Protective effect of astragalosides from Radix Astragali on adriamycin-induced podocyte injury

Abstract

Abstract. Nephrotic syndrome (NS) is the most common kidney disease in clinical practice and may lead to end-stage renal failure. Astragalosides (AST) have been clinically tested for the treatment of NS, but their mechanism of action has remained to be elucidated. The aim of the present study was to investigate the effect of AST on the structure and function of podocytes with adriamycin (ADR)-induced damage and to elucidate the underlying molecular mechanisms. The mouse podocyte clone 5 (MPC5) immortalized mouse podocyte cell line was treated with 0.5 µmol/l ADR to establish a podocyte injury model. The MPC5 podocytes were divided into a control group, a podocyte injury group and a low-, medium-and high-concentration AST treatment group. The results indicated that the survival rate of the podocyte injury group was significantly decreased compared with that in the control group and each AST-treated group had an increased survival rate compared with that in the podocyte injury group. Furthermore, each dose of AST significantly inhibited the ADR-associated increases the levels of lactate dehydrogenase and malondialdehyde and the decrease in the activity of superoxide dismutase in MPC5 podocytes. In addition, AST improved the migration ability of MPC5 podocytes and suppressed the cytoskeletal rearrangement associated with ADR-induced damage. Furthermore, matrix metalloproteinase (MMP)-2 and -9 were decreased in the podocyte injury group, which was inhibited by different concentrations of AST. Thus, AST was able to maintain the balance of oxidative stress in podocytes cultured with ADR and protect them from ADR-induced injury. The mechanism may be associated with the upregulation of MMPs.

MicroRNA-874-3p Aggravates Doxorubicin-Induced Renal Podocyte Injury via Targeting Methionine Sulfoxide Reductase B3

“…Podocytes are highly differentiated epithelial cells on the outer surface of glomerular capillaries [ 7 ], which play crucial roles in glomerular diseases. Podocyte injury has been considered as one critical factor in glomerular filtration barrier dysfunction, and continuous podocyte injury can lead to proteinuria, glomerulosclerosis, and renal impairment [ 8 – 10 ]. In addition, glomerulosclerosis, the main pathological process, can cause end-stage renal disease, and podocyte injury is crucial for the progression of glomerular disorders [ 11 ].…”

Compound Bieshe Kang’ai inhibits proliferation and induces apoptosis in HCT116 human colorectal cancer cells

“…Intriguingly, the cytotoxicity of CDK was specific to cancer cells, because CDK did not influence the viability of FHs 74 Int cells, suggesting that CBK may cause less adverse events in clinical settings. In addition, it is reported that Carapax Trionycis inhibits fibrogenesis of activated hepatic stellate cells [8], and Radix Astragali protects against podocyte injury in nephrotic syndrome [9]. The above data demonstrate that CBK is potentially superior to some chemotherapeutic anti-cancer agents, in terms of causing side effects.…”

The potential mechanism of Astragali Radix in the treatment of children with nephrotic syndrome

“…MMP-9 plays a key role in podocyte injury, and podocyte migration and Adriamycin-induced cell injury may be related to the upregulation of MMP-9 expression. Sai et al (18) found that the expression levels of MMP-2 and MMP-9 were decreased in a doxorubicin-induced podocyte injury group, while the use of Astragali Radix in the intervention group inhibited this decrease and prevented podocyte injury.…”

“…In this study, oral bioavailability (OB) and drug-likeness (DL) were used to screen out the chemical components with an OB ≥30% and a DL ≥0. 18.…”