Objective To reveal the active ingredient group of centella asiatica in the treatment of diabetic nephropathy and its synergistic mechanism.

Methods The chemical constituents of C. asiatica were systematically characterized using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Network pharmacology approaches were employed to screen active components and predict therapeutic targets and signaling pathways. Molecular docking was performed to validate binding affinity between core components and key targets.

Results Eighty compounds were identified from C. asiatica, 48 active components (including triterpenoids, polyphenols, and volatile oils) screened. These implicated 137 potential targets, among which 29 core targets (e.g., IL6, TNF, AKT1, STAT3, PPARG) were identified. The core components (kaempferol, quercetin, Asiatic acid, hydroxyasiatic acid) exerted anti-inflammatory, antioxidant, lipid metabolism improvement and renal fibrosis inhibition effects by regulating the lipid and atherosclerotic pathway, adipocytokine signaling pathway, cAMP signaling pathway, etc. Molecular docking verification revealed that the binding energy between the core component and core target was as low as –9.9 kJ/mol, indicating its strong affinity.

Conclusions The triterpenoids, polyphenols and volatile oil active components in Centella asiatica act on core targets such as IL6, AKT1 and STAT3, and synergically regulate inflammatory responses, oxidative stress and lipid metabolism-related pathways, and improve the pathological damage of diabetic nephropathy. This research provides a theoretical basis for the clinical application of centella asiatica and the development of innovative drugs for treating diabetic nephropathy.