Asperulosidic Acid, a Bioactive Iridoid, Alleviates Placental Oxidative Stress and Inflammatory Responses in Gestational Diabetes Mellitus by Suppressing NF-κB and MAPK Signaling Pathways

Pharmacology ◽  
2022 ◽  
pp. 1-9
Author(s):  
Qian Wu ◽  
Shukun Gai ◽  
Huijie Zhang
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Gestational Diabetes ◽  
Inflammatory Responses ◽  
Serum Insulin ◽  
Mapk Signaling ◽  
Tnf Α ◽  
Mapk Signaling Pathways ◽  
Placental Oxidative Stress

<b><i>Background:</i></b> Asperulosidic acid (ASP) is a bioactive iridoid exerting broad pharmacological and medicinal properties. However, it is still unknown if ASP has therapeutical effects on gestational diabetes mellitus (GDM). This study aims to evaluate the effects of ASP on GDM as well as its underlying mechanism. <b><i>Methods:</i></b> A mouse model of GDM was established and orally administrated ASP (10, 20, and 40 mg/kg) on gestation day (GD) 0. The mice were sacrificed on GD 18. <b><i>Results:</i></b> Blood glucose and serum insulin were then determined. The inflammatory cytokines including IL-6 and TNF-α and oxidative stress biomarkers including MDA, SOD, GSH, and GPx were determined by using specific ELISAs. In addition, the expressions of NF-κB and MAPK signaling pathway-related proteins were determined by using Western blotting. Treatment with ASP decreased blood glucose in the mouse model of GDM. Besides, ASP also increased serum insulin and attenuated β-cell function. Treatment with ASP suppressed IL-6 and TNF-α and regulated oxidative stress-related biomarkers. Western blotting analysis showed that treatment with ASP suppressed phosphorylation of NF-κB p65, ERK1/2, and p38 in placental tissues. <b><i>Conclusion:</i></b> ASP alleviates placental oxidative stress and inflammatory responses in GDM by the inhibition of the NF-κB and MAPK signaling pathways.

scholarly journals Oleuropein alleviates gestational diabetes mellitus by activating AMPK signaling

2020 ◽  
Author(s):  
Zhiwei Zhang ◽  
Hui Zhao ◽  
Aixia Wang
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Body Weight ◽  
Blood Glucose ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Signaling Pathway ◽  
Hepatic Glycogen ◽  
Ampk Signaling ◽  
Tnf Α

Background: Gestational diabetes mellitus (GDM) has a high incidence rate among pregnant women. The objective of the study was to assess the effect of plant-derived oleuropein in attenuating inflammatory and oxidative stress of GDM. Methods: Oleuropein was administered to GDM mice at the doses of 5 or 10 mg/kg/day. Body weight, blood glucose, insulin and hepatic glycogen levels were recorded. To evaluate the effect of oleuropein in reducing oxidative stress, enzyme-linked immunosorbent assay (ELISA) was used to measure the hepatic oxidative stress markers. The inflammation levels of GDM mice were evaluated by measuring serum levels of IL-6 and TNF-α by ELISA, and mRNA levels of IL-1β, TNF-α and IL-6 by real-time PCR (RT-PCR). The AMP-activated protein kinase (AMPK) signaling pathway was assessed by Western blot. Gestational outcome was analyzed through comparing litter size and birth weight. Results: Oleuropein attenuated the elevated body weight of GDM mice, and efficiently reduced blood glucose, insulin and hepatic glycogen levels. Oxidative stress and inflammation were alleviated by oleuropein treatment. The AMPK signaling was activated by oleuropein in GDM mice. Gestational outcome was markedly improved by oleuropein treatment. Conclusions: Our study suggests that oleuropein is effective in alleviating symptoms of GDM and improving gestational outcome in the mouse model. This effect is achieved by attenuating oxidative stress and inflammation, which is mediated by the activation of the AMPK signaling pathway.

