Ombuin ameliorates diabetic nephropathy in rats by anti‐inflammation and antifibrosis involving Notch 1 and PPAR γ signaling pathways

Abstract

Diabetic nephropathy (DN) is a common complication of diabetes and it is urgent to develop effective therapies for DN. In this study, high‐sucrose and high‐fat diet combined with streptozotocin was used to induce DN in rats to observe the effects of natural flavonoid ombuin on renal function, inflammation, and interstitial fibrosis. Immunohistochemistry and western blotting analysis were used to detect protein expression levels. Results showed that ombuin significantly improved renal function and pathological injury, inhibited accumulation of advanced glycation end‐products, suppressed the release of inflammatory cytokines, and improved renal interstitial fibrosis in DN rats. Ombuin also significantly downregulated the expressions of transforming growth factor beta1 (TGF‐β1), connective tissue growth factor (CTGF), fibronectin (FN), p65, phosphorylated (p)‐p65, Cleaved‐Notch 1, and hairy and enhancer of split 1 (Hes 1), and upregulated the expression of peroxisome proliferator‐activated receptor γ (PPAR γ). When PPAR γ activity was inhibited by T0070907, the effects of ombuin on improving DN were significantly reversed, and the expressions of TGF‐β1, FN, CTGF, p‐p65, and p65 increased, while the expressions of Cleaved‐Notch 1 and Hes 1 were not significantly affected. These results suggest that ombuin may activate PPAR γ to exert anti‐inflammatory and antifibrotic effects by inhibiting Notch 1 activity in DN. It is also possible that ombuin acts on these two independent signal pathways synchronously.

Pediococcus acidilactici (pA1c®) alleviates obesity-related dyslipidemia and inflammation in Wistar rats by activating beta-oxidation and modulating the gut microbiota

“…Furthermore, a strong upregulation of the peroxisome proliferator-activated receptor gamma ( Pparg ) in the pA1c® group was noticed. Several studies linked the overexpression of Pparg with an insulin resistance- and dyslipidemia-alleviating effect and an anti-inflammatory activity, 46–48 so this finding supports the anti-inflammatory and dyslipidemia-alleviating role of pA1c® in obesity. No differences were found in Fasn and Srebf expression in mesenteric fat.…”

Crocin Ameliorates Diabetic Nephropathy through Regulating Metabolism, CYP4A11/PPARγ, and TGF-β/Smad Pathways in Mice

“…Besides, crocin inhibited the nucleus transition of Smad2/3 in the kidney. Many studies have reported that the regulation of PPARγ or the TGF-β/Smad signaling pathway enables the alleviation of DN [ 47 , 48 ]. Activated TGF-β1 recruits and activates TGFBR1 and subsequently phosphorylates Smad2/3, which enables its translocation into the nucleus for regulation of target gene transcription [ 49 ].…”

The novel anti-colitic effect of β-adrenergic receptors via modulation of PS1/BACE-1/Aβ axis and NOTCH signaling in an ulcerative colitis model

“…In addition, the interplay between inflammation and the NOTCH signaling has been amply reviewed ( Quillard and Charreau, 2013 ; Fazio and Ricciardiello, 2016 ) and it has been reported that NOTCH1 and HES1 in co-operation with TNF-α can suppress PPAR-γ ( Maniati et al, 2011 ) to play a crucial role in the pathogenesis of ulcerative colitis ( Ghorbaninejad et al, 2019 ). On the other hand, another study stated that stimulated PPAR inhibits NOTCH1 ( Liu et al, 2022 ). These data, hence, prove the crosstalk between the assessed parameters to pin down the anti-colitic effect of the tested drugs.…”