A Compound Isolated from Phyllanthus tenellus Demonstrates Metabolic and Vascular Effects In Vitro

Abstract

Common chronic conditions such as metabolic syndrome and diabetes are increasingly associated to metabolic and cardiovascular complications. Although Phyllanthus tenellus leaves have been used in decoctions as a popular remedy to control blood glucose levels and hypertension, its use needs a scientific basis. This study was therefore undertaken to report a phytochemical analysis of P. tenellus leaves and to test if the main active compound has potential to simultaneously tackle several pathophysiological features of metabolic syndrome and diabetes-related metabolic and vascular disorders such as hyperglycaemia, increased platelet activation, and endothelial dysfunction. We performed a partition of the methanolic extract of P. tenellus leaves among different organic solvents followed by chromatographic separation guided by the rat liver microsomal glucose-6-phosphatase assay. Two known tannins were identified by spectroscopic methods as pinocembrin-7-O-[3″-O-galloyl-4″,6″-(S)-hexahydroxydiphenoyl]-α-D-glucose, named P7OG by us, and gemin D. The structural determination of the isolated compounds was based on spectral data. The ability of the main active component, P7OG, to inhibit human platelet aggregation and to modify vascular reactivity of rat aortic rings incubated with high glucose (D-glucose 55 mM) was then evaluated. P7OG was further able to inhibit platelet aggregation induced by adenosine 5′-diphosphate and collagen, showed vasorelaxant effects in arteries precontracted with phenylephrine, and reverted the endothelium-dependent impairment effect of high glucose in rat aortic rings. In conclusion, one tannin isolated from P. tenellus showed promising metabolic, antiaggregant, and vascular effects, which suggests the potential beneficial use of P. tenellus to tackle complex cardiometabolic diseases.

Key words

Phyllanthus tenellus - Phyllantaceae - metabolic syndrome - pinocembrin - human platelets - vascular reactivity

