Aspects of molecular medicine最新文献

{"title":"Personalized approaches to lung cancer treatment: A review of targeted therapies, pharmacogenomics, and combination strategies","authors":"Namini M,&nbsp;Bhagya G,&nbsp;Manjari Sharma","doi":"10.1016/j.amolm.2025.100073","DOIUrl":"10.1016/j.amolm.2025.100073","url":null,"abstract":"<div><div>Globally, lung cancer—more specifically, non-small cell lung cancer (NSCLC)—contributes significantly to the death toll from cancer. Recent advances in molecular research have identified key genetic mutations that drive tumor growth, including those in the EGFR, KRAS, ALK, and MET genes, accounting for around 80 % of lung cancers that are categorized as non-small cell lung cancer (NSCLC). The advent of targeted therapies such as Tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have revolutionized cancer treatment by specifically inhibiting oncogenic pathway. However, despite this advancements, treatment outcomes remain suboptimal due to intrinsic heterogeneity of cancers and the development of resistance mechanisms. The cancer treatment landscape is constantly changing to address these challenges and improve patient outcomes. Customization of cancer therapies through pharmacogenomics is hindered by tumor adapatability and resistance, limited prognostic biomarkers and suboptimal monotherapies, necessitating innovative research in adoptive therapies biomarker development and combination therapies. Ongoing trails aims to enhance treatment endurance via the advancement of combination regimens incorporating multiple targeted therapies or synergistic combination immunotherapy with chemotherapy. Ongoing research is focused on optimizing CRISPR-Cas9 delivery system, improving specificity and minimizing half target effect. Emphasizes the crucial role of molecular mutations, the advantages and disadvantages of targeted medicines, and the prospects for enhancing the effectiveness of lung cancer treatment results are all highlighted in this Review.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100073"},"PeriodicalIF":0.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of ultra-processed foods on cardiovascular diseases and cancer: Epidemiological and mechanistic insights","authors":"Olorunfemi Oyewole Babalola ,&nbsp;Ebenezer Akinnusi ,&nbsp;Paul Olamide Ottu ,&nbsp;Kpomah Bridget ,&nbsp;Godspower Oyubu ,&nbsp;Samuel Ayomikun Ajiboye ,&nbsp;Sakariyau Adio Waheed ,&nbsp;Amafili Chibuzo Collette ,&nbsp;Hameedah Oluwatoyin Adebimpe ,&nbsp;Chibuzo Valentine Nwokafor ,&nbsp;Ebenezer Ayomide Oni ,&nbsp;Precious Olayinka Aturamu ,&nbsp;Opeyemi Iwaloye","doi":"10.1016/j.amolm.2025.100072","DOIUrl":"10.1016/j.amolm.2025.100072","url":null,"abstract":"<div><div>Ultra-processed foods (UPFs) are increasingly recognized as contributors to the pathogenesis of cardiovascular diseases (CVDs) and cancer due to their adverse compositional and mechanistic effects. UPFs, distinguished by their high content of unhealthy fats, sodium, refined sugars, and synthetic additives, significantly increase dyslipidemia, hypertension, and obesity, which are key risk factors for CVDs. Chronic consumption leads to systemic inflammation, gut microbiota dysbiosis, endothelial dysfunction, and oxidative stress. Additives such as artificial sweeteners and sodium nitrites in UPFs are associated with carcinogenesis through mechanisms involving genotoxicity and promotion of inflammatory microenvironments. This review critically evaluates existing epidemiological, mechanistic, and clinical evidence linking UPFs consumption to CVDs and cancer, synthesizing insights into their underlying pathophysiological mechanisms and highlighting disparities in disease burden across diverse populations. Epidemiological evidence demonstrates that UPFs constitute over 50% of daily caloric intake in Western diets, with each 10% increase in UPF consumption associated with a 12% rise in CVDs risk and a comparable increase in cancer incidence. Addressing the global surge in UPF consumption through dietary guidelines, regulatory policies, and public health initiatives may mitigate these risks, improve metabolic and cardiovascular health, and reduce cancer prevalence.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100072"},"PeriodicalIF":0.