Ameliorative effect of dietary genistein on diabetes induced hyper-inflammation and oxidative stress during early stage of wound healing in alloxan induced diabetic mice

Dysfunction of macrophages (MΦs) in diabetic wounds impairs the healing. MΦs produce anti-inflammatory and pro-resolving neuroprotectin/protectin D1 (NPD1/PD1, 10 R,17 S-dihydroxy-docosa-4 Z,7 Z,11 E,13 E,15 Z,19 Z-hexaenoic acid); however, little is known about endogenous NPD1 biosynthesis by MΦs and the actions of NPD1 on diabetic MΦ functions in diabetic wound healing. We used an excisional skin wound model of diabetic mice, MΦ depletion, MΦs isolated from diabetic mice, and mass spectrometry-based targeted lipidomics to study the time course progression of NPD1 levels in wounds, the roles of MΦs in NPD1 biosynthesis, and NPD1 action on diabetic MΦ inflammatory activities. We also investigated the healing, innervation, chronic inflammation, and oxidative stress in diabetic wounds treated with NPD1 or NPD1-modulated MΦs from diabetic mice. Injury induced endogenous NPD1 biosynthesis in wounds, but diabetes impeded NPD1 formation. NPD1 was mainly produced by MΦs. NPD1 enhanced wound healing and innervation in diabetic mice and promoted MΦs functions that accelerated these processes. The underlying mechanisms for these actions of NPD1 or NPD1-modulated MΦs involved 1) attenuating MΦ inflammatory activities and chronic inflammation and oxidative stress after acute inflammation in diabetic wound, and 2) increasing MΦ production of IL10 and hepatocyte growth factor. Taken together, NPD1 appears to be a MΦs-produced factor that accelerates diabetic wound healing and promotes MΦ pro-healing functions in diabetic wounds. Decreased NPD1 production in diabetic wound is associated with impaired healing. This study identifies a new molecular target that might be useful in development of more effective therapeutics based on NPD1 and syngeneic diabetic MΦs for treatment of diabetic wounds.

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Coptisine Attenuates Diabetes—Associated Endothelial Dysfunction through Inhibition of Endoplasmic Reticulum Stress and Oxidative Stress

Molecules ◽

10.3390/molecules26144210 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4210

Author(s):

Yan Zhou ◽

Chunxiu Zhou ◽

Xutao Zhang ◽

Chi Teng Vong ◽

Yitao Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Risk Factors ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Vascular Function ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Ex Vivo ◽

Diabetic Mice ◽

And Oxidative Stress

Coptisine is the major bioactive protoberberine alkaloid found in Rhizoma Coptidis. Coptisine reduces inflammatory responses and improves glucose tolerance; nevertheless, whether coptisine has vasoprotective effect in diabetes is not fully characterized. Conduit arteries including aortas and carotid arteries were obtained from male C57BL/6J mice for ex vivo treatment with risk factors (high glucose or tunicamycin) and coptisine. Some arterial rings were obtained from diabetic mice, which were induced by high-fat diet (45% kcal% fat) feeding for 6 weeks combined with a low-dose intraperitoneal injection of streptozotocin (120 mg/kg). Functional studies showed that coptisine protected endothelium-dependent relaxation in aortas against risk factors and from diabetic mice. Coptisine increased phosphorylations of AMPK and eNOS and downregulated the endoplasmic reticulum (ER) stress markers as determined by Western blotting. Coptisine elevates NO bioavailability and decreases reactive oxygen species level. The results indicate that coptisine improves vascular function in diabetes through suppression of ER stress and oxidative stress, implying the therapeutic potential of coptisine to treat diabetic vasculopathy.

