Diabetic foot ulcers(DFUs)represent a significant global healthcare burden due to their chronic nature and poor healing response.Gynura cusimbua,a medicinal plant with traditional wound-healing applications,was invest...Diabetic foot ulcers(DFUs)represent a significant global healthcare burden due to their chronic nature and poor healing response.Gynura cusimbua,a medicinal plant with traditional wound-healing applications,was investigated for its therapeutic potential in DFU management using an integrative approach involving phytochemical profiling,network pharmacology,molecular docking,MD simulation,and angiogenesis studies.OHRLC-MS analysis identified seven major phytochemicals in the ethyl acetate fraction,which were further screened for drug-likeness and target prediction.Network pharmacology analysis identified Protein Kinase C Alpha(PRKCA)as a key target associated with DFU pathology,particularly in modulating angiogenesis,inflammation,and oxidative stress.Molecular docking studies were performed to assess the binding affinity of four selected phytochemicals—Haplophytine,Hexahydrodifenidol,1-[(1-tert-Butyl-1H-tetrazol-5-yl)-(2,4-dimethoxyphenyl)-methyl]-4-cyclohexylpiperazine,and(3β,4α)-3-Hydroxycholest-5-en-4-yl acetate—against PRKCA,with Phorbol-12-myristate-13-acetate(PMA)serving as a reference activator.Among these,Haplophytine and 1-[(1-tert-Butyl-1H-tetrazol-5-yl)-(2,4-dimethoxyphenyl)-methyl]-4-cyclohexylpiperazine(6.8 kcal/mol)exhibited the strongest binding affinities,surpassing PMA.These two ligands were taken forward for MD simulations,which confirmed their superior structural stability,hydrogen bonding interactions,and lower solvent exposure making them the most promising PRKCA activators.Angiogenesis was evaluated using the chorioallantoic membrane assay,demonstrating a dose-dependent increase in secondary and tertiary blood vessel formation,with the highest angiogenic activity observed at 45μg/mL.Collectively,these findings suggest that Gynura cusimbua exerts a multi-targeted therapeutic effect on DFU through PRKCA activation and enhanced angiogenesis,highlighting its potential for phytotherapeutic applications in diabetic wound healing.展开更多
文摘Diabetic foot ulcers(DFUs)represent a significant global healthcare burden due to their chronic nature and poor healing response.Gynura cusimbua,a medicinal plant with traditional wound-healing applications,was investigated for its therapeutic potential in DFU management using an integrative approach involving phytochemical profiling,network pharmacology,molecular docking,MD simulation,and angiogenesis studies.OHRLC-MS analysis identified seven major phytochemicals in the ethyl acetate fraction,which were further screened for drug-likeness and target prediction.Network pharmacology analysis identified Protein Kinase C Alpha(PRKCA)as a key target associated with DFU pathology,particularly in modulating angiogenesis,inflammation,and oxidative stress.Molecular docking studies were performed to assess the binding affinity of four selected phytochemicals—Haplophytine,Hexahydrodifenidol,1-[(1-tert-Butyl-1H-tetrazol-5-yl)-(2,4-dimethoxyphenyl)-methyl]-4-cyclohexylpiperazine,and(3β,4α)-3-Hydroxycholest-5-en-4-yl acetate—against PRKCA,with Phorbol-12-myristate-13-acetate(PMA)serving as a reference activator.Among these,Haplophytine and 1-[(1-tert-Butyl-1H-tetrazol-5-yl)-(2,4-dimethoxyphenyl)-methyl]-4-cyclohexylpiperazine(6.8 kcal/mol)exhibited the strongest binding affinities,surpassing PMA.These two ligands were taken forward for MD simulations,which confirmed their superior structural stability,hydrogen bonding interactions,and lower solvent exposure making them the most promising PRKCA activators.Angiogenesis was evaluated using the chorioallantoic membrane assay,demonstrating a dose-dependent increase in secondary and tertiary blood vessel formation,with the highest angiogenic activity observed at 45μg/mL.Collectively,these findings suggest that Gynura cusimbua exerts a multi-targeted therapeutic effect on DFU through PRKCA activation and enhanced angiogenesis,highlighting its potential for phytotherapeutic applications in diabetic wound healing.
