Naringenin improves insulin sensitivity in gestational diabetes mellitus mice through AMPK

Li, Sen; Zhang, Yan; Sun, Yewu; Zhang, Guangzhen; Bai, Jie; Guo, Junkang; Su, Xudong; Du, Hongquan; Cao, Xi; Yang, Jin-Kui; Wang, Ting

doi:10.1038/s41387-019-0095-8

Cited by 77 publications

(47 citation statements)

References 37 publications

(38 reference statements)

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“…To explore the molecular mechanism of oleuropein in the treatment of GDM, we focused on the AMPK signaling pathway. A number of studies have employed AMPK as a target to treat GDM (21)(22)(23). Our data are consistent with previous findings demonstrating that GDM is characterized by suppressed AMPK signaling in the liver, and oleuropein was capable of reactivating AMPK signaling (24).…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies have also implicated the link between AMPK suppression and reduced glucose uptake (20), which is a contributing factor to hyperglycemia. A number of studies have employed AMPK as a target to treat GDM (21)(22)(23). Given the important role of AMPK in GDM and the potential of oleuropein in re-activating AMPK signaling, as suggested by a previous study (24), a comprehensive evaluation of the effects of oleuropein in alleviating symptoms of GDM is warranted.…”

Section: Introductionmentioning

confidence: 99%

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Oleuropein alleviates gestational diabetes mellitus by activating AMPK signaling

Zhang

Zhao

Wang

2021

Endocrine Connections

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Oleuropein alleviates gestational diabetes mellitus by activating AMPK signaling

Zhang

Zhao

Wang

2021

Endocrine Connections

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“…Mogroside, extracted from the natural plant Siraitia grosvenorii, could also alleviate GDM through the activation of the AMPK signalling pathway 8 . Besides, naringenin and curcumin were reported to improve insulin sensitivity and ameliorate symptoms in GDM mice through the AMPK pathway 16,17 . Moreover, Astragaloside IV, which is extracted from Astragalus membranaceus, inhibited the NLR family pyrin domain containing‐3 (NLRP3) inflammasome to protect against GDM 18 .…”

Section: Discussionmentioning

confidence: 99%

“…8 Besides, naringenin and curcumin were reported to improve insulin sensitivity and ameliorate symptoms in GDM mice through the AMPK pathway. 16,17 Moreover, Astragaloside IV, which is extracted from Astragalus membranaceus, inhibited the NLR family pyrin domain containing-3 (NLRP3) inflammasome to protect against GDM. 18 All these reports suggest the potential of phytochemicals as alternative agents with potential therapeutic efficacy for GDM treatment.…”

Section: Discussionmentioning

confidence: 99%

Dendrobine attenuates gestational diabetes mellitus in mice by inhibiting Th17 cells

Feng

Jia

Feng³

et al. 2020

Basic Clin Pharma Tox

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Gestational diabetes mellitus (GDM) is a common disease in pregnant women with a prevalence from 1.4% to 14% based on the population studied. The number of patients with GDM is increasing annually, and yet, the treatment for GDM remains limited. In this study, we aimed to explore the potential of dendrobine against GDM. For this purpose, a genetic mouse model of GDM was established. GDM mice were orally administered with 20 mg/kg dendrobine daily from the beginning of pregnancy to delivery. It was found that dendrobine significantly ameliorated the symptoms of GDM, as evidenced by reduced maternal body‐weight and blood glucose levels, as well as increased insulin levels and insulin sensitivity in GDM mice. Dendrobine also remarkably attenuated the impairments to offspring, such as decreased birth‐weight and birth size. Moreover, dendrobine reduced the secretion of inflammatory cytokines by T helper 17 (Th17) cells, including interleukin‐1β, interleukin‐6, tumour necrosis factor‐α and interleukin‐17. Furthermore, we found that dendrobine also reduced the population of Th17 cells in GDM mice. In conclusion, dendrobine could effectively alleviate GDM in mice and might serve as a potential therapeutic drug candidate for GDM patients.

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“…In addition, researchers have administered NIN (1% and 3% in diet) to mice with gestational diabetes mellitus symptoms and found that NIN and NRG significantly decreased TNF-α-induced ROS production, enhanced glucose transporter type 4 (GLUT4) membrane translocation, inhibited inflammation in the liver and improved diabetes. These effects were abrogated when AMPK was inhibited, thereby suggesting a potential role of AMPK activation in NIN (50 μg/ml)-induced anti-inflammation effects [ 88 ]. Further studies are required to elucidate the mechanisms underlying the anti-inflammation activities of NIN in addition to its anti-oxidative stress properties.…”

Section: Pharmacological Effects Of Flavonoids From Afi and Af In LIVmentioning

confidence: 99%

Flavonoids from Aurantii Fructus Immaturus and Aurantii Fructus: promising phytomedicines for the treatment of liver diseases

Huang

2020

Chin Med

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Background: Liver diseases and related complications are major sources of morbidity and mortality, which places a huge financial burden on patients and lead to nonnegligible social problems. Therefore, the discovery of novel therapeutic drugs for the treatment of liver diseases is urgently required. Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF) are frequently used herbal medicines in traditional Chinese medicine (TCM) formulas for the treatment of diverse ailments. A variety of bioactive ingredients have been isolated and identified from AFI and AF, including alkaloids, flavonoids, coumarins and volatile oils. Main body: Emerging evidence suggests that flavonoids, especially hesperidin (HD), naringenin (NIN), nobiletin (NOB), naringin (NRG), tangeretin (TN), hesperetin (HT) and eriodictyol (ED) are major representative bioactive ingredients that alleviate diseases through multi-targeting mechanisms, including anti-oxidative stress, anti-cytotoxicity, anti-inflammation, anti-fibrosis and anti-tumor mechanisms. In the current review, we summarize the recent progress in the research of hepatoprotective effects of HD, NIN, NOB, NRG, TN, HT and ED and highlight the potential underlying molecular mechanisms. We also point out the limitations of the current studies and shed light on further in-depth pharmacological and pharmacokinetic studies of these bioactive flavonoids. Conclusion: This review outlines the recent advances in the literature and highlights the potential of these flavonoids isolated from AFI and AF as therapeutic agents for the treatment of liver diseases. Further pharmacological studies will accelerate the development of natural products in AFI and AF and their derivatives as medicines with tantalizing prospects in the clinical application.

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Naringenin improves insulin sensitivity in gestational diabetes mellitus mice through AMPK

Cited by 77 publications

References 37 publications

Oleuropein alleviates gestational diabetes mellitus by activating AMPK signaling

Oleuropein alleviates gestational diabetes mellitus by activating AMPK signaling

Dendrobine attenuates gestational diabetes mellitus in mice by inhibiting Th17 cells

Flavonoids from Aurantii Fructus Immaturus and Aurantii Fructus: promising phytomedicines for the treatment of liver diseases

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