S-Allylmercaptocysteine improves alcoholic liver disease partly through a direct modulation of insulin receptor signaling

Luo, Pingping; Zheng, Ming; Rui, Zhang; Zhang, Hong; Liu, Yingxia; Li, Wei; Sun, Xiaoming; Q, Yu; Tipoe, George L.; Xiao, Jia

doi:10.1016/j.apsb.2020.11.006

Cited by 25 publications

(13 citation statements)

References 50 publications

(44 reference statements)

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“…Among the GLUT subtypes, GLUT4 is mainly enriched in the liver, pancreas, and skeletal muscle [ 40 ]. During the development of T2DM, disruption of insulin signaling results in decrease of hepatic GSK-3β, along with impairment of GLUT4 translocation [ 41 , 42 ]. Our findings revealed that ICS II not only effectively promoted phosphorylation of GSK-3β, but also facilitated GLUT4 translocated onto the cell membrane and increase glucose uptake.…”

Section: Discussionmentioning

confidence: 99%

Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway

Chen

et al. 2022

Antioxidants

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Type 2 diabetes mellitus (T2DM) is a multisystem and complex metabolic disorder which is associated with insulin resistance and impairments of pancreatic β-cells. Previous studies have shown that icariside II (ICS II), one of the main active ingredients of Herba Epimedii, exerts potent anti-inflammatory and anti-oxidative properties. In this study, we investigated whether ICS II exerted anti-T2DM profile and further explored its possible underlying mechanism both in vivo and in vitro. db/db mice were administered ICS II (10, 20, 40 mg·kg−1) for 7 weeks. We found that ICS II dose-dependently attenuated hyperglycemia and dyslipidemia, as well as inhibited hepatic steatosis and islet architecture damage in db/db mice. Moreover, ICS II not only dramatically reduced inflammatory cytokines and oxidative stress, but also up-regulated PPARα/γ protein expressions, phosphorylation of Akt, GSK3β and IR, meanwhile, down-regulated phosphorylation of NF-κB(p65) and IRS1 in db/db mice. In palmitic acid (PA)-treated HepG2 or MIN6 cells, ICS II (5−20 μM) concentration-dependently promoted the cell viability via mediating PPARα/γ/NF-κB signaling pathway. PPARα/γ knockout by CRISPR-Cas9 system partly abolished the protective effects of ICS II on HepG2 or MIN6 cells following PA insults. These findings reveal that ICS II effectively confer anti-T2DM property by targeting PPARα/γ through mediation of ROS/NF-κB/IRS1 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway

Chen

et al. 2022

Antioxidants

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“…Hepatic lipid accumulation is one of the main pathological features of ALD (Luo et al, 2021). TG, the main form of fat to accommodate energy metabolism, accumulate within hepatocytes leading to steatosis (Wang et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Physcion alleviates chronic alcoholic hepatic inflammation and pyroptosis through SIRT1-AMPK activation

Bai

Guo

Wang

et al. 2022

Preprint

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BACKGROUND AND PURPOSE Alcohol-associated liver disease (ALD) caused by chronic alcohol consumption range from simple steatosis to alcoholic hepatitis, fibrosis, and cirrhosis. Physcion is an anthraquinone compound of Rheum palmatum L, a Chinese herbal medicine with possible hepatoprotective properties. This study aimed to investigate the protective effect and associated molecular mechanisms of physcion on chronic alcoholic liver injury. EXPERIMENTAL APPROACH Chronic alcoholic liver injury was induced by placing male C57BL/6 mice on Lieber-DeCarli ethanol-containing diets for 10 days and then administering a single dose of ethanol (5 g/kg body weight) via gavage. Human hepatic stellate cells line, LX-2 cells were pretreated with physcion for 1 h prior to ethanol stimulation. KEY RESULTS Physcion effectively ameliorated ALD-induced serum aminotransferase and triglyceride levels, steatosis, activated SIRT1-AMPK signaling, then inhibited hepatic NLRP3 inflammasome activation and GSDMD relevant in pyroptosis, the same as the hepato-protection of AMPK and SIRT1 agonists. Physcion suppressed ECM accumulation through inhibiting collagen-Ⅰ and α-SMA expression. Moreover, physcion prevented the accumulation of HMGB1 and NF-κB p65 nuclear translocation and release. Importantly, silencing of SIRT1-AMPK signaling eliminates the protective effect of physcion. CONCLUSIONS AND IMPLICATIONS Activation of SIRT1-AMPK signaling is involved in ALD pathogenesis, which alleviated by physcion through inhibiting NLRP3 inflammasome activation, inflammatory response and pyroptosis. Therefore, manipulation of hepatic inflammation and pyroptosis through strategies by targeting SIRT1-AMPK signaling holds great therapeutic potential for ALD.

