracts were evaluated for their antimicrobial activity against S. epidermidis and S. aureus. The result showed that the root extract had a better effect compared to the fruit extract. The methanolic extracts of both root and fruit gave significant inhibitory effects against the pathogens.^[165]

Anticancer and antioxidant Activities

Khasawneh et al. in a study on L. Pyrotechnica ethylacetate extract reported that it had a potent anticancer effect against the MCF-7 human breast cancer cell line. The report also stated that L. Pyrotechnica aerial parts ethylacetate and n-butanol extracts had significant antioxidant activity.^[166] A separate study by Saleh et al. also demonstrated the antioxidant activity of L. Pyrotechnica using 2, 2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric reducing antioxidant power (FRAP), and β-carotene and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assays. The study results showed L. Pyrotechnica had good antioxidant activities in all the assays employed.^[167] Munazir et al. also reported the radical scavenging activity of L. Pyrotechnica root part.^[165]

Wound-healing activity

Shaw and Singh evaluated L. pyrotechnica root and aerial parts petroleum ether and ethanolic extracts wound healing activity. The result shows that both parts had a wound-healing effect, however, the aerial part gave a better wound-healing activity compared to the root in Wistar rats. The presence of flavonoids and terpenoids has been implicated as the cause of wound-healing activity.^[168]

Anthelmintic activity

L. pyrotechnica methanolic extract anthelmintic activity was reported to be significant against gastrointestinal worms in a study reported by Kumar et al., The effect was highest at 100 mg/ml and was similar to that elicited by the standard drug albendazole.^[169]

Other pharmacological activities and toxicity

Other reports have also shown that L. Pyrotechnica has the potential to elicit several other pharmacological effects such as antiatheroscloretic, hypolipedemic, antdiabetic, hepatoprotective, and antitumor activities.^{[170],[171],[172]}

Watafua and Geidam in a 21-day study to evaluate L. Pyrotechnica ethanolic extract subacute toxicity in albino rats reported that the extract was only slightly toxic to the liver. Toxicity in other organs was not reported.^[173]

Pergulariadaemia

Antioxidant activity

In vitro study on P. daemia, methanolic extract to evaluate its antioxidant potential against different synthetic free radicals, namely 2,2′-Azino-bis ABTS, DPPH, and nitric oxide-free radicals revealed that the aerial part extract had potent neutralizing ABTS, DPPH, and nitric oxide-free radicals. In the study, the documented P. daemia extract IC₅₀ concentration for ABTS, DPPH, and nitric oxide was 19.72, 33.36, and 32.37 mg/ml, respectively.^[174] Similarly, P. daemia leaf ethanolic extract has also been reported to elicit significant scavenging activity against DPPH free radical and as well effectively inhibits the formation of peroxides and hydrogen peroxides.^[175] A report also documented the ability of P. daemia extract to reduce iron from ferric (Fe³⁺) to ferrous (Fe²⁺).^[176] Bioactive chemicals present in P. daemia such as alkaloids, phenols, flavonoids, phytosterols, saponins, tannins, and triterpenes have been suspected to be the culprit antioxidant agents in the plant.^[177],[178]

Diuretic activity

A study by Bhavina et al. on P. daemia alcoholic, petroleum ether, ethyl acetate, and n-butanol extracts revealed that they all gave diuretic effect in rats with the alcoholic extract having the highest activity which was similar to that of the standard drug furosemide and was in a dose-dependent manner. Specifically, alcoholic, ethylacetate, and n-butanol extracts increased both urine volume and urinary excretion of potassium (K⁺) and sodium (Na⁺) ions.^[179] Phytochemical studies revealed the presence of important secondary metabolites which are known for their diuretic activities in P. daemia. These include flavonoids, alkaloids, and steroids and they are suggested to be the cause of the diuretic activity P. daemia.^[180]

Antifertility/abortifacient activities

P. daemia ethanolic extract and steroidal fraction gave potent antifertility effect in a study by Sadik et al. Results from the study revealed that the steroidal fraction at a dose of 200 mg/kg gave significant antifertility activity against female mice in the preimplantation phase, while 600 mg/kg ethanolic extract had a late abortifacient effect.^[181]

Anti-ulcer activity

Secondary metabolites such as tannins, flavonoids, and triterpenes have been documented for their anti-ulcerogenic activity. Phytochemical studies have revealed the presence of these phytochemicals known to elicit anti-ulcer activity in P. daemia.^[182] In a pharmacological study, the plant extract at 400 mg/kg had potent curative activity against ethanol-induced ulcer in rats.^[183] A similar study by Dhananjayan et al. reported that P. daemia leaf ethanolic extract had a very good anti-ulcer activity which was dose-dependent.^[184]

Other pharmacological activities

Report from several other pharmacological studies shows that P. daemia also have other important therapeutic effects including anti-inflammatory, antiarthritic, anticancer, hepatoprotective, anthelmintic, and antidiabetic activities.^[185],[186] These claims were also supported by reports from various phytochemical studies which revealed the presence of bioactive chemicals in P. daemia known to posses these acclaimed pharmacological effects.^{[39],[183],[187],[188]}

Tylophora indica

Cardiac protective activity

T. indica hydroalcoholic extract was evaluated for its cardiac activity against isoprenaline-induced MI in rats. Pretreatment of animals with extract 200 mg/kg and propanolol 10 mg/kg had significant myocardium protection from isoprenaline damage, this was shown by a decrease in both serum creatine phosphokinase-MB (CK-MB) and lactate dehydrogenase activities, while there was an increase in activities of enzymes in the homogenate of heart tissue.^[189]

Antibacterial activity

Antibacterial activity of ethyl acetate and methanol extracts of the plant was investigated by well-diffusion method against bacterial pathogens associated with HIV. The plant extracts showed better inhibitory activity against the tested organisms. T. indica methanolic leaf extract showed the highest inhibitory activity. The activity was significant against K. pneumoniae, E. coli, S. aureus, P. aeruginosa, and S. typhi known to be found among HIV patients.^[189]

Hepatoprotective activity

T. indica leaves aqueous and alcoholic extracts hepatoprotective activity has been evaluated against ethanol-induced hepatotoxicity in rats. Pretreatment with the extracts significantly prevented the biochemical, physical, histological, and functional changes elicited in the liver by ethanol.^[190]

Antiallergic activity

In a study to evaluate the antiallergic activity of T. indica in rats, its aqueous extract and disodium cromoglycate increased the rate of flow during perfusion of sensitized rat lung. The mechanism for this activity of T. indica is postulated to be by direct bronchodilator and membrane stabilizing activities, as well as immunosuppression.^[189],[191]

