Wang Canhong, Wu Yulan, Gong Bao, Zhao Xiangsheng, Meng Hui, Mou Junyu, Cheng Xiaoling, Tan Yinfeng, Wei Jianhe
Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Haikou 570311, China.
Guangdong Key Laboratory of Green Agricultural Products Processing and Intelligent Equipment, Guangdong University of Petrochemical Technology, Maoming 525099, China.
Int J Mol Sci. 2025 Mar 3;26(5):2251. doi: 10.3390/ijms26052251.
is widely used to treat cardiovascular diseases. Our research group found that volatile oil has a good anti-myocardial ischemic effect, and its main pharmacodynamic components are trans-nerolol and its oxides. However, the exact mechanisms underlying this effect have not yet been elucidated. This study aimed to explore the potential myocardial protective effects of trans-nerolol and its underlying molecular mechanisms. Molecular docking was used to predict and visualize the possible mechanism of the anti-apoptotic myocardial protection by trans-nerolol. The myocardial protective effect of trans-nerolol was evaluated by observing pathological injury, myocardial enzyme levels, oxidation, antioxidant levels, and the expression of related proteins. Molecular docking results showed that trans-nerolol binds closely to cytochrome C (Cytc) and apoptosis-related proteins, suggesting that it may play a role in interacting with these target proteins. The results showed that pre-treatment with dose-dependent trans-nerolol significantly mitigated the myocardial histological damage; decreased lactate dehydrogenase (LDH), creatinine kinase (CK), alanine transaminase (ALT), and aspartate transaminase (AST) levels; reduced nitric oxide (NO) production, hydrogen peroxide (HO), and lipid peroxide (LPO); and increased the total antioxidant content (T-AOC), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities compared with the model group. In addition, dose-dependent trans-nerolol significantly increased the Na-K-ATPase and Ca-Mg-ATPase levels. Moreover, trans-nerolol markedly reduced the endogenous and external apoptotic pathways; downregulated the protein expression of Cytc, apoptotic protease activating factor-1 (Apaf1), Fibroblast-associated (Fas), Cysteine-aspartate protease 3 (Caspase3), Cysteine-aspartate protease 8 (Caspase8), and Cysteine-aspartate protease 9 (Caspase9); and upregulated the expression of Heat shock protein 70 (Hsp70) and B-cell lymphoma-2 (Bcl-2). These data indicate that trans-nerolol exerts protective effects against myocardial ischemia (MI), and its mechanism is associated with the suppression of the Cytc- and caspase-signaling pathways. Trans-nerolol has a therapeutic effect on MI, and its mechanism of action is related to its anti-apoptotic effect. These results suggest that has a potential role to be developed as an MI-promoting therapeutic agent.
广泛用于治疗心血管疾病。我们的研究小组发现，挥发油具有良好的抗心肌缺血作用，其主要药效成分是反式橙花叔醇及其氧化物。然而，这种作用的确切机制尚未阐明。本研究旨在探讨反式橙花叔醇潜在的心肌保护作用及其潜在的分子机制。采用分子对接技术预测并可视化反式橙花叔醇抗凋亡心肌保护的可能机制。通过观察病理损伤、心肌酶水平、氧化、抗氧化水平及相关蛋白表达来评估反式橙花叔醇的心肌保护作用。分子对接结果表明，反式橙花叔醇与细胞色素C（Cytc）及凋亡相关蛋白紧密结合，提示其可能在与这些靶蛋白相互作用中发挥作用。结果显示，与模型组相比，剂量依赖性的反式橙花叔醇预处理显著减轻了心肌组织学损伤；降低了乳酸脱氢酶（LDH）、肌酸激酶（CK）、谷丙转氨酶（ALT）和谷草转氨酶（AST）水平；减少了一氧化氮（NO）生成、过氧化氢（HO）和脂质过氧化物（LPO）；增加了总抗氧化能力（T-AOC）、谷胱甘肽（GSH）、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活性。此外，剂量依赖性的反式橙花叔醇显著提高了钠钾ATP酶和钙镁ATP酶水平。而且，反式橙花叔醇显著减少了内源性和外源性凋亡途径；下调了Cytc、凋亡蛋白酶激活因子-1（Apaf1）、成纤维细胞相关蛋白（Fas）、半胱天冬酶3（Caspase3）、半胱天冬酶8（Caspase8）和半胱天冬酶9（Caspase9）的蛋白表达；上调了热休克蛋白70（Hsp70）和B细胞淋巴瘤-2（Bcl-2）的表达。这些数据表明，反式橙花叔醇对心肌缺血（MI）具有保护作用，其机制与抑制Cytc和半胱天冬酶信号通路有关。反式橙花叔醇对MI具有治疗作用，其作用机制与其抗凋亡作用有关。这些结果表明，反式橙花叔醇有作为一种促进MI治疗药物开发的潜在作用。
