Stattic alleviates acute hepatic damage induced by LPS/<scp>d</scp>-galactosamine in mice

Li, Sijia; Hu, Kai; Li, Longjiang; Shen, Yi; Huang, Jiayi; Tang, Li; Zhang, Li; Shao, Ruyue; Han, Lu; Yang, Yongqiang

doi:10.1177/1753425920988330

Cited by 5 publications

(3 citation statements)

References 36 publications

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“…A previous study has found that the deletion of the STAT1 gene abolished LPS/D-gal-induced liver injury in mice [29]. In addition, pharmacological inhibition of STAT3 resulted in alleviated liver injury induced by LPS/D-gal [30]. These evidences indicated that the JAK-STAT pathway is crucial for the induction of in ammatory injury in liver.…”

Section: Discussionmentioning

confidence: 77%

JAK inhibitor Tofacitinib alleviated acute hepatitis induced by lipopolysaccharide/D-galactosamine in mice

Zhang

et al. 2022

Preprint

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Background: To investigate the potential effects of JAK inhibitor Tofacitinib in mice with lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced acute hepatitis, including the production of inflammatory cytokines, the induction of hepatocytes apoptosis and the degree of liver injury were determined. Methods and Results: The plasma levels of ALT and AST and liver activities of caspase-3, caspase-8, caspase-9 were determined by colorimetric assay kits. The plasma levels of TNF-a and IL-6 were detected by ELISA kits. Hepatocellular apoptosis was observed by TUNEL assay. HE staining was used to observe the histopathological changes. The expression of cleaved caspase-3 was analyzed by western blot.The results indicated that treatment with Tofacitinib in LPS/D-Gal-induced acute liver injury decreased the levels of aminotransferases, attenuated the histological abnormalities in liver and decreased the plasma levels of TNF-a and IL-6. In addition, Tofacitinib suppressed the activation of caspase cascade, decreased the expression of cleaved caspase-3 and reduced the number of TUNEL-positive cells. Conclusion: Treatment with Tofacitinib alleviated LPS/D-Gal-induced acute hepatitis. JAK maybe become a promising target for the control of inflammation-based liver disorders.

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Section: Discussionmentioning

confidence: 77%

JAK inhibitor Tofacitinib alleviated acute hepatitis induced by lipopolysaccharide/D-galactosamine in mice

Zhang

et al. 2022

Preprint

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“…100 µM stattic treatment for induced STAT3 and tubulin degradation confirming that high stattic concentration could trigger toxic effects independent of STAT3 action (72). However, in vivo experiments of mice, studies have shown that low concentrations of stattic did not cause additional toxicity (73). Similarly, Das et al have demonstrated that stattic with 20mg/kg (i.p.)…”

Section: Discussionmentioning

confidence: 97%

Bilateral Superior Cervical Sympathectomy Activates Signal Transducer and Activator of Transcription 3 Signal to Alleviate Myocardial Ischemia-Reperfusion Injury

Gao

et al. 2022

Front. Cardiovasc. Med.

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BackgroundThere is growing evidence about the effect of bilateral superior cervical sympathectomy on myocardial ischemia-reperfusion (I/R) injury. Studies have increasingly found that the signal transducer and activator of transcription 3 (STAT3) plays a protective role in myocardial I/R injury. However, the precise mechanism is unknown. The present study explored the bilateral superior cervical sympathectomy’s effect and potential mechanism in mice myocardial I/R injury.MethodsThe left heart I/R injury model was created by ligating the anterior descending branch of the coronary artery for 30 min followed by reperfusion. Bilateral superior cervical sympathectomy was performed before myocardial I/R injury. To evaluate the effect of bilateral superior cervical sympathectomy on the myocardium, we examined the myocardial infarct size and cardiac function. Then, myocardial apoptosis, inflammation, and oxidative stress were detected on the myocardium. Furthermore, the expression of STAT3 signal in myocardial tissue was measured by western blotting. To further examine the cardioprotective effect of STAT3 after bilateral superior cervical sympathectomy, the STAT3 inhibitor (static) was utilized to inhibit the phosphorylation of STAT3.ResultsThe results showed that the myocardial I/R injury decreased and the cardiac function recovered in the myocardial I/R injury after cervical sympathectomy. Meanwhile, cervical sympathectomy reduced the myocardial distribution of the sympathetic marker tyrosine hydroxylase (TH) and systemic sympathetic tone. And levels of oxidative stress, inflammatory markers, and apoptosis were reduced in myocardial tissue. We also found that the STAT3 signal was activated in myocardial tissue after cervical sympathectomy. STAT3 inhibitor can partially reverse the myocardial protective effect of cervical sympathectomy.ConclusionBilateral superior cervical sympathectomy significantly alleviated myocardial I/R injury in mice. And activation of the STAT3 signal may play an essential role in this.

