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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

Integrated Network Pharmacology and Cellular Assay to Explore the Mechanisms of Selenized Tripterine Phytosomes (Se@Tri-PTs) Alleviating Podocyte Injury in Diabetic Nephropathy

Author(s): Shiping Zhu, Qiubo Liu, Yuling Chang, Chunhua Luo, Xingwang Zhang* and Shengyun Sun*

Volume 29, Issue 38, 2023

Published on: 13 November, 2023

Page: [3073 - 3086] Pages: 14

DOI: 10.2174/0113816128275079231102071508

Price: $65

Abstract

Aim: This work aimed to elucidate the mechanisms of Se@Tri-PTs in alleviating podocyte injury via network pharmacology and in vitro cellular assay.

Background: Selenized tripterine phytosomes (Se@Tri-PTs) have been confirmed to undertake synergistic and sensitized effects on inflammation, which may be curatively promising for diabetic nephropathy (DN). However, the mechanisms of Se@Tri-PTs in alleviating podocyte injury, a major contributor to DN, still remain unclear.

Objective: The objective of the study was to find out the underlying mechanisms of Se@Tri-PTs in alleviating podocyte injury in diabetic nephropathy.

Methods: The key components and targets of Tripterygium wilfordii (TW) significant for DN as well as the signaling pathways involved have been identified. A high glucose-induced podocyte injury model was established and verified by western blot. The protective concentration of Se@Tri-PTs was screened by CCK-8 assay. Podocytes cultured with high glucose were treated with Se@Tri-PTs under protective levels. The expression of key protective proteins, nephrin and desmin, in podocytes, was assayed by western blot. Further, autophagy- related proteins and factors, like NLRP3, Beclin-1, LC3II/LC3, P62, and SIRT1, were analyzed, which was followed by apoptosis detection.

Results: Network pharmacology revealed that several monomeric components of TW, especially Tri, act on DN through multiple targets and pathways, including the NLRP3-mediated inflammatory pathway. Se@Tri-PTs improved the viability of podocytes and alleviated their injury induced by high glucose at 5 μg/L or above. High-glucose induction promoted the expression of NLRP3 in podocytes, while a low concentration of Se@Tri-PTs suppressed the expression. A long-term exposure of high glucose significantly inhibited the autophagic activity of podocytes, as manifested by decreased Beclin-1 level, lower ratio of LC3 II/LC3 I, and up- regulation of P62. This abnormality was efficiently reversed by Se@Tri-PTs. Importantly, the expression of SIRT1 was up-regulated and podocyte apoptosis was reduced.

Conclusion: Se@Tri-PTs can alleviate podocyte injury associated with DN by modulating NLRP3 expression through the pathway of SIRT1-mediated autophagy.

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