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.

Inhibition of Helicobacter pylori and Its Associated Urease by Palmatine: Investigation on the Potential Mechanism

“…chinensis alkaloids (berberine, coptisine, palmatine and epiberberine), while berberine was relatively more toxic in both in vitro and in vivo assays [33]. In our previous investigation, the IC 50 of berberine against HPU and JBU was 10.20 ± 1.10 mM and above 13.00 mM, respectively [8], indicating the anti-urease activity of berberine was weaker as compared with that of Pal. Hence, it was concluded that Pal might exert more potent gastroprotective, anti- H .…”

“…And the anti-urease effect of C . chinensis was more pronounced than its major active constituent berberine [8], implying that ingredients other than berberine might also play an important role in its urease inhibition. Palmatine (C 21 H 25 NO 4 , Pal), an active naturally occurring isoquinoline alkaloids, is another important bioactive component derived from C .…”

The Efficacy of Berberine-Containing Quadruple Therapy on Helicobacter Pylori Eradication in China: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

“…Many new strategies have been proposed, such as supplements of probiotics and TCM. Studies of TCM on H. pylori have shown that some herbs such as R. coptidis, C. phellodendri, and berberine can inhibit H. pylori (Li et al, 2016). Many clinical trials have also shown that berberine, an antimicrobial, antidiabetic, anti-inflammatory, and antitumor drug can be used to treat H. pylori-induced chronic gastritis in vitro and in vivo (Chang et al, 2011;Lin et al, 2015;Tan et al, 2017;Wu et al, 2018).…”

A LC‐MS/MS method for simultaneous determination of seven alkaloids in rat plasma after oral administration of Phellodendri chinensis cortex extract and its application to a pharmacokinetic study

“…With regard to Phellodendri chinensis cortex , the alkaloids, polysaccharides , flavonoids , phytosterols, coumarins , and triterpenes are the major ingredients. A large amount of pharmacological reports proved that alkaloid components including phellodendrine, jatrorrhizine, palmatine, berberine, magnoflorine, columbamine, protopine, and tetrahydropalmatine were the main active components of Phellodendri chinensis cortex . Modern pharmacological experiments suggested that Phellodendri chinensis cortex possessed various pharmacological actions , which has been widely prescribed to remove damp heat, eliminate dampness, counteract toxicity, purge pathogenic fire, relieve consumptive fever, diarrhea and other syndromes .…”