Lycopsamine Attenuates Diabetes Mellitus via The Nuclear Factor Kappa B-Induced 5′ Adenosine Monophosphate-Activated Protein Kinase Signal Pathway

Diabetes mellitus is a metabolic disorder characterized by inflammation, abnormal glycolipid metabolism, insulin resistance, and mitochondrial dysfunction leading to hyperglycemia. The aim of the present investigation was to determine the efficacy of lycopsamine in a rat model of diabetes mellitus to understand its mechanism. Lycopsamine treatment markedly lowered the level of total cholesterol, triglyceride, nonesterified fatty acids, and low-density lipoprotein in diabetic rats. There was also a reduction in interleukin-6, interleukin-10, C-reactive protein, and tumor necrosis factor-α levels. Lycopsamine treatment normalized the metabolism of lipid and glucose, insulin resistance, and body weight of diabetic rats. Findings of immunohistochemical analyses exhibited rise in precipitation of immunocytes in renal cells. Results potentially demonstrated that lycopsamine treatment remarkably reduced the nuclear factor-kappa B level and enhanced the 5′ adenosine monophosphate-activated protein kinase expression. Altogether, administration of lycopsamine suppressed the expression of inflammatory cytokines and attenuated the metabolic symptoms in diabetes mellitus experimental rats.

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Metformin augments doxorubicin cytotoxicity in mammary carcinoma through activation of adenosine monophosphate protein kinase pathway

Tumor Biology ◽

10.1177/1010428317692235 ◽

2017 ◽

Vol 39 (5) ◽

pp. 101042831769223 ◽

Cited By ~ 14

Author(s):

Nahla E El-Ashmawy ◽

Naglaa F Khedr ◽

Hoda A El-Bahrawy ◽

Hend E Abo Mansour

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Protein Kinase ◽

Cyclin D1 ◽

Nuclear Factor Kappa B ◽

Adenosine Monophosphate ◽

Ehrlich Carcinoma ◽

Nuclear Factor ◽

Nuclear Factor Kappa ◽

Solid Ehrlich Carcinoma

Since the incidence of breast cancer increases dramatically all over the world, the search for effective treatment is an urgent need. Metformin has demonstrated anti-tumorigenic effect both in vivo and in vitro in different cancer types. This work was designed to examine on molecular level the mode of action of metformin in mice bearing solid Ehrlich carcinoma and to evaluate the use of metformin in conjunction with doxorubicin as a combined therapy against solid Ehrlich carcinoma. Ehrlich ascites carcinoma cells were inoculated in 60 female mice as a model of breast cancer. The mice were divided into four equal groups: Control tumor, metformin, doxorubicin, and co-treatment. Metformin (15 mg/kg) and doxorubicin (4 mg/kg) were given intraperitoneally (i.p.) for four cycles every 5 days starting on day 12 of inoculation. The anti-tumorigenic effect of metformin was mediated by enhancement of adenosine monophosphate protein kinase activity and elevation of P53 protein as well as the suppression of nuclear factor-kappa B, DNA contents, and cyclin D1 gene expression. Metformin and doxorubicin mono-treatments exhibited opposing action regarding cyclin D1 gene expression, phosphorylated adenosine monophosphate protein kinase, and nuclear factor-kappa B levels. Co-treatment markedly decreased tumor volume, increased survival rate, and improved other parameters compared to doxorubicin group. In parallel, the histopathological findings demonstrated enhanced apoptosis and absence of necrosis in tumor tissue of co-treatment group. Metformin proved chemotherapeutic effect which could be mediated by the activation of adenosine monophosphate protein kinase and related pathways. Combining metformin and doxorubicin, which exhibited different mechanisms of action, produced greater efficacy as anticancer therapeutic regimen.

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Studies on the Antidiabetic and Antinephritic Activities ofPaecilomyces hepialiWater Extract in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats

Journal of Diabetes Research ◽

10.1155/2016/4368380 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 14

Author(s):

Juan Wang ◽

Lirong Teng ◽

Yange Liu ◽

Wenji Hu ◽

Wenqi Chen ◽

...

Keyword(s):

Nuclear Factor Kappa B ◽

Interleukin 2 ◽

Water Extract ◽

Interleukin 10 ◽

Diabetic Rats ◽

Diabetic Rat ◽

Nuclear Factor ◽

Sprague Dawley ◽

Nuclear Factor Kappa ◽

Paecilomyces Hepiali

Paecilomyces hepialiis a fungus widely used in Asian countries for various potential pharmacological activities. The present study aims to evaluate the antidiabetic and antinephritic effects of thePaecilomyces hepialimycelium water extract (PHC) in diabetic rat, which is established by eight-week high-fat diet administration followed by one-week tail intravenous injection of 25 mg/kg streptozotocin (STZ). After four-week 0.12 g/kg metformin and PHC at doses of 0.08, 0.4, and 2.0 g/kg treatment, an increment of body weight, a decrement of plasma glucose, low levels of total cholesterol, and low density lipoprotein cholesterol in diabetic rats were observed. PHC promotes glucose metabolism by enhancing insulin, pyruvate kinase activity, and increasing the synthesis of glycogen. PHC normalized the disturbed levels of superoxide dismutase, methane dicarboxylic aldehyde, and glutathione peroxidase in kidney. The inhibitory effects on the levels of interleukin-2, interleukin-6, interleukin-10, and tumor necrosis factor-αin serum and kidney revealed the protection of PHC against diabetic nephropathy. Compared with nontreated diabetic rats, four-week PHC treatment resulted in a decrement on nuclear factor kappa B expression in kidney. These results show thatPaecilomyces hepialipossesses antidiabetic and antinephritic effects which are related to the modulation of nuclear factor kappa B activity.

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