Introduction: Medicinal plants have many different types of chemical compounds. Therefore, these chemicals may be affected by various environmental factors when they are used for medicinal purposes in order to determine if there is a correlation between the type of Piper betle L. cultivars and their bioactive compounds. Method: In this study, four different cultivars (PB1-PB4) from the same location in Trang Province, Thailand, were investigated. The total phenolic and flavonoid contents of the ethanolic leaf extracts from each cultivar were compared. Furthermore, the free radical scavenging capacity, as well as the α-amylase and α-glucosidase inhibitory activities, were evaluated. Results: The PB2 extract exhibits total phenolic and flavonoid levels of (112.031 ± 5.976 mg GAE/g and 932.385 ± 20.093 mg QE/g, respectively. The free radical scavenging activity was found to be prominent against DPPH with an IC50 of 0.083 ± 0.003 mg/ml and against ABTS with an IC50 of 0.027 ± 0.002 mg/ml. Discussion: Cultivar PB2 exhibited the highest total phenolic and flavonoid contents, corresponding to the greatest free radical scavenging capacity among all tested cultivars. Furthermore, our in vitro studies demonstrated a highly favorable selective enzyme inhibitory profile for the bioactive compounds in PB1, characterized by potent α -glucosidase inhibition paired with minimal α - amylase activity. Conclusion: Overall, this single origin study provides evidence that the bioactivity of P. betle is primarily controlled by genetic variation and highlights cultivars PB1 and PB2 as potential candidates for developing natural therapeutic agents to manage oxidative stress and Type II diabetes.
Objective: To investigate the Structure-Activity Relationship (SAR) of polyphenolic Xanthine Oxidase (XO) inhibitors using computational approaches and to identify key molecular features that enhance binding affinity for the rational design of novel anti-hyperuricemic agents. Methods: Comparative Molecular Field Analysis (CoMFA) was performed on a series of 24 polyphenolic XO inhibitor derivatives. Multiple training–test set ratios (2:1, 1:1, 3:2, 4:3, and 5:4) were evaluated to assess model robustness and to balance underfitting and overfitting. Internal and external validation techniques were employed to determine the predictive reliability of the developed models. Contour maps were generated to visualize steric, hydrophobic, and hydrogen-bonding contributions. Molecular docking and Molecular Dynamics (MD) simulations were conducted to analyze ligand–enzyme interactions and binding stability within the XO active site. results: These research results could prove useful in the discovery of novel effective XO inhibitors with greater action towards the medical management of an elevated uric acid and gout. Results: The CoMFA models demonstrated satisfactory internal consistency and external predictability, with notable variations in statistical performance across different dataset ratios. The 2:1 training–test set ratio provided an optimal balance between model stability and predictive power. Contour map analysis revealed that steric bulk, hydrophobic regions, and hydrogen-bond donor/ acceptor features significantly influenced XO inhibitory activity. Docking and MD simulations corroborated these findings by confirming stable interactions between key functional groups of the polyphenolic compounds and critical residues of XO. Discussion: The study highlights the sensitivity of QSAR model performance to dataset partitioning and underscores the importance of selecting an appropriate training-test ratio. The combined CoMFA, docking, and MD approaches provided complementary insights into the molecular determinants governing XO inhibition. Conclusion: This computational investigation provides a robust SAR framework for polyphenolic XO inhibitors and identifies key molecular features essential for enhanced inhibitory activity.
Background: Safe and effective natural α-amylase inhibitors remain relevant for controlling postprandial hyperglycemia in Type 2 Diabetes Mellitus (T2DM). Several Cameroonian medicinal plants have shown promising inhibitory activity, but the compounds underlying these effects remain insufficiently characterized. Methods: In this study, a literature-guided plant selection strategy was used to identify candidate species and contextualize the experimental work. Crude extracts from Annona muricata, Monodora myristica, Garcinia kola, and Terminalia superba were evaluated in vitro, and the most active extract was subjected to bio-guided fractionation. Metabolite profiling of active fractions was performed using LC-MS coupled with multivariate analysis. Molecular docking and MMGBSA binding free-energy calculations were employed to explore potential interactions between identified compounds and human pancreatic α-amylase. results: Terminalia superba bark extract exhibited the highest inhibition (83.75%), comparable to acarbose. Metabolite profiling of active fractions identified 11 compounds among which thermopsoside, catechin 4-O-glucoside, and luteonyl 7-O-glucoside are suggested as major bioactive compounds. Molecular docking revealed strong interactions of these compounds with catalytic residues Asp197, Glu233, and His299 in human pancreatic α-amylase. Results: Terminalia superba bark extract exhibited the highest inhibition (83.75%), comparable to acarbose. Metabolite profiling of active fractions putatively identified 11 compounds, including luteolin- 7-O-glucoside, quercetin, and arjunolic acid derivatives, as candidate bioactive compounds. Molecular docking revealed strong interactions of these compounds with catalytic residues Asp197, Glu233, and Asp300/His299 in human pancreatic α-amylase. Discussion: The results support T. superba as a promising source of α-amylase inhibitory constituents. The convergence of bioassay-guided fractionation, LC-MS profiling, and in silico analysis suggests that the observed activity is likely mediated by several complementary phytochemicals rather than by a single compound. Conclusion: This integrative experimental study provides mechanistic insight into the α-amylase inhibitory potential of selected Cameroonian medicinal plants and supports further isolation, kinetic validation, toxicity testing, and in vivo evaluation of the most promising compounds before therapeutic relevance can be established.
