Ikewaki Nobunao, Levy Gary A, Kurosawa Gene, Iwasaki Masaru, Dedeepiya Vidyasagar D, Vaddi Suryaprakash, Senthilkumar Rajappa, Preethy Senthilkumar, Abraham Samuel J K
Department of Medical Life Science, Kyushu University of Health and Welfare, Japan.
Institute of Immunology, Junsei Educational Institute, Nobeoka, Miyazaki, Japan.
J Clin Exp Hepatol. 2022 Nov-Dec;12(6):1428-1437. doi: 10.1016/j.jceh.2022.06.008. Epub 2022 Jun 27.
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. 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 ( 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.
非酒精性脂肪性肝病(NAFLD)和非酒精性脂肪性肝炎(NASH)是高度普遍的病症,其特征为肝脏炎症和纤维化,如果不治疗,可能进展为肝硬化和肝细胞癌。传统治疗方法主要是对症治疗,没有明确的解决方案。基于β-葡聚糖的生物反应调节剂因其有益的代谢作用而成为一种潜在策略。本研究在NASH动物模型中评估了菌株AFO-202和N-163β-葡聚糖的抗纤维化和抗炎肝保护潜力。
在NASH的STAM™小鼠模型中,五组研究持续8周:(1)载体(蒸馏水),(2)AFO-202β-葡聚糖;(3)N-163β-葡聚糖,(4)AFO-202 + N-163β-葡聚糖,和(5)替米沙坦(标准药物干预)。进行血浆生化参数评估以及肝脏组织学检查,包括天狼星红染色和F4/80免疫染色。
AFO-202β-葡聚糖显著降低了与炎症相关的肝细胞气球样变和脂肪变性。N-163β-葡聚糖显著降低了纤维化和炎症(P值<0.05)。与其他组相比,AFO-202与N-163的组合显著降低了NAFLD活动评分(NAS)。
这项临床前研究支持单独或联合使用N-163和AFO-202β-葡聚糖作为NASH潜在预防和治疗药物的潜力。