A COMPREHENSIVE REVIEW ON GYNURA PROCUMBENS LEAVES

A COMPREHENSIVE REVIEW ON GYNURA PROCUMBENS LEAVES

Kanzil Mowla Mou ¹ and Pritesh Ranjan Dash ^{* 2}

Department of Pharmacy, BRAC University ¹, Dhaka, Bangladesh.

Department of Pharmacy, Jahangirnagar University ², Savar, Dhaka, Bangladesh.

ABSTRACT: Gynura procumbens (GP) commonly known as longevity spinach is one of those precious medicinal herbs of Asteraceae that are still included in a un-utilized herb in spite of the variety of useful pharmacological properties it possesses. It is mainly popular in South-East Asian countries for its traditional medicinal properties. It is usually used as a traditional medicine for the treatment of inflammation, herpes simplex virus, rashes, fever, rheumatism, kidney diseases, migraines, diabetes mellitus, cancer, and hypertension. This article provides the collective information about the phytochemical constituents isolated from leaves of this plant used in a modern scenario for the treatment of various ailments like kaempferol-3-O-rutinoside, astragalin, rutin, kaempferol, sterol glycosides, flavonoids, saponins, tannins, and terpenoids, etc. Here, we have reviewed all the reported pharmacological properties such as anti-inflammatory, anticancer, anti-diabetic, anti-herpes simplex virus, anti-ulcerogenic, vasorelaxant, toxicity, and some other activities.

Gynura procumbens, Phytoconstituents, Pharmacological properties, Toxicity

INTRODUCTION: Gynura procumbens (GP) belonging to the family Asteraceae) commonly known as longevity spinach that grows extensively in Southeast Asia, particularly in Indonesia, Malaysia, and Thailand. GP grows up to a height of 1-3 m, with a fleshy stem and purple tint. The leaves are ovate-elliptic or lanceolate, 3.5 to 8 cm long and 0.8 to 3.5 cm wide. Flowering heads are panicled, narrow, yellow and 1 to 1.5 cm long 1. It is traditionally used for the treatment of eruptive fever, rash, kidney disease, constipation, hypertension, diabetes mellitus, migraines, urinary tract infection, rheumatism, viral diseases of skin ².

Some of these traditional claims have been validated in scientific and pharmacological studies, including anti-herpes virus ³, anti-inflammatory ^{4, 5} and anti-hyperlipidemic and anti-hyperglycemic ^6-11, anti-hypertensive activities ^12-16. Recently received particular attention of GP is in the pharmacology of anti-diabetic medicinal plants probably because of its empirical evidence and efficiency in the management of diabetes mellitus. However, these scientific reports of G. procumbens have been conflicting and inconsistent ¹⁷.

The leaves of this plant are often consumed in the diet, and research shows that leaves contents are non-toxic ¹⁸. Besides, recently conducted researches are evident that GP oils play roles in dentistry, dermatology, gynecology, and pediatrics as a means of hygienic care. The GP leaves yields diversified phytoconstituents including different macroelements and microelements, alkaloids, saponins, chlorophyll, carotenoids, essential oils, etc. The following is a comprehensive and up-to-date review about the history, distribution, phytochemistry, toxicity and pharmacological properties of GP with an urge of further advancements in the medicinal uses of the herb worldwide.

History: The plant was discovered many centuries ago on the African continent. The genus Gynura (Asteraceae-Senecioneae) comprises 44 species and is distributed from tropical Africa to South and East Asia and Australasia with one species in tropical Australia. The highest species diversity is found in Southeast Asia, but the genus is least well understood particular in Thailand. It has been used both for food and as a remedy for illnesses. During the last 15 years, the plant has attracted the attention of the international scientific community as the source of many powerful biologically active substances ¹⁹.

Distribution: Gynura procumbens (GP), a fast-growing herbaceous plant, is widely found in Borneo, Java, the Philippines, and Peninsular Malaysia ²⁰. It is a native plant from China and known as ‘baibingca’²¹. It is also found in Myanmar and some Asian countries such as Indonesia and Thailand ²². This plant grows easily from stem cuttings. Seeds are not available. It is best grown in well-draining, fertile soil that is kept moist at all times. This plant prefers Semi-shade although it can be slowly adapted to grow in full sun, provided the plant does not dry out at the roots. Initial planting under direct sunshine will result in burnt leaves and stunting in growth. Growth should resume once the plant has acclimatized to its new growing conditions.

FIG. 1: (A) PLANT, (V) LEAVES AND (C) JUICE OF GYNURA PROCUMBENS

Taxonomical Classification:

Binomial Name: Gynura procumbens (Lour.) Merr. 1923.

