2. Academic Validation
  3. Ginkgolide B effectively mitigates neuropathic pain by suppressing the activation of the NLRP3 inflammasome through the induction of mitophagy in rats

Ginkgolide B effectively mitigates neuropathic pain by suppressing the activation of the NLRP3 inflammasome through the induction of mitophagy in rats

  • Biomed Pharmacother. 2024 Aug:177:117006. doi: 10.1016/j.biopha.2024.117006.
Jing-Hao Liang 1,  Heng Yu 1,  Chuan-Peng Xia 1,  Yue-Hui Zheng 2,  Zhe Zhang 1,  Yu Chen 1,  Mazhar Ali Raza 1,  Long Wu 3,  Hede Yan 4
Affiliations

Affiliations

  • 1 Department of Orthopaedics (Hand microsurgery), The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 2 Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Department of Geriatry, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 3 Department of Orthopaedics (Hand microsurgery), The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: wmuwulong@163.com.
  • 4 Department of Orthopaedics (Hand microsurgery), The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: yanhede@hotmail.com.
PMID: 38908197 DOI: 10.1016/j.biopha.2024.117006
Abstract

Neuropathic pain is a pathological state induced by the aberrant generation of pain signals within the nervous system. Ginkgolide B(GB), an active component found of Ginkgo. biloba leaves, has neuroprotective properties. This study aimed to explore the effects of GB on neuropathic pain and its underlying mechanisms. In the in vivo study, we adopted the rat chronic constriction injury model, and the results showed that GB(4 mg/kg) treatment effectively reduced pain sensation in rats and decreased the expressions of Iba-1 (a microglia marker), NLRP3 inflammasome, and inflammatory factors, such as interleukin (IL)-1β, in the spinal cord 7 days post-surgery. In the in vitro study, we induced microglial inflammation using lipopolysaccharide (500 ng/mL) / adenosine triphosphate (5 mM) and treated it with GB (10, 20, and 40 μM). GB upregulated the expression of Mitophagy proteins, such as PINK1, Parkin, LC3 II/I, Tom20, and Beclin1, and decreased the cellular production of Reactive Oxygen Species. Moreover, it lowered the expression of inflammation-related proteins, such as Caspase-1, IL-1β, and NLRP3 in microglia. However, this effect was reversed by Parkin shRNA/siRNA or the Autophagy Inhibitor 3-methyladenine (5 mM). These findings reveal that GB alleviates neuropathic pain by mitigating neuroinflammation through the activation of PINK1-Parkin-mediated Mitophagy.

Keywords

Ginkgolide B; Microglia; Mitophagy; NLRP3 inflammasome; Neuropathic pain; PINK1-Parkin.

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