Ginkgolide B effectively mitigates neuropathic pain by suppressing the activation of the NLRP3 inflammasome through the induction of mitophagy in rats.
Biomed Pharmacother
; 177: 117006, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38908197
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(4â¯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)-1ß, in the spinal cord 7 days post-surgery. In the in vitro study, we induced microglial inflammation using lipopolysaccharide (500â¯ng/mL) / adenosine triphosphate (5â¯mM) and treated it with GB (10, 20, and 40⯵M). 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-1ß, and NLRP3 in microglia. However, this effect was reversed by Parkin shRNA/siRNA or the autophagy inhibitor 3-methyladenine (5â¯mM). These findings reveal that GB alleviates neuropathic pain by mitigating neuroinflammation through the activation of PINK1-Parkin-mediated mitophagy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ratas Sprague-Dawley
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Microglía
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Ginkgólidos
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Inflamasomas
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Mitofagia
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Proteína con Dominio Pirina 3 de la Familia NLR
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Lactonas
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Neuralgia
Límite:
Animals
Idioma:
En
Revista:
Biomed Pharmacother
Año:
2024
Tipo del documento:
Article
Pais de publicación:
FR
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FRANCE
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FRANCIA
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FRANÇA