An Na, Zhang Dongxing, Xin Jile, Zhang Xinyi, Zhang Zhijuan, Ma Ligang, Zhao Le, Wu Huimin, Feng Weisheng, Zheng Xiaoke
College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
College of Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
Curr Comput Aided Drug Des. 2024 Aug 12. doi: 10.2174/0115734099305381240613114436.
Si-Ni-San (SNS) is the formula prescription of Traditional Chinese Medicine (TCM) with anti-depression properties, but its underlying mechanisms remain unclear.
This study provides novel approaches for the study of Traditional Chinese Medicine (TCM) and offers new opportunities for exploring the pharmacological properties of SNS.
The ingredients in SNS implicated in the treatment of depression were identified and studied using network pharmacology. SwissTargetPrediction and molecular docking were used to study the interaction of SNS ingredients and their targets. The protective effect of these ingredients and their cocktail in rat pheochromocytoma cells (PC12) exposed to corticosterone (Cor) were evaluated using the CCK-8 assay, Hoechst 33342 staining, 2',7'-dichlorodihydro fluorescein diacetate (H2DCFDA) staining, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, and in-cell Western analysis.
The network pharmacology study showed that the HIF-1 signaling pathway was the most crucial pathway implicated in the anti-depressive property of SNS. MAPK1 (ERK2), MAPK3 (ERK1), AKT1, VEGFA, STAT3, and EGF were identified as hub target proteins in the HIF-1 signaling pathway. Quercetin, naringenin, licochalcone A, and kaempferol from SNS, which targeted the six proteins mentioned above, were used to create a cocktail. This cocktail exerted protective properties, decreased the oxidative stress in PC12 exposed to Cor, and successfully regulated the expressions of AKT1, p-AKT1, ERK1, ERK2, p-ERK1/2, STAT3, p- STAT3, and VEGFA induced by Cor exposure. The SwissTargetPrediction and molecular docking study showed that the cocktail may regulate the HIF-1 signaling pathway by directly binding with AKT1 and MAPK1.
The cocktail from SNS comprised of quercetin, naringenin, licochalcone A, and kaempferol exerts anti-depression potentiality by modulating the HIF-1 signaling pathway via direct interactions with AKT1 and MAPK1.
四逆散（SNS）是具有抗抑郁特性的中药方剂，但其潜在机制尚不清楚。
本研究为中药研究提供了新方法，并为探索四逆散的药理特性提供了新机会。
采用网络药理学方法鉴定和研究四逆散中与抑郁症治疗相关的成分。使用瑞士靶点预测和分子对接研究四逆散成分与其靶点的相互作用。使用CCK-8法、Hoechst 33342染色、2',7'-二氯二氢荧光素二乙酸酯（H2DCFDA）染色、2,2-二苯基-1-苦基肼（DPPH）自由基清除试验和细胞内蛋白质免疫印迹分析评估这些成分及其混合物对暴露于皮质酮（Cor）的大鼠嗜铬细胞瘤细胞（PC12）的保护作用。
网络药理学研究表明，HIF-1信号通路是四逆散抗抑郁特性中最关键的通路。MAPK1（ERK2）、MAPK3（ERK1）、AKT1、VEGFA、STAT3和EGF被确定为HIF-1信号通路中的关键靶蛋白。四逆散中的槲皮素、柚皮素、甘草查尔酮A和山奈酚靶向上述六种蛋白质，用于制备混合物。该混合物具有保护作用，降低了暴露于Cor的PC12中的氧化应激，并成功调节了Cor暴露诱导的AKT1、p-AKT1、ERK1、ERK2、p-ERK1/2、STAT3、p-STAT3和VEGFA的表达。瑞士靶点预测和分子对接研究表明，该混合物可能通过与AKT1和MAPK1直接结合来调节HIF-1信号通路。
由槲皮素、柚皮素、甘草查尔酮A和山奈酚组成的四逆散混合物通过与AKT1和MAPK1直接相互作用调节HIF-1信号通路，发挥抗抑郁潜力。
