2. Academic Validation
  3. Khellin as a selective monoamine oxidase B inhibitor ameliorated paclitaxel-induced peripheral neuropathy in mice

Khellin as a selective monoamine oxidase B inhibitor ameliorated paclitaxel-induced peripheral neuropathy in mice

  • Phytomedicine. 2023 Mar;111:154673. doi: 10.1016/j.phymed.2023.154673.
Xingnan Ouyang 1,  Danyang Zhu 2,  Yujie Huang 2,  Xuejian Zhao 2,  Rui Xu 2,  Jiaying Wang 3,  Wenjun Li 4,  Xu Shen 5
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Target and Drug for Degenerative Diseases, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion of Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.
  • 2 Jiangsu Key Laboratory of Drug Target and Drug for Degenerative Diseases, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 3 Jiangsu Key Laboratory of Drug Target and Drug for Degenerative Diseases, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: wangjy@njucm.edu.cn.
  • 4 Jiangsu Key Laboratory of Drug Target and Drug for Degenerative Diseases, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: liwenjun@njucm.edu.cn.
  • 5 Jiangsu Key Laboratory of Drug Target and Drug for Degenerative Diseases, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing 210023, China.. Electronic address: xshen@njucm.edu.cn.
PMID: 36716674 DOI: 10.1016/j.phymed.2023.154673
Abstract

Background: Treatment of paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is full of challenges because of the unclear pathogenesis of PIPN. Herbal folk medicine Khellin (Khe) is a natural compound extracted from Ammi visnaga for treatment of renal colics and muscle spasms.

Purpose: Here, we aimed to assess the potential of Khe in ameliorating PIPN-like pathology in mice and investigate the underlying mechanisms.

Methods: PIPN model mice were conducted by injection of PTX based on the published approach. The capability of Khe in ameliorating the PTX-induced neurological dysfunctions was assayed by detection of nociceptive hypersensitivities including mechanical hyperalgesia, thermal hypersensitivity, and cold allodynia in mice. The underlying mechanisms were investigated by assays against the PIPN mice with MAOB-specific knockdown in spinal cord and dorsal root ganglion (DRG) tissues by injection of adeno-associated virus (AAV)-MAOB-shRNA.

Results: We determined that MAOB not MAOA is highly overexpressed in the spinal cord and DRG tissues of PIPN mice and Khe as a selective MAOB inhibitor improved PIPN-like pathology in mice. Khe promoted neurite outgrowth, alleviated Apoptosis, and improved mitochondrial dysfunction of DRG neurons by targeting MAOB. Moreover, Khe inhibited spinal astrocytes activation and suppressed neuroinflammation of spinal astrocytes via MAOB/NF-κB/NLRP3/ASC/Caspase1/IL-1β pathway.

Conclusion: Our work might be the first to report that MAOB not MAOA is selectively overexpressed in the spinal cord and DRG tissues of PIPN mice, and all findings have highly addressed the potency of selective MAOB inhibitor in the amelioration of PIPN-like pathology and highlighted the potential of Khe in treating PTX-induced side effects.

Keywords

Apoptosis; Inflammation; Khellin; MAOB; PIPN.

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