Scientific Classification:

Kingdom: Plantae

(unranked):    Angiosperms

(unranked): Eudicots

(unranked): Asterids

Order:    Asterales

Family: Asteraceae

Tribe:  Senecioneae

Genus: Gynura

Species: G. procumbens

Synonyms: Cacalia cylindriflora Wall., Cacalia finlaysoniana Wall, Cacalia procumbens Lour, Cacalia reclinata Roxb., Cacalia sarmentosa Lesch. Ex. Blume, Crassocephalum baoulense (Hutch. and Dalziel) Milne-Redh, Crassocephalum latifolium S. Moore, Gynura affinis Turcz, Gynuraa gusanensis Elmer, Gynura baoulensis Hutch.and Dalziel, Gynura buntingii S. Moore, Gynura cavaleriei Lev., Gynura clementis Merr, Gynura finlaysoniana DC., Gynura latifolia (S.Moore) Elmer, Gynura lobbiana Turcz, Gynura piperi Merr, Gynura pubigera Bold, Gynura sarmentosa (Blume) DC, Gynura scabra Turcz., Senecio baoulensis A. Chev, Senecio mindoroensis Elmer ²³.

Vernacular Names:

Thailand: Paetumpung,

Malaysia: Mollucan spinach, Sambung Nyawa,

Indonesia: Daun Dewa, Sambung Nyawa,

Chinese: Akar Sebiak, Kelemai Mearh, Nan fei Ye, Bai Bing Ca,

United States: Longevity spinach

Phytoconstituents: Considerable work has already been done to identify and isolate the chemical constituents from different extracts of GP. Numerous studies have exposed that various extract of GP leaves contains several active chemical constituents such as flavonoids, saponins, tannins, terpenoids and steroil glycosides ^{8, 24, 25}.  Previous studies had also reported that GP leaves extracts contained rutin, kaempferol and two potential antioxidant components which are kaempferol-3-O-rutinoside and astragalin ²⁶. Flavonoids are polyphenolic compounds with potential beneficial effects on human health; they reportedly have anti-allergic, antiplatelet, antiviral, anti-inflammatory, antitumor and antioxidants activities.

TABLE 1: IMPORTANT PHYTOCONSTITUENTS ISOLATED FROM GP EXTRACTS ^{8, 24-26}

S. no.	Common name	Structure
1	Flavonoid
2	Saponin
3	Tannin
4	Terpenoids
5	Kaempferol-3- O-rutinoside
6	Kaempferol
7	Astragalin
8	Rutin

Pharmacological Properties:

Anti-Inflammatory Activity: GP leaves extract is used to treat local inflammation, rheumatism, and viral ailments. The crude ethanolic extract of GP leaves has found to possess significant anti-inflammatory action. Steroids isolated from the plant extract have been proven to show anti-inflammatory activity ⁴.

Moreover, flavonoids which are mainly a polyphenolic compound which has also been reported to have an anti-inflammatory effect. Another active phytoconstituent kaempferol was found to show the anti-inflammatory effect by inhibiting glycogen synthase kinase- 3β (GSK-3β) ⁵. The administration of the original organic extract significantly inhibited the increase in ear thickness in response to croton oil. It was found that 0.75 mg/ear showed similar activity to that of 6mg/ear hydrocortisone 21-hemisuccinate sodium salt.

Anticancer Activity: Traditionally, the GP leaves have been used as an anticancer agent. In animal cancer model, ethanolic extract of GP leaves showed cytotoxic and antiproliferative activity. Ethanolic extract of GP (EGP) showed an inhibitory effect on the carcinogenicity of mice lung tumor induced by benzo (a) pyrene (BAP) and also showed antimutagenic activity on Salmonella typhimurium ²⁷. The fraction XIX-XX of ethanolic extract of GP has a cytotoxic activity on HeLa cervical cancer cells (IC₅₀ 119 µg/ml), inhibited HeLa cell proliferation and induced apoptosis ²⁸. Ethanolic extract of GP is also reported to have antiangiogenic effects ²⁹; therefore the plant is potential as antimetastasis and anti-invasion. Ethanolic extract leaves GP increased the effectiveness of doxorubicin on MCF-7 and T47D breast cancer cells ³⁰.

In-vivo study of the ethanolic extract on female rats induced by DMBA has been conducted. Ethanolic extract of GP performs chemopreventive effect to suppress breast cancer initiation ³¹ and performs suppression of breast cancer development on early state of female rats induced by DMBA ³². The ethanol extract of GP leaves act as a blocking agent in carcinogenesis initiation phase at the doses of 300 and 700 mg/kg b.w in rats which inhibits further progression towards malignancy ³³.

