Study On Chemical Constituents And Anti-Hyperglycemic Effect Of The Fruit Of Syzygium Cumini(L.) Skeels

Syzygium cumini Skeels(syn.Eugenia jamholana Lam.;Syzygium jambolanum),a member of Myrtaceace Family,is a native tree of tropics and mainly distributed in Indian subcontinent,Southeast Asia and East Africa.It is one of the widely used plants for treating diabetes in folk medicine,and different parts of the plant have been reported to possess anti-hyperglycaemic effects.Despite abundent pharmacological work supporting the hypoglycaemic property of Jamun,there is limited knowledge related to its secondary metabolites,and data on the relationship of the metabolites and its glucose regulating effects are scarce.In the current study,freeze-dried Jamun pulp powder(350.0 g)was exhaustively extracted with methanol(1.5 L×3)to yield a methanol extract(130.0 g)after solvent removal in vacuo.The methanol extract was suspended in water(500 mL)and submitted to liquid-liquid partitioning with ethyl acetate(500 mL × 5)and butanol,successively.Since we speculated that some components in Jamun fruit not previously identified,especially non-phenolics,may play an important role in diabetes prevention and/or treatment,we focused our isolation work on the ethyl acetate extract(14.5 g).In the current study,one new triterpenoid named 2-O-cis-p-coumaroyl maslinic acid(1),along with thirteen known triterpenoids 2-0-traps-p-coumaroyl maslinic acid(2),oleanolic acid(3),maslinic acid(4),arjunolic acid(5),3-O-cis-p-coumaroyl maslinic acid(6)?3-O-trans-p-coumaroyl maslinic acid(7),ursolic acid(8),corosolic acid(9),Asiatic acid(10),Guavenoic acid(11),betulinic acid(12),alphitolic acid(13),3-O-trans-p-coumaroyl alphitolic acid(14),one sesquiterpenoid clovane-2?,9?-diol(15),one cerebroside Hexadecanamide(16),and two steroids daucosterol(17)and ?-sitosterol(18)were isolated from the Jamun fruit ethyl acetate extract.Their structures were elucidated on the basis of detailed NMR and MS spectral data analysis and by comparison with literature report.The triterpenoid-enriched Jamun fruit extract(TJFE)was analyzed by HPLC-UV and two of its major triterpenes(4 and 9)were quantified.Animal studies demonstrated that TJFE(total triterpenoid content 48.7%)decreased blood glucose content in C57BL/6 mice(P<0.05)upon sucrose loading challenge,improved the glucose tolerance in mice administrated with TJFE for 2 weeks via oral gavage(100 mg/kg body weight),and increased Akt phosphorylation levels and Glut4 protein levels in skeletal muscle.Additionally,TJFE administration inhibited hepatic gluconeogenesis through suppressing the gluconeogenic gene expression of Pgc1?,Pepck,and G6Pase.The current study advances scientific knowledge of Jamun constituents and suggests that triterpenoids may play an important role in the anti-diabetic properties attributed to this edible purple berry.