ArticleEuropean journal of pharmacology2018
Sparstolonin B (SsnB) attenuates liver fibrosis via a parallel conjugate pathway involving P53-P21 axis, TGF-beta signaling and focal adhesion that is TLR4 dependent.
Article in European journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Lung-targeting lipid nanoparticle-mediated sparstolonin B delivery improves acute lung injury.Biomaterials science · 2025Article
- Kruppel-like factor 9 may regulate the inflammatory injury of chondrocytes by affecting NF-κB signaling.Journal of orthopaedic surgery and research · 2025Article
- The Toll-like Receptor-2/4 Antagonist, Sparstolonin B, and Inflammatory Diseases: A Literature Mining and Network Analysis.Cardiovascular drugs and therapy · 2025Article
- Sparstolonin B nano-formulation attenuates LPS-induced lung injury.Frontiers in pharmacology · 2025Article
- Hepatic Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor Levels Decline in Hepatitis C but Are Not Associated with Progression of Hepatocellular Carcinoma.Biomedicines · 2024Article
- BMP and activin receptor membrane bound inhibitor: BAMBI has multiple roles in gene expression and diseases (Review).Experimental and therapeutic medicine · 2024Review
- Expression and Function of BMP and Activin Membrane-Bound Inhibitor (BAMBI) in Chronic Liver Diseases and Hepatocellular Carcinoma.International journal of molecular sciences · 2023Review
- Machine learning identifies ferroptosis-related gene ANXA2 as potential diagnostic biomarkers for NAFLD.Frontiers in endocrinology · 2023Article
- Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH).Signal transduction and targeted therapy · 2022Review
- Traditional Chinese medicine: An important source for discovering candidate agents against hepatic fibrosis.Frontiers in pharmacology · 2022Review
- Current Options and Future Directions for NAFLD and NASH Treatment.International journal of molecular sciences · 2021Review
- Activity Components fromMolecules (Basel, Switzerland) · 2021Article
- Physical Training Inhibits the Fibrosis Formation in Alzheimer's Disease Kidney Influencing the TGFβ Signaling Pathways.Journal of Alzheimer's disease : JAD · 2021Article
- TLR Antagonism by Sparstolonin B Alters Microbial Signature and Modulates Gastrointestinal and Neuronal Inflammation in Gulf War Illness Preclinical Model.Brain sciences · 2020Article
- The role of MDM2-p53 axis dysfunction in the hepatocellular carcinoma transformation.Cell death discovery · 2020Review
- Advances in the Involvement of Gut Microbiota in Pathophysiology of NAFLD.Frontiers in medicine · 2020Review
- Herbal Medicine in the Treatment of Non-Alcoholic Fatty Liver Diseases-Efficacy, Action Mechanism, and Clinical Application.Frontiers in pharmacology · 2020Review
- The Role of Gut-Derived Microbial Antigens on Liver Fibrosis Initiation and Progression.Cells · 2019Review
- Effects of chronic Porphyromonas gingivalis lipopolysaccharide infusion on skeletal muscles in mice.The journal of physiological sciences : JPS · 2019Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
SsnB previously showed a promising role to lessen liver inflammation observed in a mouse model of NAFLD. Since NAFLD can progress to fibrosis, studies were designed to unravel its role in attenuating NAFLD associated fibrosis. Using both in vivo and in vitro approaches, the study probed the possible mechanisms that underlined the role of SsnB in mitigating fibrosis. Mechanistically, SsnB, a TLR4 antagonist, decreased TLR4-PI3k akt signaling by upregulating PTEN protein expression. It also decreased MDM2 protein activation and increased p53 and p21 gene and protein expression. SsnB also downregulated pro-fibrogenic hedgehog signaling pathway, inhibited hepatic stellate cell proliferation and induced apoptosis in hepatic stellate cells, a mechanism that was LPS dependent. Further, SsnB decreased fibrosis by antagonizing TLR4 induced TGFβ signaling pathway. Alternatively, SsnB augmented BAMBI (a TGFβ pseudo-receptor) expression in mice liver by inhibiting TLR4 signaling pathway and thus reduced TGFβ signaling, resulting in decreased hepatic stellate cell activation and extracellular matrix deposition. In vitro experiments on human hepatic stellate cell line showed that SsnB increased gene and protein expression of BAMBI. It also decreased nuclear co-localization of phospho SMAD2/3 and SMAD4 protein and thus attenuated TGFβ signaling in vitro. We also observed a significant decrease in phosphorylation of SMAD2/3 protein, decreased STAT3 activation, alteration of focal adhesion protein and stress fiber disassembly upon SsnB administration in hepatic stellate cells which further confirmed the antagonistic effect of SsnB on TLR4-induced fibrogenesis.
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