关键词: ALT, Alanine aminotransferase ARRIVE, Animal Research: Reporting of In Vivo Experiments IL, Interleukin MCP-1, Monocyte chemoattractant protein-1 NAFLD, Non-alcoholic fatty liver disease NAS, NAFLD Activity Score NASH, Non-alcoholic steatohepatitis PPAR, Peroxisome proliferator-activated receptor STAM, Stelic Animal Model TGF-β, Transforming growth factor beta TIMPs, Tissue inhibitors of matrix metalloproteinases TNF-α, Tumor necrosis factor alpha anti-fibrotic anti-inflammatory beta-glucans hepatoprotective non-alcoholic fatty liver disease (NAFLD) non-alcoholic steatohepatitis (NASH) telmisartan αSMA, Smooth muscle alpha-actin

来  源:   DOI:10.1016/j.jceh.2022.06.008   PDF(Pubmed)

Abstract:
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要:
非酒精性脂肪性肝病(NAFLD)和非酒精性脂肪性肝炎(NASH)是以肝脏炎症和纤维化为特征的高度流行的疾病,如果不及时治疗,可以进展为肝硬化和肝细胞癌。常规方式主要是症状,没有明确的解决方案。基于β-葡聚糖的生物反应调节剂是代替其有益代谢作用的潜在策略。在本研究中,在NASH动物模型中评价了普鲁兰梭菌菌株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™鼠模型中,五组研究8周:(1)载体(RO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)。进行血浆和肝组织学中的生化参数评估,包括天狼星红染色和F4/80免疫染色。
AFO-202β-葡聚糖显著降低了炎症相关的肝细胞膨胀和脂肪变性。N-163β-葡聚糖显著降低纤维化和炎症(P<0.05)。与其他组相比,AFO-202与N-163的组合显著降低NAFLD活性评分(NAS)。
这项临床前研究支持N-163和AFO-202β-葡聚糖单独或联合作为潜在的预防和治疗剂的潜力,对于NASH。
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