Oxymatrine and its metabolite matrine contribute to the hepatotoxicity induced by radix Sophorae�tonkinensis in mice

Abstract

Previous studies by our group demonstrated that radix Sophorae tonkinensis could induce hepatotoxicity. However, it remains unclear which components of this herb may be responsible for its hepatotoxicity. The present study aimed to investigate the hepatic toxicity of treatment with matrine (MT) and oxymatrine (OMT) alone or simultaneously. Furthermore, the current study aimed to identify whether the hepatotoxicity induced by OMT is actually the toxic characterization of its metabolite MT. Hepatotoxicity was evaluated by biochemical and histopathological approaches in subchronic toxicity in mice, as well as via evaluation of cytotoxicity and enzyme leakage in AML12 liver cells. The results indicated that treatment of mice with OMT and MT individually or simultaneously resulted in centrilobular hypertrophy in the liver at doses equivalent to that contained in radix S. tonkinensis at a hepatotoxic dose, suggesting that MT and OMT are likely hepatotoxic components of this herb. OMT-induced hepatotoxicity may be primarily exerted via its metabolite MT in mice. Furthermore, OMT combined with MT was observed to be more toxic compared with OMT or MT alone. These results extend our understanding of the hepatotoxicity of radix S. tonkinensis and its active ingredients.

Electroacupuncture Ameliorates Cerebral I/R‐Induced Inflammation through DOR‐BDNF/TrkB Pathway

“…Cell viability was determined by the cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) release. CCK-8 assay was performed according to the manufacturer's instructions (Beyotime Biotechnology, Shanghai, China) and similar to our previous study [29]. In brief, PC12 cells were seeded in 96-well plate at 1 × 10 5 cells/mL and allowed to adhere properly for 24 h. After OGD/R insult, 10 μl of the CCK-8 solution was added to each well and was incubated for another 1.5 h under the same incubator conditions.…”

A Systematic Review of the Pharmacology, Toxicology and Pharmacokinetics of Matrine

“…Matrine (MT) ( Figure 1) is a naturally occurring alkaloid and a bioactive component of Chinese herbs, including Sophora flavescens and Radix Sophorae tonkinensis (Gu et al, 2019;You et al, 2019). These herbs have a long medicinal history in China and many Eastern Asian countries.…”

Systematic analysis of chemical profiles of Sophorae tonkinensis Radix et Rhizoma in vitro and in vivo using UPLC‐Q‐TOF‐MSE

“…Alkaloids such as cytisine, matrine, oxymatrine, and sophocarpine have shown significant antiviral ability (Pan et al, 2015), hepatoprotective effect (Wan et al, 2009), and neuroprotective property (Liu, Zhang, et al, 2017; Wang et al, 2018) because of their high bioavailability. These alkaloids were also found to have neurotoxicity (Lu et al, 2014), cardiotoxicity (Wang, Xia, et al, 2019), and hepatotoxicity (Gu et al, 2019). Two triterpene saponins, soyasaponin I and soyasaponin II, have shown the hepatoprotective property (Ikeda et al, 1998).…”