Diosmetin Ameliorates Nonalcoholic Steatohepatitis through Modulating Lipogenesis and Inflammatory Response in a STAT1/CXCL10-Dependent Manner

Luo, Nanxuan; Yang, Chen; Zhu, Yong; Chen, Qianfeng; Zhang, Baoshun

doi:10.1021/acs.jafc.0c06652

Cited by 23 publications

(11 citation statements)

References 53 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…STAT1 in the cytoplasm can be phosphorylated and aggregated to form homodimers or heterodimers under the stimulation of extracellular signals, and then enters the nucleus to promote target gene transcription [ 36 ]. It has been reported that STAT1 plays an important role in inducing liver inflammation and damage [ 31 , 37 ]. Moreover, STAT1 signaling is elevated in the livers of NAFLD model mice and obese patients with NAFLD [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-379-5p regulates free cholesterol accumulation and relieves diet induced-liver damage in db/db mice via STAT1/HMGCS1 axis

Dong

et al. 2022

Mol Biomed

View full text Add to dashboard Cite

Lipotoxicity induced by the overload of lipid in the liver, especially excess free cholesterol (FC), has been recognized as one of driving factors in the transition from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). MicroRNA (miR)-379-5p has been reported to play regulatory roles in hepatic triglyceride homeostasis, but the relationship of miR-379-5p and hepatic cholesterol homeostasis has never been touched. In the current study, we found that hepatic miR-379-5p levels were decreased obviously in NAFLD patients and model mice compared with their controls. Moreover, miR-379-5p was discovered to be able to inhibit intracellular FC accumulation and alleviate mitochondrial damage induced by palmitic acid (PA) in vitro. Furthermore, overexpression of miR-379-5p in HFHC-fed db/db mice could reduce the level of hepatic total cholesterol (TC) and FC, and ameliorate hepatic injury reflected by the lower serum alanine aminotransferase (ALT) and aspartate transaminase (AST). Subsequently, by combining spectrometry (MS) and luciferase assay, we identified miR-379-5p suppressed STAT1 through transcriptional and translational regulation. Finally, we confirmed that STAT1 was a transcriptional factor of HMGCS1. In conclusion, miR-379-5p inhibits STAT1 expression and regulates cholesterol metabolism through the STAT1/HMGCS1 axis, suggesting miR-379-5p might be applied to improve lipotoxicity in the future.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA-379-5p regulates free cholesterol accumulation and relieves diet induced-liver damage in db/db mice via STAT1/HMGCS1 axis

Dong

et al. 2022

Mol Biomed

View full text Add to dashboard Cite

show abstract

“…The primers used are provided in Table S1. The relative expression of mRNA was calculated using the 2 −ΔΔCT method and normalized to GAPDH (Luo, Yang, Zhu, Chen, & Zhang, 2021).…”

Section: Methodsmentioning

confidence: 99%

Jatrorrhizine ameliorates Schwann cell myelination via inhibiting HDAC3 ability to recruit Atxn2l for regulating the NRG1‐ErbB2‐PI3K‐AKT pathway in diabetic peripheral neuropathy mice

Gong

Gui

Yang

et al. 2022

Phytotherapy Research

View full text Add to dashboard Cite

Diabetic peripheral neuropathy (DPN) is a chronic complication associated with nerve dysfunction and uncontrolled hyperglycemia. Unfortunately, due to its complicated etiology, there has been no successful therapy for DPN. Our research recently revealed that jatrorrhizine (JAT), one of the active constituents of Rhizoma Coptidis, remarkably ameliorated DPN. This work highlighted the potential mechanism through which JAT relieves DPN using db/db mice. The results indicated that JAT treatment significantly decreased the threshold for thermal and mechanical stimuli and increased nerve conduction velocity. Histopathological analysis revealed that JAT significantly increased the number of sciatic nerve fibers and axons, myelin thickness, and axonal diameters. Additionally, JAT markedly elevated the expression of myelination‐associated proteins (MBP, MPZ, and Pmp22). The screening of histone deacetylases (HDAC) determined that histone deacetylase 3 (HDAC3) is an excellent target for JAT‐induced myelination enhancement. Liquid chromatography–mass spectrometry—(MS)/MS and coimmunoprecipitation analyses further confirmed that HDAC3 antagonizes the NRG1‐ErbB2‐PI3K‐AKT signaling axis by interacting with Atxn2l to augment SCs myelination. Thus, JAT ameliorates SCs myelination in DPN mice via inhibiting the recruitment of Atxn2l by HDAC3 to regulate the NRG1‐ErbB2‐PI3K‐AKT pathway.

