Anti-hepatitis B virus activities of friedelolactones from Viola diffusa Ging

• Published in: Phytomedicine (Stuttgart) Vol. 22; no. 7-8; pp. 724 - 729
• Main Authors: Dai, Jiao-Jiao, Tao, Hua-Ming, Min, Qing-Xi, Zhu, Quan-Hong
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 15.07.2015; Urban & Fischer Verlag
• Subjects: Anti-HBV activity; Antiviral Agents - isolation & purification; Antiviral Agents - pharmacology; Care and treatment; Dicotyledons; Drugs, Chinese Herbal - pharmacology; Friedelolactone; Health aspects; Hep G2 Cells; Hepatitis B; Hepatitis B e Antigens - metabolism; Hepatitis B Surface Antigens - metabolism; Hepatitis B virus - drug effects; HepG 2.2.15 cells; Humans; Inhibitory Concentration 50; Lactones; Lactones - isolation & purification; Lactones - pharmacology; Molecular Structure; Viola - chemistry; Viola diffusa G; CC50; DMSO; HBeAg; HMBC; HBsAg; TLC; Epifriedelanol, PubChem CID: 101341; Friedelolactone; Palmitic acid, PubChem CID: 985; MTT; Cerevisterol, PubChem CID: 10181133; DMEM; Anti-HBV activity; Friedelin, PubChem CID: 91472; HMQC; SI; IC50; DEPT; NOESY; HepG 2.2.15 cells; Viola diffusa G; Clerosterol, PubChem CID: 5283638; HBV; ELISA
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2015.05.001

Hepatitis B virus (HBV) infection is the major factor of causing hepatitis B, cirrhosis and liver cancer. Interferon and nucleoside drugs, the main drugs to treat HBV infection, have disadvantages of scavenge difficulty and drug resistance respectively. Viola diffusa Ging is used as a traditional Chinese herbal medicine for the treatment of hepatitis. The aim of the study is to investigate the chemical constituents of Viola diffusa Ging and their anti-HBV activity. Chemical constituents were extracted and purified by ethanol reflux extraction and chromatographic separation technology including D-101 Macroporous resin, silica gel, Sephadex LH-20 and preparative thin-layer chromatography. Their structures were elucidated on the basis of extensive NMR and MS data. Cytotoxicity and inhibiting effects on HBsAg and HBeAg secretion of HepG2.2.15 of all compounds except 10 were studied by MTT method and ELISA method. Three friedelolactones with naturally occurring seco-ring-A friedelane triterpenoids, 2β-hydroxy-3, 4-seco-friedelolactone-27-oic acid (1), 2β, 28β-dihydroxy-3,4-seco-friedelolactone-27-oic acid (2) and 2β, 30β-dihydroxy-3,4-seco-friedelolactone-27-lactone (3), and a stigmastane, stigmast-25-ene-3β,5α,6β-triol (11) together with nine known compounds were isolated from the whole plant of Viola diffusa G. (Violaceae). Compounds 1–3, 9, 11, 12 exhibited significant activities of blocking both HBsAg and HBeAg secretion, and compound 4, 6, 7, 8 selectively inhibited HBeAg secretion while compound 13 selectively inhibited HBsAg secretion. IC50 values of compounds 1 and 2, 26.2 μM and 33.7 μM for HBsAg, 8.0 μM and 15.2 μM for HBeAg, was significantly lower than that of positive control lamivudine. Compounds 1–3, 11 are new compounds never reported before and the promising results demonstrate the potential of compound 1–3, 9, 11, 12 for the treatment of HBV infection.