Toxicity and toxicokinetics of the ethanol extract of Zuojin formula

Author:

Wang Shuo,Zhang Tao,Liu Xiaoyan,Yang Zheng,Li Ludi,Shan Danping,Gao Yadong,Li Yingzi,Li Yanying,Zhang Youbo,Wang Qi

Abstract

Abstract Background Zuojin formula, a traditional Chinese medicine, comprises Coptis chinensis and Evodia rutaecarpa. In our previous study, the total alkaloid extract from Zuojin formula (TAZF) showed potent and improved efficacy. However, its safety and toxicokinetics remain unknown. The objective of this study was to evaluate the safety of repeated administrations of TAZF and investigate the internal exposure of the main components and its relationship with toxic symptoms. Methods Sprague–Dawley rats were orally administered TAZF at 0.4, 1.2 and 3.7 g/kg for 28 days, which was followed by a 14-day recovery period. The toxic effects were evaluated weekly by assessing body weight changes, food intake, blood biochemistry and haematological indices, organ weights and histological changes. A total of eight components were detected, including berberine, coptisine, epiberberine, palmatine, jatrorrhizine, columbamine, evodiamine, and rutaecarpine. The toxicokinetic profiles of the eight components were investigated after single and repeated administrations. Linear mixed effect models were applied to analyse the associations between internal exposure and toxic symptoms. Network pharmacology analysis was applied to explore the potential toxic mechanisms. Results Compared with the vehicle group, the rats in the low- and medium-dose groups did not show noticeable abnormal changes, while rats in the high-dose group exhibited inhibition of weight gain, a slight reduction in food consumption, abdominal bloating and atrophy of the splenic white pulp during drug administration. The concentration of berberine in plasma was the highest among all compounds. Epiberberine was found to be associated with the inhibition of weight gain. Network pharmacology analysis suggested that the alkaloids might cause abdominal bloating by affecting the proliferation of smooth muscle cells. The benchmark dose lower confidence limits (based on body weight inhibition) of TAZF were 1.27 g/kg (male) and 1.91 g/kg (female). Conclusions TAZF has no notable liver or kidney toxicity but carries risks of gastrointestinal and immune toxicity at high doses. Alkaloids from Coptis chinensis are the main plasma components related to the toxic effects of TAZF.

Publisher

Springer Science and Business Media LLC

Subject

Complementary and alternative medicine

Reference46 articles.

1. Zhu C, Shi W, Chen Y, Zhu X. Clinical application and experimental research progress of Zuojin pill. J Pract Tradit Chin Med. 2019;35(5):626–9.

2. Guan M, Xu W, Li H. Advances in modern pharmacology of Zuojin pills. Acta Chin Med Pharmacol. 2020;48(5):78–81.

3. Wang Y, Ma C. Research Progress on treatment of gastric ulcer with Zuojin pill. J Pract Tradit Chin Int Med. 2021;35(5):103–6.

4. Wang J, Zhang T, Zhu L, Ma C, Wang S. Anti-ulcerogenic effect of Zuojin pill against ethanol-induced acute gastric lesion in animal models. J Ethnopharmacol. 2015;173:459–67.

5. Ye N, Liu X, Li Q. Experimental research progress of Zuojinwan and its active constituents in anti gastric cancer. China J Tradit Chin Med Pharm. 2014;29(4):1162–4.

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