Farnesol, a Dietary Sesquiterpene, Attenuates Rotenone-Induced Dopaminergic Neurodegeneration by Inhibiting Oxidative Stress, Inflammation, and Apoptosis via Mediation of Cell Signaling Pathways in Rats.
Farnesol, a Dietary Sesquiterpene, Attenuates Rotenone-Induced Dopaminergic Neurodegeneration by Inhibiting Oxidative Stress, Inflammation, and Apoptosis via Mediation of Cell Signaling Pathways in Rats.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
AE · Author affiliation · country only
Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates.Location evidence
Uppsala, SE · Author affiliation
Department of Pharmaceutical Biosciences, Drug Safety and Toxicology, Uppsala Biomedicines Centrum BMC, Husarg, 75124 Uppsala, Sweden.Location evidence
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Original abstract
Parkinson's disease is a neurodegenerative disorder that affects the elderly population worldwide. Rotenone (ROT) is an environmental toxin that impairs mitochondrial dynamics by inhibiting respiratory chain complex I and thus inducing oxidative stress. Farnesol (FSL) is a dietary sesquiterpene with antioxidant and anti-inflammatory properties reported in various in vivo models. To evaluate the efficacy of FSL in the management of PD, Wistar rats were injected with ROT (2.5 mg/kg, i.p) and pretreated with FSL. Immunohistochemical staining measured tyrosine hydroxylase-positive cells in the substantia nigra and striatum. Western blotting was employed to determine protein expression of inflammatory, apoptotic, and autophagic markers. Our results indicate that FSL significantly protected against ROT-induced inflammation by suppressing microglial and astrocytic activation through the downregulation of Toll-Like receptor 4 (TLR4), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), inhibitor of kappa B (IkB), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX), matrix metalloproteinase-9 (MMP-9) expression. FSL has also demonstrated an antioxidant effect by enhancing the activity of superoxide dismutase and catalase while reducing the level of Malondialdehyde and nitric oxide. Moreover, it restored homeostasis in ROT-induced imbalance between pro- and anti-apoptotic proteins. Impaired autophagy observed in ROT-injected rats was corrected by FSL treatment, which upregulated phosphorylated mammalian target of rapamycin (p-mTOR) expression and downregulated P62, an autophagosome marker. The protective effect of FSL was further supported by preserving the brain-derived neurotrophic factor (BDNF) and tyrosine hydroxylase in the brain. These findings demonstrate the neuroprotective ability of FSL and its potential to be developed as a pharmaceutical or nutraceutical agent for the prevention and treatment of PD by mitigating neuropathological changes observed in dopaminergic neurodegeneration.