Alpha-glucosidase inhibitor(Huadong Medicine)

Cancer remains a major global health challenge, with high prevalence and mortality rates emphasizing the urgent need for innovative treatment strategies. Although precision oncology offers tailored therapies based on genetic profiles, the clinical translation of genomic insights has been slow. Drug repurposing, using existing FDA‐approved drugs for new indications, presents a cost‐effective and time‐efficient alternative. This study investigates MGAM as a potential direct target of alpha‐glucosidase inhibitors in colorectal cancer (CRC), explores its biomarker potential, and evaluates gene expression patterns across diverse cancers. Using RNA‐Seq data from Recount3, Firebrowse, and gene set co‐expression analysis databases, we analyzed the differential expression of MGAM and its paralog MGAM2 across 33 cancer types. We examined mutation profiles, methylation status, survival impact, immune cell infiltration, and drug‐mRNA interactions. Validation was performed via real‐time PCR and whole‐exome sequencing (WES) in CRC patients. MGAM and MGAM2 showed differential expression across multiple cancers, with MGAM2 upregulated and MGAM downregulated in gastrointestinal tumors. Both genes were linked to key cancer‐related pathways, including metabolism, apoptosis, cell cycle regulation, and epithelial‐mesenchymal transition. MGAM exhibited frequent mutations and aberrant methylation in several cancers. Their expression correlated with immune cell infiltration and drug sensitivity, highlighting potential for therapy planning. Diagnostic modeling showed over 80% accuracy. In CRC patients, MGAM downregulation was confirmed in 64 samples, and WES revealed a novel MGAM mutation (rs2960746). These findings underscore MGAM and MGAM2 as promising biomarkers and therapeutic targets, supporting their relevance in advancing personalized oncology.

Background Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is a chronic metabolic disorder characterized by persistent hyperglycemia. Alpha-glucosidase inhibitors like miglitol delay carbohydrate absorption, thereby reducing postprandial glucose levels. Momordica charantia (bitter melon) has demonstrated hypoglycemic effects in various studies, yet its interactions with pharmaceutical antidiabetic agents remain poorly understood. This study investigates the molecular interactions between M. charantia phytoconstituents and miglitol's enzymatic targets using in silico methods. Methods An in silico approach was employed to assess potential herb-drug interactions between M. charantia and miglitol. Phytochemical screening identified 18 bioactive compounds from M. charantia that complied with Lipinski's Rule of Five, evaluated using SwissADME. Molecular docking was performed using AutoDock Tools (v1.5.7) to examine binding affinities between these phytoconstituents and key carbohydrate-metabolizing enzymes: lysosomal alpha-glucosidase (GAA), neutral alpha-glucosidases AB (GANAB) and C (GANC), maltase-glucoamylase (MGAM), and pancreatic alpha-amylase (AMY2A). The binding interactions were visualized using PyMOL and LigPlot+ to assess molecular stability. Results Molecular docking analysis revealed that charantin exhibited the highest binding affinity across all enzymes, particularly with neutral alpha-glucosidase AB (-12.4 kcal/mol) and maltase-glucoamylase (-12.6 kcal/mol), suggesting strong inhibitory potential. Other phytoconstituents, such as quercetin, luteolin, and kaempferol, also displayed moderate to high affinity, indicating possible synergistic effects. In contrast, compounds like cis-sabinol, myrtenol, and beta-sitosterol showed significantly weaker interactions. The binding interaction analysis confirmed stable hydrogen bonding and hydrophobic interactions between charantin and key enzymatic residues, reinforcing its role as a potent inhibitor of carbohydrate metabolism. Conclusion The study suggests that M. charantia phytoconstituents, particularly charantin, may enhance miglitol's effects by inhibiting the same carbohydrate-digesting enzymes. This could lead to increased glucose-lowering efficacy but also raises concerns about excessive inhibition, potentially resulting in postprandial hypoglycemia. These findings underscore the need for careful patient monitoring and dosage adjustments when combining M. charantia with alpha-glucosidase inhibitors. While molecular docking provides valuable insights, further in vitro and in vivo studies are essential to validate these computational predictions, assess bioavailability, and determine the clinical implications of M. charantia-miglitol co-administration.