Research on drug development utilizing natural products with both anti-NLRP3 inflammasome and anti-fibrosis properties

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07076
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Toyama Prefectural Institute for Pharmaceutical Research
• Principal Investigator: Honda Hiroe 富山県薬事総合研究開発センター, その他部局等, 副主幹研究員 (10463134)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: NLRP3インフラマソーム / カンゾウ

Outline of Final Research Achievements

We have found that the licorice component isoliquiritigenin (ILG) has an inhibitory effect on NLRP3 inflammasome activation. This study aims to 1) elucidate the mechanism of inhibitory effect of ILG on NLRP3 inflammasome and 2) validate the efficacy of ILG in a mouse model of NASH.
1) Data were obtained on candidate ILG target proteins with ATPase activity, showing their binding to ILG. ILG did not inhibit binding of ATP to the protein; the effect of ILG on ATPase activity is under continued investigation.
2) In the CDAHFD feeding-induced NASH mouse model, feeding with ILG partially ameliorated liver fibrosis histologically and improved the disease state.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

今回我々はILGの標的候補タンパクを絞り込み、ILGとの結合性を示すデータを一部取得できた。今後さらに標的タンパクとしての妥当性を検証し、標的タンパクと同定することができれば、ILGの医薬品シーズとしての有用性にエビデンスが加わり、新たな創薬ターゲットを得ることができる可能性がある。NASHについては現在承認されている治療薬は存在しないことから、新たな創薬シーズとなる可能性がある。