Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, No.81 Meishan Road, Hefei, 230032, People's Republic of China.
J Ethnopharmacol. 2021 Aug 10;276:114187. doi: 10.1016/j.jep.2021.114187. Epub 2021 May 4.
The genus Hypericum are widely distributed in China. Hypericum perforatum L. (genus Hypericum, family Hypericaceae) has a long history as a traditional Chinese medicine, which was traditionally used for the treatment of emotional distress, cardiothoracic depression, and acute mastitis. Hyperoside (Hyp) extracted from Hypericum perforatum L. has been affirmed to exert therapeutic effects on cardiovascular diseases, with widespread existence in plants of genus Hypericum. Hyp could also be extracted from Crataegus pinnatifida Bunge (genus Crataegus pinnatifida Bunge, family Rosaceae), another traditional Chinese medicine that traditionally prevented and treated heart disease in China. The cardioprotection and mechanism of Hyp comprise anti-inflammation, anti-fibrosis, activation of autophagy, and reversal of cardiac remodeling.
This study aimed to explore the Hyp effect against MI and its underlying mechanism.
The MI model was constructed in the KM mice via a ligating surgery of the left anterior descending (LAD) coronary artery. Subsequently, the mice were divided into following seven groups: Sham group, MI group, MI + Hyp 9 mg/kg group, MI + Hyp18 mg/kg group, MI + Hyp36 mg/kg group, MI + Fosinopril group, and MI + Hyp-36 mg/kg+3-MA group. Each group was treated with Hyp in different concentrations or positive medicine for two weeks except for the sham group. After two weeks, we examined the cardiac function, electrocardiogram (ECG), myocardial hypertrophy in the non-infarct area, collagen volume fraction (CVF), perivascular collagen area (PVCA) in the infarct area, and several serum cytokines. Autophagy and inflammation in cardiomyocytes were assessed via measuring autophagy-associated proteins and NLRP1 inflammasome pathway related proteins.
Hyp reversed LV remodeling and adverse ECG changes through reducing CVF and myocardial hypertrophy. Additionally, Hyp treatment could reduce inflammation levels in cardiomyocytes, compared with those in MI group. Moreover, NLRP1inflammation pathway was activated after MI. Up-regulation of autophagic flux suppressed NLRP1 inflammation pathway after Hyp treatment. However, co-treatment with 3-MA abrogated above effects of Hyp.
Hyp had obvious protective effect on heart injury in MI mice. Echocanrdiographic and histological measurements demonstrated that Hyp treatment improved cardiac function, and ameliorated myocardial hypertrophy and fibrinogen deposition after MI. The partial mechanism is that Hyp could up-regulate autophagy after MI. Furthermore, the promotion of autophagic flux would suppress NLRP1 inflammation pathway induced by MI.
贯叶金丝桃属在中国广泛分布。贯叶金丝桃（贯叶金丝桃属，金丝桃科）作为一种传统中药，具有悠久的历史，传统上用于治疗情绪困扰、心胸抑郁和急性乳腺炎。从贯叶金丝桃中提取的金丝桃苷（Hyp）已被证实对心血管疾病具有治疗作用，广泛存在于贯叶金丝桃属植物中。Hyp 也可以从另一种传统中药山楂（山楂属，蔷薇科）中提取，山楂在中国传统上用于预防和治疗心脏病。Hyp 的心脏保护作用及其机制包括抗炎、抗纤维化、自噬激活和心脏重构逆转。
本研究旨在探讨 Hyp 对心肌梗死的作用及其潜在机制。
通过结扎左前降支（LAD）冠状动脉构建 KM 小鼠心肌梗死模型。随后，将小鼠分为以下七组：假手术组、心肌梗死组、Hyp9mg/kg 组、Hyp18mg/kg 组、Hyp36mg/kg 组、Hyp36mg/kg+3-MA 组和阳性药福辛普利组。除假手术组外，其余各组分别用不同浓度的 Hyp 或阳性药治疗 2 周。2 周后，检测心功能、心电图（ECG）、非梗死区心肌肥厚、胶原容积分数（CVF）、梗死区血管周围胶原面积（PVCA）、血清细胞因子。通过检测自噬相关蛋白和 NLRP1 炎症小体途径相关蛋白，评估心肌细胞自噬和炎症。
Hyp 通过降低 CVF 和心肌肥厚，逆转 LV 重构和心电图改变。此外，Hyp 治疗可降低心肌细胞炎症水平，与心肌梗死组相比。此外，心肌梗死后 NLRP1 炎症途径被激活。Hyp 处理后，自噬流上调抑制 NLRP1 炎症途径。然而，Hyp 处理的上述作用被 3-MA 共同处理所阻断。
Hyp 对心肌梗死小鼠心脏损伤有明显的保护作用。超声心动图和组织学测量表明，Hyp 治疗可改善心脏功能，改善心肌梗死后的心肌肥厚和纤维蛋白原沉积。部分机制是 Hyp 可在心肌梗死后上调自噬。此外，自噬流的促进可抑制心肌梗死后 NLRP1 炎症途径的激活。