show abstract

“…Further, diosmetin reduces nitric oxide production, inhibits the TNF-α levels in macrophages, and suppresses the apoptosis in T48 cells by regulating AKT and ERK protein kinases [ 133 , 134 ]. In a recent study, diosmetin significantly ameliorated inflammatory responses via STAT1/CXCL10 signaling in a high-fat-diet-induced nonalcoholic steatohepatitis (NASH) mouse model and palmitic-acid-stimulated HepG2 cells, indicating diosmetin as a potential biomolecule in suppressing inflammation in NASH conditions [ 135 ].…”

Section: Natural Biomolecules Targeting Jak/stat/socs Signaling In Ad...mentioning

confidence: 99%

Potential Natural Biomolecules Targeting JAK/STAT/SOCS Signaling in the Management of Atopic Dermatitis

2022

View full text Add to dashboard Cite

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by the dysregulation of cytokines and other immune mediators. JAK/STAT is a classical signal transduction pathway involved in various biological processes, and its dysregulation contributes to the key aspects of AD pathogenesis. Suppressor of cytokine signaling (SOCS) proteins negatively regulate the immune-related inflammatory responses mediated by the JAK/STAT pathway. JAK/STAT-mediated production of cytokines including IL-4, IL-13, IL-31, and TSLP inhibits the expression of important skin barrier proteins and triggers pruritus in AD. The expression of SOCS proteins regulates the JAK-mediated cytokines and facilitates maintaining the skin barrier disruptions seen in AD. STATs are crucial in dendritic-cell-activated Th2 cell differentiation in the skin, releasing inflammatory cytokines, indicating that AD is a Th2-mediated skin disorder. SOCS proteins aid in balancing Th1/Th2 cells and, moreover, regulate the onset and maintenance of Th2-mediated allergic responses by reducing the Th2 cell activation and differentiation. SOCS proteins play a pivotal role in inflammatory cytokine-signaling events that act via the JAK/STAT pathway. Therapies relying on natural products and derived biomolecules have proven beneficial in AD when compared with the synthetic regimen. In this review, we focused on the available literature on the potential natural-product-derived biomolecules targeting JAK/STAT/SOCS signaling, mainly emphasizing the SOCS family of proteins (SOCS1, SOCS3, and SOCS5) acting as negative regulators in modulating JAK/STAT-mediated responses in AD pathogenesis and other inflammatory disorders.

show abstract

Diosmetin Ameliorates Nonalcoholic Steatohepatitis through Modulating Lipogenesis and Inflammatory Response in a STAT1/CXCL10-Dependent Manner

Cited by 23 publications

References 53 publications

MicroRNA-379-5p regulates free cholesterol accumulation and relieves diet induced-liver damage in db/db mice via STAT1/HMGCS1 axis

MicroRNA-379-5p regulates free cholesterol accumulation and relieves diet induced-liver damage in db/db mice via STAT1/HMGCS1 axis

Jatrorrhizine ameliorates Schwann cell myelination via inhibiting HDAC3 ability to recruit Atxn2l for regulating the NRG1‐ErbB2‐PI3K‐AKT pathway in diabetic peripheral neuropathy mice

Potential Natural Biomolecules Targeting JAK/STAT/SOCS Signaling in the Management of Atopic Dermatitis

Contact Info

Product

Resources

About