Puerarin Alleviates UUO-Induced Inflammation and Fibrosis by Regulating the NF-κB P65/STAT3 and TGFβ1/Smads Signaling Pathways

Abstract

Purpose Puerarin (PR), a Chinese medicine rich in natural components, has been reported to display anti-fibrotic, antioxidant, anti-inflammatory and immunomodulatory properties. However, the protective mechanism of PR against unilateral ureteral obstruction (UUO)-mediated renal injury is not fully clarified. Therefore, the aim of this study was to investigate the effects of PR on UUO mice and its possible mechanisms. Methods A total of 32 C57BL/6 mice were divided randomly into four groups (n=8): i) sham-operated group (Sham); ii) UUO group (UUO); iii) UUO + PR 50 mg/kg/day (UUO + PRL); and iv) UUO + PR 100 mg/kg/day (UUO + PRH). Continuous gavage administration for 14 days starting one week postoperatively, while the mice in Sham and UUO groups were given equal amounts of vehicle by the same means. All mice were then sacrificed and serum, 24-hour urine and tissue specimens were collected for renal function, histopathology, Western blot, immunohistochemistry. Results Renal function and histopathology revealed that PR improved UUO-mediated renal dysfunction and partially reversed tubular injury and tubulointerstitial fibrosis. Additionally, according to the results of Western blot and immunohistochemistry, PR inhibited the expression of inflammatory factors including IL-1β, IL-6, MCP-1 and ECM-related proteins including α-SMA, COL I and VIM. More importantly, the expression of fibrotic pathways TGF-β1, Smad3, p-Smad3 and inflammatory pathways NF-κB p65, NF-κB p-p65, STAT3, p-STAT3 were inhibited to various extents under the PR treatment, while Smad7 was upregulated. Conclusion These findings indicate that PR may inhibit the recruitment of inflammatory factors and extracellular matrix (ECM) deposition through the regulation of the NF-κB p65/STAT3 and TGFβ1/Smads pathways, which alleviates the UUO-induced inflammatory and fibrotic response, thereby reversing renal injury.

Natural products: potential drugs for the treatment of renal fibrosis

“…Puerarin, a natural product extracted from Radix Puerariae, has been found to have an anti-fibrotic effect in recent years, and Zhou et al found that puerarin can inhibit oxidative stress-induced tubular epithelial cell apoptosis and improve renal fibrosis by decreasing ROS production and the expression of MAPK signaling pathways in the kidneys of UUO mice [ 29 ]. Others have found that puerarin can reduce fibrosis by inhibiting the NF-κB p65/STAT3 and TGF-β/Smad signaling pathways and inhibiting the inflammation and excessive deposition of ECM in the kidney [ 30 ].…”

Topical Application of Galgeunhwanggeumhwangryeon-Tang Recovers Skin-Lipid Barrier and Ameliorates Inflammation via Filaggrin-Thymic Stromal Lymphopoietin-Interleukin 4 Pathway

“…The MoA of these natural products is not corresponding to protection of skin barrier. However, several studies showed that these compounds, including puerarin, berberine, and wogonin, regulated the mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) [70][71][72][73][74][75]. The mTOR and STAT3 signaling pathways have been known as crucial for maintaining homeostasis of skin barrier in pathophysiology of atopic dermatitis [76,77].…”

Ferroptosis, a Rising Force against Renal Fibrosis

“…Renal fibrosis implies the erosion of the renal parenchyma and the accumulation of scarring, and almost all chronic and progressive kidney diseases experience this pathological pathway, which is manifested microscopically by glomerulosclerosis, tubular injury, interstitial fibrosis, and capillary rarefaction. During renal injury and chronic inflammation, increased secretion/expression of relevant enzymes and inflammatory mediators, and cytokines enable fibroblasts to differentiate towards myofibroblasts, the main responsible cells for renal fibrosis, and myofibroblast proliferation enables overexpression of α-smooth muscle actin (α-SMA), collagen (COL), fibronectin, and matrix metalloproteinases (MMP) [99][100][101][102].…”