Salvianolic acid B attenuates membranous nephropathy by activating renal autophagy via microRNA-145-5p/phosphatidylinositol 3-kinase/AKT pathway

Abstract

The abnormal proliferation and inflammatory response of the mesangial cells play a crucial role in the progression of membranous nephropathy (MN). Herein, this study aimed to investigate the therapeutic effect of Salvianolic acid B (SalB) on MN-induced mesangial abnormalities and its underlying mechanisms. MN models were established in cationic bovine serum albumin-induced Sprague-Dawley rats and lipopolysaccharide-induced human mesangial cells (HMCs). Following SalB and microRNA-145-5p antagomir treatment, kidney function was investigated by 24-hours urine protein, serum creatinine, and blood urea nitrogen. Pathological changes of kidney were investigated by Periodic acid Schiff staining. CD68 and IgG were detected by immunofluorescence in glomerulus. Mesangial autophagosomes were observed by transmission electron microscope. MicroRNA-145-5p inhibitor, mimic, LY294002, and SalB were used to treat with HMCs. In kidney and HMCs, IL-1 , IL-2, IL-6, TNF- and microRNA-145-5p was detected by quantitative real-time PCR. Phosphatidylinositol 3-kinase (PI3K), phosphorylated AKT, AKT, beclin1, and microtubule-associated protein light chain 3 (LC3) levels were detected by Western blot. HMCs proliferation and cycle were detected by Cell Counting Kit-8 and flow cytometry. LC3 were detected by LC3-dual-fluorescent adenovirus in HMCs. Our results showed that SalB significantly ameliorated kidney function and pathological changes. Furthermore, it significantly alleviated proliferation, inflammation and activated autophagy in mesangial cells. Moreover, microRNA-145-5p antagomir accentuated MN while microRNA-145-5p inhibitor and LY294002 encouraged proliferation and inflammation through PI3K/AKT pathway in HMCs. Collectively, our study demonstrated that SalB activated renal autophagy to reduce cell proliferation and inflammation of MN, which was mediated by microRNA-145-5p to inhibit PI3K/AKT pathway, and ultimately attenuated MN.

Network pharmacology and molecular docking predictions of the active compounds and mechanism of action of Huangkui capsule for the treatment of idiopathic membranous nephropathy

“…Triptolide cures MN through modifying the P13K/AKT1/mTOR signaling pathway, according to Zhang P. et al [ 35 ] network pharmacology and experimental validation, Heymann nephritis in rats was used by Yin J et al [ 36 ] to show that Tetrandrine cures MN via altering the P13K/AKT signaling pathway. Furthermore, Chen J et al [ 37 ] showed in vitro that Salvianolic acid B reduces MN by triggering renal autophagy via the microRNA-145-5p/P13K/AKT pathway. These findings support the findings of the KEGG pathway enrichment study and show the significance of AKT1 in the occurrence, development, and management of IMN.…”

Salvianolic Acid B: A Review of Pharmacological Effects, Safety, Combination Therapy, New Dosage Forms, and Novel Drug Delivery Routes

“…In rats with cationic calf serum albumin-induced chronic glomerulonephritis, salvianolic acid B can improve renal function by inhibiting inflammation (decreased expression of IL-1β and IL-6), alleviating oxidative stress (decreased MDA levels and increased SOD and GSH activities), and promoting autophagy (decreased p62 expression and increased the LC3 II/LC3 I ratio and Beclin1 expression) [ 119 ]. Salvianolic acid B significantly ameliorated kidney function and pathological changes in rats with cationic bovine serum albumin-induced membranous nephropathy and LPS-induced human mesangial cells by upregulating miR-145-5p to inhibit the PI3K/Akt signaling pathway and by upregulating mesangial cell autophagy, thus reducing cell proliferation and inflammation [ 120 ].…”

Diosgenin protects against cationic bovine serum albumin-induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway

“…Similarly, salvianolic acid B activates renal autophagy by targeting the phosphoinositol-3 kinase (PI3K)/protein kinase B (AKT) pathway through microRNA-145-5p, consequently reducing inflammation and cell proliferation (Chen J et al. 2022 ). Additionally, salvianolate has been found to protect against MGN by inhibiting hypercoagulable states and promoting the expression of Wilms’ tumour protein 1 (WT-1), podocalyxin (PCX) and vascular endothelial growth factor (VEGF) in renal tissue, which ultimately aids in the repair of podocyte injury (Chen W et al.…”