Exploring the Bioactive Components and Therapeutic Targets of Sanzi Decoction in Antihypertensive Treatment

Sanzi Decoction, a traditional Mongolian medicinal formula composed of Gardeniae Fructus, Chebulae Fructus, and Toosendan Fructus, has long been used in the treatment of hypertension. However, the specific active components and underlying therapeutic mechanisms remain to be fully elucidated.

Active compounds and their corresponding targets of Sanzi Decoction were screened from TCMSP, and hypertension-related targets were retrieved from GeneCards, DisGeNET, and OMIM. The shared targets between Sanzi Decoction and hypertension were subjected to GO and KEGG enrichment analyses. A protein-protein interaction network in combination with four machine learning algorithms, including LASSO, random forest, SVM-RFE, and RF-RFE, was employed to robustly identify core targets. Subsequently, molecular docking and molecular dynamics simulations were employed to predict and evaluate the binding affinity and stability of key compound-target complexes.

A total of 23 bioactive compounds and 164 targets associated with Sanzi Decoction were identified, among which 81 overlapped with hypertension-related targets. Network pharmacology analysis identified four key compounds, including quercetin, kaempferol, (R)-(6-methoxy-4- quinolyl)-[(2R,4R,5S)-5-vinylquinuclidin-2-yl]methanol, and stigmasterol. Enrichment analysis revealed that the intersected targets were involved in key cardiovascular pathways, including atherosclerosis and the AGE-RAGE signaling pathway. Machine learning-assisted protein-protein interaction identification converged on three central targets: EGFR, ESR1, and TP53. Molecular docking and dynamics simulations suggested stable binding interactions within the EGFR-ligand complexes and the ESR1-quercetin complex, implying their potential physiological relevance.

This study systematically identified the key bioactive components and potential therapeutic targets of Sanzi Decoction for hypertension therapy through data mining, offering theoretical evidence-based support for its therapeutic use. Nevertheless, given the in silico nature of these findings, further in vitro and in vivo investigations are warranted to validate the pharmacological mechanisms.

Sanzi Decoction may exert antihypertensive effects via key compounds targeting EGFR, ESR1, and TP53 and modulating atherosclerosis and AGE-RAGE pathways, providing evidence- based support for its therapeutic potential.