ArticleMolecular neurobiology2025
Shikonin Ameliorates Rotenone-Induced Neurotoxicity Through Inhibition of Apoptosis via IGF-1R/PI3K/AKT Pathway in a Parkinson's Disease-Associated SH-SY5Y Cell Model.
Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Shikonin alleviates rotenone-induced Parkinson's disease neuroinflammation by targeting PKM2-mediated glycolytic MG-Hs production.Cell communication and signaling : CCS · 2025Article
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5 authors.
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Abstract
Parkinson's disease (PD) is the second most common multifactorial neurodegenerative disorder caused by several genetics and environmental factors. Rotenone a pesticide with mitotoxicity causes cytosolic proteopathy resulting in PD-associated apoptosis and modulations in cell survival pathways. Shikonin, a naphthoquinone compound extracted from the Lithospermum erythrorhizon herb, was investigated in this study for its neuroprotective properties and underlying molecular mechanisms against rotenone-induced cellular apoptosis and survival in SH-SY5Y cells. The molecular docking analysis of apoptotic proteins against Shikonin revealed that they showed a binding affinity with BAD. Shikonin effectively countered the loss of cell viability induced by rotenone, rescued annexin-positive apoptotic cells, and dose-dependently suppressed the generation of reactive oxygen species. Pre-treatment with Shikonin prevented the morphological aberrations like shrining of neurites leading to decreased LDH leakage and NO release caused due to the rotenone treatment. The α-synucleinopathy is a prime hallmark of PD, Shikonin mitigated the rotenone-induced aggregation of α-synuclein as seen from confocal imaging. Furthermore, Shikonin treatment reversed the rotenone-induced excessive production of reactive oxygen species, activation of caspases (-8 and -3), and mitochondrial dysfunction, as evidenced by the restoration of mitochondrial membrane potential and cellular ATP levels. Western blot and qPCR analysis revealed that Shikonin heightened the IGF1R/PI3K/AKT signaling associated with cell survival while concurrently downregulating rotenone-induced intrinsic apoptotic pathways. These findings underscore Shikonin as a promising candidate to prevent the onset of pesticide-induced Parkinson's disease and potentially other oxidative stress-related neurodegenerative disorders.
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