2025年7月22日 / 最終更新日 : 2025年7月22日 ad_y ニュース

2025年 新着論文 23　細胞情報学分野から論文が発表されました

Ursodeoxycholic acid alleviates multiple sclerosis via TGR5-dependent microglial regulation in mice

Eur J Pharmacol. 2025 Jul 11:1003:177941. doi: 10.1016/j.ejphar.2025.177941. Online ahead of print.

Authors

Yuhei Sonoda  1 , Fuka Aizawa  2 , Nanami Tomochika  3 , Kanaho Miyauchi  3 , Ayaka Nishibashi  3 , Shimon Takahashi  1 , Hidetaka Kosako  4 , Shota Tanida  3 , Kenta Yagi  5 , Takahiro Niimura  2 , Mitsuhiro Goda  6 , Kei Kawada  1 , Yuki Izawa-Ishizawa  7 , Keisuke Ishizawa  8

Affiliations

  • 1 Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan; Department of Pharmacy, Tokushima University Hospital, 2-50-1, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan.
  • 2 Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan; Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima-city, Tokushima 770-8503, Japan.
  • 3 Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan.
  • 4 Division of Cell Signaling, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, 3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan.
  • 5 Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan; Department of Pharmacy, Shimane University Hospital, 89-1, Enya-cho, Izumo-city, Shimane, 693-8501, Japan.
  • 6 Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan; Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical and Heath Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
  • 7 Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan; Department of Health and Nutrition, Faculty of Human Life Science, Shikoku University, 123-1, Ojin-cho, Tokushima, 771-1192, Japan.
  • 8 Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan; Department of Pharmacy, Tokushima University Hospital, 2-50-1, Kuramoto-cho, Tokushima-city, Tokushima, 770-8503, Japan; Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima-city, Tokushima 770-8503, Japan.

Abstract

Multiple sclerosis (MS) causes demyelination of the central nervous system (CNS) because of excessive inflammation of peripheral tissues. The pathophysiological mechanisms remain unclear because of disease background variability; therefore, antibody drugs and disease-modifying agents are ineffective therapeutic options. Alterations in bile acid metabolism correlate with the progression of MS. However, the effects of bile acid supplementation on the amelioration of MS have not been fully elucidated. Thus, in this study, we aimed to investigate the effects of ursodeoxycholic acid (UDCA) on the CNS in a mouse model of MS. Repeated high-dose administration of UDCA significantly improved disease scores and alleviated tissue damage in the spinal cord. The number of Iba1-positive cells increased in the MS spinal cord, which decreased after UDCA treatment. The effect of UDCA ceased with the activation of the TGR5 inhibitor in mice with MS. Proteomic analysis of UDCA-treated activated MG6 cells revealed that the TGR5 inhibitor significantly decreased the expression of 40 proteins, including anti-neuroinflammatory proteins (A2M, AHSG, ALB, APOA1, APOH, and SPP2), and significantly increased the expression of six proteins (Atxn7l3b, Basp1, Plekha3, Ptma, and Rrp15). UDCA may potentially regulate MS progression by modulating microglial activity via TGR5 in the spinal cord. Overall, these findings suggest that UDCA has potential applications as a novel therapeutic agent for MS.

Keywords: Bile acid; Experimental autoimmune encephalomyelitis; Inflammation; Multiple sclerosis; TGR5; Ursodeoxycholic acid.

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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