The Effects of Guluronic Acid (G2013), a New Emerging Treatment, on Inflammatory Factors in Nonalcoholic Steatohepatitis Patients Under in Vitro Conditions Publisher Pubmed



Tahmasebi S¹ ; Neishaboori H² ; Jafari D^{3, 4} ; Faghihzadeh E⁵ ; Esmaeilzadeh A^{3, 4} ; Mirshafiey A^{1, 6}
Source: Immunopharmacology and Immunotoxicology Published:2021

Abstract

Background: Nonalcoholic Steatohepatitis (NASH) results from the accumulation of fatty acids in the liver. The elevated production of pro-inflammatory factors is the reason for the hyper inflammation in NASH. The α-L-Guluronic acid (G2013), a new member of NSAID family, is a plant-originated agent with immunomodulatory properties. The current study investigated the effects of G2013 on inflammatory factors in PBMCs of NASH patients. Methods: PBMCs of 14 NASH patients and 14 healthy controls were isolated and cultured. The patient’s cells were treated with low (5 µg/mL) and moderate (25 µg/mL) doses of G2013 alongside the diclofenac optimum dose (3 µg/mL). The expression and secretion levels of variables were assessed by real-time PCR and ELISA, respectively. Results: Findings indicated that the expression levels of TLR4 and NF-κB, as well as the secretion levels of TNF-α and IL-6 cytokines, were significantly elevated in NASH patients compared to healthy individuals. The expression levels of TLR4 and NF-κB were strikingly downregulated in treated cells of patients in both low and moderate doses of G2013. A considerable reduction was obtained in the secretion level of IL-6 using both low and moderate doses of G2013 and in the secretion level of TNF-α using the moderate dose of G2013. Conclusion: The results indicated that G2013 could meaningfully decrease the expression and secretion levels of evaluated factors (TLR4, NF-κB, TNF-α, and IL-6) in PMBCs of NASH cases. Since there is no effective treatment for NASH patients, we hope that G2013 would be a promising immunomodulatory agent in reducing inflammation and improvement of patients. © 2021 Informa UK Limited, trading as Taylor & Francis Group.