Abstract: Atherosclerotic plaque rupture is a major contributor to acute coronary syndromes and ischemic stroke, with extracellular matrix degradation and fibrous-cap thinning being critical determinants of plaque vulnerability. This review summarizes current evidence linking AMPactivated Protein Kinase (AMPK) signaling to Matrix Metalloproteinase (MMP)-mediated regulation of atherosclerotic plaque stability. Experimental and clinical studies examining the roles of AMPK in inflammatory signaling, oxidative stress, autophagy, and vascular cell function were evaluated. Available evidence suggests that metabolic dysfunction and chronic inflammation promote MMP expression and activity, thereby contributing to the degradation of collagen and elastin within the extracellular matrix. AMPK activation may attenuate MMP expression and activity through modulation of NF-κB and Mitogen-Activated Protein Kinase (MAPK) signaling, oxidative stress, and autophagy. Furthermore, the AMPK–MMP axis appears to exert cell-specific effects in endothelial cells, vascular smooth muscle cells, and macrophages, highlighting its complex role in vascular inflammation and plaque remodeling. Overall, AMPK may act as an important metabolic and signaling regulator that integrates metabolic homeostasis, inflammatory responses, and extracellular matrix remodeling to support plaque integrity. Modulation of AMPK signaling and selected MMPs may therefore represent a potential therapeutic approach for stabilizing vulnerable atherosclerotic plaques and reducing the risk of cardiovascular and cerebrovascular events.
Introduction: Non-Small Cell Lung Cancer (NSCLC) remains a major clinical challenge and is one of the leading causes of cancer-related mortality worldwide. Its poor prognosis is driven by substantial molecular heterogeneity, dynamic interactions between tumor cells and the surrounding microenvironment, and the frequent development of therapeutic resistance. Among the signaling pathways involved, Focal Adhesion Kinase (FAK) and Proline-rich tyrosine Kinase 2 (PYK2) have emerged as important regulators that integrate oncogenic and microenvironmental signals, thereby promoting tumor progression and resistance to therapy. Methods: A narrative literature review was conducted using major scientific databases to evaluate the mechanistic, preclinical, and clinical evidence regarding the role of FAK/PYK2 signaling in NSCLC. Studies investigating pathway interactions, mechanisms of therapeutic resistance, combination treatment strategies, and nanocarrier-mediated drug delivery systems were critically analyzed. Results: FAK and PYK2 function as central signaling hubs that connect key oncogenic pathways, including Epidermal Growth Factor Receptor (EGFR), Phosphoinositide 3-Kinase/Protein Kinase B (PI3K/AKT), Mitogen-Activated Protein Kinase (MAPK), and Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling. Activation of these kinases promotes cell proliferation, survival, epithelial–mesenchymal transition, and therapeutic resistance. Although FAK/PYK2-targeted monotherapy has demonstrated limited clinical efficacy, rational combination strategies involving EGFR tyrosine kinase inhibitors, MAPK inhibitors, chemotherapy, or immunotherapy have shown promising synergistic effects. In addition, nanocarrier-based delivery systems may improve drug targeting and pharmacokinetic profiles while reducing systemic toxicity. Discussion: The adaptive quality of the disease calls for multi-pathway therapeutic strategies for the treatment of NSCLC. Blocking FAK/PYK2 may interrupt the integrated signaling pathways and compensatory mechanisms that contribute to resistance. Precision-guided combination regimens aided by the use of biomarker-driven patient selection are critical when it comes to improving clinical outcomes. Conclusion: FAK and PYK2 represent promising therapeutic targets in NSCLC. Strategies involving multi-pathway inhibition and advanced drug delivery platforms offer a rational approach to suppress tumor growth and overcome therapeutic resistance. Further investigation in translational and clinical settings is warranted to establish their therapeutic potential.
