Wang Qian, Peng Dewei, Huang Bingyu, Men Lintong, Jiang Tao, Huo Shengqi, Wang Moran, Guo Junyi, Lv Jiagao, Lin Li
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China.
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China.
Pharmaceuticals (Basel). 2023 Feb 27;16(3):361. doi: 10.3390/ph16030361.
Notopterol is a naturally occurring furanocoumarin compound found in the root of Notopterygium incisum. Hyperuricemia involves the activation of chronic inflammation and leads to cardiac damage. Whether notopterol has cardioprotective potential in hyperuricemia mice remains elusive. The hyperuricemic mouse model was constructed by administration of potassium oxonate and adenine every other day for six weeks. Notopterol (20 mg/kg) and allopurinol (10 mg/kg) were given daily as treatment, respectively. The results showed that hyperuricemia dampened heart function and reduced exercise capacity. Notopterol treatment improved exercise capacity and alleviated cardiac dysfunction in hyperuricemic mice. P2X7R and pyroptosis signals were activated both in hyperuricemic mice and in uric acid-stimulated H9c2 cells. Additionally, it was verified that inhibition of P2X7R alleviated pyroptosis and inflammatory signals in uric acid-treated H9c2 cells. Notopterol administration significantly suppressed expression levels of pyroptosis associated proteins and P2X7R in vivo and in vitro. P2X7R overexpression abolished the inhibition effect of notopterol on pyroptosis. Collectively, our findings suggested that P2X7R played a critical role in uric acid-induced NLRP3 inflammatory signals. Notopterol inhibited pyroptosis via inhibiting the P2X7R/NLRP3 signaling pathway under uric acid stimulation. Notopterol might represent a potential therapeutic strategy against pyroptosis and improve cardiac function in hyperuricemic mice.
羌活醇是一种天然存在的呋喃香豆素化合物，存在于羌活的根部。高尿酸血症涉及慢性炎症的激活，并导致心脏损伤。羌活醇在高尿酸血症小鼠中是否具有心脏保护潜力仍不清楚。通过每隔一天给予氧嗪酸钾和腺嘌呤六周来构建高尿酸血症小鼠模型。分别每日给予羌活醇（20mg/kg）和别嘌醇（10mg/kg）作为治疗。结果表明，高尿酸血症会削弱心脏功能并降低运动能力。羌活醇治疗可提高高尿酸血症小鼠的运动能力并减轻心脏功能障碍。P2X7R和细胞焦亡信号在高尿酸血症小鼠和尿酸刺激的H9c2细胞中均被激活。此外，已证实抑制P2X7R可减轻尿酸处理的H9c2细胞中的细胞焦亡和炎症信号。给予羌活醇在体内和体外均显著抑制细胞焦亡相关蛋白和P2X7R的表达水平。P2X7R过表达消除了羌活醇对细胞焦亡的抑制作用。总的来说，我们的研究结果表明P2X7R在尿酸诱导的NLRP3炎症信号中起关键作用。在尿酸刺激下，羌活醇通过抑制P2X7R/NLRP3信号通路抑制细胞焦亡。羌活醇可能代表一种针对细胞焦亡的潜在治疗策略，并改善高尿酸血症小鼠的心脏功能。
