Department of Cardiology, Xi'an No. 3 Hospital, Xi'an, Shaanxi 710018, P.R. China.
Department of Neurosurgery, Xi'an Central Hospital, Xi'an, Shaanxi 710000, P.R. China.
Int J Mol Med. 2022 May;49(5). doi: 10.3892/ijmm.2022.5119. Epub 2022 Mar 16.
Herbal medicines have attracted much attention in recent years and are increasingly being used as alternatives to pharmaceutical medicines. Thymoquinone (TQ) is one of the most active ingredients in seeds, which has several beneficial properties, including anti‑inflammatory, anti‑oxidative stress, anti‑hypertensive, anti‑apoptotic and free radical‑scavenging effects. Angiotensin II (Ang II) is involved in cardiovascular diseases. The present study aimed to investigate the potential protective effects of TQ against Ang II‑induced cardiac damage in apolipoprotein E‑deficient (ApoE) mice. Briefly, 8‑week‑old male ApoE mice were randomly divided into four groups: Control, TQ, Ang II and Ang II + TQ groups. Osmotic minipumps, filled with either a saline vehicle or an Ang II solution (1,000 ng/kg/min), were implanted in ApoE mice for up to 4 weeks. The serum levels of high‑sensitivity C‑reactive protein (hs‑CRP) and histopathological alterations in heart tissue were assessed. In addition, the mRNA and protein expression levels of molecules associated with fibrosis (collagen I and III), oxidative stress and apoptosis (Nox4 and p53), and inflammation [tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6] were analyzed by reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting. In the study, H9c2 cells were incubated with different concentrations of Ang II, and the expression levels of pro‑inflammatory cytokines were evaluated using RT‑qPCR, whereas the protein expression levels of phosphorylated‑extracellular signal‑regulated kinase (p‑ERK) were determined using western blotting. Western blotting was also performed to detect the expression levels of collagen I, collagen III, Nox4 and p53 in H9c2 cells. The results revealed that TQ inhibited the Ang II‑induced increases in serum hs‑CRP levels. TQ also significantly inhibited the high levels of TNF‑α, IL‑1β, IL‑6, collagen I, collagen III, Nox4 and p53 in Ang II‑treated mice. Furthermore, TQ protected against Ang II‑induced cardiac damage by inhibiting inflammatory cell infiltration, proinflammatory cytokine expression, fibrosis, oxidative stress and apoptosis by suppressing activation of the p‑ERK signaling pathway. In conclusion, TQ could be considered a potential therapeutic agent for Ang II‑induced cardiac damage.
近年来，草药受到了广泛关注，并且越来越多地被用作药物的替代品。 百里醌（TQ）是种子中最活跃的成分之一，具有多种有益特性，包括抗炎、抗氧化应激、抗高血压、抗细胞凋亡和清除自由基的作用。 血管紧张素 II（Ang II）参与心血管疾病。 本研究旨在探讨 TQ 对载脂蛋白 E 缺陷（ApoE）小鼠 Ang II 诱导的心脏损伤的潜在保护作用。 简而言之，将 8 周龄雄性 ApoE 小鼠随机分为四组：对照组、TQ 组、Ang II 组和 Ang II+TQ 组。 将装有盐水载体或 Ang II 溶液（1000ng/kg/min）的渗透微型泵植入 ApoE 小鼠体内长达 4 周。 检测血清高敏 C 反应蛋白（hs-CRP）水平和心脏组织的组织病理学改变。 此外，通过逆转录定量 PCR（RT-qPCR）和 Western blot 分析与纤维化（胶原 I 和胶原 III）、氧化应激和细胞凋亡（Nox4 和 p53）以及炎症[肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β 和 IL-6]相关的分子的 mRNA 和蛋白表达水平。 在该研究中，用不同浓度的 Ang II 孵育 H9c2 细胞，并用 RT-qPCR 评估促炎细胞因子的表达水平，并用 Western blot 测定磷酸化细胞外信号调节激酶（p-ERK）的蛋白表达水平。 还通过 Western blot 检测 H9c2 细胞中胶原 I、胶原 III、Nox4 和 p53 的表达水平。 结果表明，TQ 抑制了 Ang II 诱导的血清 hs-CRP 水平升高。 TQ 还显著抑制了 Ang II 处理小鼠中 TNF-α、IL-1β、IL-6、胶原 I、胶原 III、Nox4 和 p53 的高水平。 此外，TQ 通过抑制 p-ERK 信号通路的激活，抑制炎性细胞浸润、促炎细胞因子表达、纤维化、氧化应激和细胞凋亡，从而防止 Ang II 诱导的心脏损伤。 总之，TQ 可被视为 Ang II 诱导的心脏损伤的潜在治疗药物。
