Hepatoprotective Effects of Aureobasidium pullulans Derived β 1,3–1,6 Glucans in a Murine Model of Non-alcoholic Steatohepatitis

• Published in: Journal of clinical and experimental hepatology Vol. 12; no. 6; pp. 1428 - 1437
• Main Authors: Ikewaki, Nobunao, Levy, Gary A., Kurosawa, Gene, Iwasaki, Masaru, Dedeepiya, Vidyasagar D., Vaddi, Suryaprakash, Senthilkumar, Rajappa, Preethy, Senthilkumar, Abraham, Samuel J.K.
• Format: Journal Article
• Language: English
• Published: India Elsevier B.V 01.11.2022; Elsevier
• Subjects: anti-fibrotic; anti-inflammatory; beta-glucans; hepatoprotective; non-alcoholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis (NASH); Original; telmisartan; non-alcoholic fatty liver disease (NAFLD); NAS; MCP-1; NAFLD; anti-fibrotic; ARRIVE; IL; beta-glucans; telmisartan; non-alcoholic steatohepatitis (NASH); ALT; STAM; NASH; hepatoprotective; PPAR; TNF-α; anti-inflammatory; αSMA; TGF-β; TIMPs; IL, Interleukin; NASH, Non-alcoholic steatohepatitis; TNF-α, Tumor necrosis factor alpha; MCP-1, Monocyte chemoattractant protein-1; NAFLD, Non-alcoholic fatty liver disease; STAM, Stelic Animal Model; TGF-β, Transforming growth factor beta; NAS, NAFLD Activity Score; ARRIVE, Animal Research: Reporting of In Vivo Experiments; ALT, Alanine aminotransferase; αSMA, Smooth muscle alpha-actin; PPAR, Peroxisome proliferator-activated receptor; TIMPs, Tissue inhibitors of matrix metalloproteinases
• ISSN: 0973-6883; 2213-3453
• DOI: 10.1016/j.jceh.2022.06.008

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are highly prevalent conditions characterized by inflammation and fibrosis of the liver, which can progress to cirrhosis and hepatocellular carcinoma if left untreated. Conventional modalities are mainly symptomatic, with no definite solution. Beta-glucan-based biological response modifiers are a potential strategy in lieu of their beneficial metabolic effects. Aureobasidium pullulans strains AFO-202 and N-163 beta-glucans were evaluated for anti-fibrotic and anti-inflammatory hepatoprotective potentials in a NASH animal model in this study. In the STAM™ murine model of NASH, five groups were studied for 8 weeks: (1) vehicle (RO water), (2) AFO-202 beta-glucan; (3) N-163 beta-glucan, (4) AFO-202+N-163 beta-glucan, and (5) telmisartan (standard pharmacological intervention). Evaluation of biochemical parameters in plasma and hepatic histology including Sirius red staining and F4/80 immunostaining were performed. AFO-202 beta-glucan significantly decreased inflammation-associated hepatic cell ballooning and steatosis. N-163 beta-glucan decreased fibrosis and inflammation significantly (P value < 0.05). The combination of AFO-202 with N-163 significantly decreased the NAFLD Activity Score (NAS) compared with other groups. This preclinical study supports the potential of N-163 and AFO-202 beta-glucans alone or in combination as potential preventive and therapeutic agent(s), for NASH. [Display omitted]