Diuretic activity

T. indica leaves alcoholic and aqueous extracts have also been reported to possess a good diuretic effect. A scientific study on T. indica diuretic activity revealed that the ethanolic extract leave extract was most efficacious in increasing urinary electrolyte concentration of sodium, potassium, and chloride, this is followed by chloroform and aqueous extracts, while other extracts only had negligible activities with regard to the urinary electrolyte concentration.^[192]

Other pharmacological activities

Other scientific studies have been carried out on T. indica, this includes in vitro and in vivo pharmacological studies. These studies have proven T. indica to also posses antitumor, anti-asthmatic, antibacterial, and lysosomal enzyme inhibiting activities.^[193]

Conclusion

In the wake of the search for novel, efficacious, safer, and affordable therapeutic agents, medicinal plants could serve as a great source of structurally unique scaffolds and lead pharmacological agents. The Asclepiadaceae plant family is widely distributed globally and has been reported to have numerous therapeutic potentials including anticancer, antidiabetic, anti-oxidant, anti-inflammation, hepatoprotective, antibacterial, and several other activities. This review has highlighted several of its pharmacological potentials and bioactive components. Further research aimed at translating the numerous therapeutic potentials of this plant family into standard therapy will be of enormous gain to the modern health-care sector and this review could serve as a handy reference for such purpose.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Ashraf K, Haque MR, Amir M, Ahmad N, Ahmad W, Sultan S, et al. An overview of phytochemical and biological acitivities: Ficus deltoidea Jack and other Fiscus spp. J Pharm Bioall Sci 2021;13:11-25. [Full text]
2.	Mbali H, Sithole JJ, Nyondo-Mipando AL. Prevalence and correlates of herbal medicine use among Anti-Retroviral Therapy (ART) clients at Queen Elizabeth Central Hospital (QECH), Blantyre Malawi: A cross-sectional study. Malawi Med J 2021;33:153-8.
3.	Chinedu E, Ofili CC. Ocimum Species: Ethnomedicinal uses, phytochemistry and pharmacological importance. Int J Curr Res Physiol Pharmacol 2021;5:1-12.
4.	Calixto JB. The role of natural products in modern drug discovery. An Acad Bras Cienc 2019;91 Suppl 3:e20190105.
5.	Okhale SE, Akpan E, Fatokun TO, Esievo BK, Kunle FO. Annona senegalensis Persoon (Annonaceae): A review of its ethnomedicinal uses, biological activities and phytocompounds. J Pharmacogn Phytochem 2016;5:211-9.
6.	Chinedu E, Akah PA, Jacob DL, Onah AI, Ukegbu CY, Chukwuemeka CK. Antimalarial activities of butanol and ethylacetate fractions of Combretum nigricans leaf. Asian Pac J Trop Biomed 2019;9:176-80. [Full text]
7.	Amorha KC, Nwabunike IA, Okwumuo BM, Ayogu EE, Nduka SO, Okonta MJ. Use of herbal medicines in a Nigerian community and their reported adverse effects: A pilot study. Trop J Pharm Res 2018;17:2067-72.
8.	Boomibalagan P, Eswaran S, Rathinnavel S. Traditional uses of medicinal plants of Asclepiadacaea by rural people in Madurai District, Tamil Nadu, India. Int J Bot 2013;9:133-9.
9.	Lingaraju DP, Sudarshana MS, Rajashekar N. Ethnopharmacological survey of traditional medicinal plants in tribal areas of Kodagu District, Karnataka, India. J Pharm Res 2013;6:284-97.
10.	Goyder DJ. An overview of asclepiad biogeography. In: Ghazanfar SA, Beentje HJ, editors. Taxonomy and Ecology of African Plants, Their Conservation and Sustainable Use. Kew: Royal Botanic Gardens; 2006. p. 2005-14.
11.	Ganesan S, Venkateshan G, Banumathy N. Medicinal plants used by ethnic group Thottianaickans of Semmalai hills (reserved forest), Tiruchirappalli district, Tamil Nadu, India. J Tradit Knowl 2006;5:242-52.
12.	Jeeva S, Femila V. Ethnobotanical investigation of Nadars in Atoor village, Kanyakumari District, Tamil Nadu, India. Asian Pac J Trop Biomed 2012;2:593-600.
13.	Reddy CS, Reddy KN, Murthy EN, Raju VS. Traditional medicinal plants in Seshachalam hills, Andra Pradesh, India. J Med Plants Res 2009;3:408-12.
14.	The Wealth of India. A Dictionary of Indian Raw Materials and Industrial Products Raw Materials, Ca-Ci, (Revise). V-III. New Delhi: Council of Scientific & Industrial Research; 1992. p. 79-80.
15.	Chatterjee A, Pakrashi SC. The Treatise on Indian Medicinal Plants. V-IV. New Delhi: National Institute of Science Communication and Information Resources; 2003. p. 128-9.
16.	Dymock W, Warden CJ, Hooper D. Pharmacographica Indica. V-II. New Delhi: Srishti Book Distributors; 2005. p. 429-36.
17.	Bhat HR. A Field Guide to the Medicinal Plants of Devarayanadurga State Forest. Tumkur: Karnataka forest Department; 2000. p. 37.
18.	Parihar G, Balekar N. Calotropis procera: A phytochemical and pharmacological review. TJPS 2016;40:115-31.
19.	Ahmed KK, Rana AC, Dixit VK. Calotropis species (Ascelpediaceae): A comprehensive review. Pharmacogn Mag 2005;1:48-52.
20.	Anonymous. Himalaya Herbal Health Care. 2007. Available from: http://www.himalayahealthcare.com/herbfinder/h_ calotropis.htm. [Last accessed on 2022 Aug 21].