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One Week of CDAHFD Induces Steatohepatitis and Mitochondrial Dysfunction with Oxidative Stress in Liver

International Journal of Molecular Sciences ◽

10.3390/ijms22115851 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5851

Author(s):

Takehito Sugasawa ◽

Seiko Ono ◽

Masato Yonamine ◽

Shin-ichiro Fujita ◽

Yuki Matsumoto ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

High Fat Diet ◽

Early Stage ◽

Droplet Deposition ◽

Nonalcoholic Fatty Liver ◽

Stress Markers ◽

Mitochondrial Dna Copy Number ◽

Short Period ◽

And Oxidative Stress

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increasing worldwide. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has been used to create a mouse model of nonalcoholic steatohepatitis (NASH). There are some reports on the effects on mice of being fed a CDAHFD for long periods of 1 to 3 months. However, the effect of this diet over a short period is unknown. Therefore, we examined the effect of 1-week CDAHFD feeding on the mouse liver. Feeding a CDAHFD diet for only 1-week induced lipid droplet deposition in the liver with increasing activity of liver-derived enzymes in the plasma. On the other hand, it did not induce fibrosis or cirrhosis. Additionally, it was demonstrated that CDAHFD significantly impaired mitochondrial respiration with severe oxidative stress to the liver, which is associated with a decreasing mitochondrial DNA copy number and complex proteins. In the gene expression analysis of the liver, inflammatory and oxidative stress markers were significantly increased by CDAHFD. These results demonstrated that 1 week of feeding CDAHFD to mice induces steatohepatitis with mitochondrial dysfunction and severe oxidative stress, without fibrosis, which can partially mimic the early stage of NASH in humans.

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Folic Acid Promotes Wound Healing in Diabetic Mice by Suppression of Oxidative Stress

Journal of Nutritional Science and Vitaminology ◽

10.3177/jnsv.64.26 ◽

2018 ◽

Vol 64 (1) ◽

pp. 26-33 ◽

Cited By ~ 3

Author(s):

Mei ZHAO ◽

Jun ZHOU ◽

Yuan-hua CHEN ◽

Li YUAN ◽

Man-man YUAN ◽

...

Keyword(s):

Oxidative Stress ◽

Wound Healing ◽

Folic Acid ◽

Diabetic Mice

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Ameliorative Effect of the Flavonoid Rich Fraction of Monodora myristica (Gaertn) Dunel Seed Extract against Carbon Tetrachloride-Induced Hepatotoxicity and Oxidative Stress in Rats

Biochemistry & Pharmacology Open Access ◽

10.4172/2167-0501.1000232 ◽

2017 ◽

Vol 06 (03) ◽

Author(s):

Ekeanyanwu Raphael Chukwuma ◽

Jeremiah Goodness Chiamaka

Keyword(s):

Oxidative Stress ◽

Carbon Tetrachloride ◽

Seed Extract ◽

Ameliorative Effect ◽

Monodora Myristica ◽

And Oxidative Stress

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Effect of Dietary Conjugated Linoleic Acid Supplementation on Early Inflammatory Responses during Cutaneous Wound Healing

Mediators of Inflammation ◽

10.1155/2010/342328 ◽

2010 ◽

Vol 2010 ◽

pp. 1-8 ◽

Cited By ~ 18

Author(s):

Na-Young Park ◽

Giuseppe Valacchi ◽

Yunsook Lim

Keyword(s):

Oxidative Stress ◽

Wound Healing ◽

Linoleic Acid ◽

Conjugated Linoleic Acid ◽

Wound Closure ◽

Inflammatory Responses ◽

Early Stage ◽

Cutaneous Wound Healing ◽

Cutaneous Wound ◽

Anti Inflammatory

Inflammatory response is considered the most important period that regulates the entire healing process. Conjugated linoleic acid (CLA), a class of linoleic acid positional and geometric isomers, is well known for its antioxidant and anti-inflammatory properties. We hypothesized that dietary CLA supplementation accelerates cutaneous wound healing by regulating antioxidant and anti-inflammatory functions. To investigate wound closure rates and inflammatory responses, we used a full-thickness excisional wound model after 2-week treatments with control, 0.5%, or 1% CLA-supplemented diet. Mice fed dietary CLA supplementation had reduced levels of oxidative stress and inflammatory markers. Moreover, the wound closure rate was improved significantly in mice fed a 1% CLA-supplemented diet during early stage of wound healing (inflammatory stage). We conclude that dietary CLA supplementation enhances the early stage of cutaneous wound healing as a result of modulating oxidative stress and inflammatory responses.

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