State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang 550004, China.
School of Pharmacy, Guizhou Medical University, Guiyang 550004, China.
Molecules. 2023 Apr 24;28(9):3687. doi: 10.3390/molecules28093687.
Although L. (PO) has a beneficial effect on treatment of myocardial ischemia (MI), its mechanism remains unclear. This study aimed to explore the pharmacological mechanism of PO against MI through MAPK signaling pathways. Firstly, the therapeutic effect of PO was evaluated for treatment of MI mice. Using Western blot and immunohistochemistry, the influence of PO on MAPK signaling pathways and cell apoptosis was investigated. Subsequently, one key pathway (ERK) of MAPK signaling pathways was screened out, on which PO posed the most obvious impact. Finally, an inhibitor of ERK1/2 was utilized to further verify the regulatory effect of PO on the MAPK/ERK signaling pathway. It was found that PO could reduce the elevation of the ST segment; injury of heart tissue; the activity of LDH, CK, NOS, cNOS and iNOS and the levels of NO, BNP, TNF-α and IL-6. It is notable that PO could significantly modulate the protein content of p-ERK/ERK in mice suffering from MI but hardly had an effect on p-JNK/JNK and p-p38/p38. Additionally, the expressions of bax, caspase3 and caspase9 were inhibited in heart tissue in the PO-treated group. To evaluate whether ERK1/2 inhibitor (PD98059) could block the effect of PO on treatment of MI, both PO and PD98059 were given to mice with MI. It was discovered that the inhibitor indeed could significantly reverse the regulatory effects of PO on the above indicators, indicating that PO could regulate p-ERK/ERK. This study provides experimental evidence that PO extenuates MI injury, cardiomyocyte apoptosis and inflammation by activating the MAPK/ERK signaling pathway.
虽然 L.（PO）对治疗心肌缺血（MI）有有益的作用，但它的机制尚不清楚。本研究旨在通过 MAPK 信号通路探讨 PO 对抗 MI 的药理机制。首先，评估 PO 对 MI 小鼠的治疗效果。通过 Western blot 和免疫组织化学，研究 PO 对 MAPK 信号通路和细胞凋亡的影响。随后，筛选出 MAPK 信号通路的一个关键途径（ERK），PO 对其影响最为明显。最后，利用 ERK1/2 的抑制剂进一步验证 PO 对 MAPK/ERK 信号通路的调节作用。结果发现，PO 能降低 ST 段抬高；心肌组织损伤；LDH、CK、NOS、cNOS 和 iNOS 的活性及 NO、BNP、TNF-α和 IL-6 的水平。值得注意的是，PO 能明显调节 MI 小鼠中 p-ERK/ERK 的蛋白含量，但对 p-JNK/JNK 和 p-p38/p38 的影响很小。此外，PO 处理组心肌组织中 bax、caspase3 和 caspase9 的表达受到抑制。为了评估 ERK1/2 抑制剂（PD98059）是否能阻断 PO 对 MI 治疗的作用，将 PO 和 PD98059 同时给予 MI 小鼠。结果发现，抑制剂确实能显著逆转 PO 对上述指标的调节作用，表明 PO 能调节 p-ERK/ERK。本研究为 PO 通过激活 MAPK/ERK 信号通路减轻 MI 损伤、心肌细胞凋亡和炎症提供了实验依据。