21.	Verma R, Satsangi GP, Shrivastava JN. Ethno-medicinal profile of different plant parts of Calotropis procera (Ait.) R.Br. Ethnobotanical Lealf 2010;14:721-42.
22.	Jyoti DN, Kishore M, Rao YH. A medicinal importance and chemical composition of caralluma umbellata haw. Int J Adv Res Chem Sci 2015;2:33-7.
23.	Nadkarni KM. Gymnema sylvestre. In: Indian Materia Medica with Ayurvedic Unani. Vol. I. Bombay, India: Popular Prakashan; 1986. p. 596-9.
24.	Nadkarni KM, editor. “Indian Materia Medica”. In: Dr. KM Nadkarni's Indian Materia Medica: With Ayurvedic, Unani-Tibbi, Siddha, Allopathic, Homeopathic, Naturopathic & Home Remedies, Appendices and Indexes. Vol. 1. Panvel: Popular Prakashan; 1996.
25.	Anis M, Sharma MP, Iqbal M. Herbal ethnomedicine of the Gwalior forest division in Madhya Pradesh, India. Pharm Biol 2000;38:241-53.
26.	Singh VK, Umar S, Ansar SA, Iqbal M. Gymnema sylvestre for diabetics. J Herbs J Herbs Spices Med Plants 2008;14:88-106.
27.	Kirtikar KR, Basu BD. Indian Medicinal Plants. New Delhi, India: Lalit Mohan Basu, Allahabad. Jayyd Press; 1987. p. 146.
28.	Marakis G, Ziegenhage R, Lampen A, Hirsch-Ernst KI. Risk assessment of substances used in food supplements: The example of the botanical Gymnema sylvestre. EFSA J 2018;16:e16083.
29.	Mathew M. Aromatic and medicinal plants research station, Odakkali-A centre for promoting medicinal and aromatic plants. Indian Coconut J Cochin 2004;34:10-5.
30.	Chopra RN, Nayar SL, Chopra IC. Glossary of Indian Medicinal Plants. New Delhi, India: National Institute of Science Communication and Information Resources; 2002.
31.	Potawale SE, Shinde VM, Libi A, Boradem S, Dhalawatm H, Deshmukh RS. Gymnema sylvestre: A comprehensive review. Pharmacol Online 2008;2:144-57.
32.	Qasim M, Abideen Z, Adnan YM, Ansari R, Gull B, Khan MA. Traditional ethno-botanical uses of medicinal plants from coastal areas of Pakistan. J Coast Life Med 2014;2:22-30.
33.	Idrees S, Qureshi R, Bibi Y, Ishfaq A, Khalid N, Iftikhar A, et al. Ethnobotanical and biological activities of Leptadenia pyrotechnica (Forssk.) Decne.: A review. Afr J Tradit Complement Altern Med 2016;13:88-96.
34.	Ahmed H, Wariss T, Alam K, Anjum S, Mukhtar M. Ethnobotanical studies of plant resources of Cholistan Desert. Pak Int J Sci Res 2012;3:1782-8.
35.	Diallo D, Hveem B, Mahmoud MA, Berge G, Paulsen BS, Maiga S. An Ethnobotanical study of herbal drugs of Gourma District, Mali. Pharm Biol 1999;37:80-91.
36.	Ali MS, Kausar F, Malik A. Pyrotechnoic acid: A glycol-oleanolic acid conjugate from Leptadenia pyrotechnica (Asclepiadaceae). J Chem Soc Pak 2001;3:180-2.
37.	Yoganarasimhan SN. Medicinal Plants of India. Vol. 1. Bangalore: Interline Publishing Pvt. Ltd.; 2000.
38.	Dokosi OB. Herbs of Ghana. Accra: Ghana Universities Press; 1998.
39.	Karthishwaran K, Mirunalini S. Therapeutic potential of Pergularia daemia (Forsk.): The Ayurvedic wonder. Int J Pharmacol 2010;6:836-43.
40.	Kirtikar KR, Basu BD. Indian Medicinal Plants. 2^nd ed. New Delhi: Periodic Expert Book Agency; 1991. p. 1.
41.	Chopra IC, Chopra RN, Nayar SL. Glossary of Indian Medicinal Plants. New Delhi: CSIR; 1986. p. 5.
42.	Gurav S, Prakash D, Senthilkumar GP, Tembare R, Mani T. Tylophora indica: A review on its ethnobotany, phytochemical and pharmacological profile. Asian J Biochem Pharm Res 2011;3:205-414.
43.	Jain SK. Ethnobotany in modern India. Phytomorphol Gold Jubilee Issue Trends Plant Sci 2001;78:39-54.
44.	Mushir A, Jahan N, Ahmed A. A review on phytochemical and biological properties of Calotropis gigantea (Linn) R.Br. Discov Phytomed 2016;3:15-21.
45.	Chopra RN. Glossary of Indian Medicinal Plant. New Delhi: National Institute Science communication and information Resources (CSIR); 2002. p. 46.
46.	Daniel M. Medicinal Plants: Chemistry and Properties. New Delhi: Oxford & IBH Publishing; 2006. p. 131.
47.	Bulani V, Biyani K, Kale R, Joshi U, Charhate K, Kumar D, et al. Inhibitory effect of Calotropis gigantea extract on Ovalbumin-induced airway inflammation and arachidonic acid induced inflammation in a murine model of asthma. Int J Curr Bio Med Sci 2011;1:19-25.
48.	Parihar G, Balekar N. Immunomodulating potential of Calotropis procera (Ait.) root Bark ethanolic extract on experimental animal. J Adv Pharm Educ Res 2014;4:268-76.
49.	Aliyu RM, Abubakar MB, Kasarawa AB, Dabai YU, Lawal N, Bello MB, et al. Efficacy and phytochemical analysis of latex of Calotropis procera against selected dermatophytes. J Intercult Ethnopharmacol 2015;4:314-7.
50.	Quazi S, Mathur K, Arora S. Calotropis procera: An overview of its phytochemistry and pharmacology. Indian J Drugs 2013;1:63-9.
51.	Wang ZN, Wang MY, Mei WL, Han Z, Dai HF. A new cytotoxic pregnanone from Calotropis gigantea. Molecules 2008;13:3033-9.
52.	Jeyakumar JJ, Kamaraj M, Nandagopalan V, Anburaja V, Thiruvengadam M. A study of phytochemical constituents in Caralluma Umbellata by Gc-Ms anaylsis. Int J Pharm Sci Invent 2013;2:37-41.
53.	Mukherjee PK. Quality Control of Herbal Drugs, An Approaches to Evalution of Botanicals. 1^st ed. New Delhi: Business Horizones; 2002. p. 390-403.
54.	Tiwari P, Mishra BN, Sangwan NS. Phytochemical and pharmacological properties of Gymnema sylvestre: An important medicinal plant. Biomed Res Int 2014;2014:830285.