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational framework for analyzing miRNA-mRNA interactions in sarcopenia: Insights into age-related muscular degeneration","authors":"Sarvesh Sabarathinam ,&nbsp;Akash Jayaraman ,&nbsp;Ramesh Venkatachalapathy ,&nbsp;Subhiksha Shekar","doi":"10.1016/j.amolm.2025.100070","DOIUrl":"10.1016/j.amolm.2025.100070","url":null,"abstract":"<div><h3>Background</h3><div>Sarcopenia, an age-related loss of skeletal muscle mass and function, impairs mobility, fragility, and quality of life. Despite progress in pathophysiology, molecular processes remain unknown. Recent research has investigated miRNAs as biomarkers for sarcopenia diagnosis and therapy. This work analyses differentially expressed genes (DEGs) and predicts miRNA-mRNA interactions using ML methods like XG-Boost and SHAP to find biomarkers.</div></div><div><h3>Objective</h3><div>This work evaluated the function of miRNA-mRNA interactions in sarcopenia pathogenesis and identified possible biomarkers by transcriptome analysis utilizing machine learning.</div></div><div><h3>Methods</h3><div>High-throughput mRNA sequencing datasets (GSE111006, GSE111010, and GSE111016) from GEO database were combined, pre-processed, and normalized using TPM and DESeq2 methods. XG-Boost regression analysis used 80/20 training and testing sets. SHAP analysis was used to evaluate model data and find significant DEGs. PPI networks were created using the STRING database, while miRNA-mRNA interactions were predicted using Encori and displayed with Cytoscape. The degree scores of miRNA-mRNA interactions were utilized to find biomarkers<strong>.</strong></div></div><div><h3>Results</h3><div>XG-Boost and SHAP analysis revealed 20 influential DEGs linked to sarcopenia. With 97% accuracy, the model predicted accurately. PPI network research identified six hub genes: NTRK2, PCK1, DSP, SCD, MMRN1, and EDIL3. MiRNA-mRNA interaction analysis found miR-186–5p as the highest-degree biomarker candidate (36). MiR-186–5p was linked to muscle metabolism, hypertrophy, and exercise response.</div></div><div><h3>Conclusion</h3><div>The study found miR-186–5p to be a promising biomarker for sarcopenia using an integrated machine learning technique. The findings show that miR-186–5p may be a diagnostic and therapeutic target for sarcopenia, revealing its pathogenesis and enabling tailored treatments. Experimental research is needed to prove its therapeutic value.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetoplastid diseases: Insights into the mechanisms of drug action and resistance for novel drug discovery","authors":"Abdullah M. Tauheed ,&nbsp;Ammar U. Danazumi ,&nbsp;Oluwafemi A. Adepoju ,&nbsp;Patricia I. Kobo ,&nbsp;Auwal Adamu ,&nbsp;Emmanuel O. Balogun","doi":"10.1016/j.amolm.2025.100071","DOIUrl":"10.1016/j.amolm.2025.100071","url":null,"abstract":"<div><div><em>Trypanosoma</em> and <em>Leishmania</em> species are kinetoplastid protozoan parasites that cause diseases which result in significant disability-adjusted life years (DALYs) and agricultural losses in the developing world. Despite the progress recorded in understanding biology and chemotherapy of these pathogens of neglected diseases, treatment failure, due to drug resistance or toxicity-driven non-compliance remain major challenges. Advances in molecular parasitology have led to the identification of specific transport mechanisms, druggable targets and persister-like cells, which play distinct roles in the overall success of therapies. Transporters and other cellular transport mechanisms affect the internalisation of drugs and their intracellular availability which determine drug activity. Thus, we reviewed kinetoplastid drug transport mechanisms, molecular drug targets and persisters to highlight mechanisms of action and development of resistance for antikinetoplastid drugs, with the aim of providing novel insights for drug discovery programmes.