Anti-hepatitis B virus effects of the traditional Chinese herb Artemisia capillaris and its active enynes

• Published in: Journal of ethnopharmacology 2018-10, Vol.224, p.283-289
• Main Authors: Geng, Chang-An, Yang, Tong-Hua, Huang, Xiao-Yan, Yang, Jing, Ma, Yun-Bao, Li, Tian-Ze, Zhang, Xue-Mei, Chen, Ji-Jun
• Format: Article
• Language: English
• Subjects: (E)-deca-2-en-4,6-diyne-1,10-diol; (S)-3-hydroxyundeca-5,7,9-triynoic acid; (S)-deca-4,6,8-triyne-1,3-diol; (Z)-deca-2-en-4,6-diyne-1,10-diol; 2-methyl-6-phenyl-4H-pyran-4-one; 3S,​8S-​dihydroxydec-​9-​ene-​4,​6-​diyne 1-​O-​β-​d-​glucopyranoside; 3S-Hydroxyundeca-5,7,9-triynoic acid 3-O-β-d-glucopyranoside; 5-benzylthiophencarboxylic acid; 8S-deca-9-en-4,6-diyne-1,8-diol; 8S-deca-9-en-4,6-diyne-1,8-diol 1-O-β-d-glucopyranoside; Anti-HBV activity; Artemisia capillaris; atractylodin; dehydrofalcarindiol; dehydrofalcarinol; dendroarboreol B; Enynes; Structure-activity relationships
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2018.06.005

Artemisia capillaris (Yin-Chen) is a famous traditional Chinese medicine (TCM) for treating acute and chronic hepatitis in China. Enynes are one type of characteristic constituents in this herb, while their anti-hepatitis B virus (anti-HBV) properties have not been systemically investigated. This study is to reveal the active part of A. capillaris, and systemically investigate the enynes and their anti-HBV activity. The total extract and each fraction of A. capillaris were assayed for the anti-HBV activity to reveal the active part. Bioassay-guided fractionation using various chromatographic techniques yielded the enynes, whose structures were elucidated by spectroscopic analyses and ECD calculations. The anti-HBV properties inhibiting HBsAg and HBeAg secretions and HBV DNA replication were evaluated on HepG 2.2.15 cell line in vitro. ACT-2 and ACT-3 was revealed to be the respective active and toxic part of A. capillaris. Twelve enynes (1–12) involving four new ones (1–4) and two unusual enyne analogs (13–14) were isolated from the active part (ACT-2). All the isolates were assayed for their anti-HBV activity, and the preliminary structure-activity relationships were summarized based on the structural features. In particular, compound 4 could significantly inhibit the secretions of HBsAg and HBeAg, and HBV DNA replication with IC50 values of 197.2 (SI > 5.1), 48.7 (SI > 20.5) and 9.8 (SI > 102) μM. Enynes are responsible for the anti-HBV effects of A. capillaris. Hydroxyl and glycosyl groups are preferable for maintaining activity. This is the first time to systematically investigate the anti-HBV activity of enynes in A. capillaris, which provides valuable information for understanding the ethnopharmacological application of Yin-Chen. [Display omitted]