Fisetin supplementation prevents high fat diet-induced diabetic nephropathy by repressing insulin resistance and RIP3-regulated inflammation was written by Ge, Chenxu;Xu, Minxuan;Qin, Yuting;Gu, Tingting;Lou, Deshuai;Li, Qiang;Hu, Linfeng;Nie, Xuyuan;Wang, Mingxing;Tan, Jun. And the article was included in Food & Function in 2019.Safety of 1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one The following contents are mentioned in the article:
Obesity-related renal disease is related to caloric excess promoting deleterious cellular responses. However, a full understanding of the mol. mechanisms involved in progressive kidney disease, as well as a therapeutic strategy, is still absent. Fisetin (FIS), as a natural flavonoid, possesses various bioactivities in a number of disease models. However, its role in obesity-associated kidney injury is still unclear and requires elucidation. In our study, an obesity animal model was established using C57BL/6 mice fed with a normal chow diet (NCD) or high fat diet (HFD) for 16 wk with or without FIS administration (20, 40 or 80 mg kg-1). Our results indicated that chronic HFD feeding led to a significant body weight gain in mice compared to the normal control group, accompanied by a marked insulin resistance and glucose intolerance, whereas FIS treatment exerted prominently protective effects. In addition, FIS significantly attenuated HFD-induced histol. alterations in renal tissue samples. Moreover, FIS treatment down-regulated expression of kidney injury mol.-1 (KIM-1), and up-regulated nephrin and podocin expression levels in the kidneys of HFD-fed mice, improving their renal dysfunction. After HFD feeding, mice treated with FIS exhibited a decrease in phosphorylated IRS1Ser307, and an increase in phosphorylated glycogen synthase kinase 1 (IRS1Tyr608), AKT, forkhead box protein O1 (FOXO1) and glycogen synthase kinase (GSK)-3β. Furthermore, FIS administration markedly restrained the inflammatory response in the kidneys of HFD-challenged mice, as evidenced by the reduced pro-inflammatory cytokines, tumor necrosis factor- α (TNF- α), interleukin 6 (IL-6), IL-1β and IL-18, which was attributed to the blockage of nuclear factor κ B (NF-κ B) signaling. Importantly, FIS-treated obese mice exerted a remarkable decrease in RIP3 expressions in the kidneys compared to obese mice in the absence of FIS, along with an evident reduction in the NOD-like receptor protein 3 (NLRP3), an apoptosis-associated speck-like protein containing a Caspase recruitment domain (ASC) and Caspase-1. The protective effects of FIS against HFD-induced renal injury were verified in vitro using palmitate (PAL)-treated HK2 cells, an immortalized proximal tubule epithelial cell line from the adult human kidney. In summary, our results supported the notion that FIS functions as a promising agent to improve insulin resistance and inflammatory response against metabolic stress-induced renal injury. This study involved multiple reactions and reactants, such as 1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one (cas: 524-12-9Safety of 1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one).
1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one (cas: 524-12-9) belongs to benzofurans derivatives. Benzofurans are only weakly aromatic in nature and they are cleaved by many oxidative and reductive conditions. Benzofurans have also made significant and distinctive contributions to biology. They exhibit several biological activities that range from antiviral, antimicrobial, antitumor, anti-inflammatory.Safety of 1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one
Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem