biostudies-literatureXu Lthe Nation Natural Science Foundation of China106https://www.ebi.ac.uk/biostudies/studies/S-EPMC12844872biostudies-literatureUnknown19(1)<b>Background</b>: The traditional formula Liqi Yangyin (LQYY) has shown clinical and preclinical efficacy for depression with constipation, yet its molecular mechanisms remain incompletely defined. This study aimed to elucidate its mechanisms using an integrative approach. <b>Methods</b>: Constituents of LQYY were profiled by UPLC-MS/MS and integrated with network pharmacology and molecular docking to identify brain-accessible components and putative targets. A chronic unpredictable mild stress (CUMS) model was used for experimental validation. Outcomes included behavioral tests (sucrose preference test, open field test, and forced swimming test), gastrointestinal indices, including fecal water content, time of first black stool, and intestinal propulsion rate, histopathology of the prefrPharmaceuticals (Basel, Switzerland)Elucidating the Mechanism of the Liqi Yangyin Formula in Treating Depression-Constipation Comorbidity: An Integrative Approach Using Network Pharmacology and Experimental Validation.PMC1284487282274520Xu LTang ZQian YOng SSXu TDeng XLi MfalseElucidating the Mechanism of the Liqi Yangyin Formula in Treating Depression-Constipation Comorbidity: An Integrative Approach Using Network Pharmacology and Experimental Validation.<b>Background</b>: The traditional formula Liqi Yangyin (LQYY) has shown clinical and preclinical efficacy for depression with constipation, yet its molecular mechanisms remain incompletely defined. This study aimed to elucidate its mechanisms using an integrative approach. <b>Methods</b>: Constituents of LQYY were profiled by UPLC-MS/MS and integrated with network pharmacology and molecular docking to identify brain-accessible components and putative targets. A chronic unpredictable mild stress (CUMS) model was used for experimental validation. Outcomes included behavioral tests (sucrose preference test, open field test, and forced swimming test), gastrointestinal indices, including fecal water content, time of first black stool, and intestinal propulsion rate, histopathology of the prefr2026-01-01T00:00:00Z2026 Jan2026-06-17T03:18:04.19Z2026-06-17T03:07:54.24ZS-EPMC128448724159970510.3390/ph19010106