Vitexin, a fenugreek glycoside, ameliorated obesity-induced diabetic nephropathy via modulation of NF-κB/IkBα and AMPK/ACC pathways in mice

Zhou, Guozhong; Cui, Jiale; Shen, Xie; Wan, Huiying; Luo, Yan; Guo, Gang

doi:10.1093/bbb/zbab012

Cited by 12 publications

(4 citation statements)

References 65 publications

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“…Vitexin was shown to attenuate mitochondrial dysfunction in rats with Cd-induced renal toxicity. In addition, vitexin was reported to inhibit the development of diabetic nephropathy by regulating NF-κB and AMPK signaling (Zhou et al 2021 ). These results suggest promising roles for vitexin in improving kidney injury.…”

Section: Discussionmentioning

confidence: 99%

Vitexin attenuates chronic kidney disease by inhibiting renal tubular epithelial cell ferroptosis via NRF2 activation

Song,

Wang,

Sheng

et al. 2023

Mol Med

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Background Chronic kidney disease (CKD) involves a variety of pathological processes, and ferroptosis plays a vital role in CKD progression. Targeting ferroptosis is a promising strategy for the treatment of CKD. However, inhibitors of ferroptosis have not been used in the clinical treatment of CKD. Vitexin is a natural flavonoid with many biological activities and protective effects against various diseases. However, whether vitexin can prevent the progression of CKD is not known. Methods In vivo, the effect of vitexin on CKD was evaluated by using mouse models of unilateral ureteral obstruction (UUO) and unilateral ischemia–reperfusion (UIR). Western blotting, Sirius red staining and transmission electron microscopy were used to analyze renal tubular injury, interstitial fibrosis, and inflammation in the kidneys of UUO and UIR mice. In vitro, CCK8 assays and lipid peroxidation assays were performed to analyze cell viability and lipid peroxidation in human renal tubular epithelial cells (HK2 cells) induced by erastin. The activation of renal fibroblasts (NRK-49 F cells) was also analyzed. Additionally, an in-silico protein-drug docking model and coimmunoprecipitation were performed to determine the direct substrate of vitexin. Results In vivo, vitexin treatment significantly ameliorated renal tubular injury, interstitial fibrosis, and inflammation in the kidneys of UUO and UIR mice. Additionally, our results showed that vitexin significantly attenuated UUO- and UIR-induced ferroptosis in renal tubular epithelial cells by upregulating glutathione peroxidase 4 (GPX4) protein levels and inhibiting lipid peroxidation in mouse kidneys. In vitro, treatment with vitexin inhibited erastin-induced ferroptosis in HK2 cells. Moreover, vitexin inhibited the expression of collagen I and α-SMA (alpha-smooth muscle actin) in NRK-49 F cells induced by the supernatant of erastin-treated HK2 cells. Mechanistically, our results suggested that vitexin could activate the NRF2/heme oxygenase-1 (HO-1) pathway by inhibiting the KEAP1- and ubiquitination-mediated degradation of NRF2, thereby increasing the expression of GPX4, and further inhibiting lipid peroxidation and ferroptosis. Additionally, knockout of NRF2 greatly inhibited the antiferroptotic effects of vitexin. Conclusions Taken together, our results indicate that vitexin can protect against renal tubular epithelial cell ferroptosis in CKD by activating the KEAP1/NRF2/HO-1 pathway and is a promising drug to treat CKD.

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Section: Discussionmentioning

confidence: 99%

Vitexin attenuates chronic kidney disease by inhibiting renal tubular epithelial cell ferroptosis via NRF2 activation

Song,

Wang,

Sheng

et al. 2023

Mol Med

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“…HFD‐fed mice gained 1.6%–46.4% less BW when treated with vitexin at 1–60 mg/kg/day (i.g.) for 8–12 weeks (Inamdar et al, 2019; Peng et al, 2019; Zhou et al, 2021). This indicates that vitexin exhibits a strong dose–response in preventing BW gain.…”

Section: Flavonoids In Obesity Pharmacotherapiesmentioning

confidence: 99%

Natural compounds as obesity pharmacotherapies

Zhao,

Wang,

Neely

et al. 2023

Phytotherapy Research

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Obesity has become a serious global public health problem, affecting over 988 million people worldwide. Nevertheless, current pharmacotherapies have proven inadequate. Natural compounds have garnered significant attention due to their potential antiobesity effects. Over the past three decades, ca. 50 natural compounds have been evaluated for the preventive and/or therapeutic effects on obesity in animals and humans. However, variations in the antiobesity efficacies among these natural compounds have been substantial, owing to differences in experimental designs, including variations in animal models, dosages, treatment durations, and administration methods. The feasibility of employing these natural compounds as pharmacotherapies for obesity remained uncertain. In this review, we systematically summarized the antiobesity efficacy and mechanisms of action of each natural compound in animal models. This comprehensive review furnishes valuable insights for the development of antiobesity medications based on natural compounds.

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“…Research indicates that vitexin has the potential to suppress the progression of obesity-induced DN via modulation of NF-кB/IkBα and AMPK/ACC pathways. [41] 4. Glycosides and Diabetic Retinopathy (Figure 5)…”

Section: Glycosides and Diabetic Nephropathy (Figure 4)mentioning

confidence: 99%

“…Vitexin (apigenin‐8‐C‐glucoside) is a flavone glycoside obtained from fenugreek seed. Research indicates that vitexin has the potential to suppress the progression of obesity‐induced DN via modulation of NF‐κB/IkBα and AMPK/ACC pathways [41] …”

Section: Glycosides and Diabetic Nephropathy (Figure 4)mentioning

confidence: 99%

Glycosides and Vascular Complications of Diabetes

Yeram

Kulkarni

2022

Chemistry & Biodiversity

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Diabetes is linked with various microvascular and macrovascular complications. Nephropathy, neuropathy and retinopathy are important microvascular complications of diabetes. Different types of secondary metabolites including glycosides have been studied for their effects in diabetic complications. Various glycosides such as flavanoid glycosides and saponin glycosides are reported for their beneficial effects in diabetic nephropathy, neuropathy, retinopathy and cardiomyopathy by action on various pathways involved in the progression of these complications. Coumarin glycosides and cryanogenic glycosides have been studied for their effective role in diabetic nephropathy. Phenolic glycosides and anthraquinone glycosides also have beneficial role in diabetic neuropathy. The present review focuses on various classes of glycosides and their role in the prevention and treatment of vascular complications of diabetes.

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Vitexin, a fenugreek glycoside, ameliorated obesity-induced diabetic nephropathy via modulation of NF-κB/IkBα and AMPK/ACC pathways in mice

Cited by 12 publications

References 65 publications

Vitexin attenuates chronic kidney disease by inhibiting renal tubular epithelial cell ferroptosis via NRF2 activation

Vitexin attenuates chronic kidney disease by inhibiting renal tubular epithelial cell ferroptosis via NRF2 activation

Natural compounds as obesity pharmacotherapies

Glycosides and Vascular Complications of Diabetes

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