Berberine and its derivatives: mechanisms of action in myocardial vascular endothelial injury - a review

Abstract

Myocardial vascular endothelial injury serves as a crucial inducer of cardiovascular diseases. Mechanisms such as endoplasmic reticulum stress, apoptosis, inflammation, oxidative stress, autophagy, platelet dysfunction, and gut microbiota imbalance are intimately linked to this condition. Berberine and its derivatives have demonstrated potential in modulating these mechanisms. This article reviews the pathogenesis of endothelial injury in myocardial vessels, the pharmacological effects of berberine and its derivatives, particularly their interactions with targets implicated in vascular endothelial injury. Furthermore, it discusses clinical applications, methods to enhance bioavailability, and toxicity concerns, aiming to lay a foundation for the development of BBR as a therapeutic agent for cardiovascular diseases.

Keywords: berberine; cardioprotection; cardiovascular diseases; mechanism of action; myocardial vascular endothelial injury.

FIGURE 1

BBR and its derivatives are involved in endoplasmic reticulum stress mechanisms. They influence the endoplasmic reticulum stress by acting on the PERK, ATF6, IRE1, and CHOP pathways; sharp arrows (→) indicate stimulation, and blunt arrows (⊥) indicate inhibition. The figure was drawn using Figdraw.

FIGURE 2

BBR and its derivatives influence the mechanism of apoptosis. They impact the regulation of apoptosis by reducing Cyt c release, inhibiting caspase-3 expression, and modulating the activation of the JNK pathway, sharp arrows (→) indicate stimulation, and blunt arrows (⊥) indicate inhibition. The figure was drawn using Figdraw.

FIGURE 3

BBR and its derivatives are involved in cellular inflammatory mechanisms. They regulate cellular inflammation by inhibiting pro-inflammatory factors such as TNF-α and IL-1, and by suppressing the activation of the IKK complex, sharp arrows (→) indicate stimulation, and blunt arrows (⊥) indicate inhibition. The figure was drawn using Figdraw.

FIGURE 4

BBR and its derivatives are involved in oxidative stress mechanisms. They influence the oxidative stress response by increasing the activity of specific antioxidant enzymes such as SOD and CAT and reducing ROS production, sharp arrows (→) indicate stimulation, and blunt arrows (⊥) indicate inhibition. The figure was drawn using Figdraw.

FIGURE 5

BBR and its derivatives are involved in autophagy mechanisms. They influence the autophagy by inhibiting the JNK and AMPK signaling pathways, enhancing the mitochondrial PINK1/Parkin signaling pathway, and influencing ferroptosis regulatory processes, sharp arrows (→) indicate stimulation, and blunt arrows (⊥) indicate inhibition. The figure was drawn using Figdraw.

FIGURE 6

BBR and its derivatives are involved in platelet adhesion and aggregation mechanisms. They influence the platelet adhesion and aggregation by inhibiting the PI3K/Akt pathway to suppress platelet activation, regulating AR/NOX/GR activity, reducing ROS levels, and affecting thrombus formation, sharp arrows (→) indicate stimulation, and blunt arrows (⊥) indicate inhibition. The figure was drawn using Figdraw.

FIGURE 7

BBR and its derivatives are involved in gut microbiota mechanisms. They influence the gut microbiota by inhibiting CutC to reduce TMAO production, promoting SCFAs generation; enhancing FXR and TGR5 activity; mitigating endotoxin-induced inflammation, sharp arrows (→) indicate stimulation, and blunt arrows (⊥) indicate inhibition. The figure was drawn using Figdraw.

FIGURE 8

Schematic diagram of the mechanism of BBR in repairing myocardial vascular endothelial injury.