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel combination therapy of osimertinib and Tupichinol E in triple-negative breast cancer: Targeting EGFR and CDK4/6 pathways","authors":"Adyasa Samantaray,&nbsp;Debasish Pradhan","doi":"10.1016/j.amolm.2025.100069","DOIUrl":"10.1016/j.amolm.2025.100069","url":null,"abstract":"<div><div>Triple-Negative Breast Cancer (TNBC) is one of the most challenging form of breast cancer that lacks hormone receptors and HER2, limiting targeted treatment options. While a third-generation EGFR inhibitor, Osimertinib, has shown efficacy in various cancers, its role in TNBC is not well established. On the other hand, <em>Tupichinol E</em>, a novel compound, has shown promising anticancer potential in preclinical studies. This study investigates the combined effects of Osimertinib and <em>Tupichinol E</em> on TNBC cell lines, revealing a synergistic reduction in cell viability, increased apoptosis, and cell cycle arrest compared to individual treatments. Furthermore, cyclin-dependent kinases 4 and 6 (CDK4/6), important cell cycle regulators, are essential in transitioning cells from the G1 to S phase via retinoblastoma protein (RB) phosphorylation. Dysregulation of the CDK4/6-RB pathway is a hallmark in many cancers, including hormone receptor-positive breast cancers, and has become a focus of targeted therapies. Our findings not only emphasizes the therapeutic potential of combining Osimertinib with <em>Tupichinol E</em> in TNBC but also underscore the importance of CDK4/6 inhibitors in modulating cell cycle progression, offering a promising avenue for combination therapies in TNBC treatment.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143518947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of Irisin in modulating hypoxia-related disorders: New insights and implications for cancer therapy","authors":"Ghazaleh Khalili-Tanha ,&nbsp;Alireza Shoari ,&nbsp;Elham Nazari","doi":"10.1016/j.amolm.2025.100068","DOIUrl":"10.1016/j.amolm.2025.100068","url":null,"abstract":"<div><div>Regular physical activity is well-known for its health benefits, including reducing the risk of chronic diseases like cancer. Irisin, a myokine released by skeletal muscles during exercise, has emerged as a key regulator in hypoxia-related disorders.Hypoxia, defined by reduced oxygen availability, is a hallmark of various pathological conditions, especially cancer, where it drives tumor growth, metastasis, and resistance to therapy. Recent studies suggest that irisin can modulate hypoxia-induced pathways, impacting processes such as angiogenesis, inflammation, and metabolic adaptation. By targeting these mechanisms, irisin may enhance the efficacy of cancer treatments, reduce tumor aggressiveness, and potentially overcome therapy resistance. Additionally, irisin's influence on the tumor microenvironment highlights its potential as a therapeutic agent to counteract hypoxia-driven cancer progression. This review summarizes current findings on irisin's role in hypoxia-related disorders, focusing on its molecular mechanisms and potential applications in oncology. Despite promising preclinical studies, further research is necessary to fully understand irisin's therapeutic potential, optimize delivery methods, and validate its safety and efficacy in clinical settings. Exploiting exercise-derived molecules such as irisin may enable novel strategies for cancer treatment and other hypoxia-related diseases.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of pathogenic genetic variants associated with familial hypercholesterolemia in Ghanaian children","authors":"Philip Opoku-Agyeman ,&nbsp;Prince Ameyaw ,&nbsp;Selassie Bruku ,&nbsp;Gideon Ofori Addo ,&nbsp;Gideon Tetteh ,&nbsp;Esther Baafi ,&nbsp;Sandra Korkor Asare ,&nbsp;Abigail Foriwaah Frimpong ,&nbsp;Samuel Adu-Poku ,&nbsp;Sena Adzoa Matrevi ,&nbsp;Nancy Odurowah Duah-Quashie ,&nbsp;Kwesi Z. Tandoh","doi":"10.1016/j.amolm.2025.100067","DOIUrl":"10.1016/j.amolm.2025.100067","url":null,"abstract":"<div><div>Familial hypercholesterolemia (FH) is an important contributor to atherosclerotic cardiovascular disease (ASCVD) burden globally. FH disrupts cholesterol metabolism and causes lifelong elevation in low-density lipoprotein cholesterol (LDL-C). In sub-Saharan Africa (SSA), the increasing burden of ASCVD may be partly driven by genetic dyslipidemias of which FH is the commonest. However, there is absence of data on FH prevalence in SSA which delineates an important gap in the management of ASCVD. This study is the first to investigate the prevalence of pathogenic variants