SCHEDULED MAINTENANCE
Identification of key active constituents of Buchang Naoxintong capsules with therapeutic effects against ischemic stroke by using an integrative pharmacology-based approach†
Abstract
Integrative pharmacology has been used to identify the key active constituents (KACs) of Buchang Naoxintong capsules (BNCs), a traditional Chinese medical preparation; this approach involves the evaluation of the content profiles and drug-like properties of the BNC constituents and development of an ingredient-target network. In this study, we used a sensitive analytical method to simultaneously identify and quantify 16 constituents of BNCs. Metabolism of these constituents by gut microbiota and human oral bioavailability were predicted using an in silico approach, followed by construction of networks to analyze the interactions between BNC constituents, their molecular targets, and proteins known to be the molecular targets for Food and Drug Administration-approved colitis medication. Finally, an animal model of ischemic stroke was used to verify the therapeutic effects of the KACs of BNCs. Amygdalin and paeoniflorin were identified as the KACs because they were the 2 most abundant BNC constituents, having appropriate drug-like properties, and produced therapeutic effects against cerebral ischemia. Amygdalin produced an anti-cerebral ischemia effect, likely by interacting with the glucocorticoid receptor (NR3C1) and serpin peptidase inhibitor, clade C (antithrombin), member 1 (SERPINC1). These results form the basis for conducting studies to identify KACs in traditional medicinal preparations; such studies might improve quality control and allow the in vivo evaluation of synergistic interactions between the complex mixtures of compounds.
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