Protective effects of extracts of Schisandra chinensis stems against acetaminophen-induced hepatotoxicity via regulation of MAPK and caspase-3 signaling pathways.

The present study was designed to evaluate protective activity of an ethanol extract of the stems of Schisandra chinensis (SCE) and explore its possible molecular mechanisms on acetaminophen (APAP) induced hepatotoxicity in a mouse model. The results of HPLC analysis showed that the main components of SCE included schisandrol A, schisandrol B, deoxyschisandrin, schisandrin B, and schisandrin C and their contents were 5.83, 7.11, 2.13, 4.86, 0.42 mg·g-1, respectively. SCE extract was given for 7 consecutive days before a single hepatotoxic dose of APAP (250 mg·kg-1) was injected to mice. Our results showed that SCE pretreatment ameliorated liver dysfunction and oxidative stress, which was evidenced by significant decreases in aspartate transaminase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA) contents and elevations in reduced glutathione (GSH) and superoxide dismutase (SOD) levels. These findings were associated with the result that the SCE pretreatment significantly decreased expression levels of 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT). SCE also significantly decreased the expression levels of Bax, mitogen- activated protein kinase (MAPK), and cleaved caspase-3 by APAP exposure. Furthermore, supplementation with SCE suppressed the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), suggesting alleviation of inflammatory response. In summary, these findings from the present study clearly demonstrated that SCE exerted significant alleviation in APAP-induced oxidative stress, inflammation and apoptosis mainly via regulating MAPK and caspase-3 signaling pathways.

• Publication year

  2018

• Venue

  Chinese Journal of Natural Medicines

• Publication date

  2018-09-01

• Fields of study

  Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.1016/S1875-5364(18)30110-9PMID 30269847
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Improvement of Cisplatin-induced renal dysfunction by Schisandra chinensis stems via anti-inflammation and anti-apoptosis effects.

  2018cited by this paper
• Saponins (Ginsenosides) from the Leaves of Panax quinquefolius Ameliorated Acetaminophen-Induced Hepatotoxicity in Mice.

  2017cited by this paper
• Hydrogen saline suppresses neuronal cell apoptosis and inhibits the p38 mitogen-activated protein kinase-caspase-3 signaling pathway following cerebral ischemia-reperfusion injury

  2017cited by this paper
• Ameliorative Effects and Possible Molecular Mechanism of Action of Black Ginseng (Panax ginseng) on Acetaminophen-Mediated Liver Injury

  2017cited by this paper
• Caspase-Mediated Anti-Apoptotic Effect of Ginsenoside Rg5, a Main Rare Ginsenoside, on Acetaminophen-Induced Hepatotoxicity in Mice.

  2017cited by this paper
• In Vivo and In Vitro Hepatoprotective Effects of Geranium koreanum Methanolic Extract via Downregulation of MAPK/Caspase-3 Pathway

  2017cited by this paper
• Nephroprotective Effects of Saponins from Leaves of Panax quinquefolius against Cisplatin-Induced Acute Kidney Injury

  2017cited by this paper
• The beneficial effects of ozone therapy in acetaminophen-induced hepatotoxicity in mice

  2016cited by this paper
• Dioscin alleviates dimethylnitrosamine-induced acute liver injury through regulating apoptosis, oxidative stress and inflammation.

  2016cited by this paper
• Determination of lignans and phenolic components of Schisandra chinensis (Turcz.) Baill. using HPLC-ESI-ToF-MS and HPLC-online TEAC: Contribution of individual components to overall antioxidant activity and comparison with traditional antioxidant assays

  2016cited by this paper
• Schisandrol B protects against acetaminophen-induced acute hepatotoxicity in mice via activation of the NRF2/ARE signaling pathway

  2016cited by this paper
• Nrf2-mediated liver protection by esculentoside A against acetaminophen toxicity through the AMPK/Akt/GSK3β pathway.

  2016cited by this paper
• Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update

  2016cited by this paper
• Tropisetron Protects Against Acetaminophen-Induced Liver Injury via Suppressing Hepatic Oxidative Stress and Modulating the Activation of JNK/ERK MAPK Pathways

  2016cited by this paper
• Ginsenoside Rg5 Ameliorates Cisplatin-Induced Nephrotoxicity in Mice through Inhibition of Inflammation, Oxidative Stress, and Apoptosis

  2016cited by this paper
• Production of schisantherin A and gomisin G in in vitro cultures of Schisandra chinensis

  2015cited by this paper
• The therapeutic detoxification of chlorogenic acid against acetaminophen-induced liver injury by ameliorating hepatic inflammation.

  2015cited by this paper
• Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

  2015cited by this paper
• Hepato-protective effects of six schisandra lignans on acetaminophen-induced liver injury are partially associated with the inhibition of CYP-mediated bioactivation.

  2015cited by this paper
• Anti-Inflammatory Property of Plantago major Leaf Extract Reduces the Inflammatory Reaction in Experimental Acetaminophen-Induced Liver Injury

  2015cited by this paper
• Ameliorative Effects of 5-Hydroxymethyl-2-furfural (5-HMF) from Schisandra chinensis on Alcoholic Liver Oxidative Injury in Mice

  2015cited by this paper
• Suppression of MAPK and NF-κ B pathways by schisandrin B contributes to attenuation of DSS-induced mice model of inflammatory bowel disease.

  2015cited by this paper
• Schisandrin B attenuates acetaminophen‐induced hepatic injury through heat‐shock protein 27 and 70 in mice

  2014cited by this paper
• The protective mechanism of schisandrin A in d-galactosamine-induced acute liver injury through activation of autophagy

  2014cited by this paper
• Protective effects from Houttuynia cordata aqueous extract against acetaminophen-induced liver injury

  2014cited by this paper
• Inhibitory effects of Schisandra chinensis on acetaminophen-induced hepatotoxicity.