associated with FH in Ghana. We used 96 deidentified archived dried blood spot samples collected from a Ghanaian cohort, to determine the prevalence of pathogenic genetic variants associated with FH. These samples were collected from children under 9 years old as part of surveillance for antimalarial drug resistance in 2021. We searched the NCBI's ClinVar database and used <em>in silico</em> tools to identify 500–800 nucleotide base pair regions of interest in 3 genes known to harbor the commonest genetic variants associated with FH. We selected these regions of interest from the <em>LDLR</em> gene exons 4, 9 and 10, <em>APOB</em> exon 26 and <em>PCSK9</em> exon 2 loci. Next, we amplified these regions of interest using conventional polymerase chain reaction. Finally, we sequenced the amplicons using paired-end Sanger sequencing and called variants from the chromatogram files using an in-house custom built bash script utilizing the open access program Tracy. Subsequently, we did quality checks on all reported pathogenic variant calls manually using Benchling's sequence alignment tool. We identified one pathogenic variant V523 M in the <em>LDLR</em> exon 10 region and report an FH prevalence of 1% (1/96), 95% CI: [0%,3.07%], in our Ghanaian cohort. Our finding underscores the importance of FH in driving ASCVD burden in Ghana and advocates the need for implementation science-driven programs to manage this genetic dyslipidemia in Ghana and SSA.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular approaches based on investigating the therapeutic benefits of Moringa oleifera: Insights into biochemical and spermatological and metabolites studies","authors":"Sudha Sankar ,&nbsp;Subramaniam Umavathi ,&nbsp;Ekambaram Gayathiri ,&nbsp;Palanisamy Prakash","doi":"10.1016/j.amolm.2025.100065","DOIUrl":"10.1016/j.amolm.2025.100065","url":null,"abstract":"<div><div>This study aimed to investigate the potential of Moringa oleifera extract, an herbal treatment known to support male reproductive function, in improving sperm motility. Adult male guinea pigs were divided into four groups (n = 5 per group). Group 1 served as the control, while Group 2 was induced with subfertility using Carbendazim. Group 3 consisted of subfertile guinea pigs treated with <em>Moringa oleifera</em> extract, and Group 4 included subfertile guinea pigs treated with clomiphene citrate. Sperm motility parameters, including sperm counts (sperm/ml), rapid and progressive motility (sperm/ml), and sperm agglutination (%), were assessed using standard methods. In control group, guinea pigs exhibited significantly higher sperm counts (44.0 ± 0.89 x 10^6 sperm/ml) and sperm motility (57.6 ± 1.45 x 10^6 sperm/ml, rapid, progressive) compared to the Carbendazim-induced subfertile group (p &lt; 0.05). Conversely, the subfertile group displayed significantly higher sperm agglutination (30 ± 1.26%) than the control group (p &lt; 0.05). Treatment with <em>Moringa oleifera</em> L extract and clomiphene citrate resulted in improved sperm motility parameters, with both groups showing higher sperm counts and rapid, progressive motility, and lower sperm agglutination compared to the sub-fertile group. These findings suggest that Moringa oleifera extract may enhance sperm motility in male guinea pigs with carbendazim-induced subfertility, positioning herbal remedies as potential alternatives for treating male infertility. Furthermore, the study highlights the potential of Moringa oleifera as a therapeutic agent for male infertility by demonstrating its effectiveness in improving sperm motility and reducing sperm agglutination. These results underscore the importance of exploring herbal remedies as safer, natural alternatives to conventional treatments for addressing the subfertility issue. Further research is needed to discover the underlying molecular mechanisms and assess the clinical significance of these outcomes in the context of human male fertility.