Integrated network pharmacology, molecular docking, ADMET profiling and In vitro α-amylase inhibitory evaluation of Cardiospermum halicacabum Linn. Against diabetes mellitus.

UNLABELLED: Diabetes mellitus is a chronic metabolic disorder characterized by impaired glucose homeostasis, insulin resistance, and progressive complications. Although Cardiospermum halicacabum Linn. has demonstrated antihyperglycemic activity in traditional medicine, its molecular mechanisms remain poorly understood. This study investigated its antidiabetic mechanisms using network pharmacology, molecular docking, ADMET profiling, and in vitro α-amylase inhibition. Preliminary phytochemical screening was performed on the ethanolic extract. Phytoconstituents were retrieved from the IMPPAT database and screened for drug-likeness. Potential targets were predicted using SwissTargetPrediction and SuperPred, while diabetes-associated genes were collected from GeneCards and OMIM. Network pharmacology, GO and KEGG enrichment analysis, molecular docking with redocking validation, ADMET prediction, and in vitro α-amylase inhibition assays were conducted. Thirty-seven phytoconstituents, 417 compound-related targets, and 1,025 diabetes-related targets yielded 210 overlapping targets. Apigenin, luteolin, chrysoeriol, kaempferol, and quercetin were identified as principal phytoconstituents, while AKT1, PTPN1, PIK3CA, and MAPK8 emerged as hub targets. KEGG analysis highlighted the AGE-RAGE and MAPK signalling pathways. Apigenin showed the strongest predicted binding affinity toward PIK3CA (- 9.61 kcal/mol). The extract exhibited concentration-dependent α-amylase inhibition, reaching 71.27 ± 1.31% inhibition at 1000 μg/mL, with an IC50 of 218.40 μg/mL, whereas acarbose showed 97.10 ± 0.60% inhibition at 1000 μg/mL, with an IC50 of 62.43 μg/mL. Cardiospermum halicacabum may exert antidiabetic activity through multitarget mechanisms. These findings provide computational evidence supported by preliminary experimental validation; however, further target-specific in vitro, in vivo, and clinical studies are required to confirm the proposed mechanisms. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00756-8.