55.	Kanetkar PV, Singhal RS, Laddha KS, Kamat MY. Extraction and quantification of gymnemic acids through gymnemagenin from callus cultures of Gymnema sylvestre. Phytochem Anal 2006;17:409-13.
56.	Veerashree V, Anuradha CM, Kumar V. Elicitor-enhanced production of gymnemic acid in cell suspension cultures of Gymnema sylvestre R.Br. Plant Cell Tiss Organ Cult 2012;108:27-35.
57.	Yendo AC, de Costa F, Gosmann G, Fett-Neto AG. Production of plant bioactive triterpenoid saponins: Elicitation strategies and target genes to improve yields. Mol Biotechnol 2010;46:94-104.
58.	Nagarajan S, Rao LJ. Preparation of antioxidant preservative from the roots of Indian sarsaparilla (Hemidesmus indicus). Indian Pat Appl 2006;2004:595-602.
59.	Prakash K, Sethi A, Deepak D, Khare A, Khare MP. Two pregnane glycosides from Hemidesmus indicus. Phytochem 1991;30:297-9.
60.	Roy SK, Ali M, Sharma MP, Ramachandram R. Phytochemical investigation of Hemidesmus indicus R. Br. Roots. Indian J Chem 2002;41:2390-4.
61.	Darekar RS, Khetre AB, Sinha PK, Jeswani RM, Damle MC. Quantitation of lupeol octacosanoate in Hemidesmus indicus R. Br. Root powder by HPTLC. Rasayan J Chem 2008;1:526-31.
62.	Moustafa AM, Ahmed I, Mahmoud AS. Isolation, structural elucidation of flavonoid constituents from Leptadenia pyrotechnica and evaluation of their toxicity and antitumor activity. Pharm Biol 2009;46:539-52.
63.	Moustafa AM, Ahmed I, Mahmoud AS. GC-MS investigation and toxicological evaluation of alkaloids from Leptadenia pyrotechnica. Pharm Biol 2009;47:994-1003.
64.	Ananth DA, Rameshkumar A, Jeyadevi R, Aseervatham GS, Sripriya J, Bose PC, et al. Amelioratory effect of flavonoids rich Pergularia daemia extract against CFA induced arthritic rats. Biomed Pharmacother 2016;80:244-52.
65.	Subramanya SB, Venkataraman B, Meeran MF, Goyal SN, Patil CR, Ojha S. Therapeutic potential of plants and plant derived phytochemicals against acetaminophen-induced liver injury. Int J Mol Sci 2018;19:3776.
66.	Gurav S, Senthilkumar DG, Tembare R, Mani T. Tylophora indica: A review on its ethnobotany, phytochemical and pharmacological profile. Asian J Biochem Pharmaceut Res 2011;3:405-14.
67.	Habib MR, Karim MR. Effect of anhydrosophoradiol-3-acetate of Calotropis gigantea (Linn.) flower as antitumoric agent against Ehrlich's ascites carcinoma in mice. Pharmacol Rep 2013;65:761-7.
68.	Nalwaya N, Pokharna G, Deb L, Jain NK. Wound healing activity of latex of Calotropis gigantea. Int J Pharm Pharmaceut Sci 2009;1:176-81.
69.	Bairagi SM, Ghule P, Gilhotra R. Pharmacology of natural products: An recent on Calotropis gigantea and Calotropis procera. Ars Pharm 2018;59:37-44.
70.	Bulani V, Biyani K, Kale R, Joshi U, Charhate K, Kumar D, et al. Inhibitory effect of Calotropis gigantea extract on Ovalbumin-induced airway inflammation and arachidonic acid induced inflammation in a murine model of asthma. Int J Cur Bio Med Sci 2011;1: 19-25.
71.	Chitme HR, Chandra M, Kaushik S. Studies on anti-diarrhoeal activity of Calotropis gigantea R.Br. In experimental animals. J Pharm Pharm Sci 2004;7:70-5.
72.	Ali R, Amin KM, Ahmad G, Wadud A, Jahan N. Efficacy of post Beekhe Madar (Calotropis gigantea) root bark in experimentally induced diarrhoea. Hippocratic J Unani Med 2010;5:1-8.
73.	Ali R, Jahan N, Amin KM. Anti diarrhoeal activity of Calotropis gigantean root bark in experimental animals. J Res Unani Med 2012;1:1-5.
74.	Pathak AK, Argal A. Analgesic activity of Calotropis gigantea flower. Fitoterapia 2007;78:40-2.
75.	Jagtap VA, Usman MR, Salunkhe PS, Gagrani MB. Antiinflammatory activity of Calotropis gigantea Linn. Leaves extract on in vitro models. IJCPR 2010;1:1-5.
76.	Khan IN, Sarker MMI, Ajrin M. Sedative and anxiolytic effect of ethanolic extract of Calotropis gigantean (Asclepiadaceae) leaves. Asian Pac J Trop Biomed 2014;4:S400-4.
77.	Rathod NR, Chitme HR, Irchhaiya R, Chandra R. Hypoglycemic Effect of Calotropis gigantea Linn. Leaves and flowers in streptozotocin-induced diabetic Rats. Oman Med J 2011;26:104-8.
78.	Usmani S, Kushwaha P. Hepatoprotective activity of extracts of leaves of Calotropis gigantea. Asian J Pharmaceut Clin Res 2010;3:195-6.
79.	Prabhu S, Priyadharshini P, Veerave R. Effect of aqueous extracts of different plant parts of milkweed plant (Calotropis gigantea R. Br.) against ovicidal activity on Helicoverpa armigera (Hubner). Int J Adv Life Sci 2012;2:39-44.
80.	Pathan AK, Pathan MK, Garud N, Garud A. Effect of some novel medicinal plants and polyherbal formulation on stress induced alopecia. Pharmacol online 2012;3:150-7.
81.	Bharathi R, Thomas A, Thomas A, Krishnan S, Ravi TK. Anti bacterial activity of leaf extracts of Calotropis gigantea Linn. Against certain gram negative and gram positive bacteria. Int J Chem Sci 2011;9:919-23.
82.	Hossain SF, Islam MS, Parvin S, Shams T, Kadir MF, Islam SM, et al. Antimicrobial screening and brine shrimp lethality bioassay of Calotropis gigantea (Fam: Asclepiadaceae). J Nat Prod Plant Resour 2012;2:49-59.
83.	Kumar G, Karthik L, Rao KVB. Antimicrobial activity of latex of Calotropis gigantea against pathogenic microorganisms – An in vitro study. Pharmacol online 2010;3:155-63.
