Wang Shangtao, Zhu Chenghao, Zhang Shurui, Ma Siyu, Li Baoshan, Zhao Shengbo, Zhang Wei, Sun Zhirong
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
Ningqiang Tianma Research Institution Limited Liability Company, Hanzhong, Shaanxi, People's Republic of China.
J Inflamm Res. 2024 Oct 2;17:6971-6988. doi: 10.2147/JIR.S477554. eCollection 2024.
Hypertension (HTN) is closely related to endothelial damage. While tianma (TM) and gouqizi (GQZ) have the potential to be effective in the treatment of HTN in traditional Chinese medicine, their main active ingredients and whether its exert synergistic effects and the underlying mechanisms of synergistic effects are still unclear.
This study screened the active ingredients of TM and GQZ, investigated the synergistic effects of the active ingredients and explored possible mechanisms.
The potential targets and mechanisms of TM and GQZ were screened using network pharmacology, and gastrodin (GAS) and gallic acid (GA) were identified as compounds with significant antihypertensive activity. The synergistic effects of the combination of GAS and GA was assessed by measuring biomarkers of AngII-induced human umbilical vein endothelial cell (HUVECs) dysfunction model. Furthermore, the anti-apoptotic and anti-inflammatory effects were evaluated by measuring inflammatory cytokine secretion, and apoptosis-related markers. Finally, key targets of the sphingolipid signaling pathway were experimentally validated by Western blotting.
In network pharmacology, the herb-pair exerted a synergetic effect by regulating sphingolipid pathways. The GAS and GA exerted synergistic protective effects in AngII-induced HUVECs injury by improving Nitric Oxide Content (NO) levels, alleviating lactate Endothelin-1 (ET-1), and Thromboxane B2 (TX-B2) release, reducing the secretion of inflammatory factors like interleukin-6 (IL-6), interleukin-1β (IL-1β), Tumor Necrosis Factor Alpha (TNF-α)), decreasing the pro-apoptotic protein BAX, and increasing the anti-apoptotic protein BCL-2. Furthermore, the results showed that the GAS and GA combination could elevate the level of S1PR1 and inhibit the expression of ROCK2 and the phosphorylation of NF-κB, which are key targets involved in sphingolipid pathways.
Our study revealed that the combination of GAS and GA could suppress inflammation and apoptosis, which are highly correlated with sphingolipid signaling pathways, making it a potential candidate for the treatment of HTN.
高血压（HTN）与内皮损伤密切相关。虽然天麻（TM）和枸杞子（GQZ）在中医中具有治疗高血压的潜在疗效，但其主要活性成分以及是否发挥协同作用和协同作用的潜在机制仍不清楚。
本研究筛选天麻和枸杞子的活性成分，研究活性成分的协同作用并探索可能的机制。
采用网络药理学筛选天麻和枸杞子的潜在靶点及机制，确定天麻素（GAS）和没食子酸（GA）为具有显著降压活性的化合物。通过检测血管紧张素II诱导的人脐静脉内皮细胞（HUVECs）功能障碍模型的生物标志物，评估GAS和GA组合的协同作用。此外，通过检测炎性细胞因子分泌和凋亡相关标志物，评估其抗凋亡和抗炎作用。最后，通过蛋白质免疫印迹法对鞘脂信号通路的关键靶点进行实验验证。
在网络药理学中，该药对通过调节鞘脂途径发挥协同作用。GAS和GA通过提高一氧化氮含量（NO）水平、减轻乳酸内皮素-1（ET-1）和血栓素B2（TX-B2）释放、减少白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）等炎性因子分泌、降低促凋亡蛋白BAX以及增加抗凋亡蛋白BCL-2，对血管紧张素II诱导的HUVECs损伤发挥协同保护作用。此外，结果表明GAS和GA组合可提高S1PR1水平，抑制鞘脂途径关键靶点ROCK2的表达和NF-κB的磷酸化。
我们的研究表明，GAS和GA组合可抑制与鞘脂信号通路高度相关的炎症和凋亡，使其成为治疗高血压的潜在候选药物。
