Mechanism of Antihypertensive Effect of Banxia Baizhu Tianma Decoction: A Bioinformatics Study and an In Vivo Demonstration

INTRODUCTION: The Banxia Baizhu Tianma Decoction (BBTY) is a common traditional Chinese medicine (TCM) used for treating hypertension. However, the mechanisms by which BBTY depresses hypertension remain largely unclear. METHODS: The active components of BBTY were identified with reference to the TCMSP and ETCM database. The hub target and pathway enrichment analysis were performed by molecular docking or network pharmacology. The pharmacological actions of BBTY (1.35, 2.70, and 5.40 g/kg, n=8) on spontaneously hypertensive rats (SHR) over 6 weeks were determined based on blood pressure changes, holding power, and the duration of dizziness. The effects of BBTY on the core target genes or proteins were detected by RT-PCR and ELISA assay. RESULTS: We identified 145 key compounds and 199 hub targets of BBTY that were potentially involved in depressing hypertension, and the PI3K-AKT and AGE-RAGE were identified as the key pathways. In vivo, BBTY administration notably decreased systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), and dizziness in SHR while enhancing grip strength. It also significantly boosted eNOS expression and NO content, lowered ALB, INS, and Caspase-3 levels, and increased Bcl2, Esr1, Pparγ, and Akt1 mRNA expression while reducing Tnf, Il1β, and Ptgs2 mRNA expression. DISCUSSION: BBTY could reduce blood pressure, related to the effects on targets such as Pparγ, Ptgs2, Esr1, Tnf, Akt1, and Bcl2, as well as the influence on pathways of PI3K-AKT, AGERAGE, and endocrine resistance. CONCLUSION: The findings provided a novel mechanistic insight into the therapeutic effects of BBTY for hypertension.