• References

• 1 Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002; 288: 2709-2716
• 2 Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640-1645
• 3 Santilli F, Vazzana N, Liani R, Guagnano M, Davi G. Platelet activation in obesity and metabolic syndrome. Obes Rev 2012; 3: 27-42
• 4 Wu Y, Xue L, Du W, Huang B, Tang C, Liu C. Polydatin restores endothelium-dependent relaxation in rat aorta rings impaired by high glucose: a novel insight into the PPARβ-NO signaling pathway. PLoS One 2015; 10: e0126249
• 5 Sperling L, Mechanick J, Neeland I, Herrick C, Despres J, Ndumele C, Vijayaraghavan K, Handelsman Y, Puckrein G, Araneta M, Blum Q, Collins K, Cook S, Dhurandhar N, Dixon D, Egan B, Ferdinand D, Herman L, Hessen S, Jacobson T, Pate R, Ratner R, Brinton E, Forker A, Ritzenthaler L, Grundy S. The Cardiometabolic Health Alliance: working toward a new care model for the metabolic syndrome. J Am Coll Cardiol 2015; 66: 1050-1067
• 6 Buffery D. Cardiometabolic health in 2014: clinical and economic implications. Am Heart Drug Benefits 2014; 7: 427-428
• 7 Eddouks M, Maghrani M, Lemhadri A, Ouahidi ML, Jouad H. Ethnopharmacological survey of medicinal plants used for the treatment of diabetes mellitus, hypertension and cardiac diseases in the south-east region of Morocco (Tafilalet). J Ethnopharmacol 2002; 82: 97-103
• 8 Barbosa-Filho JM, Vasconcelos THC, Alencar AA, Batista LM, Oliveira RAG, Guedes DN, Falcão HS, Moura MD, Diniz MF, Modesto-Filho J. Plants and their active constituents from South, Central, and North America with hypoglycemic activity. Rev Bra Farmacogn 2005; 15: 392-413
• 9 Hoffmann P, Kathriarachchi H, Wurdack KJ. A phylogenetic classification of Phyllanthaceae (Malpighiales; Euphorbiaceae sensu lato). Kew Bull 2006; 61: 37-53
• 10 Sarin B, Verma N, Martín JP, Mohanty A. An overview of important ethnomedicinal herbs of Phyllanthus species: present status and future prospects. Sci World J 2014; 2014: 839172
• 11 Calixto JB. The plants of the genus Phyllanthus as a potential source of new drugs. Ciênc Cult 1997; 49: 422-432
• 12 Shanmugam S, Manikandan K, Rajendran K. Ethnomedicinal survey of medicinal plants used for the treatment of diabetes and jaundice among the villagers of Sivagangai District, Tamilnadu. Ethnobot Leaflets 2009; 13: 189-194
• 13 Mao X, Wu LF, Guo HL, Chen WJ, Cui YP, Shi LQ, Liang WY, Yang GH, Shao YY, Zhu D, She GM, You Y, Zhang LZ. The genus Phyllanthus: an ethnopharmacological, phytochemical, and pharmacological review. Evid Based Complement Alternat Med 2016; 2019: 7584952
• 14 Huang Y, Chen C, Hsu F, Chen C. Two tannins from Phyllanthus tenellus . J Nat Prod 1998; 61: 523-524
• 15 McCormack JG, Westergaard N, Kristiansen M, Brand CL, Lau J. Pharmacological approaches to inhibit endogenous glucose production as a means of anti-diabetic therapy. Curr Pharm Des 2001; 7: 1451-1474
• 16 Wang H, Liu Y, Feng C. Isolation and identification of a novel flavonoid from Penthorum chinense P. J Asian Nat Prod Res 2006; 8: 757-761
• 17 Estrada O, González-Guzmán JM, Salazar-Bookaman M, Fernández A, Cardozo A, Alvarado-Castillo C. Pomolic acid elicits endothelium-dependent relaxation in rat aortic rings. Phytomedicine 2011; 18: 464-469
• 18 Narvaez-Sanchez R, Calderón JC, Vega G, Trillos MC, Ospina S. Skeletal muscle as a protagonist in the pregnancy metabolic syndrome. Med Hypotheses 2019; 126: 26-37
• 19 Arion WJ, Lange AJ, Walls HE. Microsomal membrane integrity and the interactions of phlorizin with the glucose-6-phosphatase system. J Biol Chem 1980; 255: 10387-10395
• 20 Spencer CM, Cai Y, Martin R. Polyphenol complexation some thoughts and observations. Phytochemistry 1988; 27: 2397-2409
• 21 Marcucci OL, González-Mujica F, Perez-Ayuso E. Alterations of liver nuclear envelopes accompanying thioacetamide administration in rats. Act Cien Ven 1983; 34: 109-117
• 22 Markwell M, Hass S, Bieber L, Tolbert N. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein sample. Anal Biochem 1978; 87: 206-210
• 23 Burchell A, Hume R, Burchell B. A new microtechnique for the analysis of the human hepatic microsomal glucose-6-phosphatase system. Clin Chim Act 1988; 173: 183-192
• 24 Estrada O, Hasegawa M, Gonzalez-Mujica F, Motta N, Perdono E, Solórzano A, Méndez J, Méndez B, Zea EG. Evaluation of flavonoids from B. megalandra leaves as inhibitors of glucose-6-phosphatase system. Phytother Res 2005; 19: 859-863
• 25 Gonzalez-Mujica F, Motta N, Márquez A, Capote-Zulueta J. Effects of Bauhinia megalandra aqueous leaf extract on intestinal glucose absorption and uptake by enterocyte brush border membrane vesicles. Fitoterapia 2003; 74: 84-90
• 26 Cazenave J, Ohlmann P, Cassel D, Eckly A, Hechler B, Gachet C. Preparation of washed platelet suspensions from human and rodent blood. Methods Mol Biol 2004; 272: 13-28
• 27 Born G. Aggregation of blood platelet by adenosine diphosphate and its reversal. Nature 1962; 194: 927-929