84.	Ravi RG, Harikesh D, Chandrasekhar TR, Pramod YG, Angad PM. Cytotoxic activity of ethanolic root extract of Calotropis gigantea Linn. Int J Drug Dev Res 2011;3:101-8.
85.	Chacko N, Ibrahim M, Shetty P, Shastry CS. Evaluation of antivenom activity of Calotropis gigantea plant extract against Vipera russelli snake venom. IJPSR 2012;3:2272-9.
86.	Sanyal S, Maity P, Pradhan A, Bepari M, Dey SK, Roy T. Sub-acute toxicity study of Calotropis gigantealatex extracts in male swiss albino mice. Toxicol Forensic Med Open J 2016;1:54-64.
87.	Meena AK, Yadav AK, Niranjan US, Singh B, Nagariya AK, Sharma K, et al. A review on Calotropis procera Linn and its ethnobotany, phytochemical, pharmacological profile. Drug Invent Today 2010;2:185-90.
88.	Ramos MV, Aguiar VC, Melo VM, Mesquita RO, Silvestre PP, Oliveira JS, et al. Immunological and allergenic responses induced by latex fractions of Calotropis procera (Ait.) R.Br. J Ethnopharmacol 2007;111:115-22.
89.	Gupta S, Gupta B, Kapoor K, Sharma P. Ethnopharmocological potential of Calotropis procera: An overview. Int Res J Pharm 2012;3:19-22.
90.	Nascimento DC, Ralph MT, Batista JE, Silva DM, Gomes-Filho MA, Alencar NM, et al. Latex protein extracts from Calotropis procera with immunomodulatory properties protect against experimental infections with listeria monocytogenes. Phytomedicine 2016;23:745-53.
91.	Tsala DE, Nga N, Thiery BN, Bienvenue MT, Theophile D. Evaluation of the antioxidant activity and the healing action of the ethanol extract of Calotropis procera bark against surgical wounds. J Intercult Ethnopharmacol 2015;4:64-9.
92.	Kamath JV, Rana AC. Preliminary study on antifertility activity of Calotropis procera roots in female rats. Fitoterapia 2002;73:111-5.
93.	Alam P, Ali M. Phytochemical investigation of Calotropis procera Ait roots. Indian J Chem 2009;48:443-6.
94.	Cavalcante GS, de Morais SM, Andre WP, Ribeiro WL, Rodrigues AL, De Lira FC, et al. Chemical composition and in vitro activity of Calotropis procera (Ait.) latex on Haemonchus contortus. Vet Parasitol 2016;226:22-5.
95.	Sayed AD, Mohamed NH, Ismail MA, Abdel-Mageed WM, Shoreit AA. Antioxidant and antiapoptotic activities of Calotropis procera latex on catfish (Clarias gariepinus) exposed to toxic 4-nonylphenol. Ecotoxicol Environ Saf 2016;128:189-94.
96.	Oloumi H. Phytochemistry and ethno-pharmaceutics of Calotropis procera. Ethno Pharm Prod 2014;1:1-8.
97.	Vaiyapuri PS, Ali AA, Mohammad AA, Kandhavelu J, Kandhavelu M. Time lapse microscopy observation of cellular structural changes and image analysis of drug treated cancer cells to characterize the cellular heterogeneity. Environ Toxicol 2015;30:724-34.
98.	Gurung AB, Ali MA, Bhattacharjee A, AbulFarah M, Al-Hemaid F, Abou-Tarboush FM, et al. Molecular docking of the anticancer bioactive compound proceraside with macromolecules involved in the cell cycle and DNA replication. Genet Mol Res 2016;15:1-8. [Doi: 10.4238/gmr. 15027829].
99.	Bharathi KL, Rao TM, Rao BG. Nephroprotective and antioxidant activities of Caralluma umbellata Roxb. Ann Phytomed 2016;5:116-21.
100.	Babu KS, Malladi S, Nadh RV, Rambabu SS. Evaluation of in vitro antibacterial activity of Caralluma umbellata Haw used in traditional medicine by Indian tribes. Ann Res Rev Biol 2014;4:840-55.
101.	Kumar GV, Sandhya CH. Nephroprotective activity of stem extract of Caralluma umbellata Haw against cisplatin and gentamicin induced nephrotoxicity. World J Pharm Res 2014;3:1301-3.
102.	Kalyani K, Anuradha V. In vitro evaluation of antioxidant activity of root and stem extracts of Caralluma umbellata Haw (Asclepiadaceae). Int J Nat Prod Res 2013;3:115-9.
103.	Shanmugam G, Ayyavu M, Rao DM, Devarajan T, Subramaniam G. Hepatoprotective effect of Caralluma umbellate against acetaminophen induced oxidative stress and liver damage in rat. J Pharm Res 2013;6:342-5.
104.	Ray S, Nagaiah K, Khan NF. Anti-inflammatory activity of carumbelloside-III, isolated from Caralluma umbellata. NSHM J Pham Health Manage 2011;2:83-8.
105.	Ray S, Nagaiah K. Antinociceptive and anti-inflammatory activity of carumbelloside-II isolated from Caralluma umbellata. J Pharm Biomed Sci 2011;2:3.
106.	Kosta S, Tiwari A. Screening and assessment of anti-diabetic and reactive oxygen scavenging (ros), effects of herbs in streptozotacin induced mice. Pharmacol Online 2009;3:695-704.
107.	Luo H, Kashiwagi A, Shibahara T, Yamada K. Decreased bodyweight without rebound and regulated lipoprotein metabolism by gymnemate in genetic multifactor syndrome animal. Mol Cell Biochem 2007;299:93-8.
108.	Shafey AA, El-Ezabi MM, Seliem MM, Ouda HH, Ibrahim DS. Effect of Gymnema sylvestre R. Br. Leaves extract on certain physiological parameters of diabetic rats. J King Saud Univ Sci 2013;25:135-41.
109.	Shah MA, Sarker MM, Gousuddin M. Antidiabetic potential of Brassica oleracea Var. Italica in type 2 diabetic sprague dawley (sd) rats. Int J Pharmacogn Phytochem Res 2016;8:462-9.
110.	Ahmed SK, Cheekavolu C, Alasyam N, Sunil M. Evaluation of hypoglycemic property of gurmar (Gymnema sylvestre) leaves methanolic extract (GSLME) in streptozocin (STZ) induced diabetic albino rats. J Med Sci Clin Res 2017;5:31753-60.
111.	Aralelimath VR, Bhise SB. Anti-diabetic effects of Gymnema sylvestre extract on streptozotocin induced diabetic rats and possible b-cell protective and regenerative evaluations. Dig J Nanomater Bios 2012;7:135-42.
