College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China.
Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Zhengzhou 450046, China.
Molecules. 2017 Nov 12;22(11):1956. doi: 10.3390/molecules22111956.
Willd has been used to reduce edema and promote urination. -desulfoglucotropaeolin (-DG) and -desulfoglucotropaeolin (-DG) were isolated from Willd, and caused a significant increase in cell viability in a hypertonic model in NRK52e cells. In the hypertonic model, -DG and -DG significantly promoted the cell viability of NRK52e cells and inhibited the elevation of Na⁺ in the supernatant, inhibited the renin-angiotensin-aldosterone (RAAS) system, significantly reduced the levels of angiotensin II (Ang II) and aldosterone (ALD), and lowered aquaporin-2 (AQP2) and Na⁺-K⁺ ATP content in renal medulla. After treatment with -DG and -DG, expression of calcineurin (CAN) and Ca/calmodulin-dependent protein kinase II (CaMK II) was decreased in renal tissue and Ca influx was inhibited, thereby reducing the secretion of transforming growth factor-β (TGFβ), reversing the increase in adhesion and inflammatory factor E-selectin and monocyte chemotactic protein 1 (MCP-1) induced by high NaCl, while reducing oxidative stress status and decreasing the expression of cyclooxygenase-2 (COX2). Furthermore, inhibition of protein kinase C (PKC) expression also contributed to these improvements. The -DG and -DG reduced the expression of p-p44/42 MAPK, p-JNK and p-p38, inhibited the phosphorylation of the MAPK signaling pathway in NRN52e cells induced by high salt, decreased the overexpression of p-p38 and p-HSP27, and inhibited the overactivation of the p38-MAPK signaling pathway, suggesting that the p38-MAPK pathway may play a vital role in the hypertonic-induced adhesion and inflammatory response. From the results of this study, it can be concluded that the mechanism of -DG and -DG may mainly be through inhibiting the p38-MAPK signaling pathway, inhibiting the excessive activation of the RAAS system, and thereby reducing adhesion and inflammatory factors.
威灵仙可用于消肿和利尿。从威灵仙中分离得到了-去甲脱硫酸基淫羊藿苷（-DG）和-去甲脱硫酸基淫羊藿苷（-DG），它们在 NRK52e 细胞的高渗模型中显著增加细胞活力。在高渗模型中，-DG 和 -DG 显著促进 NRK52e 细胞的细胞活力，抑制上清液中 Na⁺的升高，抑制肾素-血管紧张素-醛固酮（RAAS）系统，显著降低血管紧张素 II（Ang II）和醛固酮（ALD）的水平，并降低肾髓质中水通道蛋白-2（AQP2）和 Na⁺-K⁺ATP 的含量。-DG 和 -DG 处理后，肾组织中钙调神经磷酸酶（CAN）和钙/钙调蛋白依赖性蛋白激酶 II（CaMK II）的表达减少，Ca 内流被抑制，从而减少转化生长因子-β（TGFβ）的分泌，逆转高 NaCl 诱导的黏附因子 E-选择素和单核细胞趋化蛋白 1（MCP-1）的增加，同时降低氧化应激状态，减少环氧化酶-2（COX2）的表达。此外，抑制蛋白激酶 C（PKC）的表达也有助于这些改善。-DG 和 -DG 降低了 p-p44/42 MAPK、p-JNK 和 p-p38 的表达，抑制了高盐诱导的 NRN52e 细胞中 MAPK 信号通路的磷酸化，降低了 p-p38 和 p-HSP27 的过度表达，抑制了 p38-MAPK 信号通路的过度激活，表明 p38-MAPK 通路可能在高渗诱导的黏附和炎症反应中起关键作用。从本研究结果可以得出结论，-DG 和 -DG 的作用机制可能主要是通过抑制 p38-MAPK 信号通路，抑制 RAAS 系统的过度激活，从而减少黏附因子和炎症因子。
