American Journal of PharmTech Research

Background: Memory and cognitive decline represent hallmark manifestations of Alzheimer's disease and related neurodegenerative conditions. Current pharmacological management relies predominantly on synthetic cognitive enhancers and cholinesterase inhibitors, whose long-term administration raises concerns regarding tolerability, systemic toxicity, and patient adherence. Consequently, attention has shifted toward plant-derived therapies — particularly those rich in neuroprotective and antioxidant constituents — as more sustainable and well-tolerated options for maintaining brain health. Annona reticulata, a member of the Annonaceae family, has attracted scientific interest owing to its phytochemical complexity and historically documented medicinal applications. Objective: The present investigation aimed to evaluate the cognitive-enhancing potential of the hydroalcoholic fruit extract of Annona reticulata in a scopolamine-induced murine model of cholinergic cognitive impairment. Methods: A total of thirty-six male Wistar mice were randomly allocated into six experimental groups, each comprising six animals. Group I served as the vehicle-treated normal control, while Group II received the reference nootropic, piracetam (400 mg/kg, per oral), administered daily for six consecutive days. Cholinergic cognitive impairment was established in Group III through intraperitoneal administration of scopolamine (1 mg/kg). Groups IV, V, and VI were co-administered scopolamine alongside graded doses of the hydroalcoholic fruit extract at 100, 200, and 400 mg/kg orally, respectively. Spatial learning and memory were evaluated employing the Morris Water Maze paradigm over six days. Following behavioural assessment, hippocampal tissues were harvested and processed for histopathological examination. Data were statistically analysed using one-way and two-way ANOVA, and values were reported as mean ± SEM. Results: Hydroalcoholic fruit extract of Annona reticulata elicited a statistically significant and dose-related amelioration of spatial learning and memory deficits in scopolamine-challenged animals. Extract-treated groups exhibited progressive reductions in escape latency and augmented target quadrant occupancy across training days. At the highest tested dose (400 mg/kg), cognitive performance closely approached that observed in the piracetam reference group, underscoring the extract's potent nootropic efficacy. Conclusion: Collectively, these findings indicate that Annona reticulata fruit extract harbours appreciable cognitive-enhancing and neuroprotective capabilities. The extract warrants further mechanistic and translational investigation to delineate its precise mode of action and validate its therapeutic applicability in cognitive dysfunction disorders.

The increasing prevalence of metabolic disorders, gastrointestinal diseases, immune dysregulation, and lifestyle-related illnesses has intensified global interest in preventive nutrition and gut microbiome research. Ayurveda, the traditional system of Indian medicine, emphasizes the concepts of Agni (digestive and metabolic fire) and Ahara Vidhi (dietary rules and eating practices) as the foundation of health and disease prevention. Classical Ayurvedic texts describe Agni as the central factor governing digestion, absorption, assimilation, tissue nourishment, immunity, and longevity. Disturbance of Agni leads to the formation of Ama (metabolic toxins), which is considered the root cause of many diseases. Similarly, Ahara Vidhi outlines systematic principles regarding food quality, quantity, combinations, timing, environment, and eating behaviour to maintain physiological balance. Recent advances in gut microbiome science reveal that dietary habits profoundly influence microbial diversity, intestinal permeability, immune modulation, metabolic homeostasis, and neuro-gastrointestinal interactions. Emerging evidence suggests significant conceptual parallels between Ayurvedic understanding of gut health and modern microbiota centered nutrition. Practices such as mindful eating, individualized diet planning, seasonal dietary adaptation, and proper food combinations demonstrate potential relevance in maintaining microbial balance and preventing chronic inflammatory disorders. This review aims to critically explore the correlation between Ayurvedic principles of Agni and Ahara Vidhi with current concepts of gut microbiome science and preventive nutrition. The article highlights the integrative potential of Ayurveda in developing personalized, sustainable, and preventive dietary strategies for modern healthcare systems.

Type 2 diabetes mellitus (T2DM) frequently coexists with hypertension, substantially increasing the risk of cardiovascular morbidity, mortality, and progressive renal disease. Contemporary management of these comorbid conditions relies heavily on polypharmacy, with oral antidiabetic drugs and antihypertensive agents prescribed concomitantly for prolonged durations. Among antidiabetic therapies, the fixed-dose combination of glimepiride and metformin remains widely used because it addresses both insulin resistance and impaired insulin secretion. Angiotensin receptor blockers (ARBs) are commonly recommended antihypertensive agents in patients with T2DM due to their established renoprotective and cardioprotective benefits. However, accumulating experimental and clinical evidence suggests that ARBs are not metabolically inert; instead, they may influence glucose homeostasis, insulin sensitivity, and the pharmacokinetic disposition of antidiabetic drugs. These effects raise clinically relevant concerns regarding potential pharmacokinetic and pharmacodynamic interactions when ARBs are co-administered with glimepiride-metformin combinations. Preclinical investigations have demonstrated enhanced hypoglycemic responses when certain ARBs, such as losartan and telmisartan, are combined with glimepiride-metformin, possibly due to synergistic pharmacodynamic actions or alterations in drug metabolism and transport. Telmisartan, in particular, exhibits partial peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist activity, which may confer additional insulin-sensitizing effects. Clinical evidence, however, remains limited and inconsistent, with some studies suggesting modest improvements in glycemic control and others indicating an increased risk of hypoglycemia, especially in regimens containing sulfonylureas. Moreover, most available studies lack integrated pharmacokinetic-pharmacodynamic assessments and fail to reflect chronic real-world combination therapy. This review critically synthesizes current preclinical and clinical evidence on pharmacokinetic and pharmacodynamic interactions between glimepiride-metformin combinations and ARBs. It highlights existing knowledge gaps, underscores the clinical necessity for systematic and ARB specific evaluation, and proposes future research directions aimed at optimizing safety and therapeutic outcomes in patients with coexisting T2DM and hypertension.