No abstract

Alzheimer's disease (AD) is an extensive age-associated neurodegenerative disorder. In spite of wide-ranging progress in understanding the AD pathology for the past 50 years, clinical trials based on the hypothesis of amyloid-beta (Aβ) have reserved worsening particularly at late-stage human trials. Consequently, very few old drugs are presently used for AD with inadequate clinical consequences and various side effects. We focus on widespread pharmacological and beneficial principles for existing as well as future drugs. Multitargeting approaches by means of general antioxidant and anti-inflammatory mechanisms allied with particular receptor and/or enzyme-mediated actions in neuroprotection and neurodegeneration. The plant kingdom comprises a vast range of species with an incredible diversity of bioactive metabolites with diverse chemical scaffolds. In recent times, an increasing body of facts recommended the use of phytochemicals to decelerate AD's onset and progression. The definitive goal of AD investigation is to avert the onset of neurodegeneration, thereby allowing successful aging devoid of cognitive decline. At this point, we discussed the neurological protective role of natural products and naturally derived therapeutic agents for AD from various natural polyphenolic compounds and medicinal plants. In conclusion, medicinal plants act as a chief source of different bioactive constituents.

Background and Objective: This investigation explored the neuroprotective effect of PIASA a newly designed peptide - VCSVY in in-silico and in opposition to rotenone stimulated oxidative stress, mitochondrial dysfunction, and apoptosis in an SH-SY5Y cellular model. Methods: Docking and visualization of the PIASA and rotenone was progressed against mitochondrial respiratory complex I (MCI). The in-silico analysis showed that PIASA had interaction to the binding sites of rotenone which may reduce the rotenone interaction and its toxicity too. The SH-SY5Y cells were segregated into four experimental groups: Group I: untreated control cells; Group II: rotenone-only (100 nM) treated cells; Group III: PIASA (5 µM) + rotenone (100 nM) treated cells; and Group IV: PIASA-only (5 μM) treated cells. Results: We evaluated the cell viability, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), apoptosis (dual staining technique), nuclear morphological changes (Hoechst staining technique), expression of BAX, Bcl-2, cyt c, pro-caspase 3, and caspases 3, -6, -8, -9 and cleaved caspases 3 by western blot analysis. In SH-SY5Y cells, we further observed the cytotoxicity, oxidative stress and mitochondrial dysfunction in rotenone-only treated cells, whereas pretreatment of PIASA attenuated the rotenone mediated toxicity. Moreover, rotenone toxicity is caused by complex I inhibition, which leads to mitochondrial dysfunction, increased BAX while down regulating the Bcl2 expression and cyt c release and then finally caspases activation. PIASA pretreatment prevented the cytotoxic effects via the normalization of apoptotic marker expressions influenced by rotenone. In addition, pre-clinical studies are acceptable in rodents to make use of PIASA as a revitalizing remedial agent especially for PD in future. Conclusion: Collectively, our results proposed that PIASA mitigated rotenone stimulated oxidative stress, mitochondrial dysfunction, and apoptosis in rotenone induced SH-SY5Y cells.