The anti-nephritic activity of a polysaccharide from okra (Abelmoschus esculentus (L.) Moench) via modulation of AMPK-Sirt1-PGC-1α signaling axis mediated anti-oxidative in type 2 diabetes model mice

Liao, Zhengzheng; Zhang, Jingying; Wang, Jinyu; Yan, Tingxu; Xu, Fanxing; Wu, Bo; Xiao, Feng; Bi, Kaishun; Niu, Jumin; Jia, Ying

doi:10.1016/j.ijbiomac.2019.08.149

Cited by 50 publications

(33 citation statements)

References 39 publications

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“…SIRT1, the founding member of the sirtuin family, is regarded as a major modulator of DCM, because of its antioxidative and antiapoptotic effects [46]. Combined with previous evidence, the results in our study indicate that GDF11 and SIRT1 could dramatically inhibit oxidative damage by targeting the same antioxidative molecules, thereby reducing myocardial ROS [16,17,47]. Moreover, quercetin treatment simultaneously upregulates GDF11 and SIRT1 expression in broblasts [25].…”

Section: Discussionsupporting

confidence: 77%

GDF11 alleviates pathological myocardial remodeling in diabetic cardiomyopathy through SIRT1-dependent regulation of oxidative stress and apoptosis

Zhu

Zhang

Zhai

et al. 2021

Preprint

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Background Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and cardiomyocyte injury, which induced by metabolic disorder. Nowadays, there is still a lack of drugs for the treatment of DCM. Growth differentiation factor 11 (GDF11) is a novel member of the transforming growth factor β superfamily that alleviates cardiac hypertrophy, myocardial infarction, and vascular injury by regulating oxidative stress, inflammation, and cell survival. However, the roles and underlying mechanisms of GDF11 in DCM remain largely unknown. Methods In this study, we sought to determine whether GDF11 could prevent DCM. The mouse model of diabetes was established by administering a high-fat diet and intraperitoneal injecting streptozotocin. After that, intramyocardial injection of an adeno-associated virus carrying GDF11 gene was used to achieve myocardium-specific overexpression. Results Our data showed that GDF11 overexpression remarkably improved cardiac dysfunction and interstitial fibrosis by reducing the levels of reactive oxygen species and protecting against cardiomyocyte loss. Mechanistically, decreased sirtuin 1 (SIRT1) expression was observed in diabetic mice, which was significantly increased after GDF11 overexpression. To further explore how SIRT1 mediates the role of GDF11, the selective inhibitor EX527 was used to block SIRT1 signaling pathway, which abolished the protective effects of GDF11 against DCM. In vitro studies confirmed that GDF11 protected against H9c2 cell injury in high glucose and palmitate by attenuating oxidative injury and apoptosis, and these effects were also eliminated by SIRT1 depletion. Conclusion Our results demonstrated for the first time that GDF11 protected against DCM by regulating SIRT1 signaling pathway, and GDF11 had the potential to become a novel target for reversing cardiac dysfunction in diabetic patients.

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Section: Discussionsupporting

confidence: 77%

GDF11 alleviates pathological myocardial remodeling in diabetic cardiomyopathy through SIRT1-dependent regulation of oxidative stress and apoptosis

Zhu

Zhang

Zhai

et al. 2021

Preprint

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“…In the ischemia-reperfusion AKI model, SIRT1 targets the deoxyacetylation of p53, FoxO1, and NF-κB to regulate the stress response, inflammation, cell senescence, and apoptosis (Grabowska et al, 2017;Zhang et al, 2017;Abdolvahabi et al, 2019;Wang et al, 2019). In addition, SIRT1mediated inhibition of tubular cell apoptosis has been shown to be the primary mechanism of renal protection (Liao et al, 2019;Ryu et al, 2019;Zhang et al, 2019). Our data also suggest that such a mechanism is important during cisplatin-induced AKI.…”

Section: Discussionsupporting

confidence: 52%

SIRT1 Mediates Effects of FGF21 to Ameliorate Cisplatin-Induced Acute Kidney Injury

Chen

Yang

et al. 2020

Front. Pharmacol.

