Aloperine Protects Mice against Ischemia-Reperfusion (IR)-Induced Renal Injury by Regulating PI3K/AKT/mTOR Signaling and AP-1 Activity

Abstract

Aloperine is a quinolizidine alkaloid extracted from the leaves of Sophora plants. It has been recognized with the potential to treat inflammatory and allergic diseases as well as tumors. In this report, we demonstrate that pretreatment with aloperine provided protection for mice against ischemia-reperfusion (IR)-induced acute renal injury as manifested by the attenuated inflammatory infiltration, reduced tubular apoptosis, and well-preserved renal function. Mechanistic studies revealed that aloperine selectively repressed IL-1β and IFN-γ expression by regulating PI3K/Akt/mTOR signaling and NF-κB transcriptional activity. However, aloperine did not show a perceptible impact on IL-6 and TGF-β expression and the related Jak2/Stat3 signaling. It was also noted that aloperine regulates AP-1 activity, through which it not only enhances SOD expression to increase reactive oxygen species (ROS) detoxification but also promotes the expression of antiapoptotic Bcl-2, thereby preventing tubular cells from IR-induced apoptosis. Collectively, our data suggest that administration of aloperine prior to IR insults, such as renal transplantation, could be a viable approach to prevent IR-induced injuries.

Aloperine Protects Mice against DSS-Induced Colitis by PP2A-Mediated PI3K/Akt/mTOR Signaling Suppression

“…Previous studies have shown that aloperine downregulates PI3K/Akt/mTOR signaling in HCT116 human colon cancer cells [ 10 ]. Our group confirmed that aloperine significantly attenuated ionizing radiation- (IR-) induced PI3K activation [ 11 ]. Aloperine is an alkaloid isolated from the shrub Sophora alopecuroides L. and has been recognized as an effective treatment for inflammatory and allergic diseases [ 11 – 17 ].…”

“…Our group confirmed that aloperine significantly attenuated ionizing radiation- (IR-) induced PI3K activation [ 11 ]. Aloperine is an alkaloid isolated from the shrub Sophora alopecuroides L. and has been recognized as an effective treatment for inflammatory and allergic diseases [ 11 – 17 ]. It has been shown to increase CD4 + CD25 + cells and IL-10 levels as well as alleviate inflammation in mice with 2,4,6-trinitrobenzenesulfonic acid- (TNBS-) induced colitis [ 16 ].…”

Both conditional ablation and overexpression of E2 SUMO-conjugating enzyme (UBC9) in mouse pancreatic beta cells result in impaired beta cell function

“…The isolated islets and NIT-1 cells were stimulated with 2.5 mmol/l or 10 mmol/l STZ, respectively. ROS accumulation was analysed using 2′,7′dichlorodihydrofluorescein diacetate (DCFH-DA, 10 μmol/l; Beyotime, Shanghai, China) as previously described [26] (see ESM Methods).…”

“…Analysis of NRF2 protein activity Chromatin immunoprecipitation (ChIP) assay [18], electrophoretic mobility shift assay (EMSA) [26] and dual-luciferase assay [18] were performed to analyse the activity of NRF2 (see ESM Methods).…”

Macrophages Regulate Unilateral Ureteral Obstruction-Induced Renal Lymphangiogenesis through C-C Motif Chemokine Receptor 2–Dependent Phosphatidylinositol 3-Kinase-AKT–Mechanistic Target of Rapamycin Signaling and Hypoxia-Inducible Factor-1α/Vascular Endothelial Growth Factor-C Expression

“…The sections were probed with primary antibodies against Aquaporin 1 (dilution 1:250; catalog number ab168387; Abcam, Cambridge, MA), VEGF-C (dilution 1:200; catalog number 22601-1-AP; Proteintech, Chicago, IL), F4/80 (dilution 1:50; MCA497RT; ABD Serotec, Oxford, UK), lymphatic vascular endothelial hyaluronan receptor 1 (LYVE-1; dilution 1:1000; ab14917; Abcam), CD45 (dilution 1:1000; GB11066; Goodbio Technology, Wuhan, China), CD4 (dilution 1:1500; GB11064; Goodbio Technology), CD8a (dilution 1:1500; Goodbio Technology), or myeloperoxidase (dilution 1:100; PA5-16672; Thermo Scientific, Waltham, MA) overnight at 4 C. The sections were then developed using a Vector stain ABC kit (Vector Laboratories Inc., Burlingame, CA) and further counterstained with Harris' hematoxylin as reported. 24 All sections were assessed under a microscope by two pathologists (Y.Z. and G.-C.P.)…”