Deep sea minerals ameliorate diabetic‐induced inflammation via inhibition of TNFα signaling pathways

Abstract

It has been well‐documented that the consumption of deep sea water (DSW) has beneficial effects on myocardial hypertrophy and cardiac apoptosis induced by hypercholesterolemia. However, the molecular mechanisms for the anti‐inflammatory effects of DSW on diabetic cardiomyopathy are still largely unclear. The main purpose of this present study was to test the hypothesis that DSW exerts anti‐inflammatory effects through the suppression of the TNF‐α‐mediated signaling pathways. IP injection of streptozotocin (STZ) at the dose of 65 mg/kg was used to establish a diabetes rat model. DSW mineral extracts that diluted in desalinated water were prepared in three different dosages and administered to the rats through gavages for 4 weeks. These dosages are DSW‐1X (equivalent to 37 mg Mg2+/kg/day), 2X (equivalent to 74 mg Mg2+/kg/day) and 3X (equivalent to 111 mg Mg2+ mg/kg/day). Immunofluorescence staining and Western blot showed that the protein expression level of TNF‐α was markedly higher in the STZ‐induced diabetic rat hearts than in the control group. Consequently, the phosphorylation levels of the TNF‐α‐modulated downstream signaling molecules and P38 mitogen‐activated protein kinases (MAPKs) were notably elevated in heart tissues of STZ‐induced diabetes. These higher phosphorylation levels subsequently upregulated NF‐κB‐modulated inflammatory mediators, such as cyclooxygenase (COX)‐II and inducible nitric oxide synthase (iNOS). However, treatment with DSW as well as MgSO4, the main mineral in DSW, significantly reversed all the alterations. These findings suggest that DSW has potential as a therapeutic agent for preventing diabetes‐related cardiovascular diseases.

Securidaca inappendiculata Polyphenol Rich Extract Counteracts Cognitive Deficits, Neuropathy, Neuroinflammation and Oxidative Stress in Diabetic Encephalopathic Rats via p38 MAPK/Nrf2/HO-1 Pathways

“…The mitogen-activated protein kinase (MAPK) pathway has been linked to a number of pathogenic responses including inflammation and oxidative stress. Supporting evidences have shown that MAPK signaling pathways are critically involved in the pathogenesis of several diabetic complications ( Lu et al, 2020 ). Specifically, MAPK p38 pathway has been reported to be activated in diabetes ( Ma et al, 2015 ; Zhao et al, 2021 ).…”

Luteolin/ZnO nanoparticles attenuate neuroinflammation associated with diabetes via regulating MicroRNA‐124 by targeting C/EBPA

“…55 It has been believed that miR-124-mediated reductions in USP 2 and 14 led to enhanced ubiquitination of vesicle extracellular vesicles, resulting in vesicle fusion with lysosomes and TNF-degradation. 56 Because both C/EBP-α and TNF-α are M1 polarization transcription factors, we hypothesized that miR-124 reduced inflammation by inhibiting C/EBP-α, which in turn inhibited TNF-α. 57 Similarly, the delivery of L/ZnONPs resulted in MiR-124 activation and, consequently, suppression of inflammation and C/EBP mRNA expression.…”

“…MiR‐124 was found to reduce apoptosis and alleviate renal lesions in the diabetic nephropathy rat model 55 . It has been believed that miR‐124‐mediated reductions in USP 2 and 14 led to enhanced ubiquitination of vesicle extracellular vesicles, resulting in vesicle fusion with lysosomes and TNF‐degradation 56 . Because both C/EBP‐α and TNF‐α are M1 polarization transcription factors, we hypothesized that miR‐124 reduced inflammation by inhibiting C/EBP‐α, which in turn inhibited TNF‐α 57 .…”

Research on active compounds regarding SGMD for the treatment of COVID-19 based on network pharmacology and molecular docking

“…The AGE-RAGE signaling pathway reacts on cell activation and tissue damage and has the activity of promoting the expression and release of in ammatory factors [35]. The TNF and IL-17 signaling pathways also play a crucial part in the occurrence and development of in ammation [26,36,37].…”