International Journal of Pharmacology

Volume 18 (6), 1189-1198, 2022

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Mitochondrial Potassium Channel-Dependent Anti-Inflammatory Effects of Ginsenoside Mc1 in Rat Spinal Cord Injury

Jianming Dai and Zaifeng Wu

Background and Objective: Mitochondrial improvement is the central player of neuroprotection following spinal cord injury (SCI). The present study evaluated the neuroprotective and anti-inflammatory effects of a new mitochondrial-acting drug, ginsenoside compound Mc1 (GCM), in rats with traumatic SCI, by focusing on the role of mitochondrial ATP-sensitive potassium (ATP-KCh) channels and mitochondrial biogenesis. Materials and Methods: The SCI was modelled in Sprague Dawley rats (n = 60) through laminectomy and placing an extradural aneurysm clip at the T10 vertebral level. The GCM at the concentrations of 20 and 40 μM was intraperitoneally administered to rats at 1, 6 and 12 hrs after laminectomy. Locomotor activity, spinal cord histology, mitochondrial function and biogenesis and the levels of pro-inflammatory cytokines were quantified. Results: Administration of GCM significantly reduced SCI-induced neurological locomotor deficits and histopathological findings in a dose-dependent manner, as compared with the untreated control group (p<0.01). The GCM (40 μM) significantly reversed the SCI-induced changes in mitochondrial membrane depolarization, mitochondrial reactive oxygen species (mitoROS), ATP levels, superoxide dismutase (mnSOD) and pro-inflammatory cytokines TNF-α, IL-1β, IL-8 (p<0.01). As well, the expression of mitochondrial biogenesis proteins PGC-1α, NRF1 and TFAM was upregulated following GCM 40 μM treatment. Importantly, the inhibition of mitochondrial ATP-KCh through hydroxydecanoate significantly eliminated the neuroprotective, anti-inflammatory and mitochondrial impacts of GCM. Conclusion: The GCM post-treatment had a significant neuroprotective effect on SCI which was mediated through increasing mitochondrial ATP-KCh activity and subsequent improvement of mitochondrial biogenesis and function and reduction of inflammatory responses.

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How to cite this article:

Jianming Dai and Zaifeng Wu, 2022. Mitochondrial Potassium Channel-Dependent Anti-Inflammatory Effects of Ginsenoside Mc1 in Rat Spinal Cord Injury. International Journal of Pharmacology, 18: 1189-1198.

DOI: 10.3923/ijp.2022.1189.1198

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