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. 2023 Jan 27;28(1):52.
doi: 10.1186/s40001-022-00973-9.

Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome

Juan Lv  1   2 , Guozhong Xue  3 , Yunxia Zhang  2 , Xinbin Wang  1 , Enlai Dai  4
Affiliations

Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome

Juan Lv et al. Eur J Med Res. .

Abstract

Background: Glomerular damage is a common clinical indicator of nephrotic syndrome. High-dose hormone treatment often leads to hormone resistance in patients. How to avoid resistance and improve the efficiency of hormone therapy draws much attention to clinicians.

Methods: Adriamycin (ADR) was used to induce nephropathy model in SD rats. The rats were treated with dexamethasone (DEX), icariin (ICA), and DEX + ICA combination therapy. The changes in urinary protein (UP), urea nitrogen (BUN), and serum creatinine (SCR) contents in rats were detected by enzyme-linked immunosorbent assay (ELISA), and the degree of pathological injury and the expression level of podocin were detected by HE staining and immunohistochemistry, to test the success of the model and the therapeutic effects of three different ways. The effect of treatments on podocytes autophagy was evaluated via transfection of mRFP-GFP-LC3 tandem adenovirus in vitro.

Results: The contents of UP, SCR, and BUN were significantly increased, the glomerulus was seriously damaged, and the expression of Nephrosis2 (NPHS2) was significantly decreased in the ADR-induced nephrotic syndrome rat model compared to that of the control group. DEX, ICA, and the DEX + ICA combined treatment significantly alleviated these above changes induced by ADR. The combined treatment of DEX + ICA exhibited better outcome than single treatment. The combined treatment also restored the podocyte autophagy, increased the expression of microtubule-associated protein light-chain 3II (LC3II), and reduced the expression of p62 in vitro. The combined treatment protects podocytes by mediating the PI3K/AKT/mTOR (rapamycin complex) signaling pathway.

Conclusion: ICA enhances the therapeutic effect of DEX on the nephrotic syndrome.

Keywords: Adriamycin; Autophagy; Nephrotic syndrome; Podocyte injury.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The therapeutic effect of icariin and DEX on nephrotic syndrome model. A Changes of urine protein in adriamycin-induced nephrotic syndrome model; B UP, Scr, and BUN levels were regulated by icariin and DEX; C H&E was used to evaluate the glomerulus injury; D immunohistochemical assay for podocyte injury
Fig. 2
Fig. 2
Establishment of podocytes injury and drug concentration election in vitro. A Cytotoxicity of ADR to podocytes; B the effect of icariin and DEX on ADR-induced podocytes injury model; C the therapeutic effect of icariin and DEX combination therapy on podocytes injury model
Fig. 3
Fig. 3
The action mechanism of combination therapy on podocytes injury. A Combination therapy enhanced the autophagy flux in podocytes injury; B combination therapy regulated the autophagy of podocytes via PI3K/AKT/mTOR signal
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