Song Renxing, Xiong Chunming, Bai Juncai, Bai Zhenzhou, Liu Wei
Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Department of Geriatric Cardiology, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Curr Mol Pharmacol. 2023 Oct 13. doi: 10.2174/0118761429244886230927070818.
Artemisinin (ART) is mainly derived from Artemisia annua, a traditional Chinese medicinal plant, and has been found to affect cellular biochemical processes, such as proliferation, angiogenesis, and apoptosis, in addition to its antimalarial properties. However, its effect on cardiac hypertrophy and the underlying mechanisms remain unclear.
This study aimed to investigate the effect of ART on cardiac hypertrophy and explore its possible mechanisms.
A rat model was established by intraperitoneal injection of isoproterenol (ISO) for 3 days, and the degree of myocardial hypertrophy was compared among 5 groups: a control (CON) group, an ISO group, and groups treated with different doses of ART (7 mg/kg/d, 35 mg/kg/d, and 75 mg/kg/d). Echocardiography was used to evaluate cardiac function and structure. The cross-sectional area of cardiomyocytes was measured by hematoxylin and eosin (H&E) staining. The heart weight (HW), body weight (BW), and tail length were measured, and the HW/tail length ratio and the HW/BW ratio were calculated. H9c2 rat cardiomyocytes were cultured, and different amounts of ART were added 2 hours before ISO stimulation. Phalloidin staining was used to evaluate the degree of cell hypertrophy. The levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were quantified in rat plasma and cell supernatant using enzyme-linked immunosorbent assay (ELISA), while the expression levels of p- ERK1/2, p-JNK, and p-p38 MAPK were assessed in the myocardium and H9c2 cells via western blot analysis.
Intragastric administration of ART at a dosage of 35 mg/kg/d or over mitigated the early-stage cardiac hypertrophy induced by ISO in rats led to a reduction in left ventricular posterior wall diastolic thickness, interventricular septal thickness at diastole, lowered ANP and BNP levels, as well as a decrease in HW/tail length and HW/BW ratio. studies demonstrated that ART at a concentration of 100 μM inhibited ISO-mediated hypertrophy of H9c2 cells. The ISO group showed a higher p-ERK/GAPDH ratio and p-p38 MAPK/GAPDH ratio than the control group both in vivo and . Although the p-JNK/GAPDH ratio was increased in the ISO group, there was no statistical difference. The p-ERK/GAPDH and p-p38/GAPDH ratios were significantly lower in the ART group than in the ISO group.
The mechanism of ART against cardiac hypertrophy was related to inhibition of the ERK1/2 and p38 MAPK signaling pathways.
青蒿素（ART）主要来源于传统中药材黄花蒿，除具有抗疟特性外，还被发现可影响细胞的生化过程，如增殖、血管生成和凋亡。然而，其对心脏肥大的影响及潜在机制仍不清楚。
本研究旨在探讨青蒿素对心脏肥大的影响并探索其可能的机制。
通过腹腔注射异丙肾上腺素（ISO）3天建立大鼠模型，比较5组的心肌肥大程度：对照组（CON）、ISO组以及用不同剂量青蒿素（7mg/kg/d、35mg/kg/d和75mg/kg/d）处理的组。采用超声心动图评估心脏功能和结构。通过苏木精-伊红（H&E）染色测量心肌细胞的横截面积。测量心脏重量（HW）、体重（BW）和尾长，并计算HW/尾长比值和HW/BW比值。培养H9c2大鼠心肌细胞，在ISO刺激前2小时加入不同量的青蒿素。采用鬼笔环肽染色评估细胞肥大程度。使用酶联免疫吸附测定（ELISA）定量大鼠血浆和细胞上清液中的心房利钠肽（ANP）和脑利钠肽（BNP）水平，同时通过蛋白质印迹分析评估心肌和H9c2细胞中p-ERK1/2、p-JNK和p-p38 MAPK的表达水平。
以35mg/kg/d及以上剂量灌胃给予青蒿素可减轻ISO诱导的大鼠早期心脏肥大，并导致左心室后壁舒张期厚度、舒张期室间隔厚度降低，ANP和BNP水平降低，以及HW/尾长和HW/BW比值降低。研究表明，100μM浓度的青蒿素可抑制ISO介导下的H9c2细胞肥大。ISO组在体内和体外的p-ERK/GAPDH比值和p-p38 MAPK/GAPDH比值均高于对照组。虽然ISO组的p-JNK/GAPDH比值升高，但无统计学差异。青蒿素组的p-ERK/GAPDH和p-p38/GAPDH比值显著低于ISO组。
青蒿素抗心脏肥大的机制与抑制ERK1/2和p38 MAPK信号通路有关。