112.	Kumar P, Rani S, Arunjyothi B, Chakrapani P, Rojarani A. Evaluation of antidiabetic activity of Gymnema sylvestre and Andrographis paniculata in streptozotocin induced diabetic Rats. Int J Pharmacogn Phytochem Res 2017;9:22-5.
113.	Sugihara Y, Nojima H, Matsuda H, Murakami T, Yoshikawa M, Kimura I. Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema sylvestre leaves in streptozotocin-diabetic mice. J Asian Nat Prod Res 2000;2:321-7.
114.	Khanna G. Non-proliferative activity of saponins isolated from the leaves of Gymnema sylvestre and Eclipta prostrata on HepG2 cells-in vitro study. Int J Pharm Sci Res 2010;1:38-42.
115.	Srikanth AV, Sayeeda M, Lakshmi N, Ravi M, Kumar P, Madhava RB. Anticancer activity of Gymnema sylvestre R.Br. Int J Pharm Sci Nanotechnol 2010;3:897-9.
116.	Imai Y, Tsukahara S, Asada S, Sugimoto Y. Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. Cancer Res 2004;64:4346-52.
117.	Mao Q. Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS J 2005;7:118-33.
118.	Rupanar SV, Pingale SS, Dandge CN, Kshirsagar D. Phytochemical screening and in vitro evaluation of antioxidant antimicrobial activity of Gymnema sylvestre. Int J Curr Res 2012;8:43480-6.
119.	Rahman MM, Habib MR, Hasan MA, Al Amin M, Saha A, Mannan A. Comparative assessment on in vitro antioxidant activities of ethanol extracts of Averrhoa bilimbi, Gymnema sylvestre and Capsicum frutescens. Pharmacognosy Res 2014;6:36-41.
120.	Ohmori R, Iwamoto T, Tago M, Takeo T, Unno T, Itakura H, et al. Antioxidant activity of various teas against free radicals and LDL oxidation. Lipids 2005;40:849-53.
121.	Gunasekaran V, Srinivasan S, Rani SS. Potential antioxidant and antimicrobial activity of Gymnema sylvestre related to diabetes. J Med Plants 2019;7:5-11.
122.	Rachh PR, Patel SR, Hirpara HV, Rupareliya MT, Rachh MR, Bhargava AS. In-vitro evaluation of antioxidant activity of Gymnema sylvestre R.Br. leaf extract. Rom J Biol Plant Biol 2009;54:141-8.
123.	Arun LB, Arunachalam AM, Arunachalam KD, Annamalai SK, Kumar KA. In vivo anti-ulcer, anti-stress, anti-allergic, and functional properties of gymnemic acid isolated from Gymnema sylvestre R Br. BMC Complement Altern Med 2014;14:70.
124.	Kishore L, Singh R. Protective effect of Gymnema sylvestre L. against advanced glycation end-product, sorbitol accumulation and aldose reductase activity in homoeopathic formulation. Indian J Res Homoeopathy 2015;9:240-8. [Full text]
125.	Chakrapani LN, Periandavan K. Protective role of gymnemic acid in curbing high fat diet and high fructose induced pancreatic oxidative stress mediated type-2 diabetes in wistar rats. Int J Pharm Sci Res 2018;9:2130-9.
126.	Kumar AR, Rathinam KS, Kumar CA. Evaluation of anti-inflammatory activity of some selected species of Asclepiadaceae Family. Int J Chem Sci 2012;10:548-56.
127.	Diwan PV, Margaret I, Ramakrishna S. Influence of Gymnema sylvestre on inflammation. Inflammopharmacol 1995;3:271-7.
128.	Malik JK, Manvi FV, Nanjware BR, Dwivedi DK, Purohit P, Chouhan S. Anti-arthritic activity of leaves of Gymnema sylvestre R.Br. leaves in rats. Pharm Lett 2010;2:336-41.
129.	Yasukawa K, Okuda S, Nobushi Y. Inhibitory effects of Gymnema (Gymnema sylvestre) leaves on tumour promotion in two-stage mouse skin carcinogenesis. Evid Based Complement Alternat Med 2014;2014:328684.
130.	Srividya AR, Varma S, Dhanapal SP, Vadivelan R, Vijayan P. In vitro and in vivo evaluation of hepatoprotective activity of Gymnema sylvestre. Int J Pharm Sci Nanotechnol 2010;2:768-73.
131.	Dholi SK, Raparla RK. In vivo anti-diabetic evaluation of gymnemic acid in streptozotocin induced rats. J Pharm Innov 2014;3:82-6.
132.	Yogi B, Mishra A. Hepatoprotective effects of polyherbal formulation against carbon tetrachloride-induced hepatic injury in albino rats: A toxicity screening approach. Asian J Pharm Clin Res 2016;10:192-8.
133.	Singh DK, Kumar N, Sachan A, Lakhani P, Tutu S, Nath R, et al. Hypolipidaemic effects of Gymnema sylvestre on high fat diet induced dyslipidaemia in wistar rats. J Clin Diagn Res 2017;11:F01-5.
134.	Rachh P, Rachh M, Ghadiya N, Modi D, Modi K, Patel N. Antihyperlipidemic activity of Gymnema sylvestre R. Br. Leaf extract on rats fed with high cholesterol diet. Int J Pharmacol 2010;6:138-41.
135.	Pasha C, Sayeed S, Ali MS, Khan MZ. Antisalmonella activity of selected medicinal plants. Turk J Biol 2009;33:59-64.
136.	Paul J, Jayapriya KP. Screening of antibacterial effects of Gymnema sylvestre (L.) R.Br. – A medicinal plant. Pharmacol Online 2009;3:832-6.
137.	Karthikeyan M, Ahamed AJ, Karthikeyan C, Kumar PV. Enhancement of antibacterial and anticancer properties of pure and REM doped ZnO nanoparticles synthesized using Gymnema sylvestre leaves extract. SN Appl Sci 2019;1:355.
138.	Ramalingam R, Dhand C, Leung CM, Ong ST, Annamalai SK, Kamruddin M. Antimicrobial properties and biocompatibility of electrospun poly-ε-caprolactone fibrous mats containing Gymnema sylvestre leaf extract. Mat Sci Engl 2019;98:503-14.
139.	Swami J, Prabakaran T. Studies on antibacterial activity of Gymnema sylvestre against respiratory infection causing bacteria. Int J Curr Adv Res 2012;1:1-4.
