scholarly journals Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 582 ◽  
Author(s):  
Jeremy C. Sprouse ◽  
Chethan Sampath ◽  
Pandu R. Gangula
Keyword(s):  
Nitric Oxide ◽  
Gastric Emptying ◽  
Mitogen Activated Protein Kinase ◽  
Related Factor ◽  
Metabolic Homeostasis ◽  
Ovariectomized Mice ◽  
Mitogen Activated Protein ◽  
17Β Estradiol ◽  
Oxide Synthase

Gastroparesis (Gp) is a multifactorial condition commonly observed in females and is characterized by delayed or rapid gastric emptying (GE). The role of ovarian hormones on GE in the pathogenesis of obesity induced type 2 diabetes mellitus (T2DM) is completely unknown. The aims of our study are to investigate whether supplementation of 17β-estradiol (E2) or progesterone (P4) restores impaired nuclear factor erythroid 2-related factor 2 (Nrf2, an oxidative stress-responsive transcription factor) and nitric oxide (NO)-mediated gastric motility in ovariectomized (OVX) mice consuming a high-fat diet (HFD, a model of T2DM). Groups of OVX+HFD mice were administered daily subcutaneous doses of either E2 or P4 for 12 weeks. The effects of E2 and P4 on body weight, metabolic homeostasis, solid GE, gastric antrum NO-mediated relaxation, total nitrite levels, neuronal nitric oxide synthase (nNOSα), and its cofactor expression levels were assessed in OVX+HFD mice. HFD exacerbated hyperglycemia and insulinemia while accelerating GE (p < 0.05) in OVX mice. Exogenous E2, but not P4, attenuated rapid gastric emptying and restored gastric nitrergic relaxation, total nitrite levels, nNOSα, and cofactor expression via normalizing Nrf2-Phase II enzymes, inflammatory response, and mitogen-activated protein kinase (MAPK) protein expression in OVX+HFD mice. We conclude that E2 is beneficial in normalizing metabolic homeostasis and gastric emptying in obese, diabetic OVX mice consuming a fat-rich diet.

scholarly journals Angelicae Gigantis Radix Regulates LPS-Induced Neuroinflammation in BV2 Microglia by Inhibiting NF-κB and MAPK Activity and Inducing Nrf-2 Activity

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3755 ◽  
Author(s):  
You-Chang Oh ◽  
Yun Hee Jeong ◽  
Wei Li ◽  
Younghoon Go
Keyword(s):  
Nitric Oxide ◽  
High Performance ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Factors ◽  
Related Factor ◽  
Nuclear Factor ◽  
Mapk Activity ◽  
Mitogen Activated Protein ◽  
Bv2 Microglia ◽  
Oxide Synthase

Angelicae Gigantis Radix (AGR) has been widely used as a traditional medicine in East Asia. The effects of AGR on neuroinflammation have not previously been studied in detail. In the study presented here, we investigated the antineuroinflammatory properties of this herb and its mechanism of operation. The effects of AGR on neuroinflammation were studied by measuring the production of inflammatory factors and related enzymes, and analyzing the expression levels of proteins and genes involved its activity, in lipopolysaccharide (LPS)-stimulated BV2 microglia. We found that AGR pretreatment strongly inhibits the production of nitric oxide (NO), cytokines, and the enzymes inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2, and effectively induces the activation of heme oxygenase (HO)-1 and its regulator, nuclear factor erythroid 2-related factor 2 (Nrf-2). We also found that AGR effectively regulates the activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK). We confirmed the antineuroinflammatory effects of the main constituents of the plant as identified by high-performance liquid chromatography (HPLC). Our results indicate that the neuroinflammation inhibitory activity of AGR occurs through inhibition of NF-κB and MAPK and activation of Nrf-2.

Molecular targets of nitric-oxide-donating aspirin in cancer

2005 ◽  
Vol 33 (4) ◽  
pp. 701-704 ◽  
Author(s):  
K. Kashfi ◽  
B. Rigas
Keyword(s):  
Nitric Oxide ◽  
Cell Signalling ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Inhibition Of Proliferation ◽  
Mitogen Activated Protein ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase

Nitric-oxide-donating aspirin (NO-ASA), consisting of ASA (aspirin) plus an -ONO2 moiety linked to it via a molecular spacer, is a new drug for cancer prevention. NO-ASA seems to overcome the low potency and toxicity of traditional ASA. The -ONO2 moiety is responsible for releasing NO, and it appears to be required for biological activity. In studies in vitro, NO-ASA inhibits the growth of colon, pancreatic, prostate, lung, skin, leukaemia and breast cancer cells, and is up to 6000-fold more potent than traditional ASA. This effect is owing to cell kinetics [inhibition of proliferation, induction of apoptosis (multiple criteria) and blocking the G1 to S cell-cycle transition] and cell signalling [inhibition of Wnt signalling (IC50=0.2 μM), inhibition of NF-κB (nuclear factor κB) activation (IC50=7.5 μM), inhibition of nitric oxide synthase-2 expression (IC50=48 μM), inhibition of MAPK (mitogen-activated protein kinase) signalling (IC50=10 μM) and induction of cyclo-oxygenase-2 at approx. 10 μM]. In studies in vivo, NO-ASA inhibits intestinal carcinogenesis in Min mice (tumour multiplicity was reduced by 59% after 3 weeks, with no effect in control animals and no side effects) and in the N-nitrosobis(2-oxopropyl)amine model of pancreatic cancer, where there was an 89% reduction in NO-ASA (3000 p.p.m. in the diet)-treated animals (P<0.001). There was no statistically significant effect by traditional ASA at equimolar doses. Our data indicate that NO-ASA is a highly promising agent for the prevention and/or treatment of cancer.

scholarly journals Role of Resveratrol in Regulating Cutaneous Functions

2020 ◽  
Vol 2020 ◽  
pp. 1-20 ◽  
Author(s):  
Si Wen ◽  
Jiechen Zhang ◽  
Bin Yang ◽  
Peter M. Elias ◽  
Mao-Qiang Man
Keyword(s):  
Protective Role ◽  
The Body ◽  
Sirtuin 1 ◽  
Mitogen Activated Protein Kinase ◽  
Keratinocyte Differentiation ◽  
Related Factor ◽  
Keratinocyte Proliferation ◽  
Mitogen Activated Protein ◽  
Peptide Expression

Protective role of the skin is against external insults and maintenance of electrolyte homeostasis of the body. Cutaneous dysfunction can account for the development of both cutaneous and systemic disorders. Thus, improvements in cutaneous functions can benefit a number of extracutaneous and cutaneous functions. Resveratrol, a natural ingredient, displays multiple benefits for various systems/organs, including the skin. The benefits of resveratrol for cutaneous functions include stimulation of keratinocyte differentiation and antimicrobial peptide expression, inhibition of keratinocyte proliferation and cutaneous inflammation, UV protection, anticancer, antiaging, and inhibition of melanogenesis. The mechanisms of action of resveratrol include activation of sirtuin 1 and nuclear factor erythroid 2-related factor 2, and inhibition of mitogen-activated protein kinase signaling. Evidence suggests that topical resveratrol could be a valuable alternative not only for daily skin care, but also for the prevention and treatment of various cutaneous disorders. This review summarizes the benefits of resveratrol for cutaneous functions.

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