Study On Sulfur-containing Spiroketal Sesquiterpene From Breynia Fruticosa And Its Activity

Breynia Fruticosa is a shrub belonging to the genus Breynia(Euphorbiaceae).This genus is comprised of many species,six of which are found in China.They are all traditional medicinal plants,mainly used for anti-inflammatory,hypolipidemic and antimicrobial effects.It has been found that Breynins compounds isolated from the genus Breynia have strong oral hypolipidemic activity,but there are few reports about their anti-inflammatory and other active ingredients.Breynins have special structure and are extremely rare in nature.It was found that breynins are also anti-inflammatory active ingredients of Breynia Fruticosa in previous activity tracing.Based on this,the main contents of this paper are as follows:(1)The whole plant of Breynia Fruticosa were powerd and extracted by methanol.Sesquiterpenes were preliminarily enriched by n-butanol extraction,NM200 column chromatography,on-line two-dimensional column chromatography based on CG161 M and Toyopearl,and Silica gel column chromatography.Eleven monomer compounds with high purity were separated from sesquiterpene enriched fractions by Silica gel,RP-18,CG161 M,Sephadex and other modern column chromatography techniques,as well as preparative high performance liquid chromatography and preparative thin layer chromatography.The structures of 10 breynins(1-10)and one lignan(11)were identified by mass spectrometry,nuclear magnetic resonance,high resolution mass spectrometry and circular dichroism.Compound 5-11 has been reported in literature.Compound 1 has novel structure,with ring opening on aglycones and side chains containing thioacetyl amino groups are connected on ring A.Compound 2-4 has not been reported in the literature,and the number and species of glycosyl groups have changed.(2)Among the 10 breynins,compound 5(reported epibreynin D)was the main component.The anti-inflammatory and hypolipidemic activities of sesquiterpene fractions and compound 5 were evaluated respectively.In the capillary permeability model induced by acetic acid in mice,the sesquiterpene fraction significantly inhibited the capillary permeability of mice at a dosage of 50 mg/kg,with an inhibition rate of 37%.The effect was similar to that of indomethacin at a dosage of 10 mg/kg.Besides,in the dose range of 50-200 mg/kg,the dose-effect relationship was obvious.In complete Freund's adjuvant-induced rheumatoid arthritis model of rats,Epibreynin D showed obvious anti-rheumatoid activity.When the dosage was 0.2 mg/kg/d,the ulceration degree of legs and feet in rats was lower than that of model group,and the swelling degree of rats' feet was significantly reduced.Compared with the positive control group of indomethacin(2 mg/kg/d),the inhibition rate was 46%.When the dosage was 2 mg/kg/d,the inhibition rate was higher than that of model group.There was only slight swelling in the foot of rats before administration,and no joint disorder was observed.The inhibition rate was 72%.The results showed that Epibreynin D had strong anti-inflammatory activity.In the acute hyperlipidemia model induced by poloxamer 407 in mice,both sesquiterpene fraction and monomer compound Epibreynin D could significantly reduce the content of total cholesterol and triglyceride in mice,while the activity of monomer compound Epibreynin D was significantly stronger than that of sesquiterpene enrichment fraction.When the dosage of sesquiterpene fraction was 10 mg/kg,the inhibition rates of total cholesterol and triglyceride in whole blood of mice were 72.9% and 70.3%,respectively.When epibreynin D was given at 0.5 mg/kg,the inhibition rates of total cholesterol and triglyceride in whole blood of mice were 67.6% and 73.1%,respectively.