Mechanism Prediction of Banxia Baizhu Tianma Tang and Danggui Shaoyao San Intervention in Ménière's Disease Based on LC-MS Technology Combined with Network Bioinformatics
ObjectiveThis study aims to analyze the pharmacodynamic material basis and multi-target mechanism of action of Banxia Baizhu Tianma Tang combined with Danggui Shaoyao San in the treatment of Meniere's disease(MD).MethodsUltra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) (mobile phase: gradient elution with 0.1% formic acid aqueous solution-acetonitrile. Mass spectrometry scanning range: m/z 90-1 300) was used to identify the chemical components of the compound recipe and components absorbed into blood. The core mechanism was predicted by combining network pharmacology (target screening via SwissTargetPrediction and GeneCards databases, and construction of protein-protein interaction (PPI) network by STRING) and molecular docking (evaluated by Autodock, with binding energy ≤ -5.0 kcal·mol-1). For animal experiment validation, 36 Sprague Dawley (SD) rats were divided into a blank group, a model group (postauricular injection of lipopolysaccharide (LPS) at 1 mg·kg-1), low/medium/high-dose Chinese medicine groups (5.94, 11.88, and 23.76 g·kg-1·d-1, respectively), and Western medicine group (betahistine at 0.1 mg·kg-1·w-1). After eight weeks of intervention, the gene and protein expressions in cochlear tissue were detected.Results①A total of 2 831 chemical components and 173 components absorbed into blood were identified, with terpenoids showing the highest absorption rate into blood(10.28%). ②60 common drug-disease targets were screened, with core targets including tumor necrosis factor-α(TNF-α),interleukin-6(IL-6), Toll-like receptor 4(TLR4), angiotensin-converting enzyme(ACE), and endothelial nitric oxide synthase(NOS3).These targets were enriched in the nuclear factor-κB(NF-κB) signaling pathway and renin-angiotensin system(P<0.05). Molecular docking showed that the active component YC-1 had a strong binding ability to TNF(binding energy-9.66 kcal·mol-1). ③In animal experiments, the high-dose Chinese medicine group significantly down-regulated the expression of pro-inflammatory factors TNFmRNA(P<0.01)and up-regulated vascular regulatory factors NOS3 protein(P<0.01), and alleviated cochlear pathological damage(HE score: from 4 to 2).ConclusionThis compound recipe synergistically regulates the TNF/NF-κB inflammatory pathway and ACE/NOS3 vascular homeostasis pathway through flavonoids, triterpenoids, and other components, thereby inhibiting endolymphatic hydrops and cochlear damage. It provides a scientific basis for the theory of "simultaneous treatment of phlegm and blood stasis" in traditional Chinese medicine.