Lonicerae japonicae flos ameliorates radiotherapy-induced mesenteric artery endothelial dysfunction through GTPCH1/BH4/eNOS pathway

Abstract

Background: As a traditional Chinese medicine, Lonicerae japonicae flos (LJF) and its main component chlorogenic acid (CGA) have anti-oxidant, anti-bacterial and anti-tumor effects. However, there is no research on the potential of LJF for vascular protection in radiotherapy.

Purpose: To elucidate the potential and possible mechanisms of the LJF extract and CGA in alleviating endothelial dysfunction caused by abdominal radiotherapy.

Methods: LJF was extracted with water and the CGA content was analyzed by HPLC. Male Sprague-Dawley rats received abdominal radiotherapy for 21 days. Seven days after irradiation, Laser Doppler and ex vivo vascular tension experiments were performed. Nitric oxide (NO), superoxide anion levels and tetrahydrobiopterin (BH₄) content were detected. Western blot, flow cytometry and molecular docking were used.

Results: In the radiotherapy group, the mesenteric arterial blood perfusion, NO, and superoxide anion levels were significantly reduced; rats treated with the LJF extract or CGA showed a certain extent of recovery of these indicators. Vascular tension experiments showed that CGA and the LJF extract improved the vasodilation of mesenteric arteries. Cell experiments demonstrated that CGA increased the NO content and reduce superoxide anion production and cell apoptosis. The expression levels of GTPCH1/BH₄/eNOS signaling pathway were significantly increased due to the use of the LJF extract or CGA in vivo and in vitro.

Conclusions: Our study demonstrated for the first time that LJF and its main component, CGA could prevent abdominal radiotherapy-induced vascular endothelial dysfunction via GTPCH1/BH₄/eNOS pathway. LJF could be a potential therapeutic herbal agent.

Keywords: Abdominal radiotherapy; Chlorogenic acid; Endothelial dysfunction; Lonicerae japonicae flos; Radiation-induced normal tissue toxicity.