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Aloperine Protects Against Cisplatin-Induced Injury in Kidney Cells Via Modulating PI3K/AKT/Nfκb-Mediated NLRP3
Mingning Qiu1,2,3, Shuai Zhang3, Jinglan Liang4
1Key Laboratory of Research in Maternal and Child Medicine and Birth Defects, Guangdong Medical University, Foshan, 528300, Guangdong, China.
Background:
Aloperine (ALO) is a vital alkaloid present in the traditional Chinese herb Sophora alopecuroides, which has demonstrated effective anti-inflammatory activity. However, the effects and the mechanism of action of ALO on cisplatin (CDDP)-induced nephrotoxicity remain unclear.
Objective:
This study aimed to investigate the effects of ALO on CDDP-induced nephrotoxicity and its potential mechanism of action in vitro.
Methods:
Cell viability, lactate dehydrogenase cytotoxicity, apoptosis, activity of Caspase-Glo 3/7 and 1, in-cell western blotting, immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA) were performed to assess the influence of ALO on CDDP-treated kidney cells. Inhibitors of phosphatidylinositol 3-kinase (PI3K, LY294002), protein kinase B (Akt, AKT inhibitor VIII), and nuclear factor kappa B (NFκB, BAY 11-7082) were used to determine their potential mechanisms of action.
Results:
The results indicated that ALO significantly reversed the inhibition of cell viability, cytotoxicity, apoptosis, and the release of inflammatory factors induced by CDDP in kidney cells. ALO attenuated the PI3K/AKT/NFκB-mediated pathway activated by CDDP treatment and downregulated the CDDP-induced nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome. Furthermore, the PI3K and AKT inhibitors diminished the effects of ALO on CDDP-treated kidney cells. Additionally, NFκB inhibitors reversed the effects of the PI3K and AKT inhibitors on ALO in CDDP-treated kidney cells.
Conclusion:
These results suggest that ALO protects against CDDP-induced injury in kidney cells by modulating the PI3K/AKT/NFκB-mediated NLRP3 inflammasome.
Insights
Aloperine (ALO) protects kidney cells from cisplatin (CDDP) damage by inhibiting the PI3K/AKT/NFκB pathway and NLRP3 inflammasome. This study clarifies ALO
Area of Science:
- Pharmacology
- Toxicology
- Cell Biology
Background:
- Aloperine (ALO), an alkaloid from Sophora alopecuroides, exhibits anti-inflammatory properties.
- The protective effects and mechanism of ALO against cisplatin (CDDP)-induced nephrotoxicity are not well understood.
Purpose of the Study:
- To investigate the protective effects of ALO on CDDP-induced nephrotoxicity in vitro.
- To elucidate the underlying molecular mechanisms, focusing on the PI3K/AKT/NFκB pathway and NLRP3 inflammasome.
Main Methods:
- Cell viability, cytotoxicity (LDH), and apoptosis assays were used to assess kidney cell injury.
- Western blotting and ELISA measured inflammatory factors and pathway activation.
- Specific inhibitors (PI3K, AKT, NFκB) were employed to explore the mechanism of action.
Main Results:
- ALO significantly reversed CDDP-induced decreases in cell viability, increases in cytotoxicity, and apoptosis.
- ALO attenuated the activation of the PI3K/AKT/NFκB pathway and downregulated the NLRP3 inflammasome.
- Inhibitor studies confirmed the involvement of the PI3K/AKT/NFκB pathway in ALO's protective effects.
Conclusions:
- Aloperine demonstrates significant protective effects against CDDP-induced nephrotoxicity in vitro.
- ALO exerts its protective effects by modulating the PI3K/AKT/NFκB signaling pathway and the NLRP3 inflammasome.
- These findings highlight ALO as a potential therapeutic agent for preventing chemotherapy-induced kidney damage.
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