Two Sulfur Glycoside Compounds Isolated from Lepidium apetalum Willd Protect NRK52e Cells against Hypertonic-Induced Adhesion and Inflammation by Suppressing the MAPK Signaling Pathway and RAAS

Abstract

Lepidium apetalum Willd has been used to reduce edema and promote urination. Cis-desulfoglucotropaeolin (cis-DG) and trans-desulfoglucotropaeolin (trans-DG) were isolated from Lepidium apetalum Willd, and caused a significant increase in cell viability in a hypertonic model in NRK52e cells. In the hypertonic model, cis-DG and trans-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 cis-DG and trans-DG, expression of calcineurin (CAN) and Ca/calmodulin-dependent protein kinase II (CaMK II) was decreased in renal tissue and Ca2+ 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 cis-DG and trans-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 cis-DG and trans-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.

Excessive Activation of Notch Signaling in Macrophages Promote Kidney Inflammation, Fibrosis, and Necroptosis

“…These cytokines are closely related to inflammation in many tissues. These inflammatory factors are important regulators of the renal inflammatory response and renal interstitial fibrosis (45). Our study also confirmed these findings.…”

Mechanism of Anti-Inflammatory and Antibacterial Effects of QingXiaoWuWei Decoction Based on Network Pharmacology, Molecular Docking and In Vitro Experiments

“…Likewise, the MAPK signaling pathway is responsible for transmitting signals from the cellular membrane toward the nucleus in response to various stimuli. This pathway regulates a broader spectrum of cellular events such as growth, stress responses, and inflammation, thus, it is a broadly implicated therapeutic target for tumor and peripheral inflammatory conditions (Yuan et al, 2017). TNF is a well-known pleiotropic cytokine and has been demonstrated with several important roles in disease pathogenesis as well as homeostasis.…”

Geniposide from Gardenia jasminoides var. radicans Makino Attenuates Myocardial Injury in Spontaneously Hypertensive Rats via Regulating Apoptotic and Energy Metabolism Signalling Pathway

“…When the concentration of extracellular Na + is higher than that in the cell, the osmotic pressure increases, which leads to the cardiac myocyte enlargement and gradual apoptosis. 11 …”

“…When the concentration of extracellular Na + is higher than that in the cell, the osmotic pressure increases, which leads to the cardiac myocyte enlargement and gradual apoptosis. 11 The results showed that cell viability in the model group was significantly lower than that in the normal group (P<0.01). After the cells were treated with geniposide at different concentrations, their viability increased (P<0.01), and the most effective concentration of geniposide was determined to be 0.5 μmol/L.…”