Antioxidant activities of ginsenoside Rg1 against cisplatin-induced hepatic injury through Nrf2 signaling pathway in mice

Abstract

Oxidative stress is mainly caused by reactive oxygen species (ROS). The damage causes a net stress on normal organs, leading to a gradual loss of vital physiological function. ROS, such as free radicals, represent a class of molecules which are derived from the metabolism of oxygen and exist inherently. However, excessive produced ROS can damage all aerobic organisms. Ginseng is one of the most commonly used alternative herbal medicines, also as a traditional Chinese medicine. The aim of this study is to investigate the antioxidant potential function of ginsenoside Rg1 against cisplatin-caused hepatic damage. Male mice were treated with cisplatin to induce oxidative stress to mimic the side effect of anti-cancer drug cisplatin. Ginsenoside Rg1 effectively prevented against cisplatin-induced hepatotoxicity, alleviating histological lesions. Antioxidant functions of Rg1 were restrained by the activation of p62-Keap1-Nrf2 signaling pathway, simultaneously accompanied with expression of protein products. Accumulative p62 and increased activation of JNK in hepatocytes promoted the activation of Nrf2. For the other, degradation of Nrf2 was guided by tyrosine phosphorylation, ubiquitin, and Keap1. In summary, Rg1 prevents hepatotoxicity mainly by inhibiting the binding of Keap1 and Nrf2, partly by p62 accumulation, and more importantly by increasing the production of antioxidative proteins associated to Nrf2. Pharmacological activation of Nrf2 is an effective way in combating against liver injury.

Ginsenoside Rg1 protects against ischemic/reperfusion-induced neuronal injury through miR-144/Nrf2/ARE pathway

“…It has been proven that Rg1 protects the brain against oxidative stress in many pathological conditions, such as Parkinson's disease [42,43], Alzheimer disease [44], D-galactose-induced brain aging [45], and others. Our previous study showed that Rg1's hepatic protection effect was mainly due to its antioxidant activity [35,46]. However, whether the efficacy of Rg1 against oxidative stress is involved in its antistroke capability has not been reported until now.…”

“…The pellet and supernatant were treated separately. Brain samples were lysed by adding 10 times volume/quantity of cytosol extraction buffer A, and the subsequent protocol was the same as previously described [35].…”

Clinical Efficacy and Safety of Aidi Injection Plus Docetaxel‐Based Chemotherapy in Advanced Nonsmall Cell Lung Cancer: A Meta‐Analysis of 36 Randomized Controlled Trials

“…Liu L and et.al [88] had shown that Astragalus injection ameliorated the cisplatin-induced nephrotoxicity through regulating the Bax and Bcl-2 expression in mice. Other study [89] had shown that ginsenoside Rg1 also had antioxidant activities which ameliorated the cisplatin-induced hepatic injury through Nrf2 signaling pathway in mice. All these revealed that Astragalus and Ginseng could ameliorate chemotherapy related toxicity through enhancing the antimyelotoxicity activity, antiapoptotic, and antioxidant activities.…”

CCl4-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway

“…Dysfunction of detoxification and the metabolic pathways of the liver lead to liver injury and various liver diseases such as hepatitis, fatty liver disease, and fibrosis [2][3][4]. Currently, drugs used to treat liver injury are limited in efficacy or elicit many adverse reactions [5,6]. e drug pair Astragalus membranaceus (Huangqi)-Pueraria lobata (Gegen) was originally described in "Zhengzhihuibu," written during the Qing Dynasty of China.…”