Anti-Diabetic Activity: GP extracts have a potent anti-diabetic effect. A lot of studies and efforts were conducted to confirm the anti-diabetic effect of GP leaves extract. Ethanolic extract of GP leaves have been shown to possess anti-hyperglycaemic and anti-hyperlipidemic activities in diabetic rats ^{6, 7} and the n-butanol fraction from the GP leaves also has hypoglycemic effects ⁸. Another study had shown that hexane and ethyl acetate fractions have potential in stimulating glucose uptake in 3 T3-F44 adipocytes ⁹.

Furthermore, the methanol extract of GP was able to increase insulin secretion in the insulin-secreting cell line, BRIN-BD11¹⁰. In the most recent study, the GP leaves extract was reported to produce a significant elevation in the fasting blood glucose (FBG) levels of normal rats, but a decrease in diabetic rats ¹¹. In acute dose (1g/kg), the extract significantly lowered fasting blood glucose (FBG) in streptozotocin-induced diabetic rats. This activity is most potent when extracted in 25% ethanol-water solvent combination.

Anti-Herpes Simplex Virus Activity: GP leaves extract possess anti-herpes simplex virus activity ³. To demonstrate the anti-HSV type 1 activity, 30 medicinal plants were investigated in Indonesia with water and methanol extract on the plaque assay at a concentration of 100 mg/mL GP leaves extracts showed potent therapeutic activity. Water extract and methanolic extracts of GP leaves showed 85% and 97.4% plaque formation respectively.

FIG. 2:   (a) PHARMACOLOGICAL ACTION OF GP (b) PHYTOCONSTITUENTS OF GP

Anti-Ulcerogenic Activity: The gastrointestinal disorder can be treated with the blessings of having different folk medicines as a potential remedy. Ethanolic extract of GP leaves can be such remedy which has demonstrated anti-ulcerogenic activity ³⁴. It can give a gastroprotective effect in adult Sprague Dawley rats. GP leaves could significantly protect the gastric mucosa against ethanol-induced injury. Such protection was shown to be a dose-dependent as ascertained by the reduction of ulcer areas in the gastric wall as well as the reduction in the inhibition of edema and leukocytes infiltration of submucosal layers and protection was most prominent at a dose of 400 mg/kg.

Vasorelaxant Activity: Some plant-derived compounds have been proven to have anti-hypertensive activity. GP has also been found to demonstrate antihypertensive activities in rat ¹² by inhibiting ACE activity ¹³ and cause vasodilation via inhibition of calcium channels ¹⁴. Screening of leaves extract yields several components among which flavonoids have been found to possess antihypertensive ^{15, 16} and vasodilatory properties ^{35, 36}. Butanolic fraction contains putative hypotensive compounds that appear to inhibit calcium influx via receptor-operated and voltage-dependent calcium channels to cause vasodilation and a consequent fall in blood pressure (10 and 20 mg/kg) ²¹.

Antiplasmodial Activity: GP leaves extracts to have potent antiplasmodial activity ³⁷. Aqueous and ethanol extract of GP were evaluated for anti-plasmodial activities in-vitro and in-vivo. Both extracts were found to inhibit parasite proliferation to varying degrees, identified by parasite lactate dehydrogenase (PLDH) assay. The aqueous extract was more potent than the ethanol extract at suppressing the growth of both parasites in-vitro. At 250 mg/kg/day, only the aqueous plant extract showed >90% chemo-suppression, which improved the median survival time compared with non-treated infected mice.

Toxicity: The leaves of GP extract are often consumed in the diet, and research shows that leaves contents are not having any toxic effects ¹⁰. In the implementation of complementary medicine must be proven effectiveness and toxicity. Toxicity of ethanol extract of GP to the gastric histopathology analysis of rat Sprague-Dawley showed that ethanol extract did not change gastric histopathology of white male rat Sprague -Dawley strain and effective dose and also increasing dose did not result against gastric damage. Administration of a methanol extract of GP did not produce mortality or significant changes in various parameters in both acute and sub-chronic toxicity studies ²⁴.

CONCLUSION: The literature review of GP represents that it has extensive pharmacological properties which effectively perform to treat several disorders. The leaves extracts from different solvents had successfully identified the exertion of different therapeutic purposes including anti-diabetic, anti-hypertensive, anti-proliferative, antioxidant, anti-plasmodial, vasorelaxant activity. The study demonstrated on its phytochemistry, and various biological properties of the extracts and constituents might provide an incentive for proper evaluation of the use of the plant in medicine.

