Showing papers by "Syed Ibrahim Rizvi published in 2017"

Neuroprotection Through Rapamycin-Induced Activation of Autophagy and PI3K/Akt1/mTOR/CREB Signaling Against Amyloid-β-Induced Oxidative Stress, Synaptic/Neurotransmission Dysfunction, and Neurodegeneration in Adult Rats.

Abstract: Autophagy is a catabolic process involved in the continuous removal of toxic protein aggregates and cellular organelles to maintain the homeostasis and functional integrity of cells. The mechanistic understanding of autophagy mediated neuroprotection during the development of neurodegenerative disorders remains elusive. Here, we investigated the potential role of rapamycin-induced activation of autophagy and PI3K/Akt1/mTOR/CREB pathway(s) in the neuroprotection of amyloid-beta (Aβ1-42)-insulted hippocampal neurons in rat model of Alzheimer’s disease (AD) like phenotypes. A single intra-hippocampal injection of Aβ1-42 impaired redox balance and markedly induced synaptic dysfunction, neurotransmission dysfunction, and cognitive deficit, and suppressed pro-survival signaling in the adult rats. Rapamycin administration caused a significant reduction of mTOR complex 1 phosphorylation at Ser2481 and a significant increase in levels of autophagy markers such as microtubule-associated protein-1 light chain-3 (LC3), beclin-1, sequestosome-1/p62, unc-51-like kinase 1 (ULK1). In addition, rapamycin induced the activation of autophagy that further activated p-PI3K, p-Akt1 (Ser473), and p-CREB (Ser183) expression in Aβ1-42-treated rats. The activated autophagy markedly reversed Aβ1-42-induced impaired redox homeostasis by decreasing the levels of prooxidants—ROS generation, intracellular Ca2+ flux and LPO, and increasing the levels of antioxidants—SOD, catalase, and GSH. The activated autophagy also provided significant neuroprotection against Aβ1-42-induced synaptic dysfunction by increasing the expression of synapsin-I, synaptophysin, and PSD95; and neurotransmission dysfunction by increasing the levels of CHRM2, DAD2 receptor, NMDA receptor, and AMPA receptor; and ultimately improved cognitive ability in rats. Wortmannin administration significantly reduced the expression of autophagy markers, p-PI3K, p-Akt1, and p-CREB, as well as the autophagy mediated neuroprotective effect. Our study demonstrate that autophagy can be an integrated part of pro-survival (PI3K/Akt1/mTOR/CREB) signaling and autophagic activation restores the oxidative defense mechanism(s), neurodegenerative damages, and maintains the integrity of synapse and neurotransmission in rat model of AD.

Novel strategies for anti-aging drug discovery

Abstract: Introduction: Scientific achievements in the last few decades, leading to effective therapeutic interventions, have dramatically improved human life expectancy. Consequently, aging has become a significant problem and represents the major risk factor for most human pathologies including diabetes, cardiovascular diseases, neurological disorders, and cancer. Scientific discoveries over the past two decades have been instrumental in dissecting molecular mechanism(s) which play important roles in determining longevity. The same understanding has also led to the acknowledgement of the plurality of ‘causes’ which act either alone or in combination to create the condition which can be defined as ‘aging’.Areas covered: Over the years, several concepts have been put forward for the development of a viable anti-aging regimen. In this review, the authors extensively review anti aging interventions based on caloric restriction, activation of telomerase, autophagy inducers, senolytic therapeutics, plasma membr...

Autophagy Activation Alleviates Amyloid-β-Induced Oxidative Stress, Apoptosis and Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells

Abstract: Autophagy is an evolutionary conserved catabolic process that ensures continuous removal of damaged cell organelles and long-lived protein aggregates to maintain cellular homeostasis. Although autophagy has been implicated in amyloid-β (Aβ) production and deposition, its role in pathogenesis of Alzheimer's disease remains elusive. Thus, the present study was undertaken to assess the cytoprotective and neuroprotective potential of autophagy on Aβ-induced oxidative stress, apoptosis and neurotoxicity in human neuroblastoma SH-SY5Y cells. The treatment of Aβ1-42 impaired the cell growth and redox balance, and induced apoptosis and neurotoxicity in SH-SY5Y cells. Next, the treatment of rapamycin (RAP) significantly elevated the expression of autophagy markers such as microtubule-associated protein-1 light chain-3 (LC3), sequestosome-1/p62, Beclin-1, and unc-51-like kinase-1 (ULK1) in SH-SY5Y cells. RAP-induced activation of autophagy notably alleviated the Aβ1-42-induced impairment of redox balance by decreasing the levels of pro-oxidants such as reactive oxygen species, lipid peroxidation and Ca2+ influx, and concurrently increasing the levels of antioxidant enzymes such as superoxide dismutase and catalase. The RAP-induced autophagy also ameliorated Aβ1-42-induced loss of mitochondrial membrane potential and apoptosis. Additionally, the activated autophagy provided significant neuroprotection against Aβ1-42-induced neurotoxicity by elevating the expression of neuronal markers such as synapsin-I, PSD95, NCAM, and CREB. However, 3-methyladenine treatment significantly exacerbated the neurotoxic effects of Aβ1-42. Taken together, our study demonstrated that the activation of autophagy provided possible neuroprotection against Aβ-induced cytotoxicity, oxidative stress, apoptosis, and neurotoxicity in SH-SY5Y neuronal cells.

