Guo Qinglong, Zhao Li, You Qidong, Yang Yong, Gu Hongyan, Song Guoliang, Lu Na, Xin Jian
Department of Physiology, China Pharmaceutical University, Nanjing, China.
Antiviral Res. 2007 Apr;74(1):16-24. doi: 10.1016/j.antiviral.2007.01.002. Epub 2007 Jan 24.
The traditional Chinese medicine Scutellaria radix has been used for thousands of years, mainly for the treatment of inflammatory conditions including hepatitis. The major active constituent, wogonin (WG), isolated from S. radix has attracted increasing scientific attention in recent years due to its potent biological activities. However, pharmacologic studies have primarily been focused on wogonin's anti-inflammatory and anti-cancer activities. In this study, we have investigated wogonin's anti-hepatitis B virus (HBV) activity both in vitro and in vivo. In the human HBV-transfected liver cell line HepG2.2.15, wogonin effectively suppressed the secretion of the HBV antigens with an IC(50) of 4 microg/ml at day 9 for both HBsAg and HBeAg. Consistent with the HBV antigen reduction, wogonin also reduced HBV DNA level in a dose-dependent manner. Duck hepatitis B virus (DHBV) DNA polymerase was dramatically inhibited by wogonin with an IC(50) of 0.57 microg/ml. In DHBV-infected ducks wogonin dosed i.v. once a day for 10 days reduced plasma DHBV DNA level with an ED(50) of 5mg/kg. The in vivo anti-HBV effect of wogonin in ducks was confirmed by Southern blotting of DHBV DNA in the liver. Histopathological evaluation of the liver revealed significant improvement by wogonin. In addition, in human HBV-transgenic mice, wogonin dosed i.v. once a day for 10 days significantly reduced plasma HBsAg level. Immunohistological staining of the liver confirmed the HBsAg reduction by wogonin. In conclusion, our results demonstrate that wogonin possesses potent anti-HBV activity both in vitro and in vivo. Currently, wogonin is under early development as an anti-HBV drug candidate.
中药黄芩已被使用了数千年，主要用于治疗包括肝炎在内的炎症性疾病。从黄芩中分离出的主要活性成分汉黄芩素（WG），近年来因其强大的生物活性而受到越来越多的科学关注。然而，药理研究主要集中在汉黄芩素的抗炎和抗癌活性上。在本研究中，我们研究了汉黄芩素在体外和体内的抗乙型肝炎病毒（HBV）活性。在人HBV转染的肝癌细胞系HepG2.2.15中，汉黄芩素在第9天有效抑制HBV抗原的分泌，HBsAg和HBeAg的IC50均为4μg/ml。与HBV抗原减少一致，汉黄芩素也以剂量依赖性方式降低HBV DNA水平。鸭乙型肝炎病毒（DHBV）DNA聚合酶被汉黄芩素显著抑制，IC50为0.57μg/ml。在感染DHBV的鸭中，汉黄芩素静脉注射给药，每天一次，持续10天，可降低血浆DHBV DNA水平，ED50为5mg/kg。通过对肝脏中DHBV DNA进行Southern印迹分析，证实了汉黄芩素在鸭体内的抗HBV作用。肝脏的组织病理学评估显示汉黄芩素能显著改善肝脏状况。此外，在人HBV转基因小鼠中，汉黄芩素静脉注射给药，每天一次，持续10天，可显著降低血浆HBsAg水平。肝脏的免疫组织化学染色证实了汉黄芩素可降低HBsAg水平。总之，我们的结果表明，汉黄芩素在体外和体内均具有强大的抗HBV活性。目前，汉黄芩素作为一种抗HBV药物候选物正处于早期开发阶段。
