Plumbagin ameliorates hepatic ischemia-reperfusion injury in rats: Role of high mobility group box 1 in inflammation, oxidative stress and apoptosis.

Ischemia-reperfusion (I/R) injury is a pathological process which magnifies with the ensuing inflammatory response and endures with the increase of oxidants especially during reperfusion. The present study was conducted to assess the possible modulatory effects of plumbagin, the active constituent extracted from the roots of traditional medicinal plant Plumbago zeylanica L., on the dire role of high mobility group box 1 (HMGB1) as well as the associated inflammation, oxidative stress and apoptotic cell death following hepatic I/R. Four groups of rats were included: sham-operated, sham-operated treated with plumbagin, I/R (30 min ischemia and 1 h reperfusion) and I/R treated with plumbagin. Pretreatment with plumbagin markedly improved hepatic function and structural integrity compared to the I/R group, as manifested by depressed plasma transaminases and lactate dehydrogenase (LDH) activities as well as alleviated tissue pathological lesions. Plumbagin prominently hampered HMGB1 expression and subsequently quelled inflammatory cascades, as nuclear factor κB (NF-κB), tumor necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) activity. It also interrupted reactive oxygen species (ROS)-HMGB1loop as evident by restored liver reduced glutathione (GSH), elevated glutathione peroxidase (GPx) activity, along with decreased liver lipid peroxidation. Simultaneously, plumbagin significantly ameliorated apoptosis by amending the mRNA expressions of both anti-apoptotic (Bcl-2) and pro-apoptotic (Bax). The present results revealed that plumbagin is endowed with hepatoprotective activity ascribed to its antioxidant, anti-inflammatory and anti-apoptotic properties which are partially mediated through dampening of HMGB1 expression.

• Publication year

  2018

• Venue

  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

• Publication date

  2018-10-01

• Fields of study

  Biology, Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.1016/j.biopha.2018.07.004PMID 29990872
• 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.

• Ischemic preconditioning modulates ROS to confer protection in liver ischemia and reperfusion

  2017cited by this paper
• Plumbagin inhibits neuronal apoptosis, intimal hyperplasia and also suppresses TNF-α/NF-κB pathway induced inflammation and matrix metalloproteinase-2/9 expression in rat cerebral ischemia

  2017cited by this paper
• Plumbagin suppresses chronic periodontitis in rats via down-regulation of TNF-α, IL-1β and IL-6 expression

  2017cited by this paper
• Plumbagin Protects Mice from Lethal Sepsis by Modulating Immunometabolism Upstream of PKM2

  2016cited by this paper
• Plumbagin exerts protective effects in nucleus pulposus cells by attenuating hydrogen peroxide-induced oxidative stress, inflammation and apoptosis through NF-κB and Nrf-2.

  2016cited by this paper
• Plumbagin protects liver against fulminant hepatic failure and chronic liver fibrosis via inhibiting inflammation and collagen production

  2016cited by this paper
• Treatment with bone marrow mesenchymal stem cells combined with plumbagin alleviates spinal cord injury by affecting oxidative stress, inflammation, apoptotis and the activation of the Nrf2 pathway.

  2016cited by this paper
• Plumbagin Mediates Cardioprotection Against Myocardial Ischemia/Reperfusion Injury Through Nrf-2 Signaling

  2016cited by this paper
• Cytosolic HMGB1 controls the cellular autophagy/apoptosis checkpoint during inflammation.

  2015cited by this paper
• Plumbagin Nanoparticles Induce Dose and pH Dependent Toxicity on Prostate Cancer Cells.

  2015cited by this paper
• Antidepressant-like activity of plumbagin in unstressed and stressed mice

  2015cited by this paper
• Plumbagin Ameliorates CCl4-Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway

  2015cited by this paper
• Histopathologic Changes in Liver and Kidney Tissues from Male Sprague Dawley Rats Treated with Rhaphidophora Decursiva (Roxb.) Schott Extract

  2014cited by this paper
• Inhibitions of NF-κB and TNF-α Result in Differential Effects in Rats with Acute on Chronic Liver Failure Induced by d-Gal and LPS

  2014cited by this paper
• Hepatocyte‐specific high‐mobility group box 1 deletion worsens the injury in liver ischemia/reperfusion: A role for intracellular high‐mobility group box 1 in cellular protection

  2014cited by this paper
• Intracellular Hmgb1 inhibits inflammatory nucleosome release and limits acute pancreatitis in mice.