Black tea supplementation augments redox balance in rats: relevance to aging.

Abstract: Several health beneficial effects have been attributed to tea consumption, most of the effects are due to the strong antioxidant property of tea catechins. The present study evaluates the effect of black tea extract (BTE) supplementation on the redox balance of rats at different stages in their life span. We have evaluated erythrocyte and plasma redox status in young (4 months), middle-aged (12 months) and old-aged (24 months) male Wistar rats, by quantifying an array of parameters linked to redox status. Our results show that BTE augments redox status, measured in terms of intracellular reduced glutathione (GSH), malondialdehyde (MDA), advanced oxidation protein products (AOPPs), plasma membrane redox system (PMRS) and ferric reducing antioxidant potential (FRAP) of plasma, in rats from three different age groups. This study provides experimental evidence of a strong antioxidant property of black tea on rats in different stages of their lifespan.

Amylase inhibitory and metal chelating effects of different layers of onion (Allium cepa L.) at two different stages of maturation in vitro

Abstract: Researches on traditional medicinal plants are consolidating the belief that this system of medicine provides a viable alternative to conventional drugs for various free radical mediated diseases, e.g., diabetes. Onion (Allium cepa L.) is one of the oldest cultivated plants with multiple functional and biological properties. These are attributed to the presence of active phytomolecules, e.g ., phenolic acids, flavonoids (especially quercetin), cepaenes, thiosulfinates and anthocyanins. In the present study, outer layers (transitional layer with the first living cells below the dry onion peel) and innermost layers from two different sizes of onion were studied for their -amylase inhibiting activity, flavonoid content, hydroxyl radical scavenging activity (HRSA) and metal chelating activity. Our results demonstrate that the outermost living layers had higher flavonoid content (ranging from 40.27 to 45.0 mg), followed by a continuous decrease towards the inner part of the bulb (ranging from 29.10 to 31.81 mg). Outermost living layers of the onion extracts were found most powerful hydroxyl radical scavenger and having higher ferrous ion chelating effects compared to the inner layers with higher HRSA of outer layers of smaller onion. Differences in % -amylase inhibitory activity were also observed among different layers and sizes of onions, ranging 52.0 to 44.8% in case of outer layers and 36.00 to 39.12% in case of inner layers, showing high inhibitory activity in outer layers of onion (p < 0.05). Quercetin was a potent inhibitor with inhibitory activity ranging from 69.6 to 84.3% at different concentrations, respectively. The findings may explain the antioxidative and antidiabetic effect of onion and also foods containing quercetin.

Protein Content in Silken Webs of Cellar Spiders (Family-Pholcidae): Effect of Habitat and Senescence

Abstract: Different class of spiders spin silk to construct different web architectures. Spider’s silk is an extraordinary semi-crystalline biopolymer, which is highly tough and elastic. In the present study we have assessed the total protein content in spider webs produced by young and old cellar spiders (family pholcidae) inhabiting different environments. Data revealed that the total protein content in webs spun by young spiders was higher compared to old spiders of the same spider family. Also, the total protein content in webs spun by garden spiders was significantly higher compared to house spiders of the same spider family.

Plant Polyphenols in Healthcare and Aging

Abstract: Aging is characterized by a progressive inability of organs of biological systems to defend against environmental stressors. Oxidative stress, a state of imbalance between cellular production of oxygen free radicals and reactive oxygen species (ROS) and their removal by antioxidants, has emerged as a critical player in aging process. Indeed, oxidative stress status is observed during aging and in numerous age-related diseases. The accumulation of deleterious oxidative damages occurring in cells with advancing age would induce damage of the vital cellular macromolecules, lipids, proteins, and DNA, which can potentially lead to cell dysfunction and death. Hence, organs and tissues accumulate free radical damage over time under conditions in which their endogenous antioxidant defenses are overwhelmed, resulting in overall cellular redox imbalance and impaired organ physiology. Dietary antioxidants are bioactive molecules, which can scavenge ROS and decrease the incidence of oxidative stress-induced damage. Plant antioxidants, including polyphenols, have been extensively studied for their beneficial health effects in human. There is evidence that populations consuming diets rich in polyphenols are less susceptible to oxidative damage and diseases during aging. The present chapter deals with the free radical theory of aging, providing current evidence of dietary interventions aimed at limiting the aging process. This chapter also describes the biological activities of some abundantly occurring polyphenols and their possible roles in healthcare as well as in prevention and treatment of age-related diseases.