Objective To systematically analyze the blood-absorbed and brain-absorbed components of the classical formula Kaixin San (KXS) in normal and depression model rats, and preliminarily elucidate the pharmacological material basis of its antidepressant effect. Methods A depression model rat was established using the chronic unpredictable mild stress (CUMS) method, and behavioral verification was performed through open field test, novel object recognition test, sucrose preference test, and forced swimming test. The components in the serum and brain tissue from normal and model rats after intragastric administration of KXS were comprehensively analyzed by UPLC-Q-Exactive Orbitrap MS/MS. Results In the control rats, 143 (including 47 prototypes and 96 metabolites) and 11 components were identified in serum and brain tissue, respectively. In contrast, the overall number in the depression model rats significantly decreased, with only 83 (including 28 prototypes and 55 metabolites) and 4 components detected in serum and brain tissue, respectively. Among them, four prototype components were confirmed to cross the brain in serum and brain tissue samples of the CUMS model rats, including β-asarone, ginsenoside Rg₁, ginsenoside Rb₁, and polygalaxanthone III. Conclusion This study identified four key active components from the blood-absorbed and brain-absorbed components of KXS in normal and depression model rats, providing experimental evidence for screening quality markers of KXS and in-depth analysis its antidepressant mechanism.

Kaixin San  /  UPLC-Q-Exactive Orbitrap MS/MS  /  depression  /  blood-absorbed components  /  brain-absorbed components