ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2016
Sparstolonin B attenuates early liver inflammation in experimental NASH by modulating TLR4 trafficking in lipid rafts via NADPH oxidase activation.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Repurposed metformin-apigenin combination therapy for metabolic dysfunction-associated steatohepatitis: from integrative multi-omics discovery toFrontiers in pharmacology · 2026Article
- Lung-targeting lipid nanoparticle-mediated sparstolonin B delivery improves acute lung injury.Biomaterials science · 2025Article
- The Toll-like Receptor-2/4 Antagonist, Sparstolonin B, and Inflammatory Diseases: A Literature Mining and Network Analysis.Cardiovascular drugs and therapy · 2025Article
- Nicotinamide Adenine Dinucleotide Phosphate Oxidases and Metabolic Dysfunction-Associated Steatotic Liver Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Sparstolonin B nano-formulation attenuates LPS-induced lung injury.Frontiers in pharmacology · 2025Article
- Flotillins affect LPS-induced TLR4 signaling by modulating the trafficking and abundance of CD14.Cellular and molecular life sciences : CMLS · 2024Article
- Phytocannabinoids Reduce Inflammation of Primed Macrophages and Enteric Glial Cells: An In Vitro Study.International journal of molecular sciences · 2023Article
- Machine learning identifies ferroptosis-related gene ANXA2 as potential diagnostic biomarkers for NAFLD.Frontiers in endocrinology · 2023Article
- Anti-Inflammatory Effect of Sparstolonin B through Inhibiting Expression of NF-κB and STAT-1.International journal of molecular sciences · 2022Article
- Sparstolonin B suppresses free fatty acid palmitate-induced chondrocyte inflammation and mitigates post-traumatic arthritis in obese mice.Journal of cellular and molecular medicine · 2022Article
- Efferocytosis in multisystem diseases (Review).Molecular medicine reports · 2022Review
- Misregulation of Wnt Signaling Pathways at the Plasma Membrane in Brain and Metabolic Diseases.Membranes · 2021Review
- Sparstolonin B exerts beneficial effects on prostate cancer by acting on the reactive oxygen species-mediated PI3K/AKT pathway.Journal of cellular and molecular medicine · 2021Article
- Current Concepts, Opportunities, and Challenges of Gut Microbiome-Based Personalized Medicine in Nonalcoholic Fatty Liver Disease.Cell metabolism · 2021Review
- Early microcystin-LR exposure-linked inflammasome activation in mice causes development of fatty liver disease and insulin resistance.Environmental toxicology and pharmacology · 2020Article
- TLR Antagonism by Sparstolonin B Alters Microbial Signature and Modulates Gastrointestinal and Neuronal Inflammation in Gulf War Illness Preclinical Model.Brain sciences · 2020Article
- Natural products that target macrophages in treating non-alcoholic steatohepatitis.World journal of gastroenterology · 2020Review
- Herbal Medicine in the Treatment of Non-Alcoholic Fatty Liver Diseases-Efficacy, Action Mechanism, and Clinical Application.Frontiers in pharmacology · 2020Review
- Role of Nutrition in the Pathogenesis and Prevention of Non-alcoholic Fatty Liver Disease: Recent Updates.International journal of biological sciences · 2019Review
- 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.European journal of pharmacology · 2018Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Although significant research data exist on the pathophysiology of nonalcoholic steatohepatitis (NASH), finding an efficient treatment regimen for it remains elusive. The present study used sparstolonin B (SsnB), a novel TLR4 antagonist derived from the Chinese herb Sparganium stoloniferum, as a possible drug to mitigate early inflammation in NASH. This study used an early steatohepatitic injury model in high-fat-fed mice with CYP2E1-mediated oxidative stress as a second hit. SsnB was administered for 1 wk along with bromodichloromethane (BDCM), an inducer of CYP2E1-mediated oxidative stress. Results showed that SsnB administration attenuated inflammatory morphology and decreased elevation of the liver enzyme alanine aminotransferase (ALT). Mice administered SsnB also showed decreased mRNA expression of proinflammatory cytokines TNF-α, IFN-γ, IL-1β, and IL-23, while protein levels of both TNF-α and IL-1β were significantly decreased. SsnB significantly decreased Kupffer cell activation as evidenced by reduction in CD68 and monocyte chemoattractant protein-1 (MCP1) mRNA and protein levels with concomitant inhibition of macrophage infiltration in the injured liver. Mechanistically, SsnB decreased TLR4 trafficking to the lipid rafts, a phenomenon described by the colocalization of TLR4 and lipid raft marker flotillin in tissues and immortalized Kupffer cells. Since we have shown previously that NADPH oxidase drives TLR4 trafficking in NASH, we studied the role of SsnB in modulating this pathway. SsnB prevented NADPH oxidase activation in vivo and in vitro as indicated by decreased peroxynitrite formation. In summary, the present study reports a novel use of the TLR4 antagonist SsnB in mitigating inflammation in NASH and in parallel shows a unique molecular mechanism of decreasing nitrative stress.
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