The RAS (renin-angiotensin system) is the part of the endocrine system that plays a prime role in the control of essential hypertension. Since the discovery of brain RAS in the seventies, continuous efforts have been put by the scientific committee to explore it more. The brain has shown the presence of various components of brain RAS such as angiotensinogen (AGT), converting enzymes, angiotensin (Ang), and specific receptors (ATR). AGT acts as the precursor molecule for Ang peptides—I, II, III, and IV—while the enzymes such as prorenin, ACE, and aminopeptidases A and N synthesize it. AT1, AT2, AT4, and mitochondrial assembly receptor (MasR) are found to be plentiful in the brain. The brain RAS system exhibits pleiotropic properties such as neuroprotection and cognition along with regulation of blood pressure, CVS homeostasis, thirst and salt appetite, stress, depression, alcohol addiction, and pain modulation. The molecules acting through RAS predominantly ARBs and ACEI are found to be effective in various ongoing and completed clinical trials related to cognition, memory, Alzheimer’s disease (AD), and pain. The review summarizes the recent advances in the brain RAS system highlighting its significance in pathophysiology and treatment of the central nervous system-related disorders.

Depression is a neuropsychiatric disorder characterized by altered emotion and cognition. Alpha lipoic acid (ALA) is a potent natural antioxidant and exhibits neuroprotective effects. However, its antidepressant activity and its mechanism of action in rats exposed to chronic unpredictable mild stress (CUMS) need to be evaluated. The rats were divided into six groups. Group, I vehicle control (without stress), II- CUMS, III- fluoxetine (FLX) (50 mg/kg p.o.), IV, V, and VI were treated with ALA (50, 100, 200 mg/kg, p.o.), respectively. All the groups, except I, were subjected to CUMS + treatments from day 1 to day 42. Body weight and behavioral parameters like sucrose preference test (SPT), Morris water maze (MWM), resident intruder test (RIT), and marble-burying test (MBT) were performed on day 0, day 21, and day 42, and forced swim test (FST) on last day 42 and 43 only. The rats were further sacrificed for biochemical and histopathological evaluation. ALA significantly improved behavioral function, increased antioxidant strength, reduced lipid peroxidation, restored monoamines, and protected CA3 neurons. Further, docking studies revealed strong binding of ALA on the 5HT3 receptor. The study demonstrates that ALA might be exhibiting antidepressant effects in part by restoring monoamines and modulating the 5HT3 receptor.

No abstract

No abstract

Purpose: Stress is an important factor having a high impact on psychological development which alters emotion, cognition and related behavioural outputs. Alpha lipoic acid (ALA) is a potent neuroprotectant and antioxidant; however, it has not been studied in clinically relevant, chronic unpredictable mild stress (CUMS) induced behaviour deficits model in rats as well as its mechanism of action is unclear. Hence, the purpose of this study was to determine its antidepressant activity in CUMS induced depression-like behaviour and to understand its mechanism of action using brain monoamine estimations and molecular docking study.Methods: The Wistar rats were divided into 6 groups. Group I vehicle control (without stress), Group II- CUMS, Group III- fluoxetine (FLX) (50 mg/kg), Group IV, V, and VI were treated with ALA (50, 100, 200 mg/kg, p.o.) respectively. All the groups, except I, were subjected to CUMS along with the treatments which were given orally from day 1 to day 42. The behavioural parameters like sucrose preference test (SPT), Morris water maze (MWM), resident intruder test (RIT), marble-burying test (MBT) were performed on day 0, day 21, and day 42 and forced swim test (FST) on day 42 only. Animals were sacrificed at the end of the study; the brain homogenate was prepared and used for the antioxidant, histopathology and monoamine estimations.Results: When compared with CUMS group, ALA (50, 100, 200) treatment displays improved behavioural parameters, increased GSH, SOD, catalase and reduced MDA, NO. Concentrations of monoamines (5-HT, DA, NE) were also found to be restored in brain homogenate. Histopathological results indicated the protection of CA3 neurons in the hippocampus. Computational molecular docking revealed strong binding of ALA on the 5HT3 receptor. Conclusion: Consequently, the study demonstrates that ALA might be exhibiting antidepressant effects in part by restoring monoamines as well as may be modulating the 5HT3 receptor.

Pterostilbene (PTE) (3-5 dimethoxy-4-hydroxy-trans-stilbenes) is an analogue of resveratrol. It is extracted and isolated from a natural source of the heartwood of Pterocarpus marsupium Roxb., red grape skin, and blueberries (Vaccinium spp.). Substantial evidence suggested that PTE displayed numerous preventive and therapeutic properties in many metabolic disorders such as diabetes and obesity. Metabolic diseases result in Insulin resistance (IR) which advances to impaired sensitivity to insulin-mediated glucose disposal. The prominent role of SIRT (silent information regulator proteins) is now getting emphasized in metabolic disorders. SIRT1 represses Uncoupling protein 2 (UCP2) expressions which are further responsible for improving synthesis of ATP from glucose. This results in improving glucose utilization and insulin secretion, thus preventing IR. SIRT1 also exhibits prominent role in facilitating fatty acid mobilization thereby inhibiting adiposity. Metabolic disorders are therefore the consequences of SIRT1 downregulation. Pterostilbene, being a SIRT1 activator, increases insulin sensitivity reduces adiposity, therefore can prove to be beneficial in diabetes as well as obesity. The review summarizes therapeutic effects portrayed by Pterostilbene via the SIRT1 pathway in metabolic diseases.