Altered Placental Oxidative Stress Status in Gestational Diabetes Mellitus

Placenta ◽  
2004 ◽  
Vol 25 (1) ◽  
pp. 78-84 ◽  
Author(s):  
M.T. Coughlan ◽  
P.P. Vervaart ◽  
M. Permezel ◽  
H.M. Georgiou ◽  
G.E. Rice
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Oxidative Stress Status ◽  
Placental Oxidative Stress

scholarly journals The Effect of Resveratrol on Blood Glucose and Blood Lipids in Rats with Gestational Diabetes Mellitus

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Guanli Zhang ◽  
Xiuli Wang ◽  
Baofeng Ren ◽  
Qiongqiong Zhao ◽  
Fang Zhang
Keyword(s):  
Diabetes Mellitus ◽  
Body Weight ◽  
Insulin Secretion ◽  
Blood Glucose ◽  
Treatment Group ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Blood Lipids ◽  
Metformin Hydrochloride ◽  
Tnf Α

Background. Previous studies have reported that resveratrol has various biological effects such as anti-inflammatory, antioxidant, and antitumor. This study aimed to investigate the effects of resveratrol on blood glucose and blood lipids in rats with gestational diabetes mellitus (GDM). Methods. The rat diabetes model was prepared by one-time intraperitoneal injection of streptozotocin (STZ, 35 mg/kg). Fasting blood glucose was measured by using a blood glucose meter. The ELISA method was used to detect the levels of insulin, leptin, adiponectin, resistin, TNF-α, and IL-6. The content of TC, TG, LDL-C, and HDL-C was determined by using an automatic biochemical detector. Results. Compared with the GDM group, the insulin level in the resveratrol (120 and 240 mg/kg) treatment group was significantly increased. But, the blood glucose level and body weight were significantly reduced. The content of TC, TG, and LDL-C in the resveratrol (240 mg/kg) treatment group was significantly reduced, and the content of HDL-C was significantly increased. In addition, leptin, resistin, TNF-α, and IL-6 levels in the 240 mg/kg resveratrol treatment group were significantly reduced, and adiponectin was significantly increased. Also, resveratrol (240 mg/kg) was stronger than metformin hydrochloride in improving insulin secretion and regulating blood lipids and adipokine content. Conclusion. Resveratrol has a dose-dependent effect on GDM rats to increase insulin secretion, reduce blood glucose and body weight, and regulate blood lipids and plasma adipokines.

scholarly journals Analysis on the Effect of Metformin Hydrochloride Combined with Insulin Pump for Gestational Diabetes Mellitus

2022 ◽  
Author(s):  
Xinghua Li ◽  
Guilian Li ◽  
Yan Liu ◽  
Fanchun Meng ◽  
Lihong Han ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Gestational Diabetes ◽  
Research Group ◽  
Pregnancy Outcomes ◽  
Insulin Pump ◽  
Control Group ◽  
Metformin Hydrochloride ◽  
Tnf Α ◽  
Adverse Pregnancy

Background: U To analyze the effect of metformin hydrochloride combined with insulin pump for gestational diabetes mellitus (GDM). Methods: Overall, 216 patients with GDM in Zhangqiu Maternity and Child Care Hospital, Jinan, China from Aug 2018 to Dec 2020 were enrolled and randomized into research and control groups. Patients in the control group were treated with insulin pump, while those in the research group were treated with metformin hydrochloride combined with insulin pump. The clinical efficacy, blood glucose levels, serum Betatrophin, C reactive protein (CRP), Cystatin C (Cys-C), homocysteine (Hcy), adiponectin, tumor necrosis factor (TNF-α), interleukin-6 (IL-6) content, incidence of adverse pregnancy outcomes and incidence of adverse newborns of patients in the two groups were compared. Results: After treatment, the total clinical efficiency of the research group was 84.26%, significantly higher than that of the control group (68.52%). The levels of FPG, 2hPG, HbAlc, serum Betatrophin, CRP, CysC, Hcy, adiponectin factors, TNF-α, and IL-6 in the research group were lower than those in the control group, with statistically significant differences (P<0.05). The overall incidence of adverse pregnancy outcomes was 10.19% in the research group, and 25.93% in the control group. The comparative differences between the two groups were statistically significant (P<0.05). The overall incidence of adverse newborns was 9.26% in the research group, and 21.30% in the control group. The comparative differences between the two groups were statistically significant as well (P<0.05). Conclusion: Metformin hydrochloride combined with insulin pump for GDM can significantly reduce blood glucose level, regulate serum protein factor levels, and improve adverse outcomes for mother and child, which deserves clinical promotion.   

scholarly journals Activation of the NF-κB and MAPK Signaling Pathways Contributes to the Inflammatory Responses, but Not Cell Injury, in IPEC-1 Cells Challenged with Hydrogen Peroxide

