Ginkgolide B ameliorates MPTP-induced neuroinflammation and neurodegeneration by improving mitochondrial electron transport chain complex I

Year 2024, Volume: 16 Issue: 3, 1214 - 1228, 13.01.2025

Irene Mary Praveen Vigil S Anbiah Latchoumycandane Calivarathan

https://doi.org/10.37212/jcnos.1574037

Abstract

Although the pathology and clinical symptoms of Parkinson's disease (PD) are well-defined, the cellular and molecular mechanisms underlying the selective degeneration of dopaminergic neurons remain unclear. Mitochondrial dysfunction and neuroinflammation are increasingly recognized as central contributors to the pathogenesis of PD. The leaf extract of Ginkgolide, Ginkgo biloba, is known for its neuroprotective properties in several neurodegenerative diseases. In the present study, we sought to investigate the neuroprotective mechanism of Ginkgolide B (BN52021), a terpene lactone derived from the leaf of Ginkgo biloba, in an animal model of PD. Adult C57BL/6 mice treated with MPTP (30 mg/ kg b.wt.) exhibited significant motor deficits, ameliorated by cotreatment with BN52021 (20 mg/ Kg b.wt.), as evidenced by improved motor behaviors. MPTP administration resulted in a marked reduction in the mitochondrial complex I activity and antioxidant enzymes, specifically in the substantia nigra, whereas the striatum remained unaffected. Notably, BN52021 cotreatment restored the complex I function and antioxidant enzymes in the substantia nigra, highlighting its region-specific neuroprotective properties. Additionally, MPTP exposure significantly increased myeloperoxidase activity, a marker of oxidative stress and inflammation mitigated by BN52021. Moreover, the inflammatory markers NLRP3, MCP-1, and IL-1β were significantly upregulated following MPTP administration, indicating the activation of the inflammasome pathway. However, coadministration of MPTP with BN52021 effectively suppressed the upregulation of these inflammatory markers, suggesting a strong anti-inflammatory effect. These findings underscore the therapeutic potential of Ginkgolide in PD, primarily through its ability to enhance mitochondrial electron transport complex I activity, restore antioxidant defense, and suppress neuroinflammation.

Keywords

Ginkgolide B, Inflammasome, MPTP, Neurodegeneration, Neuroprotection, Parkinson's disease

Ethical Statement

Approval of the Research Protocol: N/A Informed Consent: N/A Registry and Registration No. of the Study: The present animal studies were approved by the Institutional Animal Ethics Committee, Rajah Muthiah Medical College, Annamalai University (Approval ID: AU-IAEC/PR/1283/10/20). Animal Studies: All animal studies were carried out following the national and international guidelines and the relevant national laws on the protection of animals. Patient Consent for Publication: N/A

Supporting Institution

Annamalai University

Project Number

1

Thanks

The authors acknowledge DST-FIST for sponsoring the Department of Biotechnology, School of Integrative Biology, Central University of Tamil Nadu.

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