Hepatoprotective Effect of Polysaccharides Isolated from Dendrobium officinale against Acetaminophen‐Induced Liver Injury in Mice via Regulation of the Nrf2‐Keap1 Signaling Pathway

Abstract

The effect of polysaccharides isolated from Dendrobium officinale (DOP) on acetaminophen- (APAP-) induced hepatotoxicity and the underlying mechanisms involved are investigated. Male Institute of Cancer Research (ICR) mice were randomly assigned to six groups: (1) control, (2) vehicle (APAP, 230 mg/kg), (3) N-acetylcysteine (100 mg/kg), (4) 50 mg/kg DOP, (5) 100 mg/kg DOP, and (6) 200 mg/kg DOP. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum and glutathione (GSH), malondialdehyde (MDA), catalase (CAT), total antioxidant capacity (T-AOC), myeloperoxidase (MPO), and reactive oxygen species (ROS) levels in the liver were determined after the death of the mice. The histological examination of the liver was also performed. The effect of DOP on the Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was evaluated using Western blot analysis and real-time polymerase chain reaction (PCR). The results showed that DOP treatment significantly alleviated the hepatic injury. The decrease in ALT and AST levels in the serum and ROS, MDA, and MPO contents in the liver, as well as the increases in GSH, CAT, and T-AOC in the liver, were observed after DOP treatment. DOP treatment significantly induced the dissociation of Nrf2 from the Nrf2−Keap1 complex and promoted the Nrf2 nuclear translocation. Subsequently, DOP-mediated Nrf2 activation triggered the transcription and expressions of the glutamate–cysteine ligase catalytic (GCLC) subunit, glutamate–cysteine ligase regulatory subunit (GCLM), heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1) in APAP-treated mice. The present study revealed that DOP treatment exerted potentially hepatoprotective effects against APAP-induced liver injury. Further investigation about mechanisms indicated that DOP exerted the hepatoprotective effect by suppressing the oxidative stress and activating the Nrf2−Keap1 signaling pathway.

Chrysanthemum extract attenuates hepatotoxicity via inhibiting oxidative stress in vivo and in vitro

“…The change in ROS expression is consistent. The same result is found in other studies (55, 56). In addition, significant upregulation of HO-1 expression occurred in BZE + APAP-treated cells.…”

Salvianolic Acid C against Acetaminophen-Induced Acute Liver Injury by Attenuating Inflammation, Oxidative Stress, and Apoptosis through Inhibition of the Keap1/Nrf2/HO-1 Signaling

“…Nrf2 also has a crucial role in maintaining cellular redox homeostasis that allows adaptation and survival against mitochondrial damage and cell death. HO-1/Nrf2 signals have potentials to avoid the drug-induced hepatocellular injury [32]. In this study, we showed that SAC stimulated the expression of HO-1 and Nrf2 proteins by reducing oxidative damage and regulating antioxidative enzymes to protect against APAP-induced hepatotoxicity.…”

“…Oxidative stress is highly correlated with APAP-induced hepatotoxicity that promotes ROS and NO overproduction because APAP-induced acute liver failure reduced antioxidant enzyme expression [31]. SOD, CAT, and GPx are antioxidant enzymes protecting cells from oxidative stress [32]. The Nrf2/Keap1 pathway is a key cellular defense mechanism that plays a key role in the regulation of phase II detoxifying and antioxidant enzymes in preventing APAP-induced acute liver failure [33].…”

“…GCLC, GCLM, NQO1, and HO-1 are phase II enzymes regulated by Nrf2. GCL, composed of the catalytic subunit GCLC and the modified subunit GCLM, is a rate-limiting enzyme that regulates GSH biosynthesis [32]. The induction of these two proteins by SAC is accompanied by an increase in GSH levels, which may explain how SAC/APAP cotreatment can increase GSH levels.…”

Structure Identification of ViceninII Extracted from Dendrobium officinale and the Reversal of TGF-β1-Induced Epithelial–Mesenchymal Transition in Lung Adenocarcinoma Cells through TGF-β/Smad and PI3K/Akt/mTOR Signaling Pathways

“…According to Chinese medicine theory, (Bulpitt, 2007 #502; Yu, 2018 #503) D. officinale clears heat and nourishes the lung, thereby treating lung-related diseases and improving the overall life quality of patients with lung cancer [29]. In modern pharmacological studies, (Bulpitt, 2007 #502; Yu, 2018 #503) D. officinale has displayed significant bio-active functions, including immunomodulatory [30,31], antioxidant [32,33], anti-inflammatory [34], antitumor [35,36] and hepatoprotective functions [37]. To date, most of the research in this area has been focused on polysaccharides and extracts from (Bulpitt, 2007 #502; Yu, 2018 #503) D. officinale , but flavonoids are a widespread group of significant substances with various biological pharmacological functions [38].…”