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Kan Xiao ◽  
Congcong Liu ◽  
Zhixiao Tu ◽  
Qiao Xu ◽  
Shaokui Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Signaling Pathways ◽  
Cell Injury ◽  
Inflammatory Responses ◽  
Mapk Signaling ◽  
Intestinal Cell ◽  
Ldh Activity ◽  
Junction Protein ◽  
Mapk Signaling Pathways

Oxidative stress can lead to intestinal cell injury as well as the induction of inflammation. It is not clear whether inflammation is an important factor leading to cell injury caused by oxidative stress. The purpose of this study was to investigate the role of inflammation in intestinal injury caused by hydrogen peroxide (H2O2). Our results revealed that H2O2 stimulation significantly decreased the viability of intestinal porcine epithelial cells (IPEC-1), increased lactate dehydrogenase (LDH) activity, and disrupted the distribution of the tight junction protein claudin-1. H2O2 significantly increased the mRNA expression of interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α). H2O2 stimulation also led to increased phosphorylation of p38 and jun N-terminal kinase (JNK), and p65 NF-κB protein translocation into the nucleus of IPEC-1 cells. Cells treated with the NF-κB inhibitor (BAY11-7082), the p38 inhibitor (SB202190), or the JNK inhibitor (PD98059) significantly decreased mRNA and protein expression of IL-6, IL-8, and TNF-α. However, treatment with mitogen-activated protein kinase (MAPK) or NF-κB inhibitors did not prevent the damage effect on cell viability, LDH activity, or the distribution of claudin-1 in cells challenged with H2O2. In summary, our data demonstrate that activation of the NF-κB and MAPK signaling pathways can contribute to the inflammatory response, but not cell injury, in IPEC-1 cells challenged with H2O2.

scholarly journals Nox4 NADPH oxidase-derived reactive oxygen species, via endogenous carbon monoxide, promote survival of brain endothelial cells during TNF-α-induced apoptosis

2011 ◽  
Vol 300 (2) ◽  
pp. C256-C265 ◽  
Author(s):  
Shyamali Basuroy ◽  
Dilyara Tcheranova ◽  
Sujoy Bhattacharya ◽  
Charles W. Leffler ◽  
Helena Parfenova
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Nadph Oxidase ◽  
Cell Survival ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Tnf Α ◽  
Mapk Signaling Pathways

We investigated the role of reactive oxygen species (ROS) in promoting cell survival during oxidative stress induced by the inflammatory mediator tumor necrosis factor-α (TNF-α) in cerebral microvascular endothelial cells (CMVEC) from newborn piglets. Nox4 is the major isoform of NADPH oxidase responsible for TNF-α-induced oxidative stress and apoptosis in CMVEC. We present novel data that Nox4 NADPH oxidase-derived ROS also initiate a cell survival mechanism by increasing production of a gaseous antioxidant mediator carbon monoxide (CO) by constitutive heme oxygenase-2 (HO-2). TNF-α rapidly enhanced endogenous CO production in a superoxide- and NADPH oxidase-dependent manner in CMVEC with innate, but not with small interfering RNA (siRNA)-downregulated Nox4 activity. CORM-A1, a CO-releasing compound, inhibited Nox4-mediated ROS production and enhanced cell survival in TNF-α-challenged CMVEC. The ROS-induced CO-mediated survival mechanism requires functional interactions between the protein kinase B/Akt and extracellular signal-related kinase (ERK)/p38 MAPK signaling pathways activated by TNF-α. In Akt siRNA-transfected CMVEC and in cells with pharmacologically inhibited Akt, Erk1/2, and p38 mitogen-activated protein kinase (MAPK) activities, CORM-A1 was no longer capable of blocking Nox4 activation and apoptosis caused by TNF-α. Overall, Nox4 NADPH oxidase-derived ROS initiate both death and survival pathways in TNF-α-challenged CMVEC. The ROS-dependent cell survival pathway is mediated by an endogenous antioxidant CO, which inhibits Nox4 activation via a mechanism that includes Akt, ERK1/2, and p38 MAPK signaling pathways. The ability of CO to inhibit TNF-α-induced ERK1/2 and p38 MAPK activities in an Akt-dependent manner appears to be the key element in ROS-dependent survival of endothelial cells during TNF-α-mediated brain inflammatory disease.

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