Chemical Constituents And Bioactivities Of Swertia Bimaculata And Alangium Chinense

Swertia bimaculata was recorded as Zhang Yacai in Jiuhuang Bencao in Chinese Ming Dynasty for the first time. The whole plant is a well-known ethnomedicine for the treatment of hepatitis and dyspepsia. Some plants of Swertia genus were found to be effective in anti-diabetic models. In our previous work, we found that the ethanol, dichloromethane and n-butanol extracts of Swertia bimaculata were the most effective extracts for the treatment of diabetes in high fat and sucrose fed combined with low dose streptozocin induced diabetic rats. And 21 compounds were isolated from the dichloromethane and ethyl acetate extracts. But the mechanism of anti-diabetic activity and the constituents from the n-butanol extract were not clear. Therefore, this study was desiged to evaluate the anti-diabetic activity of the axtracts and the constituents related with the anti-diabetic activity.Alangium chinense belongs to the Alangium genus of family Alangiaceae.The roots of this plant have historically been used in traditional Chinese medicine for the treatment of arthritis and heart failure. Yet, more than 50 constituents were isolated from the roots and leaves of this plant. But the anti-inflammatory activitiy of this plant has not been researched.Objective 1) The activities of Swertia bimaculata on anti-oxidant enzymes levels, hepatic and pancreas tissues, and glucose metabolism disorder in diabetic rats were researched to illuminate the anti-diabetic activity. And the constituents from the n-butanol extract were isolated and identified.2) Phytochemical studies along with anti-inflammatory activitiy on Alangium chinense were carried out in this work.Methods 1) We designed some examinations and tests on the tissues of diabetic rats, including anti-oxidant enzymes levels in plasma and liver, the histopathological examination on hepatic and pancreas tissues, glycogen content in liver and muscle tissues, and liver key enzymes related to glucose metabolism. And the isolated compounds from Swertia bimaculata were evaluated for their a-glucosidase inhibitory activity in vitro. The isolated compounds from Alangium chinense were evaluated for their anti-inflammatory activity against lipopolysaccharide-induced mouse macrophage RAW264.7 cells. And the expressions of nitric oxide, prostaglandin E2, tumor necrosis factor alpha, interleukin-1?, and interleukin-6 were evaluated in this study.2) The constituents of the n-butanol extracts from Swertia bimaculata and Alangium chinense were isolated and identified by extensive chromatographic and spectroscopic methods.Results and Conclusions 1) The ethanol, dichloromethane and n-butanol extracts of Swertia bimaculata significantly improved the activity of anti-oxidant enzymes in plasma and liver, protected hepetic and pancreas tissues from damage of STZ or high glucose, improved the activity of key enzymes in liver and increased glycogen content in muscle and liver tissues. And the activity was more effective than Metformin. The flavone and xanthone aglycones showed significant a-glucosidase inhibitory activity. And bimaculatone A (7), norbellidifolin (14), isoscutellarein 8-methyl ether (20),8-methoxyluteolin (21), luteolin (22) and kaempferol (23) were the most effective compounds with their IC50 less than 100?M. Chinenside A (1), gentisic acid-5-O-?-D-glucoside (9) and isotachioside (10) from Alangium chinense showed the anti-inflammatory activity. Especially, chinenside A (1) from Alangium chinense could significantly inhibit the expression of nitric oxide (20.8?M), prostaglandin E2 (654.2 ng/mL), tumor necrosis factor alpha (272.0 pg/mL), interleukin-1? (14.6 pg/mL), and interleukin-6 (0.69 ng/mL) in vitro. And the anti-inflammatory activity was stronger than the Triptolide (28.2?M,700.8 ng/mL,13340 pg/mL,16.2 ng/mL,4.3 ng/mL).2) A total of 46 compounds were obtained and identified from the n-butanol extract of Swertia bimaculata, including 13 xanthone aglycones (7-19),16 xanthone glycosides (1-6,25-34),5 flavone aglycones (20-24),9 flavone glycosides (35-43), and three compounds of other types. Among them,7 new compounds (1-7) were isolated. A total of 35 compounds were obtained and identified from the n-butanol extract of Alangium chinense, including 13 phenolic glycosides (1,3-14),3 lignans (15-17),3 megastigmane glycosides (2,18-19),3 terpenoids (20-22),6 alkaloids (23-28), and seven compounds of other types. Among them,3 new compounds were identified. Especially, compounds (1,3) were new phenolic glycosides, and compound 2 was a new megastigmane glycoside.Innovations 1) It turned out that Swertia bimaculata could protect hepetic and pancreas tissues from damage through its anti-oxidant activity. Besides the extracts could also improve glucose metabolism disorder in high fat and sucrose fed combined with low dose streptozocin induced diabetic rats.This study could evaluate the anti-diabetic activity of Swertia bimaculata.2) A total of 46 compounds were isolated from the n-butanol extract of Swertia bimaculata, including 7 new cpmpounds. And we found that the flavone and xanthone aglycones showed significant a-glucosidase inhibitory activity which figured out the possible constituents related with the anti-diabetic activity.3) A total of 35 compounds were isolated from the n-butanol extract of Alangium chinense, including 3 new compounds. And we found that chinenside A (1), gentisic acid-5-O-?-D-glucoside (9) and isotachioside (10) which were leading compounds for the treatment of arthritis showed significant anti-inflammatory activity against lipopolysaccharide-induced mouse macrophage cells.