Optimization of Vinegar Processing for Yuanhu Zhitong Formula Enhances Antigastric Ulcer Efficacy: An Integrated Pharmacokinetic–Pharmacodynamic and Network Pharmacology Study

ABSTRACT This study aimed to explore the processing mechanism of single medicinal herbs in compound prescriptions, compare the pharmacodynamic and pharmacokinetic changes of Yuanhu Zhitong Formula before and after processing, and elucidate its underlying mechanism against gastric ulcers. The results showed that six components, namely, corydaline, coptisine chloride, palmatine, berberine chloride, phellopterin, and imperatorin, exerted anti‐ulcer activities. The optimal vinegar‐processing parameters for Corydalis yanhusuo were determined as follows: processing temperature of 84°C, vinegar dosage of 37%, and baking time of 35 min. Vinegar‐processed Corydalis yanhusuo could accelerate the in vivo distribution of alkaloid components in the formula, elevate the plasma concentration, and prolong the in vivo retention time of coumarin components. The synergistic effects of the two types of active ingredients endow the vinegar‐processed Yuanhu Zhitong Formula with significantly superior antigastric ulcer activity compared with the raw formula. Moreover, network pharmacology results revealed that this formula exerts therapeutic effects against gastric ulcers mainly by regulating the PI3K/AKT/mTOR signaling pathway. This study clarified the optimal processing technology and the pharmacodynamic material basis of Yuanhu Zhitong Formula against gastric ulcers, confirmed the efficacy‐enhancing effect of processing, and provided data support for the formulation of its processing production standards and clinical medication.