Dataset Information

The Hypoglycemic and Renal Protection Properties of Crocin via Oxidative Stress-Regulated NF-?B Signaling in db/db Mice.

ABSTRACT: Background:As the main ingredient of Crocus sativus L. (Iridaceae) extract, crocin- I (CR) has been reported to show various pharmacological activities. The aim of this study was to investigate the hypoglycemic and renal protection properties of CR in db/db mice. Methods:Eight-week-old db/db mice were treated with metformin (Met) (100 mg/kg) and CR (50 mg/kg) for eight weeks. Results:CR treatment showed hypoglycemic functions indicated by reduced bodyweight, food and water intake, plasma glucose, and serum levels of glycated hemoglobin A1c. Additionally, the CR group showed increased serum levels of insulin and pyruvate kinase, hypolipidemic functions indicated by the suppressed levels of total cholesterol and triglyceride, and enhanced levels of high-density lipoprotein cholesterol, which are also indicators of hypoglycemic functions. The renal protection function of CR was demonstrated by its protection of renal structures and its regulation of potential indicators of nephropathy. The anti-oxidation and anti-inflammation effects of CR were verified by enzyme-linked immunosorbent assay. In the kidneys of db/db mice, CR decreased the expression of phospho-I?B? and phospho-nuclear factor-?B (NF-?B), whereas it enhanced the expression of nuclear respiratory factor 2, manganese superoxide dismutase 1, heme oxygenase-1, and catalase. Conclusions:The anti-diabetic and anti-diabetic nephritic effects of CR were related to its modulation of oxidative stress-mediated NF-?B signaling.

SUBMITTER: Qiu Y

PROVIDER: S-EPMC7212392 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Hypoglycemic and Renal Protection Properties of Crocin <i>via</i> Oxidative Stress-Regulated NF-κB Signaling in db/db Mice.

Qiu Ye Y Jiang Xue X Liu Danping D Deng Zichun Z Hu Weiwei W Li Zhiping Z Li Yuxin Y

Frontiers in pharmacology 20200430

<h4>Background</h4>As the main ingredient of <i>Crocus sativus L</i>. (Iridaceae) extract, crocin- I (CR) has been reported to show various pharmacological activities. The aim of this study was to investigate the hypoglycemic and renal protection properties of CR in db/db mice.<h4>Methods</h4>Eight-week-old db/db mice were treated with metformin (Met) (100 mg/kg) and CR (50 mg/kg) for eight weeks.<h4>Results</h4>CR treatment showed hypoglycemic functions indicated by reduced bodyweight, food and ...[more]

PMID: 32425787

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Project description:This study investigated the hypoglycemic and renal protective effects of scutellarin (SCU) in db/db mice and elucidated the underlying mechanisms. The oral administration of metformin hydrochloride (Met) at 120?mg/kg and SCU at 25, 50, and 100?mg/kg over an eight-week period had hypoglycemic effects, demonstrated by decreases in body weight, blood glucose, food and water intake, and glycated hemoglobin activity and by augmented insulin levels and pyruvate kinase activity in the serum of db/db mice. SCU alleviated dyslipidemia by decreasing the levels of triglycerides and total cholesterol and enhancing the levels of high-density lipoprotein cholesterol in the serum of db/db mice. SCU reversed the overexpression of mRNA of renal damage markers (receptor for advanced glycation end products, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1), macrophage marker CD11b, and T cell marker CD3 in kidney of db/db mice. Pathological examination confirmed that SCU improved the organ structures of hyperglycemia-damaged livers, kidneys, and pancreas islets. Antibody array assay and enzyme-linked immunosorbent assay were combined to screen and analyze the regulatory effects of SCU on inflammatory factors and oxidative enzymes. SCU exerted anti-inflammatory effects by inhibiting the levels of proinflammatory cytokines (glycogen synthase kinase, intercellular adhesion molecule 2, and interleukin 1? and 2) and promoting anti-inflammatory cytokines (interleukin 4). SCU decreased the reactive oxygen species and malondialdehyde concentrations and increased the activity levels of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and catalase) in serum and kidneys. Furthermore, SCU upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which in turn improved heme oxygenase 1 (HO-1), superoxide dismutase 1 and 2, and catalase expression levels in kidneys. The study showed that SCU has at least partial hypoglycemic and renal protective effects in db/db mice, and the mechanism is the modulation of the Nrf2/HO-1 signaling pathway.

Project description:BackgroundPeople with diabetes mellitus (DM) suffer from multiple chronic complications due to sustained hyperglycemia, especially diabetic cardiomyopathy (DCM). Oxidative stress and inflammatory cells play crucial roles in the occurrence and progression of myocardial remodeling. Macrophages polarize to two distinct phenotypes: M1 and M2, and such plasticity in phenotypes provide macrophages various biological functions.AimTo investigate the effect of atorvastatin on cardiac function of DCM in db/db mice and its underlying mechanisms.MethodsDCM mouse models were established and randomly divided into DM, atorvastatin, and metformin groups. C57BL/6 mice were used as the control. Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson staining was used to examine the morphology and collagen fibers in myocardial tissues. The expression of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β),M1 macrophages (iNOS+), and M2 macrophages (CD206+) were demonstrated by immunohistochemistry and immunofluorescence staining. The levels of TGF-β1, IL-1β, and TNF-α were detected by ELISA and real-time quantitative polymerase chain reaction. Malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) ac-tivities were also measured.ResultsTreatment with atorvastatin alleviated cardiac dysfunction and decreased db/db mice. The broken myocardial fibers and deposition of collagen in the myocardial interstitium were relieved especially by atorvastatin treatment. Atorvastatin also reduced the levels of serum lactate dehydrogenase, creatine kinase isoenzyme, and troponin; lowered the levels of TGF-β1, TNF-α and IL-1β in serum and myocardium; decreased the concentration of MDA and increased SOD activity in myocardium of db/db mice; inhibited M1 macrophages; and promoted M2 macrophages.ConclusionAdministration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated with the antioxidative stress and anti-inflammatory effects of atorvastatin on diabetic myocardium through modulating macrophage polarization.

Dataset Information

The Hypoglycemic and Renal Protection Properties of Crocin via Oxidative Stress-Regulated NF-?B Signaling in db/db Mice.

Publications

The Hypoglycemic and Renal Protection Properties of Crocin <i>via</i> Oxidative Stress-Regulated NF-κB Signaling in db/db Mice.

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