140.	Tahir M, Rasheed MA, Niaz Q, Ashraf M, Anjum AA, Ahmed MU. Evaluation of antibacterial effect of Gymnema sylvestre R.Br. Species cultivated in Pakistan. Pak Vet J 2017;37:245-50.
141.	Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha Shanmugasundaram K, Kizar Ahmath B. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol 1990;30:281-94.
142.	Li Y, Zheng M, Zhai X, Huang Y, Khalid A, Malik A, et al. Effect of-Gymnema sylvestre, citrullus colocynthis and artemisia absinthium on blood glucose and lipid profile in diabetic human. Acta Pol Pharm 2015;72:981-5.
143.	Chattopadhyay RA. Comparative evaluation of some blood sugar lowering agents of plant origin. J Ethnopharmacol 1999;67:367-72.
144.	Shiyovich A, Sztarkier I, Nesher L. Toxic hepatitis induced by Gymnema sylvestre, a natural remedy for type 2 diabetes mellitus. Am J Med Sci 2010;340:514-7.
145.	Ogawa Y, Sekita K, Umemura T, Saito M, Ono A, Kawasaki Y, et al. Gymnema sylvestre leaf extract: A 52-week dietary toxicity study in wistar rats. Shokuhin Eiseigaku Zasshi 2004;45:8-18.
146.	Turrini E, Calcabrini C, Tacchini M, Efferth T, Sacchetti G, Guerrini A, et al. In vitro study of the cytotoxic, cytostatic, and antigenotoxic profile of Hemidesmus indicus (L.) R.Br. (Apocynaceae) crude drug extract on T lymphoblastic cells. Toxins (Basel) 2018;10:70.
147.	Mehta A, Sethiya NK, Mehta C, Shah GB. Anti-arthritis activity of roots of Hemidesmus indicus R.Br. (Anantmul) in rats. Asian Pac J Trop Med 2012;5:130-5.
148.	Swathi S, Amareshwari P, Venkatesh K, Roja Rani A. Phytochemical and pharmacological benefits of Hemidesmus indicus: An updated review. J Pharmacog Phytochem 2019;8:256-62.
149.	Iddamaldeniya SS, Wickramasinghe N, Thabrew I, Ratnatunge N, Thammitiyagodage MG. Protection against diethylnitrosoamine-induced hepatocarcinogenesis by an indigenous medicine comprised of Nigella sativa, Hemidesmus indicus and Smilax glabra: A preliminary study. J Carcinog 2003;2:6. [PUBMED] [Full text]
150.	Ferruzzi L, Turrini E, Burattini S, Falcieri E, Poli F, Mandrone M, et al. Hemidesmus indicus induces apoptosis as well as differentiation in a human promyelocytic leukemic cell line. J Ethnopharmacol 2013;147:84-91.
151.	Gayathri M, Krishnan K. Antidiabetic activity of 2-hydroxy 4-methoxy benzoic acid isolated from the roots of Hemidesmus indicus on streptozotocin-induced diabetic rats. Int J Diabet Metabol 2009;17:53-7.
152.	Nair SA, Sabulal B, Radhika J, Arunkumar R, Subramoniam A. Promising anti-diabetes mellitus activity in rats of β-amyrin palmitate isolated from Hemidesmus indicus roots. Eur J Pharmacol 2014;734:77-82.
153.	Tirumani P, Venu S, Sridhar G, Praveen Kumar M, Rajashekhar AV, Naga Raju T. Delaying of cataract through intervention of Hemidesmus indicus in STZ induced diabetic rats. Nat Prod Res 2018;32:1295-8.
154.	Chatterjee I, Chakravarty AK, Gomes A. Daboia russelii and Naja kaouthia venom neutralization by lupeol acetate isolated from the root extract of Indian sarsaparilla Hemidesmus indicus R.Br. J Ethnopharmacol 2006;106:38-43.
155.	Esposito F, Mandrone M, Del Vecchio C, Carli I, Distinto S, Corona A, et al. Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action. Pathog Dis 2017;75:1-5. [doi: 10.1093/femspd/ft×065].
156.	Bicchi C, Rubiolo P, Ballero M, Sanna C, Matteodo M, Esposito F, et al. HIV-1-inhibiting activity of the essential oil of Ridolfia segetum and Oenanthe crocata. Planta Med 2009;75:1331-5.
157.	Penumala M, Zinka RB, Shaik JB, Mallepalli SK, Vadde R, Amooru DG. Phytochemical profiling and in vitro screening for anticholinesterase, antioxidant, antiglucosidase and neuroprotective effect of three traditional medicinal plants for Alzheimer's disease and diabetes mellitus dual therapy. BMC Complement Altern Med 2018;18:77.
158.	Saritha K, Rajesh A, Manjulatha K, Setty OH, Yenugu S. Mechanism of antibacterial action of the alcoholic extracts of Hemidesmus indicus (L.) R. Br. ex Schult, Leucas aspera (Wild.), Plumbago zeylanica L., and Tridax procumbens (L.) R. Br. ex Schult. Front Microbiol 2015;6:577.
159.	Khandelwal VK, Balaraman R, Pancza D, Ravingerová T. Hemidesmus indicus and Hibiscus rosa-sinensis affect ischemia reperfusion injury in isolated rat hearts. Evid Based Complement Alternat Med 2011;2011:802937.
160.	Rekha K, Kumar K, Singh M. Antifungal potential of Leptadenia pyrotechnica against some pathogenic fungi. Int J Eng Sci Invent 2013;2:27-9.
161.	Fabry W, Okemo PO, Ansorg R. Antibacterial activity of East African medicinal plants. J Ethnopharmacol 1998;60:79-84.
162.	Ahmad I, Mehmood Z, Mohammad P, Ahmed S. Antimicrobial potency and synergistic activity of five traditionally used Indian medicinal plants. J Med Aromat Plant Sci 2000;22:173-6.
163.	de Boer HJ, Kool A, Broberg A, Mziray WR, Hedberg I, Levenfors JJ. Anti-fungal and anti-bacterial activity of some herbal remedies from Tanzania. J Ethnopharmacol 2005;96:461-9.
164.	Al-Fatimi M, Wurster M, Schröder G, Lindequist U. Antioxidant, antimicrobial and cytotoxic activities of selected medicinal plants from Yemen. J Ethnopharmacol 2007;111:657-66.
165.	Munazir M, Qureshi R, Munir M. In vitro antioxidant activity of methanolic extracts of various parts of Leptadenia pyrotechnica (Forssk.) Decne. Pak J Pharm Sci 2015;28:535-9.
