Evalution of the effects of a natural products derived from fungi in the non-alcoholic steatohepatitis (NASH) mouce model

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20897
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Showa University
• Principal Investigator: Yamaguchi Tomoaki 昭和大学, 薬学部, 助教 (20966197)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 非アルコール性脂肪肝炎 / 線維化 / 可溶性エポキシヒドラーゼ

Outline of Final Research Achievements

Mortality in non-alcoholic steatohepatitis (NASH) is purportedly associated with hepatic fibrosis, driving the quest for pharmacological interventions targeting fibrosis inhibition in NASH patients. In recent years, there has been anticipation surrounding the potential of nitric oxide synthase activation to attenuate hepatic fibrosis. Fungal compound #27 is hypothesized to activate nitric oxide synthase by impeding the phosphatase activity of soluble　epoxyhydrolase. Our investigation unveiled that fungal compound #27 attenuated fibrosis in NASH model mice. This compound holds promise as an innovative NASH therapeutic agent with a distinct therapeutic mechanism compared to existing agents.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

近年、NASH 患者は増加をたどり、NASH を原因とする肝細胞癌の増加も社会問題となりつつある。現状、NASH から肝線維化および肝細胞癌の抑制効果を示した治療薬はなく、日本において NASH に対する保険適応をもった治療薬はない。真菌由来化合物 #27 は NASH モデルマウスにおいて線維化を抑制することにより、新規 NASH 治療薬となる可能性を秘めている。新規 NASH 治療薬の候補化合物を見出せたことは、臨床的に非常に意義深いことである。