The continuous production and efflux of reactive oxygen/nitrogen species from endogenous and exogenous sources can damage biological molecules and initiate a cascade of events. Mitochondria are pivotal in controlling cell survival and death. Cumulative oxidative stress, disrupted mitochondrial respiration, and mitochondrial damage are related with various neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and others. Biochemical cascades of apoptosis are mediated in signaling molecules, including protein kinases and transcription factors. The expressions in the pro-apoptotic signal transduction networks may indeed promote cell death and degeneration in brain cells. The regulation of that protein phosphorylation by kinases and phosphatases is emerging as a prerequisite mechanism in the control of the apoptotic cell death program. In this review, we attempt to put forth the evidence for possible mechanistic explanations for involvement of free radicals in the pathogenesis of neurodegenerative diseases.

In this study, Antioxidant activity ofCyperus rotundusrhizomes extract (CRRE) was evaluveted in a series ofin vitroassay involving free radicals and reactive oxygen species and IC50values were determined. CRRE exhibited its scavenging effect in concentration dependent manner on superoxide anion radicals, hydroxyl radicals, nitric oxide radical, hydrogen peroxide, and property of metal chelating and reducing power. The extract was also studied for lipid peroxidation assay by thiobarbituric acid–reactive substances (TBARS) using young and aged rat brain mitochondria. The extract was also effective in preventing mitochondrial lipid peroxidation induced by FeSO4/ ascorbate in concentration dependent manner. The results obtained in the present study indicate thatC. rotundusrhizomes extract can be a potential source of natural antioxidant.

The increasing lifespan in developed countries results in age-associated chronic diseases. Biological aging is a complex process associated with accumulated cellular damage by environmental or genetic factors with increasing age. Aging results in marked changes in brain structure and function. Age-related neurodegenerative diseases and disorders (NDDs) represent an ever-growing socioeconomic challenge and lead to an overall reduction in quality of life around the world. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are most common degenerative neurological disorders of the central nervous system (CNS) in aging process. The low levels of acetylcholine and dopamine are major neuropathological feature of NDDs in addition to oxidative stress, intracellular calcium ion imbalance, mitochondrial dysfunction, ubiquitin-proteasome system impairment and endoplasmic reticulum stress. Current treatments minimally influence these diseases and are ineffective in curing the multifunctional pathological mechanisms. Synthetic neuroprotective agents sometimes have negative reactions as an adverse effect in humans. Recently, numerous ethnobotanical studies have reported that herbal medicines for the treatment or prevention of NDDs are significantly better than synthetic drug treatment. Medicinal herbs have traditionally been used around the world for centuries. Radix Glycyrrhizae (RG) is the dried roots and rhizomes of Glycyrrhiza uralensis or G. glabra or G. inflata from the Leguminosae/Fabaceae family. It has been used for centuries in traditional medicine as a life enhancer, for the treatment of coughs and influenza, and for detoxification. Diverse chemical constituents from RG have reported including flavanones, chalcones, triterpenoid saponins, coumarines, and other glycosides. Among them, flavanone liquiritigenin (LG) and its precursor and isomer chalcone isoliquiritigenin (ILG) are the main bioactive constituents of RG. In the present review, we summarize evidence in the literature on the structure and phytochemical properties and pharmacological applications of LG and ILG in age-related diseases to establish new therapeutics to improve human health and lifespan.

Parkinson’s disease (PD) is characterized by selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc). α-synuclein (α-syn) is known to regulate mitochondrial function and both PINK1 and Parkin have been shown to eliminate damaged mitochondria in PD. Mechanistic target of rapamycin (mTOR) is expressed in several distinct subcellular compartments and mediates the effects of nutrients, growth factors, and stress on cell growth. However, the contributions of these various regulators to DAergic cell death have been demonstrated mainly in culture with serum, which is known to dramatically influence endogenous growth rate and toxin susceptibility through nutrient and growth factor signaling. Therefore, we compared neurotoxicity induced by the mitochondrial inhibitor rotenone (ROT, 5 or 10 μM for 24 h) in SH-SY5Y cells cultured with 10% fetal bovine serum (FBS), 1% FBS, or 1% bovine serum albumin (BSA, serum-free). In addition, C57BL/6J mice were injected with 12 μg ROT into the right striatum, and brains examined by histology and Western blotting 2 weeks later for evidence of DAergic cell death and the underlying signaling mechanisms. ROT dose-dependently reduced SH-SY5Y cell viability in all serum groups without a significant effect of serum concentration. ROT injection also significantly reduced immunoreactivity for the DAergic cell marker tyrosine hydroxylase (TH) in both the mouse striatum and SNpc. Western blotting revealed that ROT inhibited TH and Parkin expression while increasing α-syn and PINK1 expression in both SH-SY5Y cells and injected mice, consistent with disruption of mitochondrial function. Moreover, expression levels of the mTOR signaling pathway components mTORC, AMP-activated protein kinase (AMPK), ULK1, and ATG13 were altered in ROT-induced PD. Further, serum level influenced mTOR signaling in the absence of ROT and the changes in response to ROT. Signs of endoplasmic reticulum (ER) stress and altered expression of tethering proteins mediating mitochondria-associated ER contacts (MAMs) were also altered concomitant with ROT-induced neurodegeneration. Taken together, this study demonstrates that complex mechanism involving mitochondrial dysfunction, altered mTOR nutrient-sensing pathways, ER stress, and disrupted MAM protein dynamics are involved in DAergic neurodegeneration in response to ROT.

We evaluated the preventive effects of Terminalia chebula (T. chebula) aqueous extract on oxidative and antioxidative status in liver and kidney of aged rats compared to young albino rats. The concentrations of malondialdehyde (MDA), lipofuscin (LF), protein carbonyls (PCO), activities of xantione oxidase (XO), manganese-superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), and glucose-6-phosphate dehydrogenase (G6PDH), levels of glutathione (GSH), vitamin C and vitamin E were used as biomarkers. In the liver and kidney of aged animals, enhanced oxidative stress was accompanied by compromised antioxidant defences. Administration of aqueous extract of T. cheubla effectively modulated oxidative stress and enhanced antioxidant status in the liver and kidney of aged rats. The results of the present study demonstrate that aqueous extract of T. cheubla inhibits the development of age-induced damages by protecting against oxidative stress.