Berberine Ameliorates Angiotensin II-Induced Endothelial Dysfunction by Blocking AT1R, Inhibiting PDE4b and...

Area of Science:

• Cardiovascular Research
• Pharmacology
• Molecular Biology

Background:

• Endothelial dysfunction is a key factor in hypertension-related vascular complications.
• Angiotensin II (Ang II) plays a critical role in inducing endothelial dysfunction.
• Berberine (BBR) is a natural compound with potential therapeutic properties.

Purpose of the Study:

• To investigate whether BBR can attenuate Ang II-induced endothelial dysfunction.
• To explore the underlying mechanisms involving the Ang II type 1 receptor (AT1R) and the phosphodiesterase 4b (PDE4b) signaling pathway.

Main Methods:

• Primary endothelial cells and ex vivo mouse aortae were treated with Ang II and BBR.
• Gene and protein expression of AT1R, PDE4b, Akt, and eNOS were analyzed using qPCR and Western blot.
• Endothelium-dependent relaxation (EDR) assays and molecular docking were performed.

Main Results:

• BBR reversed Ang II-induced impairment of endothelium-dependent relaxation and nitric oxide levels.
• BBR demonstrated direct binding to AT1R, similar to valsartan.
• BBR suppressed Ang II-induced upregulation of PDE4b and restored Akt/eNOS phosphorylation.

Conclusions:

• BBR ameliorates Ang II-induced endothelial dysfunction by antagonizing AT1R and modulating the PDE4b/Akt/eNOS pathway.
• These findings elucidate the protective mechanisms of BBR against vascular complications.
• BBR shows significant therapeutic potential for hypertension-related vascular diseases.