Metabolic Activation and Covalent Protein Binding of Berberrubine: Insight into the Underlying Mechanism Related to Its Hepatotoxicity

Wang, Kai; Rao, Jinqiu; Zhang, Tingting; Gao, Qing; Zhang, Jichao; Guang, Chenxi; Ding, Lei; Qiu, Feng

doi:10.2147/dddt.s274627

Cited by 10 publications

(2 citation statements)

References 43 publications

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“…Berberrubine, a natural isoquinoline alkaloid containing an MDP moiety, is widely distributed in many TCM remedies, such as the Huanglian Jiedu decoction, Huanglian Shangqing pills, and Niuhuang Qingxin pills. Wang et al [117] provided evidence for the formation of quinone metabolites from berberrubine, which can react with the cysteine residues of proteins to form protein adducts. Thus, protein adduction may play a significant role in berberrubine-induced hepatotoxicity.…”

Section: Metabolic Activation Of Natural Products In Tcmmentioning

confidence: 99%

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

Liu,

Wang,

Liu

et al. 2024

Acupuncture and Herbal Medicine

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Ensuring the safety of traditional Chinese medicines (TCM) has perennially presented a universal challenge in the healthcare realm. Meticulous investigations into the toxicological intricacies of natural products are of paramount significance, particularly regarding the metabolic transformation of these substances and the subsequent generation of reactive intermediates. This biochemical process underlies the genesis of diverse toxic manifestations, including hepatotoxicity, nephrotoxicity, pulmonary toxicity, and genotoxicity. Compounds sorted within TCM, including pyrrolizidine alkaloids, anthraquinones, furanoterpenoids, alkenylbenzenes, bisbenzylisoquinoline alkaloids, flavonoids, and methylenedioxyphenyl derivatives, evince a spectrum of deleterious mechanisms upon metabolic activation. This review provides a comprehensive delineation of the pathways through which these compounds induce toxicity via metabolic activation. This review emphasizes the chemical mechanisms involved in the metabolic activation of natural products that may trigger a toxic cascade, rather than a superficial phenomenon. Furthermore, this study enriches the extant literature by delving into advancements in elucidating the mechanisms of toxicity engendered by metabolic activation. In conclusion, this review highlights the importance of scrutinizing the mechanisms of toxicity and provides insights into the judicious and safe use of TCM.

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Section: Metabolic Activation Of Natural Products In Tcmmentioning

confidence: 99%

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

Liu,

Wang,

Liu

et al. 2024

Acupuncture and Herbal Medicine

View full text Add to dashboard Cite

show abstract

“…Some drugs, such as selinexor, aspirin, and penicillin, can modify the amino acids at specific sites of their target protein and inhibit the activity of the target protein, thus exerting therapeutic effects. Additionally, reactive (electrophilic) intermediates resulting from the metabolic activation of some xenobiotics can attack protein to form covalent modification, leading to changes in protein functions, which has been considered as one of important mechanisms of toxic action. − …”

Section: Introductionmentioning

confidence: 99%

Asparagine and Glutamine Residues Participate in Protein Covalent Binding by Epoxide Metabolite of 8-Epidiosbulbin E Acetate In Vitro and In Vivo

Zhang

Yang

et al. 2022

Chem. Res. Toxicol.

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Dioscorea Bulbifera L. (DBL), an effective traditional Chinese medicine, has been restricted because of multiple reports that it can cause severe hepatotoxicity. 8-Epidiosbulbin E acetate (EEA), one of the main components of DBL, can induce severe liver injury. It has been reported that EEA can be metabolized by CYP3A to the corresponding cis-enedial intermediate which alkylates the lysine residues of proteins to form pyrroline derivatives. The present study unexpectedly found that the reactive intermediate reacted with the amide groups of asparagine (Asn) and glutamine (Gln) residues of hepatic proteins of mice treated with EEA. The amide-derived protein modification increased with the increase in the dose administered. Like the adduction of the primary amine of lysine residues, the electrophilic metabolite reacted with the amide groups of Asn and Gln residues to offer the corresponding pyrrolines. The structures of the pyrrolines were confirmed by mass spectrometry and nuclear magnetic resonance spectroscopy.

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Phytochemical analysis and in vitro and in vivo antioxidant properties of Plagiorhegma dubia Maxim as a medicinal crop for diabetes treatment

Sun

Chen

et al. 2023

Arabian Journal of Chemistry

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Metabolic Activation and Covalent Protein Binding of Berberrubine: Insight into the Underlying Mechanism Related to Its Hepatotoxicity

Cited by 10 publications

References 43 publications

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

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

Asparagine and Glutamine Residues Participate in Protein Covalent Binding by Epoxide Metabolite of 8-Epidiosbulbin E Acetate In Vitro and In Vivo

Phytochemical analysis and in vitro and in vivo antioxidant properties of Plagiorhegma dubia Maxim as a medicinal crop for diabetes treatment

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