Danggui Buxue Decoction and its components dilate coronary artery through activating the inward rectification K⁺ channels pathway

Ethnopharmacological relevance: Danggui Buxue Decoction (DBD), a classic representative prescription of invigorating Qi and producing blood, is used to treat coronary heart disease angina pectoris and vascular injury diseases. Abnormal coronary artery is an important cause of cardiovascular disease. However, the mechanism of DBD dilates coronary arteries is still unclear.

Aim of the study: This study aimed to elucidate the impacts and distinctions among DBD, Astragalus, Angelica sinensis, and identified active components on pre-constricted coronary arteries, as well as to delve deeper into their respective mechanisms.

Materials and methods: After the preconstriction of a rat isolated coronary artery ring with either 30 mM KCl or 200 nM U46619, the vascular tension was observed following the addition of DBD, and other components. Subsequently, the impact of these active components on coronary blood flow (CBF) was confirmed through in vivo testing. Further investigation into the underlying mechanism was carried out using a combination of blockers, molecular docking, surface plasmon resonance (SPR), cell heat transfer analysis (CETSA), and patch-clamp techniques.

Results: In vitro experiments showed that DBD and its components butylidenephthalide, ligustilide, calycosin, and quercetin could dilate coronary artery preconstricted with either 30 mM KCl or 200 nM U46619. In addition, the active ingredient was found to significantly increase CBF. Mechanistically, BaCl₂ was found to reduce the relaxation effect of the drug by adding a blocker. Molecular docking, SPR and CETSA results showed that the active ingredients had a strong binding potential with inward rectification K⁺ channels (K_IR) channel protein. Patch clamp studies demonstrate that quercetin can increase K_IR current, and BaCl₂ can significantly reduce its current.

Conclusions: The active components of DBD, butylidenephthalide, ligustilide, calycosin, and quercetin, activate K_IR channels to relax coronary artery and increase CBF.