Metabolism‐based herb–drug interaction of Corydalis Bungeanae Herba with berberine in vitro and in vivo in rats

Abstract

Corynoline (CRL) and berberine (BER) are the major bioactive components found in traditional Chinese medicines Corydalis Bungeanae Herba (Corydalis bungeanae) and Coptidis Rhizoma, respectively. The two herbs serve as anti‐inflammatory agents and are generally applied to many prescriptions. The aims of the study were to evaluate herb–drug interaction of C. bungeanae with BER and to investigate the mechanisms of the interaction action. Pre‐treatment of BER caused reduction of plasma CRL in rats with increased formation of its three oxidative metabolites (M1–M3). Compared with the vehicle‐treated group, the peak concentration and area under the concentration–time curve of CRL decreased by ~60% (given CRL) and ~50% (given extracts) in rats pre‐treated with BER, respectively, along with 130 and 100% increases in apparent clearance. More M1–M3 were formed in liver microsomes of rats pretreated with BER (7 days) than in those pretreated with vehicle. Additionally, elevated activities of rCYPs2D2 and 1A2 (CYPs2D6 and 1A2) were observed in the BER‐induced group. Up‐regulated expression of hepatic rCYP2D2 (CYP2D6) was found in animals after 7 days of treatment of BER. The study illustrated that C. Bungeanae and BER produced metabolic herb–drug interaction and provided important information that combination of C. bungeanae with BER‐containing herbal medicines may encounter the risk of decreased efficacy of CRL.

Chemical nature of metabolic activation of natural products in traditional Chinese medicines possibly associated with toxicities

“…This intermediate subsequently reacts with the enzyme, resulting in quasi-irreversible or irreversible enzyme inhibition [109] . Inhibition of P450s is widely recognized as the primary factor contributing to drug-drug interactions (DDIs) [110] . For MDP natural products, the metabolic oxidation of MDP groups results in the generation of carbene intermediates, which can complex with heme iron in P450s [108] .…”

Pharmacokinetic of berberine, the main constituent of Berberis vulgaris L.: A comprehensive review

“…Pre-treatment with berberine enhanced the level of these enzymes in rats. Thus, concomitant administration of berberine and corynoline reduced the AUC value of the corynoline by 50% and elevated its apparent clearance by almost 100% (Mao et al, 2019). Zhou et al (2012) evaluated the interaction between ketoconazole and berberine in rats.…”