Studies On The Anti-HBV Constituents Of Alternanthera Philoxeroides(Mart.) Griseb

Hepatitis B virus (HBV) infection has serious influence to public health. Interferon and nucleoside analogs are the major drugs for HBV infections. However, drug resistance and significant side effects limite their application. Therefor, the search for anti-viral new constituents from Chinese herbal medicines is one of the most effective ways.Alternanthera philoxeroides(Mart.) Griseb is a perennial ratoon herb, which was once recorded in China pharmacopoeia in1977. Its major constituents are triterpenoid saponins, flavones, phytosterols, anthraquinones and organic acids. It has effectively anti-viral activities, such as anti-HSV, anti-HBV and anti-EHFV.The n-BuOH fraction of Alternanthera philoxeroides(Mart.) Griseb was chosen to be researched for three reseasons below. First, some triterpenoid saponins and flavones, which can anti-HBV effectively , have been found by the research in our lab. The preliminary experiments indicate these constituents distribute in the n-BuOH fraction extensively. Second, some of the flavonoid glycosides’glycon is boivinose, which is rare in the nature. So it can lay the foundation for the search of new bioactive drugs. Third, Alternanthera philoxeroides(Mart.) Griseb’s super breeding ability prvides abundant resources for the research.The chemical investigation of the n-BuOH fraction of this plant resulted in the isolation of 17compounds by various of chromatography means, and 12 compounds were identified on the basis of spectral data, including MS, 1H-NMR, 13C-NMR, HMBC, HSQC , IR, etc. As follows:1. Four flavons luteolin-6-C- -D-boivinopyranosyl-3 -O- - D- glucopyranoside (kxx1), luteolin-6-C- -D-boivinopyranosyl-4 -O- -D-glucopyranoside (kxx2), altern -anthin-4 -O- - D-glucopyranoside(kxx3), alternanthin (kxx5) ;2. Five triterpenoid saponins: 3-O- -D-glucopyranosyl (1 3) -O-[ -D-glu-copyranosyl]-oleanoic acid-28-O- -D-glucuronopyranoside (kxx4), calenduloside E (kxx7), chikusetsusaponin a(kxx8), taibainoside (kxx9), HN-Saponins K(kxx10);3. One anthraquinone: 2-methyl-1, 3, 6-trihydroxyl-9, 10-anthraquinone-3-O - -L- rhamnose(1 2)- - D- glucoside (kxx6); 4. Two sterols: daucosterol (kxx11), -sitosterol(kxx12).Among them, kxx1, kxx2, kxx3 and kxx4 are new compounds. kxx6, kxx9 and kxx10 were first isolated from the plant.Through the anti-HBV assay of the isolated compounds, two active compounds (kxx2 and kxx3) were reported for the first time. Both of them blocked effectively the secretion of HBsAg with IC50 value of 31.54 and 22.20 M/L.Combined other flavonoid-C-boivinopyranosides, the preliminary structure -activity relationship has been researched.1. The location of glycosidation can influence the interaction between drugs and HBV.2. The anti-HBV activity of flavone monoglucoside is better than that of flavone diglucoside, but the cytotoxicity of flavone monoglucoside is bigger.3. The dissolvability in the culture medium has nothing to do with the cytotoxicity, but it can be influence the pharmacodynamic action.4. The existence of 3 -OH is important to the anti-HBV activity, but its methylation is less influential.The active compounds are new, so further pharmacodynamical study would help make them to be anti-viral leading compounds and find other anti-viral activities. Whether their activity is related to boivinose needs much more research.