Baicalin alleviates doxorubicin-induced nephrotic syndrome by regulating the tumor necrosis factor-β/Smad signaling pathway and NOD-like receptor family, pyrin domain-containing protein 3 inflammasome.

Adriamycin (ADR)-induced nephrotic syndrome (NS) is a common renal disease model characterized by proteinuria, glomerular damage, and inflammatory responses. Baicalin, a bioactive flavonoid derived from Scutellaria baicalensis, demonstrates anti-inflammatory and anti-fibrotic properties. This study aims to investigate whether baicalin alleviates ADR-induced NS by regulating the transforming growth factor-beta (TGF-β)/Smad signaling pathway and the NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome. A murine NS model in vivo was established by administering 10 mg/kg ADR to male C57BL/6J mice. Experimental groups were treated orally with 20 mg/kg or 40 mg/kg baicalin for 6 weeks. The following parameters were measured in each group: 24-h urinary protein, serum creatinine (Scr), blood urea nitrogen (BUN), total protein, albumin, total cholesterol, and triglycerides. In vitro, a cellular NS model was established by treating mouse podocyte cells (MPC5) with 0.75 µmol/L ADR, and the protective effects of baicalin were evaluated. Protein expression levels of the TGF-β/Smad signaling pathway and NLRP3 inflammasome were analyzed by Western blot. The secretion levels of interleukin-4 (IL-4), interleukin-8 (IL-8), interleukin-1β (IL-1β), and interleukin-18 (IL-18) were assessed by enzyme-linked immunosorbent assay, and the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were measured in cells. ADR reduced MPC5 cell viability to below 50% and increased MDA levels (≥6 nmol/mg prot). The expression of NLRP3 (upregulated by 4-fold), α-smooth muscle actin (upregulated by 3-fold), N-cadherin (upregulated by 3-fold), and IL-8/IL-1β/IL-18 (all upregulated by more than 1-fold) was significantly elevated. Treatment with 12.5 µmol/L baicalin markedly reversed these changes, restoring cell viability to over 85% and bringing pathway protein and cytokine levels close to those of the control group. In vivo, ADR-induced NS mice exhibited doubled 24-h urinary protein, Scr, and BUN levels, along with renal interstitial inflammatory infiltration and a 60% downregulation of podocin expression. Treatment with 40 mg/kg of baicalin restored these indicators to levels comparable to those in untreated mice, with effects similar to irbesartan (P<0.05). We concluded that baicalin demonstrated significant renoprotective effects in both in vivo and in vitro models of ADR-induced NS by regulating the TGF-β/Smad pathway and NLRP3 inflammasome, mitigating renal injury and inflammation. These results offer experimental support for the potential use of baicalin as a therapeutic agent for NS.