Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, PIN-781101, Assam, India.
Toxicology & Experimental Medicine, CSIR - Central Drug Research Institute (CDRI), Lucknow 226 031, India.
Life Sci. 2022 Jan 1;288:120159. doi: 10.1016/j.lfs.2021.120159. Epub 2021 Nov 18.
Pathological cardiac hypertrophy is a characteristic feature in many cardiovascular diseases (CVDs). Aloin is an anthraquinone glycoside from Aloe species, and the effect of aloin on cardiac hypertrophy and associated fibrotic changes have not been elucidated. This study investigated the effect of aloin against the isoproterenol (ISO)-induced cardiac hypertrophy in rats.
Cardiac hypertrophy experimental model was induced in rats by subcutaneous injection of ISO for 14 days. Meanwhile, the animals were administered orally with aloin at doses of 25 and 50 mg/kg/day. On the 15th day, cardiac echocardiography was performed, the heart was collected and subjected for histopathological, gene expression, and immunoblot studies. Additionally, the effect of aloin on ISO-induced hypertrophic changes in H9c2 cells was investigated.
Aloin markedly alleviated ISO-induced heart injury, reduced cardiac hypertrophy, improved cardiac function, and histological alterations in the heart. Mechanistically, aloin attenuated ISO-induced fibrosis via inhibition of the levels of collagen I, α-smooth muscle actin (α-SMA), fibronectin, transforming growth factor-β (TGF-β) and pSmad2/3 proteins in the heart. Aloin alleviated ISO-induced myocardial oxidative damage and up-regulated the levels of antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins. Moreover, aloin treatment attenuated ISO-induced hypertrophic changes and the generation of reactive oxygen species (ROS) in H9c2 cells in vitro.
Our findings demonstrated that aloin alleviated ISO-induced cardiac hypertrophy and fibrosis via inhibiting TGF-β/pSmad2/3 signaling and restoring myocardial antioxidants, and therefore has promising therapeutic potential against cardiac hypertrophy and fibrosis.
病理性心肌肥厚是许多心血管疾病（CVDs）的特征。芦荟大黄素是从芦荟属植物中提取的蒽醌糖苷，其对心肌肥厚和相关纤维化变化的影响尚未阐明。本研究探讨了芦荟大黄素对异丙肾上腺素（ISO）诱导的大鼠心肌肥厚的作用。
通过皮下注射 ISO 14 天诱导大鼠心肌肥厚实验模型。同时，动物口服给予芦荟大黄素 25 和 50mg/kg/天。第 15 天，进行心脏超声心动图检查，收集心脏进行组织病理学、基因表达和免疫印迹研究。此外，还研究了芦荟大黄素对 ISO 诱导的 H9c2 细胞肥大变化的影响。
芦荟大黄素显著减轻 ISO 诱导的心脏损伤，减少心肌肥厚，改善心脏功能和心脏组织学改变。机制上，芦荟大黄素通过抑制胶原 I、α-平滑肌肌动蛋白（α-SMA）、纤维连接蛋白、转化生长因子-β（TGF-β）和 Smad2/3 蛋白在心内的水平来减轻 ISO 诱导的纤维化。芦荟大黄素减轻 ISO 诱导的心肌氧化损伤，并上调核红细胞相关因子 2（Nrf2）和血红素加氧酶-1（HO-1）蛋白的抗氧化转录因子水平。此外，芦荟大黄素处理可减轻 ISO 诱导的体外 H9c2 细胞肥大变化和活性氧（ROS）的产生。
我们的研究结果表明，芦荟大黄素通过抑制 TGF-β/Smad2/3 信号通路和恢复心肌抗氧化剂来减轻 ISO 诱导的心肌肥厚和纤维化，因此具有治疗心肌肥厚和纤维化的潜在应用前景。
