Resveratrol mitigates pancreatic TF activation and autophagy-mediated beta cell death via inhibition of CXCL16/ox-LDL pathway: A novel protective mechanism against type 1 diabetes mellitus in mice

Darwish, Mostafa A.; Abdel-Bakky, Mohamed Sadek; Messiha, Basim Anwar Shehata; Abo-Saif, Ali A.; Abo-Youssef, Amira M.

doi:10.1016/j.ejphar.2021.174059

Cited by 18 publications

(11 citation statements)

References 41 publications

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“…Being an exceptional chemokine, CXCL16 exists in two forms: the transmembrane that acts as a receptor for ox-LDL [ 52 ] and the soluble form resulting from cleavage of its transmembrane form by ADAM (ADAM10 or ADAM17), and consequently, the released part can attract CXCR6-expressing T-cells to the site of injury [ 53 ]. On this basis, we reported the involvement and the role of the chemokine CXCL16 with its processing enzyme, ADAM10, for the first time, as well as its associated signaling mechanism in the development of T1D.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Inhibited ADAM10 Mediated CXCL16-Cleavage and T-Cells Recruitment to Pancreatic β-Cells in Type 1 Diabetes Mellitus in Mice

et al. 2022

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Background: CXCL16 attracts T-cells to the site of inflammation after cleaving by A Disintegrin and Metalloproteinase (ADAM10). Aim: The current study explored the role of ADAM10/CXCL16/T-cell/NF-κB in the initiation of type 1 diabetes (T1D) with special reference to the potential protecting role of resveratrol (RES). Methods: Four sets of Balb/c mice were created: a diabetes mellitus (DM) group (streptozotocin (STZ) 55 mg/kg, i.p.], a control group administered buffer, a RES group [RES, 50 mg/kg, i.p.), and a DM + RES group (RES (50 mg/kg, i.p.) and STZ (55 mg/kg, i.p.) administered daily for 12 days commencing from the fourth day of STZ injection). Histopathological changes, fasting blood insulin (FBI), glucose (FBG), serum and pancreatic ADAM10, CXCL16, NF-κB, T-cells pancreatic expression, inflammatory, and apoptotic markers were analyzed. Results: FBG, inflammatory and apoptotic markers, serum TNF-α, cellular CXCL16 and ADAM10 protein expression, pancreatic T-cell migration and NF-κB were significantly increased in diabetic mice compared to normal mice. RES significantly improved the biochemical and inflammatory parameters distorted in STZ-treated mice. Conclusions: ADAM10 promotes the cleaved form of CXCL16 driving T-cells into the islets of the pancreatic in T1D. RES successfully prevented the deleterious effect caused by STZ. ADAM10 and CXCL16 may serve as novel therapeutic targets for T1D.

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Section: Discussionmentioning

confidence: 99%

Resveratrol Inhibited ADAM10 Mediated CXCL16-Cleavage and T-Cells Recruitment to Pancreatic β-Cells in Type 1 Diabetes Mellitus in Mice

et al. 2022

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“…126 The team of Darwish investigated the therapeutic effect of resveratrol on type 1 diabetes mellitus (T1DM) and found that resveratrol reduced macrophage infiltration into the pancreatic islets by inhibiting the CXCL16/NF-κB p65 signaling pathway and induced tissue factor (TF) activation and beta-cell autophagy by activating the CXC chemokine ligand 16 (CXCL16)/ox-LDL pathway. 127,128 Park et al , Lagouge et al and Arunachalam et al showed that resveratrol regulated energy and metabolic homeostasis by increasing renal cortex adiponectin receptor (AdipoR)-1 and AdipoR-2, activating the AMPK-SIRT1-PGC-1α axis and PPAR-α, and increasing the activity of eNOS. 129–131 In addition, Park et al found that resveratrol inhibited FoxO1 and FoxO3a phosphorylation, increased estrogen-related receptor (ERR)-1α and p-ACC expression, down-regulated SREBP 1, and reduced TG content.…”

Section: Pharmacological Actions and Mechanisms Of Non-flavonoids In ...mentioning

confidence: 99%

“…127,128 Park et al, Lagouge et al and Arunachalam et alshowed that resveratrol regulated energy and metabolic homeostasis by increasing renal cortex adiponectin receptor (AdipoR)-1 and AdipoR-2, activating the AMPK-SIRT1-PGC-1α axis and PPAR-α, and increasing the activity of eNOS [129][130][131]. In addition, Park et al found that resveratrol inhibited FoxO1 and FoxO3a phosphorylation, increased estrogen-related receptor (ERR)-1α and p-ACC expression, down-regulated SREBP 1, and reduced TG content 129.…”

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confidence: 99%

Natural polyphenols: a potential prevention and treatment strategy for metabolic syndrome

Wang

Meng

et al. 2022

Food Funct.

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“…At the same time, resveratrol can also be used to treat diabetes and its complications. For example, it inhibits islet macrophage infiltration and β-cell death in T1D mice by inactivation of the C-X-C motif chemokine ligand 16 (CXCL16)/ox-LDL pathway or the CXCL16/NF-κB signaling pathway [ 159 , 160 ]. Not only that, but resveratrol also confers neuroprotective effects in diabetes-induced peripheral neuropathy by increasing NRF2 expression [ 161 ].…”

Section: Non-flavonoidsmentioning

confidence: 99%

Natural Polyphenols in Metabolic Syndrome: Protective Mechanisms and Clinical Applications

Zhang

et al. 2021

IJMS

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Metabolic syndrome (MetS) is a chronic disease, including abdominal obesity, dyslipidemia, hyperglycemia, and hypertension. It should be noted that the occurrence of MetS is closely related to oxidative stress-induced mitochondrial dysfunction, ectopic fat accumulation, and the impairment of the antioxidant system, which in turn further aggravates the intracellular oxidative imbalance and inflammatory response. As enriched anti-inflammatory and antioxidant components in plants, natural polyphenols exhibit beneficial effects, including improving liver fat accumulation and dyslipidemia, reducing blood pressure. Hence, they are expected to be useful in the prevention and management of MetS. At present, epidemiological studies indicate a negative correlation between polyphenol intake and MetS incidence. In this review, we summarized and discussed the most promising natural polyphenols (including flavonoid and non-flavonoid drugs) in the precaution and treatment of MetS, including their anti-inflammatory and antioxidant properties, as well as their regulatory functions involved in glycolipid homeostasis.

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Resveratrol mitigates pancreatic TF activation and autophagy-mediated beta cell death via inhibition of CXCL16/ox-LDL pathway: A novel protective mechanism against type 1 diabetes mellitus in mice

Cited by 18 publications

References 41 publications

Resveratrol Inhibited ADAM10 Mediated CXCL16-Cleavage and T-Cells Recruitment to Pancreatic β-Cells in Type 1 Diabetes Mellitus in Mice

Resveratrol Inhibited ADAM10 Mediated CXCL16-Cleavage and T-Cells Recruitment to Pancreatic β-Cells in Type 1 Diabetes Mellitus in Mice

Natural polyphenols: a potential prevention and treatment strategy for metabolic syndrome

Natural Polyphenols in Metabolic Syndrome: Protective Mechanisms and Clinical Applications

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