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“…In the inflammatory state, the activation phosphorylation of p65 ( ser536 ) and p50 ( ser337 ) leads to the activation of NF-κB and the expression of a series of downstream inflammatory factors, such as IL-1β and IL-6. STAT3 (signal transducer and activator of transcription 3) is a key regulator of the inflammatory response induced by lipopolysaccharide (LPS) ( Li et al, 2021 ), and the JAK-STAT (Janus kinase-signal transducer and activator of transcription) pathway is one of the important inflammatory signal transduction pathways, which can mediate the immune response ( Zhao et al, 2021 ). Taken together, this study reveals that G-Rh4 might exert its anti-inflammatory effects through both NF-κB and STAT3 pathways.…”

Section: Discussionmentioning

confidence: 99%

Integrative network pharmacology and experimental verification to reveal the anti-inflammatory mechanism of ginsenoside Rh4

Zhu

Wang

et al. 2022

Front. Pharmacol.

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Inflammation is an innate immune response to infection, and it is the main factor causing bodily injury and other complications in the pathological process. Ginsenoside Rh4 (G-Rh4), a minor ginsenoside of Panax ginseng C. A. Meyer and Panax notoginseng, has excellent pharmacological properties. However, many of its major pharmacological mechanisms, including anti-inflammatory actions, remain unrevealed. In this study, network pharmacology and an experimental approach were employed to elucidate the drug target and pathways of G-Rh4 in treating inflammation. The potential targets of G-Rh4 were selected from the multi-source databases, and 58 overlapping gene symbols related to G-Rh4 and inflammation were obtained for generating a protein–protein interaction (PPI) network. Molecular docking revealed the high affinities between key proteins and G-Rh4. Gene ontology (GO) and pathway enrichment analyses were used to analyze the screened core targets and explore the target–pathway networks. It was found that the JAK-STAT signaling pathway, TNF signaling pathway, NF-κB signaling pathway, and PI3K-Akt signaling pathway may be the key and main pathways of G-Rh4 to treat inflammation. Additionally, the potential molecular mechanisms of G-Rh4 predicted from network pharmacology analysis were validated in RAW264.7 cells. RT-PCR, Western blot, and ELISA analysis indicated that G-Rh4 significantly inhibited the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β, as well as inflammation-related enzymes in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Moreover, in vitro experiments evaluated that Ginsenoside Rh4 exerts anti-inflammatory effects via the NF-κB and STAT3 signaling pathways. It is believed that our study will provide the basic scientific evidence that G-Rh4 has potential anti-inflammatory effects for further clinical studies.

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Stattic alleviates acute hepatic damage induced by LPS/d-galactosamine in mice

Cited by 5 publications

References 36 publications

JAK inhibitor Tofacitinib alleviated acute hepatitis induced by lipopolysaccharide/D-galactosamine in mice

JAK inhibitor Tofacitinib alleviated acute hepatitis induced by lipopolysaccharide/D-galactosamine in mice

Bilateral Superior Cervical Sympathectomy Activates Signal Transducer and Activator of Transcription 3 Signal to Alleviate Myocardial Ischemia-Reperfusion Injury

Integrative network pharmacology and experimental verification to reveal the anti-inflammatory mechanism of ginsenoside Rh4

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