  2014cited by this paper
• Plumbagin Protects Against Spinal Cord Injury-induced Oxidative Stress and Inflammation in Wistar Rats through Nrf-2 Upregulation

  2014cited by this paper
• Plumbagin from Plumbago Zeylanica L induces apoptosis in human non-small cell lung cancer cell lines through NF- κB inactivation.

  2013cited by this paper
• The activation of HMGB1 as a progression factor on inflammation response in normal human bronchial epithelial cells through RAGE/JNK/NF-κB pathway

  2013cited by this paper
• Efficacy of DHMEQ, a NF-&kgr;B Inhibitor, in Islet Transplantation: II. Induction DHMEQ Treatment Ameliorates Subsequent Alloimmune Responses and Permits Long-Term Islet Allograft Acceptance

  2013cited by this paper
• Neuropeptide Y induces secretion of high-mobility group box 1 protein in mouse macrophage via PKC/ERK dependent pathway.

  2013cited by this paper
• Conditional ablation of HMGB1 in mice reveals its protective function against endotoxemia and bacterial infection

  2013cited by this paper
• Plumbagin inhibits tumorigenesis and angiogenesis of ovarian cancer cells in vivo

  2013cited by this paper
• Effect of NF‑κB inhibitor on high‑mobility group protein B1 expression in a COPD rat model.

  2013cited by this paper
• Molecular mechanisms of liver ischemia reperfusion injury: insights from transgenic knockout models.

  2013cited by this paper
• Reactive oxidants and myeloperoxidase and their involvement in neutrophil extracellular traps

  2013cited by this paper
• Nitrosative and Oxidative Stresses Contribute to Post-Ischemic Liver Injury Following Severe Hemorrhagic Shock: The Role of Hypoxemic Resuscitation

  2012cited by this paper
• ALK+ALCLs induce cutaneous, HMGB-1-dependent IL-8/CXCL8 production by keratinocytes through NF-κB activation.

  2012cited by this paper
• Antidiabetic effect of plumbagin isolated from Plumbago zeylanica L. root and its effect on GLUT4 translocation in streptozotocin-induced diabetic rats.

  2012cited by this paper
• HMGB1 promotes the synthesis of pro-IL-1β and pro-IL-18 by activation of p38 MAPK and NF-κB through receptors for advanced glycation end-products in macrophages.

  2012cited by this paper
• Plumbagin, a plant derived natural agent inhibits the growth of pancreatic cancer cells in in vitro and in vivo via targeting EGFR, Stat3 and NF‐κB signaling pathways

  2012cited by this paper
• Cell biology of ischemia/reperfusion injury.

  2012cited by this paper
• Development of a porcine model of post-hepatectomy liver failure.

  2011cited by this paper
• HMGB1 in ischemic and non-ischemic liver after selective warm ischemia/reperfusion in rat

  2011cited by this paper
• HMGB‐1 induces IL‐6 production in human synovial fibroblasts through c‐Src, Akt and NF‐κB pathways

  2011cited by this paper
• Modulation of T cell proliferation and cytokine response by Plumbagin, extracted from Plumbago zeylanica in collagen induced arthritis

  2011cited by this paper
• Effects of taurine on glutathione peroxidase, glutathione reductase and reduced glutathione levels in rats.

  2011cited by this paper
• HMG modifications and nuclear function.

  2010cited by this paper
• Anti-inflammatory and Analgesic Effect of Plumbagin through Inhibition of Nuclear Factor-κB Activation

  2010cited by this paper
• Plumbagin, a novel Nrf2/ARE activator, protects against cerebral ischemia

  2010cited by this paper
• Toll‐like receptor 9 inhibition confers protection from liver ischemia–reperfusion injury

  2010cited by this paper
• HMGB1 contributes to kidney ischemia reperfusion injury.

  2010cited by this paper
• SIRT1 modulates high‐mobility group box 1‐induced osteoclastogenic cytokines in human periodontal ligament cells

  2010cited by this paper
• Anti-inflammatory effects of plumbagin are mediated by inhibition of NF-kappaB activation in lymphocytes.

  2009cited by this paper
• Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells.

  2009cited by this paper
• Calnexin is involved in apoptosis induced by endoplasmic reticulum stress in the fission yeast.

  2008cited by this paper
• High-Mobility Group Box-1 in Ischemia-Reperfusion Injury of the Heart

  2008cited by this paper
• Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein.

  2008cited by this paper
• Plumbagin‐induced apoptosis of human breast cancer cells is mediated by inactivation of NF‐κB and Bcl‐2

  2008cited by this paper
• How do enzymes activate oxygen without inactivating themselves?

