title: [Active components of Ligustrum lucidum inhibiting hepatitis C virus replicase activity].
abstract: Based on previous report that the Chinese herb Ligustrum lucidum (LL) extract directly inhibited hepatitis C virus (HCV) replicase (NS5B) activity, the active components of LL extract to inhibit HCV NS5B activity and their inhibition mode were investigated in this study. LL extract was separated using ethyl acetate and thin layer chromatography (TLC). The inhibitory activity of separated fractions on HCV NS5B was analyzed by the inhibitory assay of NS5B activity. The results showed that only fractions 1 and 2 inhibited NS5B activity, and fraction 2 possessed higher inhibitory activity than fraction 1. HPLC analysis combined with inhibitory assays indicated that ursolic acid and oleanolic acid are the active components within fractions 1 and 2 to inhibit NS5B activity, separately. Moreover, oleanolic acid possessed higher inhibitory activity than ursolic acid. Further inhibition mode analysis found that both oleanolic acid and ursolic acid suppressed NS5B activity as noncompetitive inhibitors. The Ki values of ursolic acid and oleanolic acid were about 4.7 microg x mL(-1) (10 micromol x kg(-1)) and 2.5 microg x mL(-1) (5.5 micromol x kg(-1)), respectively. Taken together, these results demonstrated that oleanolic acid and ursolic acid suppressed NS5B activity as noncompetitive inhibitors, implying that the two natural products have potential value for HCV therapy.
authors.affiliation: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang 330045, China.
authors.forename: Rui-na
authors.initials: RN
authors.lastname: Sun
authors.affiliation: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang 330045, China.
authors.forename: Yan-ni
authors.initials: YN
authors.lastname: Zhang
authors.affiliation: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang 330045, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang 330045, China.
authors.forename: Hao-ju
authors.initials: HJ
authors.lastname: Liu
authors.affiliation: College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang 330045, China.
authors.forename: Ling-bao
authors.initials: LB
authors.lastname: Kong
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D031659:Ligustrum / Q000737:chemistry*; D009828:Oleanolic Acid / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000097245:Ursolic Acid; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D004365:Drugs, Chinese Herbal; D009828:Oleanolic Acid; D014315:Triterpenes; D017361:Viral Nonstructural Proteins; D000097245:Ursolic Acid; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase