2. Academic Validation
  3. Hydroxyfasudil regulates immune balance and suppresses inflammatory responses in the treatment of experimental autoimmune encephalomyelitis

Hydroxyfasudil regulates immune balance and suppresses inflammatory responses in the treatment of experimental autoimmune encephalomyelitis

  • Int Immunopharmacol. 2023 Aug 22;124(Pt A):110791. doi: 10.1016/j.intimp.2023.110791.
Guo-Guo Chu 1,  Jing Wang 2,  Zhi-Bin Ding 3,  Jin-Zhu Yin 4,  Li-Juan Song 5,  Qing Wang 2,  Jian-Jun Huang 4,  Bao-Guo Xiao 6,  Cun-Gen Ma 7
Affiliations

Affiliations

  • 1 The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong 030619, China.
  • 2 Dept. of Neurology, First Hospital of Shanxi Medical University, Taiyuan 030001, China.
  • 3 The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong 030619, China; Dept. of Neurology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, China.
  • 4 Dept. of Neurosurgery/The Key Laboratory of Prevention and Treatment of Neurological Disease of Shanxi Provincial Health Commission, Sinopharm Tongmei General Hospital, Datong 037003, China.
  • 5 The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong 030619, China; Dept. of Neurosurgery/The Key Laboratory of Prevention and Treatment of Neurological Disease of Shanxi Provincial Health Commission, Sinopharm Tongmei General Hospital, Datong 037003, China.
  • 6 Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200433, China. Electronic address: [email protected].
  • 7 The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong 030619, China. Electronic address: [email protected].
PMID: 37619413 DOI: 10.1016/j.intimp.2023.110791
Abstract

Multiple sclerosis (MS) is a central nervous system (CNS) disease with complicated etiology. Multifocal demyelination and invasion of inflammatory cells are its primary pathological features. Fasudil has been confirmed to improve experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, Fasudil is accompanied by several shortcomings in the clinical practice. Hydroxyfasudil is a metabolite of Fasudil in the body with better pharmaceutical properties. Therefore, we attempted to study the influence of Hydroxyfasudil upon EAE mice. The results demonstrated that Hydroxyfasudil relieved the symptoms of EAE and the associated pathological damage, reduced the adhesion molecules and chemokines, decreased the invasion of peripheral immune cells. Simultaneously, Hydroxyfasudil modified the rebalance of peripheral T cells. Moreover, Hydroxyfasudil shifted the M1 phenotype to M2 polarization, inhibited inflammatory signaling cascades as well as inflammatory factors, and promoted anti-inflammatory factors in the CNS. In the end, mice in the Hydroxyfasudil group expressed more tight junction proteins, indirectly indicating that the blood-brain barrier (BBB) was protected. Our results indicate that Hydroxyfasudil may be a prospective treatment for MS.

Keywords

Anti-inflammation; Experimental autoimmune encephalomyelitis; Hydroxyfasudil; Immunomodulation; Multiple sclerosis.

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