166.	Khasawneh MA, Elwy HM, Hamza AA, Fawzi NM, Hassan AH. Antioxidant, Anti-Lipoxygenase and cytotoxic activity of Leptadenia pyrotechnica (Forsk.) decne polyphenolic constituents. Molecules 2011;16:7510-21.
167.	Saleh I, Aehs G, Amani SA, Abd ER, Mohammed D. Anti-inflammatory activity, safety and protective effects of Leptadenia pyrotechnica, haloxylon salicornicum and Ochradenus baccatus in ulcerative colitis. Phytopharmacol 2012;2:58-71.
168.	Shaw NR, Singh GK. Wound healing activity of ethanolic extract of aerial and root part of Leptadenia pyrotechnica (Fork.) Decne. Int J Pharm Biol Sci 2014;5:671-5.
169.	Kumar S, Chaudhary S, Jha KK. Anthelminthic activity on the Leptadenia pyrotechnica (forsk.) Decne. J Nat Prod Plant Resour 2011;1:56-9.
170.	Tewari U, Partap S, Sharma K, Kishore K. Hepatoprotective activity of whole plant extract of Leptadenia pyrotechnica against paracetamol induced damage in rats. J Drug Deliv Ther 2014;4:36-9.
171.	Sudipta KM, Swamy KM, Balasubramanya S, Anuradha M. Cost effective approach for in vitro propagation of (Leptadenia reticulata Wight & Arn.) – A threatened plant of medicinal importance. J Phytol 2011;3:72-9.
172.	Verma N, Jha KK, Chaudhary S, Singh O, Kumar A. Phytochemistry, pharmacology and traditional uses of Leptadenia pyrotechnica. An important medicinal plant. Indian J Pharm Bio Res 2014;2:128-34.
173.	Watafua M, Geidam MA. Effects of the ethanolic extract of aerials of Leptaden pyrotechnica (forsk.) Decne on the liver function of Wistar strain Albino Rats. Int J Sci Res Manage 2014;2:605-10.
174.	Cook NC, Samman S. Flavonoids-chemistry, metabolism, cardioprotective effects, and dietary sources. J Nutr Biochem 1996;7:66-76.
175.	Dosumu OO, Ajetumobi OO, Omole OA, Onocha PA. Phytochemical composition and antioxidant and antimicrobial activities of Pergularia daemia. J Med Plant Econ Dev 2019;3:1-8.
176.	Karthishwaran K, Mirunalini S. Assessment of the antioxidant potential of Pergularia daemia (Forsk.) extract in vitro and in vivo experiments on hamster buccal pouch carcinogenesis. Asian Pac J Trop Dis 2012;2:S509-16.
177.	Sarkodie J, Squire S, Kretchy I, Domozoro C, Ahiagbe K, Twumasi M. The antihyperglycemic, antioxidant and antimicrobial activities of Ehretia cymosa. J Pharmacogn Phytochem 2015;4:105-11.
178.	Mishra G, Chandra HK, Sahu N, Nirala SK, Bhadauria M. Ameliorative effect of Pergularia daemia (Forssk.) Chiov. Leaves extract against anti-tuberculosis drugs induced liver injury in rats. Asian Pac J Trop Med 2018;11:518-25.
179.	Bhavin V, Ruchi V, Dd S. Diuretic potential of whole plant extracts of Pergularia daemia (Forsk.). Iran J Pharm Res 2011;10:795-8.
180.	Anjaneyulu A, Raju D, Rao S. Chemical examination of Pergularia extensa. Indian J Chem B 1998;37:318-20.
181.	Sadik MG, Gafur M, Bhuiyan MS, Rahman MM, Biswas HU. Antifertility activity of the alkaloidal fraction of Pergularia daemia. J Med Sci 2001;1:217-9.
182.	Borrelli F, Izzo AA. The plant kingdom as a source of anti-ulcer remedies. Phytother Res 2000;14:581-91.
183.	Ananth DA, Deviram G, Mahalakshmi V, Bharathi VR. Active status on phytochemistry and pharmacology of Pergularia daemia Forsk. (Trellis-vine): A review. Clin Phytosci 2021;7:1-13.
184.	Dhananjayan K, Venugopal V, Majumder P. Evaluation of in-vivo antiulcer activity of extracts from leaves of Pergularia daemia (Forsk.) against ethanol induced ulcer in albino rats. Ind J Res Pharma Biotech 2014;2:1141.
185.	Libby P. Inflammatory mechanisms: The molecular basis of inflammation and disease. Nutr Rev 2007;65:S140-6.
186.	Hina I, Rose JC. In vitro anti-inflammatory and anti arthritic activity of Pergularia daemia leaves and roots. J Int J Drug Dev Res 2018;10:10-3.
187.	Vaithiyanathan V, Mirunalini S. Assessment of anticancer activity: A comparison of dose response effect of ethyl acetate and methanolic extracts of Pergularia daemia (Forsk). Oral Sci Int 2016;13:24-31.
188.	Mirunalini S, Karthishwaran K, Vaithiyanathan V. Antiproliferative potential of Pergularia daemia (Forsk.) on human oral epidermoid carcinoma (KB) cells by inducing apoptosis and modifying oxidant antioxidant status. Asian J Pharm Clin Res 2014;7:89-95.
189.	Gurav S, Devprakash GP, Tembare R, Mani T. Tylophora indica: A review on its ethnobotany, phytochemical and pharmacological profile. Asian J Biochem Pharm Res 2011;3:205-414.
190.	Gujrati V, Patel N, Rao VN, Nandakumar K, Gouda TS, Shalam M, et al. Hepatoprotective activity of alcoholic and aqueous extracts of leaves of Tylophora indica (Linn.) in rats. Indian J Pharmacol 2007;39:43-7. [Full text]
191.	Tiwari R, Latheef SK, Ahmed I, Iqbal HM, Bule MH, Dhama K, et al. Herbal immunomodulators – A remedial panacea for designing and developing effective drugs and medicines: Current scenario and future prospects. Curr Drug Metab 2018;19:264-301.
192.	Meera R, Devi P, Muthumani P, Kameswari B, Eswarapriya B. Evaluation of diuretic activity from Tylophora indica leaves extracts. J Pharma Sci Res 2009;1:112-6.
193.	Rani AS, Patnaik S, Sulakshanaand G, Saidulu B. Review of Tylophora indica – An antiasthmatic plant. FS J Res Basic Appl Sci 2012;1:20-1.