6-Gingerol ameliorates sepsis-induced liver injury through the Nrf2 pathway

Hong, Mu-Keng; Hu, Lanlan; Zhang, Yaxin; Xu, Yongqiang; Liu, Xiaoyu; He, Peikun; Jia, Yuhua

doi:10.1016/j.intimp.2020.106196

Cited by 65 publications

(44 citation statements)

References 45 publications

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“…71 In a different study evaluating 6‐gingerol, Hong et al reported that 6‐gingerol alleviated sepsis‐induced liver injury by inhibiting macrophage pyroptosis. They also showed that this inhibitory effect was exerted through activation of the Nrf‐2 signaling pathway 72 . Moreover, 6‐gingerol exhibited anti‐inflammatory effects as assessed by upregulation of mitogen‐activated protein kinase phosphatase‐5 (MKP5) in prostatic epithelial cells, 73 and blocking the p38 MAP kinase‐NF‐κB signaling cascade in mouse skin 67 …”

Section: Treatment Of Sepsis With Polyphenolic Compoundsmentioning

confidence: 99%

The role of phytochemicals in sepsis: A mechanistic and therapeutic perspective

et al. 2020

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Sepsis and septic shock are still a leading cause of mortality and morbidity in intensive care units worldwide. Sepsis is an uncontrolled and excessive response of the innate immune system toward the invading infectious microbes, characterized by the hyper‐production of pro‐inflammatory mediators such as interleukin (IL)‐1β, IL‐6, tumor‐necrosis factor (TNF)‐α, and high‐mobility group box 1 (HMGB1). In severe sepsis, the overwhelming production of pro‐inflammatory cytokines and reactive oxygen species may compromise organ function and lead to the induction of abnormal apoptosis in different organs, resulting in multiple organ dysfunction syndrome and death. Hence, compounds that are able to attenuate inflammatory responses may have therapeutic potential for sepsis treatment. Understanding the pathophysiology and underlying molecular mechanisms of sepsis may provide useful insights in the discovery and development of new effective therapeutics. Therefore, numerous studies have invested much effort into elucidating the mechanisms involved with the onset and development of sepsis. The present review mainly focuses on the molecules and signaling pathways involved in the pathogenicity of sepsis. Additionally, several well‐known natural bioactive herbal compounds and phytochemicals, which have shown protective and therapeutic effects with regard to sepsis, as well as their mechanisms of action, are presented. This review suggests that these phytochemicals are able to attenuate the overwhelming inflammatory responses developed during sepsis by modulating different signaling pathways. Moreover, the anti‐inflammatory and cytoprotective activities of phytochemicals make them potent compounds to be included as complementary therapeutic agents in the diets of patients suffering from sepsis in an effort to alleviate sepsis and its life‐threatening complications, such as multi‐organ failure.

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Section: Treatment Of Sepsis With Polyphenolic Compoundsmentioning

confidence: 99%

The role of phytochemicals in sepsis: A mechanistic and therapeutic perspective

et al. 2020

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“…Consistent with the need for high endogenous antioxidant capacity, activation of Nrf2 has been shown to prevent or at least significantly reduce AKI in this disease model [64,[72][73][74]. Similarly, sepsis-initiated acute liver injury can be prevented or ameliorated by pharmacological Nrf2 activation or by its genetic stabilization by Keap1 disruption [44,75]. This also accounts for acute lung injury, and its most severe occurrence is acute respiratory distress syndrome (ARDS).…”

Section: Preclinical Sepsis Models Of Nrf2 Functionmentioning

confidence: 81%

Nrf2—A Molecular Target for Sepsis Patients in Critical Care

et al. 2020

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The transcription factor NF-E2 p45-related factor 2 (Nrf2) is an established master regulator of the anti-oxidative and detoxifying cellular response. Thus, a role in inflammatory diseases associated with the generation of large amounts of reactive oxygen species (ROS) seems obvious. In line with this, data obtained in cell culture experiments and preclinical settings have shown that Nrf2 is important in regulating target genes that are necessary to ensure cellular redox balance. Additionally, Nrf2 is involved in the induction of phase II drug metabolizing enzymes, which are important both in degrading and converting drugs into active forms, and into putative carcinogens. Therefore, Nrf2 has also been implicated in tumorigenesis. This must be kept in mind when new therapy approaches are planned for the treatment of sepsis. Therefore, this review highlights the function of Nrf2 in sepsis with a special focus on the translation of rodent-based results into sepsis patients in the intensive care unit (ICU).

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“…In China, XBJ is used as a treatment for sepsis and organ dysfunction syndrome. Studies had shown that XBJ could inhibit the uncontrolled release of inflammatory mediators, alleviate excessive innate immune responses and maintain physiological function of organs (Qi et al, 2011;Wang et al, 2015;Hong et al, 2020). These findings suggest that treating sepsis with XBJ is an effective strategy, however, few studies have investigated the specific protective mechanisms of XBJ against sepsis-induced liver injury.…”

Section: Discussionmentioning

confidence: 99%

Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway

Cao

Ren

et al. 2021

Front. Pharmacol.

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Xuebijing (XBJ), the only drug approved for the sepsis and multiple organ dysfunction, and its protective effects against acute liver injury (ALI) and its mechanism. The aim of this study was to evaluate the protective effect of XBJ on cecal ligation and perforation (CLP)-induced mouse ALI model and LPS-induced RAW264.7 cell ALI model. Mice were pretreated with XBJ before the CLP model was established, and serum and liver tissues were collected at the end of the experiment to assess the levels of inflammatory factors and liver injury. Results showed that XBJ pretreatment reduced liver/body weight, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in serum, and inhibited levels of pro-inflammatory factors in serum. Cells were treatment with XBJ and modeled by LPS modeling increased cell viability in the XBJ-treated group compared to the model group and XBJ also decreased serum pro-inflammatory factors in a dose-dependent manner. Western blot detected that XBJ also up-regulated the phosphorylated levels of glycogen synthase kinase-3β (p-GSK-3β) and cAMP-response element-binding protein (p-CREB) and down-regulated the phosphorylated level of nuclear factor kappa-B (p-NF-κB) in liver and cell. After overexpression of GSK-3β in cells, the mechanism was further investigated using CO-IP analysis. The binding of p-NF-κB and p-CREB to CREB-binding protein (CBP) was increased and decreased, respectively, indicating that GSK-3β regulated inflammation by regulating the binding of p-NF-κB and p-CREB to CBP. The present studies suggested that the hepatoprotective effect of XBJ may be through up-regulation of GSK-3β (Ser9) and increasing the binding of p-CREB to CBP, thereby alleviating the inflammatory response.

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6-Gingerol ameliorates sepsis-induced liver injury through the Nrf2 pathway

Cited by 65 publications

References 45 publications

The role of phytochemicals in sepsis: A mechanistic and therapeutic perspective

The role of phytochemicals in sepsis: A mechanistic and therapeutic perspective

Nrf2—A Molecular Target for Sepsis Patients in Critical Care

Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway

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