ACKNOWLEDGEMENT: Nil

CONFLICT OF INTEREST: Nil

REFERENCES:

1. Rahman AFMM and Asad MSA: Chemical and biological investigations of the leaves of Gynura procumbens. International Journal of Biosciences 2013; 3(4): 36-43.
2. Afandi A, Zulkiffli H, Sadikun A and Ismail S: Antioxidant properties of Gynura procumbens extracts and their inhibitory effects on two major human recombinant cytochrome P450S using a high throughput luminescence assay. Asian Journal of Pharmaceutical and Clinical Research 2014; 7(5): 36-41.
3. Nawawi A, Nakamura N, Hattori M, Kurokawa M and Shiraki K: Inhibitory effects of Indonesian medicinal plants on the infection of herpes simplex virus Type 1. Phytotherapy Research 1999; 13: 37-41.
4. Iskander M, Song Y and Jiratchariyakul WC: Anti-inflammatory screening of the medicinal plant Gynura procumbens. Plant Foods Hum Nutr 2002; 57: 233-244.
5. Wong SK, Jann MLS, Sudi S, Hasan M, Chin LP, Embi N and Sidek HM: Anti-malarial and Anti-inflammatory Effects of Gynura procumbens are mediated by kaempferol via inhibition glycogen synthase kinase-3β (GSK3β). Sains Malaysiana 2015; 44(10): 1489-1500.
6. Chan LK, Lim SY and Pan LP: Micropropagation of Gynura procumbens (Lour.) Merr. An important medicinal plant. Journal of Medicinal Plants Research 2009; 3: 105-111.
7. Zhang XF and Tan BKH: Effects of an ethanolic extract of Gynura procumbens on serum glucose, cholesterol and triglyceride levels in normal and Streptozotocin-induced diabetic rats. Singapore Med J 2000; 41: 9-13.
8. Akowuah GA, Sadikum A and Mariam A: Flavonoid identification and hypoglycaemic studies of the butanol fraction from Gynura procumbens. Pharm Biol 2002; 40: 405-410.
9. Bohari M, Pauliena SH, Muhajir, Shaari, Lajis K and Nordin: Glucose uptake. Stimulatory activity of Gynura procumbens in 3T3- F442A adipocytes. Sarawak: Malaysian Medicinal Plant: Chemistry and Biological Activity: UNIMAS and Malaysian Natural Products Society, 2000.
10. Rasadah MA, Hamid M, Saufi MB and Nik Musadah M: Study on anti-diabetic properties of Gynura procumbens Poster presented at Natural Products Seminar, Kota Kinabalu 2002; 23-24.
11. Hassan Z, Yam MF, Ahmad M and Yusof AP: Anti-diabetic properties and mechanism of action of Gynura procumbens water extract in streptozotocin-induced diabetic rats. Molecules 2010; 15(12): 9008-23.
12. Lam SK, Idris A, Bakar ZAA and Ismail R: Gynura procumbens and blood pressure in the rats: a preliminary study. Asia Pacific J of Pharmacology 1998; 13: 14-15.
13. Hoe SZ, Kamaruddin MY and Lam SK: Inhibition of angiotensin-converting enzyme activity by a partially purified fraction of Gynura procumbens in spontaneously hypertensive rats. Med Princ Pract 2007; 16: 203-208.
14. Hoe SZ, Lee CN, Mok SL, Kamaruddin MY and Lam SK: Gynura procumbens Decreases blood pressure in rats by vasodilatation via inhibition of calcium channels. Clinics, 2011; 66: 143-150.
15. Balasuriya N and Rupasinghe HPV: Antihypertensive properties of flavonoid-rich apple peel extract. Food Chem 2012; 135: 2320-2325.
16. Lokesh D and Shankar DA: Evaluation of a mechanism for antihypertensive action of Clerodendrum colebrookianum, used by folklore healers in north-east India. J Ethnopharmacol 2012; 143: 207-212.
17. Algariri K, Meng KY, Atangwho IJ, Asmawi MZ, Sadikum A and Murugaiyah NI: Hypoglycemic and anti-hyperglycemic study of Gynura procumbens leaf extracts. Asian Pacific Journal of Tropical Biomedicine 2013; 3(5): 358-366.
18. Rosidah, Yam MF, Sadikun A, Ahmad M, Akowuah GA and Asmawi MZ: Toxicology evaluation of standardized methanol extract of Gynura procumbens. Journal of Ethnopharmacol 2009; 123: 244-249.
19. Vanijajiva O: The genus Gynura (Asteraceae: Senecioneae) in Thailand. Thai Journal of Botany 2009; 1(1): 25-36.
