👤 Minhajul Arfeen

Type 2 Diabetes Mellitus (T2DM) is a widespread metabolic disorder that can affect brain health, primarily through the damaging effects of prolonged hyperglycemia. This condition increases oxidative stress (OS), neuroinflammation, and neuroapoptosis, ultimately impairing cognitive function. Acrylamide (ACY), a neurotoxicant formed during high-temperature food processing and present in cigarette smoke, may further aggravate these neurological disturbances. The present experiment examined the exacerbating effects of T2DM and ACY exposure on cognitive function, neurodegeneration, OS, neuroinflammation, and neuroapoptosis in diabetic rats. T2DM was induced via intraperitoneal injections of nicotinamide and streptozotocin, followed by daily oral doses of ACY for a month. Behavioral assessments (EPM, NOR, and Y-maze) evaluated cognitive performance. Brain tissues were analyzed for biochemical markers of neurodegeneration (GSK-3β, AChE, BACE1), OS (MDA, GSH, Catalase), neuroinflammation (NF-κB, TNF-α, PGE2, COX-2), and neuroapoptosis (Bcl-2, Bax, Caspase-3). Immunohistochemistry of Bcl-2, Bcl-6, CD138, and NF assessed structural brain changes. Results indicated that T2DM and ACY exposure significantly increased the incidence of neurological disturbances. Notably, through increased COX-2, PGE2, MDA, Bax, Bcl-6, Caspase-3, and cognitive decline deficits. This study highlights the harmful neurotoxic amplification of T2DM and ACY exposure, emphasizing the importance of public health measures to reduce ACY exposure through dietary and lifestyle changes, particularly among T2DM populations. Further research into neuroprotective strategies and underlying mechanisms is necessary. Show less

Tobacco consumption, a leading cause of over 8 million deaths annually, exposes individuals to acrylamide (ACY), a neurotoxin in cigarette smoke that disrupts neurotransmitter function and induces oxidative stress, contributing to neurodegeneration. This study evaluated neuroprotective potential of montelukast (MTLU), a leukotriene receptor antagonist with anti-inflammatory and antioxidant properties, against ACY-induced neurotoxicity. Cognitive performance was assessed using elevated plus maze, novel object recognition, and Y-maze tests over 14 days. Biomarkers associated with neurodegeneration (BACE1, GSK-3β, AChE), neuroinflammation (COX-2, PGE2, TNF-α, NF-κB), oxidative stress (GSH, MDA, CAT), and apoptosis (Bcl-2, Caspase-3, Bax) were analyzed. Histopathological analyses of brain tissues were conducted to examine structural damage, and computational studies provided additional support for selected in vivo findings. MTLU significantly ameliorated ACY-induced cognitive deficits and reduced levels of GSK-3β, AChE, COX-2, PGE2, TNF-α, NF-κB, MDA, Bax, and Caspase-3 while enhancing antioxidant defenses (GSH) and upregulating Bcl-2. Histopathological analysis confirmed reduced structural brain damage, and molecular docking indicated strong binding potential for MTLU with AChE, COX-2, GSK-3β, BACE-1, and Caspase-3. While these findings suggest a protective role for MTLU in mitigating ACY-induced cognitive impairments, oxidative stress, neuroinflammation, and apoptosis, further research is needed to confirm its therapeutic potential and clinical relevance. Show less

Diabetes mellitus (DM), a widespread endocrine disorder characterized by chronic hyperglycemia, can cause nerve damage and increase the risk of neurodegenerative diseases such as Alzheimer's disease (AD). Effective blood glucose management is essential, and sitagliptin (SITG), a dipeptidyl peptidase-4 ( T2DM was induced in rats using nicotinamide (NICO) and streptozotocin (STZ), and biomarkers of AD and DM-linked enzymes, inflammation, oxidative stress, and apoptosis were evaluated in the brain. Computational studies supported the in vivo findings. SITG significantly reduced the brain enzyme levels of acetylcholinesterase ( These findings highlight SITG's neuroprotective molecular targets in T2DM-associated neurodegeneration and its potential as a therapeutic approach for AD, warranting further clinical investigations. Show less

Alzheimer's disease (AD) is a neurodegenerative disorder associated with the dysregulation of several key enzymes, including acetylcholinesterase (AChE), cyclooxygenase-2 (COX-2), glycogen synthase kinase 3β (GSK-3β), β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), and caspase-3. In this study, machine learning algorithms such as Random Forest (RF), Gradient Boost (GB), and Extreme Gradient Boost (XGB) were employed to screen US-FDA approved drugs from the ZINC15 database to identify potential dual inhibitors of COX-2 and AChE. The models were trained using molecules obtained from the ChEMBL database, with 5039 molecules for AChE and 3689 molecules for COX-2. Specifically, 1248 and 3791 molecules were classified as active and inactive for AChE, respectively, while 858 and 2831 molecules were classified as active and inactive for COX-2. The three machine learning models achieved prediction accuracies ranging from 92% to 95% for both AChE and COX-2. Virtual screening of US-FDA drugs from the ZINC15 database identified sertraline (SETL) as a potential dual inhibitor of AChE and COX-2. Further docking studies of SETL in the active sites of AChE and COX-2, as well as BACE-1, GSK-3β, and caspase-3, revealed strong binding affinities for all five proteins. In vivo validation was conducted using a lipopolysaccharide (LPS)-induced rat model pretreated with SETL for 30 days. The results demonstrated a significant decrease in the levels of AChE ( Show less