GLP-1 and Underlying Beneficial Actions in Alzheimer’s Disease, Hypertension, and NASH

GLP-1 is derived from intestinal L cells, which takes effect through binding to GLP-1R and is inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Since its discovery, GLP-1 has emerged as an incretin hormone for its facilitation in insulin release and reduction of insulin resistance (IR). However, GLP-1 possesses broader pharmacological effects including anti-inflammation, neuro-protection, regulating blood pressure (BP), and reducing lipotoxicity. These effects are interconnected to the physiological and pathological processes of Alzheimer’s disease (AD), hypertension, and non-alcoholic steatohepatitis (NASH). Currently, the underlying mechanism of these effects is still not fully illustrated and a better understanding of them may help identify promising therapeutic targets of AD, hypertension, and NASH. Therefore, we focus on the biological characteristics of GLP-1, render an overview of the mechanism of GLP-1 effects in diseases, and investigate the potential of GLP-1 analogues for the treatment of related diseases in this review.

Foetal Neuro-Protection-Role of Magnesium Sulphate

Foetal Neuro-Protection-Role of Magnesium Sulphate

Failure of Glial Cell-Line Derived Neurotrophic Factor (GDNF) in Clinical Trials Orchestrated By Reduced NR4A2 (NURR1) Transcription Factor in Parkinson’s Disease. A Systematic Review

Parkinson’s disease (PD) is one of the most common neurodegenerative maladies with unforeseen complex pathologies. While this neurodegenerative disorder’s neuropathology is reasonably well known, its etiology remains a mystery, making it challenging to aim therapy. Glial cell-line derived neurotrophic factor (GDNF) remains an auspicious therapeutic molecule for treating PD. Neurotrophic factor derived from glial cell lines is effective in rodents and nonhuman primates, but clinical findings have been equivocal. Laborious exertions have been made over the past few decades to improve and assess GDNF in treating PD (clinical studies). Definitive clinical trials have, however, failed to demonstrate a survival advantage. Consequently, there seemed to be a doubt as to whether GDNF has merit in the potential treatment of PD. The purpose of this cutting edge review is to speculate as to why the clinical trials have failed to meet the primary endpoint. We introduce a hypothesis, “Failure of GDNF in clinical trials succumbed by nuclear receptor-related factor 1 (Nurr1) shortfall.” We demonstrate how Nurr1 binds to GDNF to induce dopaminergic neuron synthesis. Due to its undisputable neuro-protection aptitude, we display Nurr1 (also called Nr4a2) as a promising therapeutic target for PD.

D-galactose induced dysfunction in mice hippocampus and the possible antioxidant and neuro-modulatory effects of selenium

Aging is an ultimate reality that everyone has to face. D-galactose (D-gal) has been used extensively to develop aging model. Trace elements such as selenium (Sel) have been used as a potential antioxidant for neuro-protection. The present work aims to develop therapeutic agents such as Sel for the treatment of aging-induced neurological ailments such as anxiety, depression, and memory impairment. For this purpose, mice were treated with D-gal at a dose of 300 mg/ml/kg and various doses of Sel (0.175 and 0.35mg/ml/kg) for 28 days. Behavioural tests were monitored after treatment days. After the behavioural assessment mice were decapitated and their brains were collected. Hippocampi were removed from the brain for biochemical and neurochemical analysis. The present findings of behavioural analysis showed that D-gal induced anxiety and depression-like symptoms were inhibited by both doses of Sel. D-gal induced memory alteration was also prevented by repeated doses (0.175 and 0.35mg/ml/kg) of Sel. Biochemical analysis showed that D-gal induced increase of oxidative stress marker and decrease of antioxidant enzymes in the hippocampus was prevented by Sel administration. An increase in the activity of acetylcholinesterase was also diminished by Sel. The neurochemical assessment showed that D-gal induced increased serotonin metabolism and decreased acetylcholine levels in the hippocampus were restored by repeated treatment of Sel. It is concluded that D-gal induced dysfunction in mice hippocampus caused anxiety, depression, memory impairment, oxidative stress that were mitigated by Sel via its antioxidant potential and modulating capability of serotonergic and cholinergic functions.

Effectiveness of Unani regimen in management of over active bladder: An open labelled, single arm clinical study

Purpose: To study the efficacy of Unani pharmacopoeial formulations viz Jawarish Zarooni, Majoon Kundur and Arq e Badiyaan as a treatment regimen in patients of overactive bladder and evaluate its effect on their quality of life. Materials and Method: This open labeled, single arm clinical study was conducted at Regional Research Institute of Unani Medicine (RRIUM), Srinagar. Patients fulfilling the inclusion criteria were enrolled in the study after signing the informed consent form. Jawarish Zarooni and Arq e Badiyaan were prescribed orally in the dosage of 7g and 30 ml respectively twice a day along with 7g single oral dose of Majoon Kundur. The duration of treatment was for 82 days. The patients were followed up on first, fourth, eighth and twelfth week. The results were expressed as Mean ± SEM. Symptomatic relief was assessed as percentage change in terms of presence of any symptom at baseline and at 82nd day. Results: Of the 36 patients enrolled 31 patients completed the study. The study demonstrated highly significant results (p<0.001) for nocturia and QOL as measured by patients perception of bladder control (PPBC), urinary incontinence and daytime micturation whereas very significant results were observed (p<0.01) for urgency. Conclusions: The Unani regimen was highly effective in managing the symptoms of OAB as the regimen has an array of phyto-constituents which demonstrated muscuranic antagonism, Ca2+ channel blocking, K channel opening, neuro-protection, neuro-toning and anxiety relieving properties. About 50% of the ingredients of the regimen were Ca2+ blockers. The synergism of these phyto-constituents probably made Ca2+ blockers effective in OAB. Keywords: Over Active Bladder, Ca2+ blocker, antimuscuranics