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chalcone-related small molecules as potent antibacterial and antifungal agents: Design, synthesis, In vitro, and computational approaches","authors":"Narmin Hamaamin Hussen ,&nbsp;Larin Barzan Hussein ,&nbsp;Aso Hameed Hasan ,&nbsp;Shokhan Jamal Hamid ,&nbsp;Chawan Othman Abdl ,&nbsp;Bakhcha Sarkar ,&nbsp;Kozhin Muhammed ,&nbsp;Daroon Muhamad","doi":"10.1016/j.amolm.2025.100066","DOIUrl":"10.1016/j.amolm.2025.100066","url":null,"abstract":"<div><div>Infectious diseases caused by bacteria and fungi are a global health concern due to resistance to traditional antimicrobial medications. A variety of chalcone-related small molecules have been designed, synthesized, and characterized small molecules using FTIR, NMR, and MS to find antimicrobial agents for treating these infections. These designed compounds (<strong>9, 11, 13</strong>) were evaluated for their potential inhibitory activity against five bacterial strains and one fungal strain using disc diffusion and MIC assays utilizing ampicillin and fluconazole as reference drugs. The MIC values ranged from 2.5 to 160 μg/mL, which can be attributed to improved membrane penetration and increased ligand-protein binding capability. Among them, molecule 9 exhibited a broad spectrum of antibacterial activity against gram-negative bacteria, with an MICs of 40 μg/mL against <em>P. aeruginosa</em> and 80 μg/mL against <em>E. coli</em>. Compound <strong>11</strong> showed potent activity against gram-positive bacteria and fungi, with a MICs of 40 μg/mL against <em>S. aureus</em> and 80 μg/mL against <em>C. albicans</em>. Furthermore, similar to <em>in vitro</em> study results, molecular docking demonstrated that compounds <strong>9</strong> and <strong>11</strong> had a better binding affinity against gram-positive and gram-negative bacteria and fungal species than reference drugs. Finally, physicochemical and drug-likeness results showed that all the compounds can pass Lipinski's rule of five, are absorbed through the GIT, and are suitable for oral administration.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in silico Anti-diabetes mechanism of phytochemicals from Curculigo pilosa and its pharmacokinetic profiling via α-amylase inhibition","authors":"Damilola A. Omoboyowa ,&nbsp;Temitope C. Aribigbola ,&nbsp;Simbo T. Akinsulure ,&nbsp;Damilola S. Bodun ,&nbsp;Ezekiel A. Olugbogi ,&nbsp;Ebenezer A. Oni","doi":"10.1016/j.amolm.2025.100064","DOIUrl":"10.1016/j.amolm.2025.100064","url":null,"abstract":"<div><div>Diabetes mellitus is characterized by elevated blood glucose resulting from carbohydrate metabolism via glucose metabolizing enzymes such as α-amylase. <em>Curculigo pilosa</em> is traditionally used as herbal medication as anti-diabetes therapy but its mechanism of action is yet to be explored. This study investigates α-amylase inhibitory potential of <em>C. pilosa</em> using in vitro and in silico approaches. The ethylacetate, n-butanol and methanol extracts of <em>C. pilosa</em> were subjected to in vitro α-amylase inhibitory assay, followed by identification of the bioactive compounds from the most potent extract using HPLC. Integrated computational analyses were performed on ten (10) active compounds against α-amylase using Maestro Schrodinger (v2). The results of the in vitro α–amylase assay revealed n-butanol extract as the potent extract with IC₅₀ of 132.70 μg/mL, although the standard drug (acarbose IC₅₀ = 128.70 μg/mL) inhibits α-amylase better than the extracts. The HPLC result revealed the presence of ten (10) active compounds. Acarbose was observed to possess better binding affinity (−11.502 kcal/mol) than all the compounds but curculigoside was the hit compound with binding affinity of −8.797 kcal/mol. Some of the compounds showed appreciable inhibitory pIC₅₀ and fitness scores comparable to the standard drug. The pharmacokinetic profile revealed that none of the compounds violated more than one Lipinski's rule of five while the standard drug (acarbose) violated three (3) of the rules. The root mean square deviation shows reasonable level of stability within the simulation period for both curculigoside and acarbose. The result of in silico study showed significant inhibitory potential of the active compounds against α-amylase which was consistent with the in vitro inhibition of α amylase by the plant extract suggesting this as the possible mechanism of antidiabetes action of <em>C. pilosa</em>.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143146624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}