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“…The liver was selected according to the meridian network, which is also the key target tissue for insulin resistance in T2DM. INSR on hepatocyte surface would activate insulin receptor substrate (IRS) after binding with insulin, and then functionally mediate downstream like glucose/lipid metabolism, hepatocyte proliferation, DNA synthesis, and cell cycle regulation [ 64 ]. While PTPN1 dephosphorylates INSR and attenuates insulin signal transduction cascade, and human studies also demonstrated that PTPN1 expression increases in obese individuals and those with T2DM [ 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

Mechanism exploration of Gouqi-wentang formula against type 2 diabetes mellitus by phytochemistry and network pharmacology-based analysis and biological validation

et al. 2021

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Background The Gouqi-wentang formula (GQWTF) is a herbal formula used by Academician Xiao-lin Tong for the clinical treatment of T2DM. GQWTF is beneficial to qi, nourishes Yin, clears heat, and promotes fluid production, but the effective components and their mechanism of action remain unclear. Methods The main components of GQWTF were detected by LC–MS, and the multi-target mechanisms of GQWTF in T2DM were elucidated using network pharmacology analysis, including target prediction, protein–protein interaction network construction and analysis, Gene Ontology (GO) terms, Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway annotation, and other network construction. Finally, the efficacy of the GQWTF was verified using biological experiments. Results First, the “herb-channel tropism” network suggested that GQWTF focuses more on treating diseases by recuperating the liver, which is considered as an important insulin-sensitive organ. Subsequently, a total of 16 active ingredients in GQWTF were detected and screened, and their biological targets were predicted. Then, “compound-target” network was constructed, where enrichment analysis of GQWTF targets reflected its potential pharmacological activities. After T2DM-related target identification, 39 cross targets of GQWTF and T2DM were obtained, and 30 key targets highly responsible for the beneficial effect of GQWTF on T2DM were identified by PPI analysis. GO analysis of these key targets showed that many biological processes of GQWTF in treating T2DM are key in the occurrence and development of T2DM, including components related to inflammatory/immune response, insulin, and metabolism. KEGG analysis revealed the regulation of multiple signalling pathways, such as insulin resistance, PPAR signalling pathway, FoxO signalling pathway, Fc epsilon RI signalling pathway, and pathways that influence diabetes primarily by regulating metabolism as well as other T2DM directly related pathways. Furthermore, a “formula-compound-pathway-symptom” network was constructed to represent a global view of GQWTF in the treatment of T2DM. Conclusions This study explored the mechanism of action of GQWTF in T2DM by multi-component and multi-target multi pathways, which could provide a theoretical basis for the development and clinical application of GQWTF.

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S-Allylmercaptocysteine improves alcoholic liver disease partly through a direct modulation of insulin receptor signaling

Cited by 25 publications

References 50 publications

Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway

Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway

Physcion alleviates chronic alcoholic hepatic inflammation and pyroptosis through SIRT1-AMPK activation

Mechanism exploration of Gouqi-wentang formula against type 2 diabetes mellitus by phytochemistry and network pharmacology-based analysis and biological validation

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