  2007cited by this paper
• HMGB1 release induced by liver ischemia involves Toll-like receptor 4–dependent reactive oxygen species production and calcium-mediated signaling

  2007cited by this paper
• Hemorrhagic Shock Induces NAD(P)H Oxidase Activation in Neutrophils: Role of HMGB1-TLR4 Signaling1

  2007cited by this paper
• HMGB1 and LPS induce distinct patterns of gene expression and activation in neutrophils from patients with sepsis-induced acute lung injury

  2007cited by this paper
• Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1

  2007cited by this paper
• The Relationship between Apoptosis and High-Mobility Group Protein 1 Release from Murine Macrophages Stimulated with Lipopolysaccharide or Polyinosinic-Polycytidylic Acid1

  2007cited by this paper
• A novel pathway of HMGB1‐mediated inflammatory cell recruitment that requires Mac‐1‐integrin

  2007cited by this paper
• The extracellular release of HMGB1 during apoptotic cell death.

  2006cited by this paper
• Acyl Coenzyme A-binding Protein Augments Bid-induced Mitochondrial Damage and Cell Death by Activating μ-Calpain*

  2006cited by this paper
• Opening mitoKATP increases superoxide generation from complex I of the electron transport chain.

  2006cited by this paper
• The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion

  2005cited by this paper
• Involvement of Toll-like Receptors 2 and 4 in Cellular Activation by High Mobility Group Box 1 Protein*

  2004cited by this paper
• Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning.

  2003cited by this paper
• Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells.

  2003cited by this paper
• High mobility group 1 B‐box mediates activation of human endothelium

  2003cited by this paper
• Activation of gene expression in human neutrophils by high mobility group box 1 protein.

  2003cited by this paper
• HMGB-1, a DNA-binding protein with cytokine activity, induces brain TNF and IL-6 production, and mediates anorexia and taste aversion.

  2002cited by this paper
• Role of nitric oxide in liver ischemia and reperfusion injury

  2002cited by this paper
• Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

  2001cited by this paper
• High Mobility Group 1 Protein (Hmg-1) Stimulates Proinflammatory Cytokine Synthesis in Human Monocytes

  2000cited by this paper
• Nitric oxide synthase and postischemic liver injury.

  2000cited by this paper
• The mechanism for NOx storage

  2000cited by this paper
• Complement activates Kupffer cells and neutrophils during reperfusion after hepatic ischemia.

  1993cited by this paper
• Role of tumor necrosis factor-alpha in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat.

  1990cited by this paper
• Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker.

  1982cited by this paper
• Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.

  1979cited by this paper
• A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.

  1976cited by this paper
• Improved method for the determination of blood glutathione.

  1963cited by this paper
• Iranian Journal of Basic Medical Sciences Liver Ischemia Preconditions the Heart against Ischemia- Reperfusion Arrhythmias

  year unknowncited by this paper

• Discovery of Bergamotanes against Hepatic Ischemia-Reperfusion Injury Based on DeepSAT Technology from Paraconiothyrium sp. H-B.

  2025cites this paper
• The Occurrence, Uses, Biosynthetic Pathway, and Biotechnological Production of Plumbagin, a Potent Antitumor Naphthoquinone

  2025cites this paper
• Novel mechanistic insights of the potential role of gasotransmitters and autophagy in the protective effect of metformin against hepatic ischemia/reperfusion injury in rats

  2025cites this paper
• Targeting sirtuin 1/nuclear factor erythroid 2-related factor 2/tumor necrosis factor-α pathway to modulate hepatic ischemia reperfusion-induced injury

  2025cites this paper
• Fluorescent probe for evaluating the preventive utility of plumbagin in ischemia–reperfusion injury

  2024cites this paper
• Plumbagin inhibits fungal growth, HMGB1/LOX-1 pathway and inflammatory factors in A. fumigatus keratitis

  2024cites this paper
• Unravelling the potent anti-oxidant and anti-inflammatory actions of plumbagin: A review of preclinical discoveries

  2024cites this paper
• Synergistic Protection of Vitamin B Complex and Alpha-Lipoic Acid Against Hepatic Ischemia–Reperfusion Injury: Boosting Antioxidant Defenses in Rats

  2024cites this paper
• Oral administration of plumbagin is beneficial in in vivo models of Duchenne muscular dystrophy through control of redox signaling.