20. Ng HK, Poh TF, Lam SK and Hoe SZ: Potassium channel openers and prostacyclin play a crucial role in mediating the vasorelaxant activity of Gynura procumbens, BMC Complementary and Alternative Medicine 2013; 13: 188.
21. Bhore SJ, Nithiya R and Loh CY: Screening of endophytic bacteria isolated from leaves of Sambung Nyawa (Gynura procumbens) for cytokinin-like compounds. Bioinformation 2010; 5(5): 191-197.
22. Dwijayanti DR and Rifa M: Gynura procumbens ethanolic extract promotes lymphocyte activation and regulatory T cell generation in-vitro. 2015; 5(1): 14-19.
23. Global Biodiversity Information Facility. The plant list, Gynura procumbens (Lour) Merr www. gbif.org/species, 2011.
24. Zahra AA, Kadir FA, Mahmood AA, Hadi AAA, Suzy SM, Sabri SZ, Latif II and Ketuly KA: Acute toxicity study and wound healing potential of Gynura procumbens leaf extract in rats. Journal of Medicinal Plants Research 2011; 15(12):2551-2558.
25. Kaewseejan N, Puangpronpitag D and Nakornriab M: Evaluation of phytochemical composition and antibacterial property of Gynura procumbens Asian Journal of Plant Sciences 2012; 1-5.
26. Yam M, Sadikun A and Asmawi M: Antioxidant potential of Gynura procumbens. Pharm Biol 2008; 46(9): 616-25.
27. Sugiyanto, Sudarto B, Meiyanto E, Nugroho AE and Jenie UA: Anticarcinogenic activity of plant Isolate. Indo J Pharm 2003; 14(4): 216-225.
28. Meiyanto E and Septisetyani EP: Antiproliferative activity and apoptosis induction of phenolic fraction Gynura procumbens (Lour.) Merr. leaves ethanolic extract on HeLa Cells. Artocarpus 2005; 5(2): 74-80.
29. Jenie RI and Meiyanto E: Antiangiogenic effect of Sambung Nyawa (Gynura procumbens (Lour.) Merr.) leaves ethanolic extract on chick chorio allantois membrane. Indo J Pharm 2006; 17(1): 50-55.
30. Jenie RI and Meiyanto E: Co-chemotherapy of Sambung Nyawa (Gynura procumbens (Lour.) Merr.) leaves ethanolic extract and doxorubicin on breast cancer Cells. Indo J Pharm 2007; 18(2): 81-87.
31. Meiyanto E, Susilowati S, Tasminatun S, Murwanti R and Dan S: Chemopreventive effect of ethanolic extract of Gynura procumbens (Lour), Merr on the carcinogenesis of rat breast cancer development. Indo J Pharm 2007; 18(3): 154-161.
32. Meiyanto E, Tasminatun S, Susilowati S, Murwanti R and Dan S: Suppression of DMBA-induced carcinogenesis of breast cancer in post initition stage by ethanolic extract of Gynura procumbens (Lour), Merr leaves. Indo J Pharm 2007; 18(4): 169-175.
33. Ghofur A, Hamid IS and Listyorini D: Anticarcinogenic activity of Gynura procumbens extract through cytochrome P450 and glutathione S-transferase. Int J Pharm Tech Res 2015; 8(1): 24-29.
34. Mahmood AA, Mariod AA, Bayaty FA and Wahab SIA: An anti-ulcerogenic activity of Gynura procumbens leaf extract extracts against experimentally-induced gastric lesions in rats. Journal of Medicinal Plants Research 2010; 4(8): 685-691.
35. Herrera MD, Zarzuelo A, Jiménez J, Marhuenda E and Duarte J: Effects of flavonoids on rat aortic smooth muscle contractility: Structure-activity relationships. General Pharmacology: The Vascular System 1996; 27: 273-277.
36. Cook NC and Samman S: Flavonoids-Chemistry, metabolism, cardioprotective effects, and dietary sources. J Nutr Biochem 1996; 7: 66–76.
37. Vejanan V, Latip J, Chin LP, Embi N and Sidek HM: In-vitro and in-vivo anti-plasmodial activities of Gynura procumbens. Sains Malaysiana 2012; 41(12): 1535-1542.
    

    ---

    How to cite this article:

    Mou KM and Dash PR: A comprehensive review on Gynura procumbens leaves. Int J Pharmacognosy 2016; 3(4): 167-74. doi link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.3(4).167-74.

    ---

    This Journal licensed under a Creative Commons Attribution-Non-commercial-Share Alike 3.0 Unported License.

    ---