Jianpi Tongluo Formula improves hypertension in rats by regulating the Th17/Treg balance through the JAK/STAT3 pathway

Hypertension, as a major global public health problem, has a complex pathogenesis and limited therapeutic effects at present. Jianpi Tongluo Formula (JPTL) has demonstrated potential antihypertensive properties, although its precise mechanisms remain to be fully elucidated. JPTL and hypertensive related targets were screened from the public database and protein-protein interaction network was established. GO and KEGG analysis were conducted to reveal key pathways. Spontaneous hypertensive rats and Wistar Kyoto were used to evaluate the therapeutic effect of JPTL on hypertension, and Colivelin was used for mechanistic validation. Hemodynamic parameters, including blood pressure and cardiac hypertrophy indices were monitored. Pathological changes were observed by HE and Masson staining, while the levels of serum AngII, creatinine, urea and inflammatory factors were detected by ELISA. The JAK/STAT3 pathway were analyzed by Western blot and qRT-PCR, while flow cytometry evaluated Th17/Treg balance. Network pharmacology screened out 365 targets related to JPTL and hypertension. KEGG analysis showed that the JAK/STAT3 pathway was significantly enriched. Animal experiments have confirmed that JPTL dose-dependently reduced the blood pressure of SHR and alleviated pathological damage and fibrosis of the heart and kidneys. Mechanistically, JPTL inhibits the phosphorylation of JAK/STAT3, thereby down-regulating the pro-inflammatory factors (IL-17, IL-6, TNF-α, and IL-23) and up-regulating the anti-inflammatory factors (IL-10 and TGF-β1). Given the critical role of Th17/Treg imbalance in promoting inflammation and vascular injury in hypertension, flow cytometry confirmed that SHR Th17 decreased and Treg increased after JPTL treatment. Colivelin partially reversed the above effects. JPTL improves hypertension by inhibiting JAK/STAT3-mediated Th17/Treg imbalance, highlighting its potential as a multi-target therapeutic agent.