Matrine alleviates cisplatin‐induced acute kidney injury by inhibiting mitochondrial dysfunction and inflammation viaSIRT3/OPA1pathway

Abstract

Cisplatin is extensively used to treat malignancies. However, its clinical use is always limited due to the serious side effects, especially the nephrotoxicity. Matrine (MAT), a tetracyclic quinolizine alkaloid found in sophora genus, exerts multiple pharmacological roles, including anti‐oxidative stress, anti‐inflammation and anti‐apoptosis, but the role of MAT on acute kidney injury (AKI) has not been evaluated. Here, we found that MAT potently inhibited cell injury induced by cisplatin in HK2 cells in vitro, which was associated with the inhibition of oxidative injury and NF‐κB‐mediated inflammation. Moreover, MAT treatment could activate the SIRT3/OPA1 axis and subsequently suppress the mitochondrial fragmentation and improve mitochondrial function. More importantly, SIRT3 knockdown suppressed the deacetylation of OPA1, which blocked the protective role of MAT on cisplatin‐induced cell injury. In vivo, MAT treatment alleviated renal dysfunction, histological damage and inflammation induced by cisplatin in mice. Furthermore, consistent with the founding in vitro, MAT also activated SIRT3‐mediated deacetylation of OPA1 and alleviated mitochondrial dysfunction in AKI mice. Our study proved that MAT protected against cisplatin‐induced AKI by synergic anti‐oxidative stress and anti‐inflammation actions via SIRT3/OPA1‐mediated improvement of mitochondrial function, suggesting that MAT may be a novel and effective strategy for AKI.

The cardioprotective effect of human glucagon‐like peptide‐1 receptor agonist (semaglutide) on cisplatin‐induced cardiotoxicity in rats: Targeting mitochondrial functions, dynamics, biogenesis, and redox status pathways

“…The results herein are in harmony with previous reports of Ijaz et al, where CP injection has disrupted mitochondrial function as observed by reduced (ETC) enzymes, as succinic‐coenzyme Q, NADH dehydrogenase, cytochrome c‐oxidase, and mitochondria ΔΨm 30 . Similarly, Yuan et al, reported low ATP and decline in mitochondrial ΔΨm upon CP injection 31 . The current study has shown the protective effect of semaglutide against mitochondrial damage induced by CP.…”

From Physiology to Pathology: The Role of Mitochondria in Acute Kidney Injuries and Chronic Kidney Diseases

“…Recent studies have demonstrated mitochondrial structural and functional changes in kidney injuries induced by cisplatin, APAP, aminoglycoside, and contrast agents [47–50]. Consistent with other studies, our findings have shown that cisplatin-induced mitochondrial injury is characterized by impaired energy metabolism and increased ROS production, dysregulated mitochondrial dynamics, and altered mitophagy [42, 43, 48, 51–55]. As with I/R-induced AKI, cisplatin-induced AKI is also accompanied with FAO disruption and inducing FAO improves cisplatin-induced AKI [56, 57].…”

Matrine inhibits cell proliferation, invasion, and stem cell formation in hepatocellular carcinoma by regulating the ELAVL1/RBM3‐mediated Wnt/β‐catenin signaling pathway

“…Nowadays, there is convincing evidence that many natural products from TCM have been popularly used in health care, which is gaining more and more attention all over the world (Liu, Yang, Wang, Lu, et al., 2020; Wang, Wong, et al., 2018). As a naturally occurring alkaloid from sophora favescens, Martine has long been applied for the treatment of inflammation diseases and tumors (Lin et al., 2022; Yuan et al., 2022). Beyond that, it has been reported that applying Martine displayed some health benefits, such as analgesic, anti‐viral, and anti‐tumor activity (Zhang et al., 2020).…”