Sun Yusen, Ma Xiaoqian, Gong Yanning, Guo Hongmin, Zhou Congfa, Hu Qixing, Zhou Zhiying, Zhang Yuanyuan, Liang Shangdong, Li Guilin
School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, PR China.
Second Clinical Medical School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, PR China.
Neurotoxicology. 2025 Jul;109:1-10. doi: 10.1016/j.neuro.2025.05.008. Epub 2025 May 22.
Hypericin (HYP), a primary active compound derived from Hypericum perforatum has been studied in the context of diabetes. The purpose of this study is to observe whether HYP can improve diabetic cardiac autonomic neuropathy (DCAN) and its possible mechanism. The current findings suggest that multiple drivers of ferroptosis in DCAN converge on the antioxidant protein nuclear factor erythroid 2-related factor 2(Nrf2). Overactivated P2X7 receptor (P2X7R) increases Nrf2 degradation by increasing proteasome activity through calcium ion accumulation. This work showed that HYP inhibited P2X7R expression, leading to elevated Nrf2 levels, thereby counteracting ferroptosis. This inhibition improves abnormal changes in cardiac function during the pathological process of DCAN in diabetic rats, including heart rate (HR), blood pressure (BP), heart rate variability (HRV), and sympathetic nerve discharge (SND). In summary, HYP enhances Nrf2 protein levels by suppressing P2X7R expression, reducing calcium-induced proteasome activity, and inhibits ferroptosis and inflammation. Thus, HYP alleviated DCAN progression.
金丝桃素（HYP）是一种从贯叶连翘中提取的主要活性化合物，已在糖尿病背景下进行了研究。本研究的目的是观察HYP是否能改善糖尿病性心脏自主神经病变（DCAN）及其可能的机制。目前的研究结果表明，DCAN中多种铁死亡驱动因素都集中在抗氧化蛋白核因子红细胞2相关因子2（Nrf2）上。过度激活的P2X7受体（P2X7R）通过钙离子积累增加蛋白酶体活性，从而增加Nrf2的降解。这项研究表明，HYP抑制P2X7R表达，导致Nrf2水平升高，从而对抗铁死亡。这种抑制作用改善了糖尿病大鼠DCAN病理过程中心脏功能的异常变化，包括心率（HR）、血压（BP）、心率变异性（HRV）和交感神经放电（SND）。总之，HYP通过抑制P2X7R表达、降低钙诱导的蛋白酶体活性来提高Nrf2蛋白水平，并抑制铁死亡和炎症。因此，HYP缓解了DCAN的进展。