  2024cites this paper
• Pharmacological Features and Therapeutic Implications of Plumbagin in Cancer and Metabolic Disorders: A Narrative Review

  2024cites this paper
• Synthesis, characterization, in-silico and in-vitro anticancer studies of Plumbagin encapsulated albumin nanoparticles for breast cancer treatment

  2023cites this paper
• A potential review of its traditional uses, Phytochemistry, pharmacology, and toxicity of Plumbago zeylanica

  2023cites this paper
• Bioactive Indole Alkaloid from Aspergillus amoenus TJ507 That Ameliorates Hepatic Ischemia/Reperfusion Injury.

  2023cites this paper
• Plumbagin, a Natural Compound with Several Biological Effects and Anti-Inflammatory Properties

  2023cites this paper
• MicroRNA-146a Improved Acute Lung Injury Induced by hepatic Ischemia-reperfusion Injury by Inhibiting PRDX1

  2023cites this paper
• Establishment of direct regeneration protocol for Plumbago auriculata plantlets and comparative HPTLC analysis of plumbagin

  2022cites this paper
• Renoprotective effect of vinpocetine against ischemia/reperfusion injury: Modulation of NADPH oxidase/Nrf2, IKKβ/NF‐κB p65, and cleaved caspase‐3 expressions

  2022cites this paper
• Plumbagin ameliorates bile duct ligation-induced cholestatic liver injury in rats.

  2022cites this paper
• Plumbagin relieves rheumatoid arthritis through nuclear factor kappa-B (NF-κB) pathway

  2022cites this paper
• Anti‐inflammatory, antioxidant, anti‐fibrotic and schistosomicidal properties of plumbagin in murine schistosomiasis

  2022cites this paper
• Ameliorative Effect of D-Carvone against Hepatic Ischemia-Reperfusion-Induced Injury in Rats

  2022cites this paper
• Inhibition of the TLR/NF-κB Signaling Pathway and Improvement of Autophagy Mediates Neuroprotective Effects of Plumbagin in Parkinson's Disease

  2022cites this paper
• Fenofibrate Ameliorates Hepatic Ischemia/Reperfusion Injury in Mice: Involvements of Apoptosis, Autophagy, and PPAR-α Activation

  2021influential citation
• Natural Antioxidants in New Age-Related Diseases

  2021cites this paper
• Berberine-loaded nanostructured lipid carriers mitigate warm hepatic ischemia/reperfusion-induced lesion through modulation of HMGB1/TLR4/NF-κB signaling and autophagy.

  2021cites this paper
• Trem1 mediates neuronal apoptosis via interaction with SYK after spinal cord ischemia-reperfusion injury.

  2021cites this paper
• Phytochemistry and pharmacological studies of Plumbago zeylanica L.: a medicinal plant review

  2021cites this paper
• Plumbagin protects the myocardial damage by modulating the cardiac biomarkers, antioxidants, and apoptosis signaling in the doxorubicin‐induced cardiotoxicity in rats

  2020cites this paper
• Renoprotective effect of vildagliptin following hepatic ischemia/reperfusion injury

  2020influential citation
• Anti-Inflammatory and Anti-Microbial Potential of Plumbago zeylanica L.: A Review

  2020cites this paper
• Effect of plumbagin on autophagy activity in rat hepatocellular carcinoma and underlying mechanism

  2020cites this paper
• Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review

  2020cites this paper
• Plumbagin reduces obesity and nonalcoholic fatty liver disease induced by fructose in rats through regulation of lipid metabolism, inflammation and oxidative stress.

  2019cites this paper
• Evaluation of wound healing activity of plumbagin in diabetic rats.

  2019cites this paper
• The effect of Liv-52 on liver ischemia reperfusion damage in rats

  2019cites this paper
• Protective effect of ulinastatin on hepatic ischemia reperfusion injury through autophagy activation in Chang liver cells

  2019cites this paper
• Long noncoding RNA HOTAIR regulates autophagy via the miR-20b-5p/ATG7 axis in hepatic ischemia/reperfusion injury.

  2019cites this paper
• Comparison of the Hyperdehydrogenasemic Effects of Erythropoietin and U-74389 G on Lactate Dehydrogenase Levels

  2019cites this paper
• Spermidine ameliorates liver ischaemia-reperfusion injury through the regulation of autophagy by the AMPK-mTOR-ULK1 signalling pathway.

  2019cites this paper
• miR-214 Down-Regulation Promoted Hypoxia/Reoxygenation-Induced Hepatocyte Apoptosis Through TRAF1/ASK1/JNK Pathway

  2018cites this paper
• World Journal of Hepatology

  year unknowninfluential citation