Protective effects of catalpol on mitochondria of hepatocytes in cholestatic liver injury

Abstract

cholestasis, which is caused by the obstruction of bile flow, can lead to rapid organ injury, cell apoptosis and necrosis of hepatocytes, and may eventually develop into fibrosis and cirrhosis. Oxidative stress and mitochondrial dysfunction are the key pathogenic signs of hepatic cholestasis. Catalpol has pharmacological activities, including antioxidative and anti-inflammatory effects, and may relieve mitochondrial damage and restore mitochondrial membrane potential. However, the potential roles and mechanisms of catalpol in cholestasis-induced liver injury are not clear. in the present study, liver function-related indexes were measured in the serum of mice by commercial kits. In addition, levels of serum inflammatory factors were detected by ELISA. Hematoxylin and eosin staining was performed to observe histopathological changes, and mitochondrial membrane potential was detected using JC-1 staining. Mitochondrial adenosine triphosphate (ATP), reactive oxygen species (ROS) and malondialdehyde levels were determined using a luciferase reporter kit, flow cytometry and a thiobarbituric acid reactive substance assay kit, respectively. Western blotting was performed to detect the expression levels of apoptosis-related proteins in liver tissues. The findings revealed that catalpol reduced liver damage caused by cholestasis, improved the mitochondrial membrane potential, and increased the aTP content and glutathione content of cholestasis model mice. Moreover, catalpol also reduced the roS level, inhibited lipid peroxidation, and regulated oxidative stress and apoptotic protein expression. Thus, the present study preliminarily confirmed that catalpol can reduce liver injury in a mouse model of cholestasis through inhibiting oxidative stress and enhancing mitochondrial membrane potential.

The Mechanism of Catalpol in Alzheimer’s Disease by Modulating Mitochondrial Function Through miR-124-Mediated STIM2

“…ΔΨm in AD cells was decreased while ΔΨm was increased after catalpol treatment. Catalpol reduces ROS level and enhanced mitochondrial ΔΨm in mice with liver injury, and reduces mitochondrial damage in ischemic injury (Cai et al, 2018;Gao et al, 2020). These results demonstrated that catalpol reduced Aβ 1−42 -induced mitochondrial damage and ROS generation.…”

The Jieduan-Niwan (JDNW) Formula Ameliorates Hepatocyte Apoptosis: A Study of the Inhibition of E2F1-Mediated Apoptosis Signaling Pathways in Acute-on-Chronic Liver Failure (ACLF) Using Rats

“… 45 Catalpol improves the mitochondrial membrane potential and regulates inflammatory cytokines and the expression of apoptotic proteins through antioxidant effects and protects the liver from cholestasis-mediated injury. 46 GA inhibits lipid accumulation, apoptosis and inflammation in hepatocytes by activating AMPK. 47 CA alleviates oxidative stress in the liver by scavenging mitochondria and intracellular ROS, inhibits steatosis, hepatocyte apoptosis and liver fibrosis, and improves alcoholic liver injury.…”

Catalpol inhibits hepatic stellate cell activation by reducing the formation and changing the contents of hepatocyte-derived extracellular vesicles

“…Catalpol (CTP), an iridoid glycoside extracted from traditional Chinese medicine Rehmannia glutinosa , has been reported to have antitumor (Zhu et al 2017), antidiabetic (Zhu et al 2016; Bao et al 2016), anti‐inflammatory (Park 2016), anti‐asthma (Chen et al 2017), antioxidant, and other remarkable pharmacological effects. CTP also has a palliative effect on hepatic fibrosis and has been shown to alleviate CCl 4 ‐induced hepatic fibrosis in rats and cholestasis‐induced mouse liver injury (Liu et al 2018; Gao et al 2020). However, whether CTP could alleviate mouse hepatic fibrosis and the underlying mechanisms remain unknown.…”