Novel Role of Resveratrol

Xu, Wei; Lü, Yang; Yao, Jihong; Li, Zhenlu; Chen, Zhao; Wang, Guangzhi; Jing, Huirong; Zhang, Xinyuan; Li, Mingzhu; Peng, Jinrong; Tian, Xiaofeng

doi:10.1097/shk.0000000000000225

Cited by 86 publications

(57 citation statements)

References 32 publications

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“…32 Conversely, when a Sirt1 inhibitor (nicotinamide) was used as a pre-treatment before CLP induction, the rats exhibited aggravated damage, oxidative stress, and apoptosis in the liver. 31 In contrast to a pre-treatment paradigm, administration of a Sirt1 inhibitor (EX-527) at 24 h after CLP induction when these animals are in the hypo-inflammatory phase significantly increased the survival rate of septic mice compared to the untreated septic mice. 26 Therefore, the beneficial effect of Sirt1 activation on sepsis may be dependent on the inflammatory status of the animals.…”

Section: Discussionmentioning

confidence: 93%

“…43 It has been reported that the generation of free radicals is increased in the liver of septic animals. 31 Furthermore, we previously have demonstrated that SRT1720 treatment inhibits oxidative stress, reduces apoptosis, and restores mitochondrial integrity in the liver of mice after hepatic ischemia-reperfusion injury. 15 Upregulation of Sirt1 has also been shown to inhibit apoptosis and protect against oxidative stress, ameliorating hepatic steatosis and acute liver injury.…”

Section: Discussionmentioning

confidence: 97%

“…19 Although in their study SRT3025 is given starting 48 h before CLP, we administered SRT1720 at 5 h after CLP. Resveratrol, a less specific Sirt1 activator, reduces AST, ALT, and histologic liver damage in septic rats induced by CLP 31 , and it decreases pulmonary edema and lung pathological alterations in the mouse model of sepsis induced by lipopolysaccharide (LPS). 32 Conversely, when a Sirt1 inhibitor (nicotinamide) was used as a pre-treatment before CLP induction, the rats exhibited aggravated damage, oxidative stress, and apoptosis in the liver.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of Sirt1 associated with the reduced expression of proinflammatory cytokines has also been observed in the septic animals induced by CLP or LPS with treatment of resveratrol. 31,32 Moreover, stimulation of Sirt1 by SRT3025 reduces the levels of proinflammatory cytokines in the lungs of animals challenged with S. pneumoniae . 19 Macrophages are the major source of proinflammatory cytokines after activation.…”

Section: Discussionmentioning

confidence: 99%

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SRT1720, a sirtuin 1 activator, attenuates organ injury and inflammation in sepsis

Khader

Yang

Hansen

et al. 2017

Journal of Surgical Research

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Background Sepsis affects 800,000 patients in the US annually with a mortality rate of up to 30%. Recent studies suggest that sepsis-associated metabolic derangements due to hypoxic tissue injury, impaired oxygen utilization, and mitochondrial dysfunction contribute to mortality. Sirtuin 1 (Sirt1) is a crucial modulator of energy metabolism during starvation states and has anti-inflammatory effects. Here, we hypothesized that SRT1720, a Sirt1 activator, could attenuate the severity of sepsis. Materials and Methods Male C57BL/6 mice (20–25g) were subjected to cecal ligation and puncture (CLP) to induce sepsis. SRT1720 (5 or 20 mg/kg BW) or 10% dimethyl sulfoxide (vehicle) in 0.2 ml saline was injected intravenously at 5 h after CLP. Control animals were not subjected to any surgery. Blood and liver samples were harvested at 20 h after CLP for analysis. Results Administration of SRT1720 markedly reduced the serum levels of tissue injury markers (AST, ALT, and LDH) and renal injury markers (BUN and creatinine) in a dose-dependent manner after CLP. Furthermore, the levels of proinflammatory cytokines IL-1β and IL-6 in the serum and liver were significantly inhibited by SRT1720 treatment after CLP. SRT1720 treatment resulted in a significantly decreased mRNA expression of inflammasome components [nucleotide oligomerization domain-like receptor protein 3 (NLRP3), adapter apoptosis-associated speck-like protein containing caspase-recruitment domain (ASC), IL-1β, and IL-18] in the liver, compared to the vehicle group. Conclusions SRT1720 treatment attenuates multi-organ injury in septic mice. SRT1720 treatment also decreases the production of proinflammatory cytokines and reduces inflammasome activation. Thus, pharmacologic stimulation of Sirt1 may present a promising therapeutic strategy for sepsis.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

SRT1720, a sirtuin 1 activator, attenuates organ injury and inflammation in sepsis

Khader

Yang

Hansen

et al. 2017

Journal of Surgical Research

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“…Sirtuin-1 was recently identified as a novel mediator of deacetylation of HMGB1 [153]. Resveratrol could upregulate sirtuin-1, which may also contribute to inhibiting translocation of HMGB1 [154]. In addition to inhibiting translocation, resveratrol was also shown to decrease HMGB1 expression in an atopic dermatitis mouse model [155].…”

Section: Active Compounds From Chinese Herbal Medicine For Targeting mentioning

confidence: 99%

Targeting ONOO<sup>-</sup>/HMGB1/MMP-9 Signaling Cascades: Potential for Drug Development from Chinese Medicine to Attenuate Ischemic Brain Injury and Hemorrhagic Transformation Induced by Thrombolytic Treatment

Chen¹,

Guan²,

Shen³

2016

Integr Med Int

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Stroke is the leading cause of death and disability worldwide, and ischemic stroke accounts for more than 85% of the stroke incidence. Tissue plasminogen activator (t-PA) is the only FDA-approved drug for ischemic stroke treatment with a narrow treatment time window of 4.5 h. Hemorrhagic transformation (HT) is a severe complication of delayed t-PA treatment in ischemic stroke. Thus, it is critically important to develop combination therapies to reduce HT and extend the therapeutic time window of t-PA. Current progress suggests that peroxynitrite (ONOO^-)/high-mobility group box 1 protein (HMGB1)/matrix metalloproteinase-9 (MMP-9) signaling cascades could be important for attenuating HT during thrombolytic treatment for acute ischemic stroke. Recently, important progress has been made in seeking for natural compounds from Chinese medicine for reducing ischemic stroke injury, with some of them targeting ONOO^-/HMGB1/MMP-9 signaling cascades. Herein, we analyze the roles and interactions of these three targets in mediating HT; subsequently, we summarize the potential compounds from Chinese herbal medicine for attenuating HT and analyze the related targets. Finally, we raise the potential issues to be addressed in further development of these compounds as combination therapy.

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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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Novel Role of Resveratrol

Abstract: Resveratrol protects against sepsis-induced liver injury through the SIRT1-mediated HMGB1 nucleocytoplasmic translocation pathway, a new potential therapeutic target in sepsis-induced liver injury.

Cited by 86 publications

References 32 publications

SRT1720, a sirtuin 1 activator, attenuates organ injury and inflammation in sepsis

SRT1720, a sirtuin 1 activator, attenuates organ injury and inflammation in sepsis

Targeting ONOO<sup>-</sup>/HMGB1/MMP-9 Signaling Cascades: Potential for Drug Development from Chinese Medicine to Attenuate Ischemic Brain Injury and Hemorrhagic Transformation Induced by Thrombolytic Treatment

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

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