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Acute kidney injury (AKI) is a common complication in cancer patients. Kidney function is closely related to patients' quality of life and tumor prognosis. Cisplatin is a highly effective anti-tumor drug. However, the use of cisplatin is limited by its nephrotoxicity. It has been reported that FGF21 has a renal-protective function, but the mechanisms by which it does so remain unclear. In this study, we show that the expression of FGF21 is significantly upregulated in both in vitro and in vivo cisplatin-induced AKI models. Administration of recombinant FGF21 to cisplatin-induced AKI mice resulted in significantly decreased blood urea nitrogen (BUN) and serum creatinine levels, as well as significantly reduced protein levels of kidney injury molecule-1 (TIM-1), C-caspase 3, and Bax. H&E-stained kidney sections from cisplatin-induced AKI mice treated with recombinant FGF21 showed a relatively normal renal tissue structure, a reduced number of necrotic sites and vacuolar changes, and decreased casts, suggesting alleviated renal tubular injury. Experiments with an AKI cell model (cisplatin-treated HK-2 cells) yielded similar results as the mouse model; recombinant FGF21 significantly downregulated protein expression levels of TIM-1, C-caspase 3, and Bax. Furthermore, administration of recombinant FGF21 to cisplatin-treated AKI models significantly increased SIRT1 expression, and the beneficial effects of FGF21 on kidney injury were reversed by SIRT1 knockdown. Collectively, our results suggest that SIRT1 mediates the protective effect of FGF21 on cisplatin-induced kidney injury.

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“…Therefore, this model was frequently used to investigate the influence of pharmacological and risk factors on the function and structure in the pancreas and intestine. Polysaccharide, as a main component of okra, exhibits protective effects on the kidneys in vivo and regulation of intestinal microbial disorders and other effects 26,38 . However, few studies have reported the effects of okra polysaccharides on acute pancreatitis.…”

Section: Discussionmentioning

confidence: 99%

Okra pectin relieves inflammatory response and protects damaged intestinal barrier in caerulein‐induced acute pancreatic model

Xiong

Zhang

et al. 2020

J Sci Food Agric

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BACKGROUNDProtecting the intestinal mucosa from being destroyed helps reduce the inflammation caused by acute pancreatitis (AP). In this study, whether okra pectin (OP) could attenuate the inflammation of AP through protecting the intestinal barrier was investigated.RESULTSOP was obtained from crude okra pectin (COP) through the purification by DEAE cellulose 52 column. Supplementation with OP or COP in advance reduced the severity of AP, as revealed by lower serum amylase and lipase levels, abated pancreatic edema, attenuated myeloperoxidase activity and pancreas histology. OP or COP inhibited the production of pancreatic proinflammatory cytokines, including tumor necrosis factor‐α and interleukin‐6. In addition, the upregulation of AP‐related proteins including ZO‐1, occludin, the antibacterial peptide‐defensin‐1 (DEFB1) and cathelicidin‐related antimicrobial peptide (CRAMP), as well as the histological examination of colon injuries, demonstrated that OP or COP provision could effectively maintain intestinal barrier function. Ultimately, dietary OP or COP supplementation could inhibit AP‐induced intestinal inflammation. For the above, the effect of OP was better than COP.CONCLUSIONDietary OP supplementation could be considered as a preventive method that effectively interferes with intestinal damage and attenuates inflammatory responses trigged by AP. © 2020 Society of Chemical Industry

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The anti-nephritic activity of a polysaccharide from okra (Abelmoschus esculentus (L.) Moench) via modulation of AMPK-Sirt1-PGC-1α signaling axis mediated anti-oxidative in type 2 diabetes model mice

Cited by 50 publications

References 39 publications

GDF11 alleviates pathological myocardial remodeling in diabetic cardiomyopathy through SIRT1-dependent regulation of oxidative stress and apoptosis

GDF11 alleviates pathological myocardial remodeling in diabetic cardiomyopathy through SIRT1-dependent regulation of oxidative stress and apoptosis

SIRT1 Mediates Effects of FGF21 to Ameliorate Cisplatin-Induced Acute Kidney Injury

Okra pectin relieves inflammatory response and protects damaged intestinal barrier in caerulein‐induced acute pancreatic model

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