  2014cited by this paper
• Schisandra chinensis Prevents Alcohol-Induced Fatty Liver Disease in Rats

  2014cited by this paper
• Fas receptor-deficient lpr mice are protected against acetaminophen hepatotoxicity due to higher glutathione synthesis and enhanced detoxification of oxidant stress.

  2013cited by this paper
• Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation.

  2012cited by this paper
• Targeting nitrosative stress for neurovascular protection: new implications in brain diseases.

  2012cited by this paper
• Lignans in Schisandra chinensis in vitro cultures.

  2011cited by this paper
• Acetaminophen induced acute liver failure via oxidative stress and JNK activation: Protective role of taurine by the suppression of cytochrome P450 2E1

  2010cited by this paper
• Integral pharmacokinetics of multiple lignan components in normal, CCl4-induced hepatic injury and hepatoprotective agents pretreated rats and correlations with hepatic injury biomarkers.

  2010cited by this paper
• Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine.

  2008cited by this paper
• Mitochondrial protection by the JNK inhibitor leflunomide rescues mice from acetaminophen‐induced liver injury

  2007cited by this paper
• TNF receptor superfamily‐induced cell death: redox‐dependent execution

  2006cited by this paper
• Mitochondria as the target of the pro-apoptotic protein Bax.

  2006cited by this paper
• Nitric oxide, oxidants, and protein tyrosine nitration

  2004cited by this paper
• Interleukin 6 and hepatocyte regeneration in acetaminophen toxicity in the mouse.

  2003cited by this paper

• Facile electrochemical determination of acetaminophen at micromolar levels utilizing conjugated bimetallic Co–Zn porphyrin polymer electrodes as sensing platforms

  2025cites this paper
• Unraveling chemotherapy-evoked hepatic dysfunction: a deep dive into cyclophosphamide-related liver injury

  2025cites this paper
• Polymer-engineered delivery systems for Schisandra lignans: A review of advances in hepatic-targeted therapy.

  2025cites this paper
• Levomilnacipran alleviates cyclophosphamide-induced hepatic dysfunction in male Wistar albino rats; emerging role of α-Klotho/TLR4/p38-MAPK/NF-κB p65 and caspase-3-driven apoptosis trajectories.

  2025cites this paper
• 牡荆素-4″-O-葡萄糖苷对对乙酰氨基酚诱导急性肝损伤有改善作用

  2025cites this paper
• Two rare C14-C15 chemical bond-breaking 7/5/5 skeleton schinortriterpenoids and their neuroprotective activities of against CORT-induced apoptosis of PC12 from the Schisandra chinensis leaves and stems.

  2025cites this paper
• A strategy to comprehensively and quickly identify the chemical constituents in Wuteng tablets by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

  2024cites this paper
• A transcriptomics and network pharmacology approach to elucidate the mechanism of action of geniposide on carbon tetrachloride-induced liver injury in rats.

  2023cites this paper
• Natural Products for Acetaminophen-Induced Acute Liver Injury: A Review

  2023cites this paper
• Dibenzocyclooctadiene lignans from the family Schisandraceae: A review of phytochemistry, structure-activity relationship, and hepatoprotective effects.

  2023cites this paper
• Characterization of chemical constituents and metabolites in vivo and in vitro after oral administration of Wuteng tablets in rats by UHPLC-Q/TOF-MS.

  2023cites this paper
• Inhibitory effect of Schisandrin on the pharmacokinetics of poziotinib in vivo and in vitro by UPLC‐MS/MS

  2023cites this paper
• Schisandrin B Diet Inhibits Oxidative Stress to Reduce Ferroptosis and Lipid Peroxidation to Prevent Pirarubicin-Induced Hepatotoxicity

  2022cites this paper
• Ferulic acid alleviates lipopolysaccharide-induced acute liver injury in Megalobrama amblycephala

  2021cites this paper
• Artemisia kruhsiana leaf extract induces autophagic cell death in human prostate cancer cells.

  2021cites this paper
• The potential effect of phytochemicals and herbal plant remedies for treating drug-induced hepatotoxicity: a review

  2021cites this paper
• The influence of dibenzocyclooctadiene lignans on macrophage glutathione and lipid metabolism associated with Chlamydia pneumoniae-induced foam cell formation

  2021cites this paper
• 4-Hydroxy-2-nonenal in food products: A review of the toxicity, occurrence, mitigation strategies and analysis methods

  2020cites this paper
• Integrated Plasma and Bile Metabolomics Based on an UHPLC-Q/TOF-MS and Network Pharmacology Approach to Explore the Potential Mechanism of Schisandra chinensis-Protection From Acute Alcoholic Liver Injury

  2020cites this paper
• Herbal Therapy for the Treatment of Acetaminophen-Associated Liver Injury: Recent Advances and Future Perspectives

  2020cites this paper
• Acetaminophen-induced apoptosis: Facts versus fiction

  2020cites this paper
• Modern Trends in the In Vitro Production and Use of Callus, Suspension Cells and Root Cultures of Medicinal Plants

  2020cites this paper
• Combination Therapy of Wuweizi (Schisandrae Chinensis Fructus) and Dexamethasone Alleviated Dexamethasone-Induced Glucocorticoid Osteoporosis in Rats with Idiopathic Pulmonary Fibrosis

  2020cites this paper
• Urinary and plasmatic metabolomics strategy to explore the holistic mechanism of lignans in S. chinensis in treating Alzheimer's disease using UPLC-Q-TOF-MS.

  2019cites this paper
• Hepatoprotective Effect of Baicalein Against Acetaminophen-Induced Acute Liver Injury in Mice

  2018cites this paper