title: Comparison of Helicobacter pylori Urease Inhibition by Rhizoma Coptidis, Cortex Phellodendri and Berberine: Mechanisms of Interaction with the Sulfhydryl Group.
abstract: Rhizoma Coptidis, Cortex Phellodendri, and berberine were reported to inhibit Helicobacter pylori. However, the underlying mechanism remained elusive. Urease plays a vital role in H. pylori colonization and virulence. In this work, aqueous extracts of Rhizoma Coptidis, Cortex Phellodendri of different origins, and purified berberine were investigated against H. pylori urease and jack bean urease to elucidate the inhibitory capacity, kinetics, and mechanism. Results showed that berberine was the major chemical component in Rhizoma Coptidis and Cortex Phellodendri, and the content of berberine in Rhizoma Coptidis was higher than in Cortex Phellodendri. The IC50 values of Rhizoma Coptidis were significantly lower than those Cortex Phellodendri and purified berberine, of which Coptis chinensis was shown to be the most active concentration- and time-dependent urease inhibitor. The Lineweaver-Burk plot analysis indicated that the inhibition pattern of C. chinensis against urease was noncompetitive for both H. pylori urease and jack bean urease. Thiol protectors (L-cysteine, glutathione, and dithiothreithol) significantly protected urease from the loss of enzymatic activity, while fluoride and boric acid showed weaker protection, indicating the active-site sulfhydryl group was possibly responsible for its inhibition. Furthermore, the urease inhibition proved to be reversible since C. chinensis-blocked urease could be reactivated by glutathione. The results suggested that the anti-urease activity of Rhizoma Coptidis was superior to that of Cortex Phellodendri and berberine, which was believed to be more likely to correlate to the content of total alkaloids rather than berberine monomer. The concentration- and time-dependent, reversible, and noncompetitive inhibition against urease by C. chinensis might be attributed to its interaction with the sulfhydryl group of the active site of urease.
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China.
authors.forename: Cailan
authors.initials: C
authors.lastname: Li
authors.affiliation: Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Xie
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China.
authors.forename: Zhizhun
authors.initials: Z
authors.lastname: Mo
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wu
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China.
authors.forename: Yeer
authors.initials: Y
authors.lastname: Liang
authors.affiliation: The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China.
authors.forename: Zuqing
authors.initials: Z
authors.lastname: Su
authors.affiliation: Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China.
authors.forename: Yucui
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China.
authors.forename: Ziren
authors.initials: Z
authors.lastname: Su
authors.affiliation: Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yang
mesh_terms: D001599:Berberine / Q000494:pharmacology; D032449:Canavalia / Q000201:enzymology; D002681:China; D039323:Coptis / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000201:enzymology; D032102:Phellodendron / Q000737:chemistry*; D014510:Urease / Q000037:antagonists & inhibitors*
chemical_list: D004365:Drugs, Chinese Herbal; C528424:huangbai; D001599:Berberine; D014510:Urease