<p>Wogonin Ameliorates Renal Inflammation and Fibrosis by Inhibiting NF-κB and TGF-β1/Smad3 Signaling Pathways in Diabetic Nephropathy</p>

Abstract

Introduction: Diabetic nephropathy (DN) has become an increasing threat to health, and inflammation and fibrosis play important roles in its progression. Wogonin, a flavonoid, has been proven to suppress inflammation and fibrosis in various diseases, including acute kidney injury. This study aimed at investigating the effect of wogonin on diabetes-induced renal inflammation and fibrosis. Materials and Methods: Streptozotocin (STZ)-induced diabetic mouse models received gavage doses of wogonin (10, 20, and 40 mg/kg) for 12 weeks. Metabolic indices from blood and urine and pathological damage of glomerulus in the diabetic model were assessed. Glomerular mesangial cells SV40 were cultured in high glucose (HG) medium containing wogonin at concentrations of 1.5825, 3.125, and 6.25 μg/mL for 24 h. Inflammation and fibrosis indices were evaluated by histopathological, Western blotting, and PCR analyses. Results: Wogonin treatment ameliorated albuminuria and histopathological lesions in diabetic mice. Inflammatory cytokines, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and related signaling pathway NF-κB were downregulated after the administration of wogonin in vivo and in vitro. Furthermore, wogonin reduced the expression of extracellular matrix (ECM), including fibronectin (FN), collagen IV (Col-IV), α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1) in the kidneys of diabetic mice and HG-induced mesangial cells. Moreover, the inhibition of TGF-β1/Smad3 pathway might be responsible for these changes. Conclusion: Wogonin may ameliorate renal inflammation and fibrosis in diabetic nephropathy by inhibiting the NF-κB and TGF-β1/Smad3 signaling pathways.

Wogonin Alleviates Kidney Tubular Epithelial Injury in Diabetic Nephropathy by Inhibiting PI3K/Akt/NF-κB Signaling Pathways

“…[8][9][10] Wogonin inhibits the proliferation of HG-treated mesangial cells. 11 Wogonin inhibits H 2 O 2 -induced angiogenesis via suppressing PI3K/Akt/NF-κB pathway. 28 In order to better understand the effects of wogonin, our laboratory tested biochemical indices in diabetic mice.…”

“… 10 Furthermore, wogonin can effectively inhibit inflammation and fibrosis in HG-induced mesangial cells. 11 Wogonin enhances oxaliplatin-induced gastric cancer cell death by promoting excessive autophagy. 12 However, the role of wogonin in renal tubular epithelial cells during DN is unknown.…”

Astragaloside IV alleviates silica‑induced pulmonary fibrosis via inactivation of the TGF‑β1/Smad2/3 signaling pathway

“…The phosphorylated Smad2 and Smad3 binds to Smad4 to form the Smads complex, which is transferred to the nucleus by cytoplasmic nuclear transporters and acts on the TGF-β1 target gene to regulate transcription of target genes. When the external stimulus inducing the signal ends, p-Smads are rapidly dephosphorylated, and the Smads protein in the cytoplasm and nucleus is rapidly metabolized by the ubiquitin-proteasome system, returning the cytoplasmic levels to resting levels (29). Under pathological conditions, the p-Smad2/Smad2 ratio and p-Smad3/Smad3 ratio are increased.…”

The Underlying Mechanism of Chinese Herb of Regulating Marrow in the Treatment of Osteonecrosis of the Femoral Head Based on Network Pharmacology and Molecular Docking

“…It has multiple pharmacological effects reported by many studies, such as protecting the bone, reduceing blood glucose, blood pressure, and lipid, and immunomodulatory, anti-in ammatory, and antioxidation activities (19)(20)(21). Wogonin, a compound extracted from the Scutellaria baicalensis plant, exhibits high anti-in ammatory and antioxidative properties, which is achieved reduce expression of transforming growth factor β1 (TGF-β1), high temperature receptor A1 (HTRA1), matrix metalloprotease 13 (MMP-13) and nuclear factor kappa-lightchain-enhancer of activated B cells (NF-κB) (22,23). Moreover, kaempferol have a wide range of pharmacological and biological activities, which mainly include cardioprotective, anxiolytic, anti-allergic, anti-cancer, anti-microbial, anti-hyperlipidemic, anti-oxidative, anti-in ammatory and anti-osteoporotic effects(24-26).…”