| Swertia macrosperma C.B. Clark belongs to the Swertia genus of family Gentianaceae, and is predominately distributed in Asian areas. In China, Swertia macrosperma is widely used as a folk medicine called "Dida" or "Zangyinchen" in ethnomedicine of Tibet, Yunnan and Sichuan province in favor of its anti-hepatitis virus and antipyretic and antidotal effects. Some plants of Swertia genus, such as Swertia chirayita, Swertia japonica, Swertia punicea Hemsl and Swertia kouitchensis, were found effective in anti-diabetic models. Yet, the anti-diabetic effect and the chemical components of Swertia macrosperma have not been researched. With the support of National Natural Science Foundation of China, we carried out this study aiming at evaluating the anti-diabetic effect of Swertia macrosperma and figuring out the possible leading compounds contribute to the anti-diabetic effect.In order to find out whether Swertia macrosperma has anti-diabetic activity, the extracts of swertia macrosperma were evaluated for theirs glucose lowering effects in HepG2cell line. The results showed that Swertia macrosperma had significant activities in increasing the glucose consumption in HepG2cells, especially ethanol extract(EE) and n-butanol extract(BE).Based on the results of glucose consumption in HepG2cells, EE and BE were chosen to be researched in diabetic Wistar rats for their in vivo anti-diabetic effects. The study was carried out on high-fat-fed and low STZ induced diabetic rats. After28days intervention with EE or BE, the diabetic rats represented significant decrease in fasting blood glucose level. Moreover, EE and BE can also improve glucose tolerance, lipid metabolism and insulin resistance of the diabetic rats at significant level.For the purpose of illuminating the possible mechanisms by which EE and BE acted their anti-diabetic effects, we designed and made some examinations and tests with the diabetic rats tissues, including Histopathological examination of hepatic and pancreas tissues, anti-oxidant enzymes levels in plasma, liver key enzymes related to glucose metabolism, glycogen content in liver and muscle tissues, and important protein expression content of PI3K/AKT pathway. It turned out that EE and BE can significantly improve the activity of anti-oxidant enzymes in plasma, increase glycogen content in liver and muscle tissues, and activate the signaling transduction in PI3K/AKT pathway. These would be involved in the anti-diabetic effect of EE and BE.On the basis of the pharmacology results, an investigation of chemical constituents was carried out on n-butanol extract of Swertia macrosperma. Considering the HPLC profile of EtOAc extract was similar with n-butanol extract, the investigation of EtOAc extract was made along with n-butanol extract. The investigation of chemical constituents led to the isolation and elucidation of42compounds as following:tetrahydromacrospersone A-D(1-4), β-sitosterol(5), oleanolic aicd(6),1-hydroxy-2,3,4,5-tetramethoxyxanthone(7),1,8-dihydroxy-3,5-dimethoxyxanthone(8),1-hydroxy-3,5,8-trimethoxyxanthone(9),1,5,8-trihydroxy-3-methoxyxanthone(10),1,7-Dihydroxy-3,8-dimethoxyxanthone(11),1,3,8-tri-hydroxy-5-methoxyxanthone(12),1,7-dihydroxy-3-methoxyxanthone(13),1,3,5,8-tetrahydroxyxanthone(14),1,3,7-trihydroxyxanthone(15),1,3-dihydroxyxanthone (16),1,3,5-trihydroxyxanthone(17),1,5-dihydroxy-3-methoxyxanthone(18),1,3,7,8-tetrahydroxyxanthone(19), Swertianolin(20), Isoswertianolin(21),7-(β-D-glucopyranosyloxy)-1-hydroxy-3-methoxyxanthone(22), Norswertianolin(23),3-(β-D-glucopyranosyloxy)-1-hydroxy-4,5-dimethoxyxanthone(24),3-(P-D-glucopyranosyloxy)-1,8-dihydroxy-5-methoxyxanthone(25),3-(β-D-glucopyranosyloxy)-1,8-dihydroxy-4,5-dimethoxyxanthone(26), neolancerin(27), mangiferin(28), Campestroside(29), Astragaline (30),3-0-(β-D-glucopyranosyl)-5,7,3’,4’-tetrahydroxyflavon(31),6-(β-D-glucopyranosyl)-5,7,4’-trihydroxyflavon(32), Deacetylcentapicrin(33), Swertiamarin(34), Swerpunilactones B(35),(7aH,8’aH)-4,4’,8a,9-tetrahydroxy-3,3’-dimethoxy-7,9’-epoxylignan(36), Isolariciresinol(37),3,4-dihydroxy benzoic(38), benzene-1,2,3,4-tetraol(39),4-hydroxy-3-methoxy benzoic acid(40),3-hydroxy benzoic acid(41),(Z)-3-(2,4,5-trihydroxyphenyl) acrylic acid(42). Among these compounds, compounds1-4are new ones, and28compounds (7、9、12-13、15-19、21-22、24-27、30-33、35-42) were isolated from Swertia macrosperma for the first time.HepG2cells glucose consumption test showed that1,3,5,8-tetra-hydroxyxanthone(14),1,3,7,8-tetrahydroxyxanthone(19), Swertianolin(20), Isoswertianolin(21), Norswertianolin(23), Mangiferin(28) and Swerpunilactones B(35) have potential anti-hyperglycemic activity. Further in vivo anti-diabetic activity are worthy to be studied. |
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