Neuroprotective mechanism of trans,trans-Farnesol in an ICV-STZ-induced rat model of Alzheimer's pathology.

BACKGROUND: Alzheimer's disease (AD) is a prominent cause of dementia, resulting in neurodegeneration and memory impairment. This condition imposes a considerable public health burden on both patients and their families due to the patients' functional impairments as well as the psychological and financial constraints. It has been well demonstrated that its aetiology involves proteinopathy, mitochondriopathies, and enhanced reactive oxygen species (ROS) generation, which are some of the key features of AD brains that further result in oxidative stress, excitotoxicity, autophagy, and mitochondrial dysfunction. OBJECTIVE: The current investigation was created with the aim of elucidating the neurological defence mechanism of trans,trans-Farnesol (TF) against intracerebroventricular-streptozotocin (ICV-STZ)-induced Alzheimer-like symptoms and related pathologies in rodents. MATERIALS AND METHODS: The current investigation involved male SD rats receiving TF (25-100 mg/kg, per oral) consecutively for 21 days in ICV-STZ-treated animals. An in silico study was carried out to explore the possible interaction between TF and NADH dehydrogenase and succinate dehydrogenase. Further, various behavioural (Morris water maze and novel object recognition test), biochemical (oxidants and anti-oxidant markers), activities of mitochondrial enzyme complexes and acetylcholinesterase (AChE), pro-inflammatory (tumor necrosis factor-alpha; TNF-α) levels, and histopathological studies were evaluated in specific brain regions. RESULTS: Rats administered ICV-STZ followed by treatment with TF (25, 50, and 100 mg/kg) for 21 days had significantly better mental performance (reduced escape latency to access platform, extended time spent in target quadrant, and improved differential index) in the Morris water maze test and new object recognition test models when compared to control (ICV-STZ)-treated groups. Further, TF treatment significantly restored redox proportion, anti-oxidant levels, regained mitochondrial capacities, attenuated altered AChE action, levels of TNF-α, and histopathological alterations in certain brain regions in comparison with control. In in silico analysis, TF caused greater interaction with NADH dehydrogenase and succinate dehydrogenase. CONCLUSION: The current work demonstrates the neuroprotective ability of TF in an experimental model with AD-like pathologies. The study further suggests that the neuroprotective impacts of TF may be related to its effects on TNF-α levels, oxidative stress pathways, and mitochondrial complex capabilities.

Resveratrol restores the level of key inflammatory cytokines and RANKL/OPG ratio in the femur of rat osteoporosis model.

Resveratrol's effect on bone mineral density (BMD) and expression of cytokines in ovariectomized rats (postmenopausal osteoporosis model) was studied. The study was conducted on 3-month-old Sprague-Dawley rats that were (a) sham-operated, (b) ovariectomized, (c) ovariectomized and treated with ß-estradiol (487.5 µg/kg weight/day), and (d) ovariectomized and treated with resveratrol (625 µg/Kg body weight/day). The treatment was for 4 weeks. After sacrifice BMD and gene expression (RANKL, OPG, IL-23, and IL-17A, IL-1ß, and TNFα) were measured in tibia and femur respectively. Resveratrol could restore RANKL/OPG ratio, slightly increase BMD, and moderately but significantly reduce IL-23, IL-17A, IL-1ß, and TNF-α cytokine expression levels.

Coenzyme Q10 treatment ameliorates cognitive deficits by modulating mitochondrial functions in surgically induced menopause.

The mechanisms associated with cognitive decline in post-menopausal state driven by loss of ovarian function and reduced estrogen levels are not well understood. The aim of the present study is to investigate the role of mitochondrial dysfunctions in cognitive impairment in post-menopausal state and to evaluate the protective effect of Coenzyme Q10 (CoQ10). A significant decline in cognitive functions was observed in mice after four weeks of ovariectomy as assessed by morris water maze and elevated plus maze. Administration of CoQ10 (10 mg/kg body weight, orally) daily for 4 weeks was found to reverse cognitive deficits observed in ovariectomized (Ovx) mice. The activity of mitochondrial electron transport chain components; NADH: cytochrome c reductase, succinate dehydrogenase and cytochrome c oxidase was significantly reduced in the brain of Ovx mice. This was accompanied by higher levels of ROS, protein carbonyls, lipid peroxidation, mitochondrial swelling and reduced activity of aconitase. The levels of GSH were observed to be significantly lowered resulting in reduced redox ratio (GSH/GSSG) in brain of Ovx mice. Activities of antioxidant enzymes; superoxide dismutase and catalase were also found to be reduced in brain of Ovx animals. CoQ10 supplementation to Ovx mice mitigated the mitochondrial dysfunctions and oxidative stress. Thus, the data indicates that CoQ10 improves cognitive decline in post-menopausal state by modulating mitochondrial functions and oxidative stress.