The effects of guluronic acid (G2013), a new emerging treatment, on inflammatory factors in nonalcoholic steatohepatitis patients under in vitro conditions.

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.

• Authors: Safa Tahmasebi, Hassan Neishaboori, Davood Jafari, Elham Faghihzadeh, Abdolreza Esmaeilzadeh, Abbas Mirshafiey
• Journal: Immunopharmacology and immunotoxicology (Immunopharmacol Immunotoxicol) Vol. 43 Issue 5 Pg. 562-570 (Oct 2021) ISSN: 1532-2513 [Electronic] England
• PMID: 34314306 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Hexuronic Acids
• Immunomodulating Agents
• Inflammation Mediators
• guluronic acid

Topics

• Adolescent
• Adult
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Cells, Cultured
• Female
• Hexuronic Acids (pharmacology, therapeutic use)
• Humans
• Immunomodulating Agents (pharmacology, therapeutic use)
• In Vitro Techniques
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Leukocytes, Mononuclear (drug effects, metabolism)
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease (drug therapy, immunology, metabolism)
• Young Adult