Emodin in Rheum undulatum inhibits oxidative stress in the liver via AMPK with Hippo/Yap signalling pathway

Abstract

Context: Emodin is a compound in Rheum undulatum Linne (Polygonaceae) that has been reported to exert anti-inflammatory, antibacterial, and antiallergic effects. Objective: Oxidative stress is a causative agent of liver inflammation that may lead to fibrosis and hepato-carcinoma. In this study, we investigated the antioxidant effects of emodin and its mechanism. Materials and methods: We used the hepatocyte stimulated by arachidonic acid (AA) þ iron cotreatment and the C57B/6 mice orally injected with acetaminophen (APAP, 500 mg/kg, 6 h), as assessed by immunoblot and next generation sequencing (NGS). Emodin was pre-treated in hepatocyte (3 $ 30 lM) for 1 h before AA þ iron, and in mice (10 and 30 m/kg, P.O.) for 3 days before APAP. Results: In vitro, emodin treatment inhibited the cell death induced by AA þ iron maximally at a dose of 10 lM (EC 50 > 3 lM). In addition, emodin attenuated the decrease of anti-apoptotic proteins, and restored mitochondria membrane potential as mediated by the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. LKB1 mediated AMPK activation was verified using the LKB1 deficient cell line, HeLa. Emodin (10 lM; after 10 min) also induced the phosphorylation of Yes-associated protein 1 (YAP1), the main downstream target of the Hippo signalling pathway that mediated oxidative stress or the ROS-initiated signalling pathway. In vivo, the oral treatment of emodin (10 and 30 m/kg, 3 days) decreased APAP-induced hepatic damage, as indicated by decreases in antioxidant genes as well as tissue damage. Conclusion: Our results show that emodin inhibits oxidative liver injury via the AMPK/YAP mediated pathway.

Emodin Attenuates Acetaminophen-Induced Hepatotoxicity via the cGAS-STING Pathway

“…Emodin (1,3,8trihydroxy-6-methylanthraquinone) (Fig. 1), a natural anthraquinone derivative, is the main active component and the quality control index of RP [16,17]. Emodin has been shown to have various biological activities, such as hepatoprotective, anticancer, antibacterial, neuroprotective, antidiabetic, antiin ammation, and anti-oxidants [18,19].…”

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

“…Emodin (1, 3, 8-trihydroxy-6-methylanthraquinone) is a natural anthraquinone derivative, and is the main ingredient of many herbs including rhubarb, polygonum multiflorum , and polygonum cuspidatum ( Dong et al., 2016 ; Monisha et al., 2016 ). Pharmacological studies have shown that emodin, as a polyvalent molecule, has a variety of biological functions, such as anti-inflammatory ( Li X. et al., 2020 ; Xu et al., 2020 ), anti-bacterial ( Ji et al., 2020 ), anti-cancer ( Wu C. et al., 2019 ; Ma et al., 2020 ; Rossi et al., 2020 ) and inhibition of oxidative stress( Lee et al., 2020 ). Emodin has also been shown to have potent anti-cardiovascular activities in vitro and in vivo , including anti-inflammatory ( Wu et al., 2007 ), antioxidant damage ( Du and Ko, 2005 ), inhibition of myocardial cell fibrosis ( Evans et al., 2020 ) and other pharmacological effects.…”

Emodin‐Induced Oxidative Inhibition of Mitochondrial Function Assists BiP/IRE1α/CHOP Signaling‐Mediated ER‐Related Apoptosis

“…Abnormal ROS levels and oxidative stress always participate in the following toxic effects induced by internal toxicants or xenobiotic exposure [ 15 , 16 ]. A previous study reported that emodin treatment promoted ROS content in the rat liver [ 17 ], but several studies found that low doses of emodin could inhibit ROS-mediated oxidative stress in HeLa cells and rat macrophages [ 12 , 18 ]. In conformity with earlier findings related to non-hepatocytes, our results demonstrated that emodin-induced ROS generation was associated with emodin-caused hepatic cytotoxicity.…”

“…Unfortunately, no report is currently available that emodin induces ROS generation and the consequent ER stress- and/or mitochondrial-related apoptosis in hepatocytes. Instead, emodin (10 μ M) could inhibit oxidative stress generated by arachidonic acid plus iron [ 12 ]. Thus, the role of ROS-mediated mitochondrial dysfunction, ER stress, and related apoptotic cell death in hepatotoxicity caused by emodin needs to be explored.…”