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Geniposide Combined With Notoginsenoside R1 Attenuates Inflammation and Apoptosis in Atherosclerosis via the AMPK/mTOR/Nrf2 Signaling Pathway.

ABSTRACT: Inflammation and apoptosis of vascular endothelial cells play a key role in the occurrence and development of atherosclerosis (AS), and the AMPK/mTOR/Nrf2 signaling pathway plays an important role in alleviating the symptoms of AS. Geniposide combined with notoginsenoside R1 (GN combination) is a patented supplement for the prevention and treatment of AS. It has been proven to improve blood lipid levels and inhibit the formation of AS plaques; however, it is still unclear whether GN combination can inhibit inflammation and apoptosis in AS by regulating the AMPK/mTOR/Nrf2 signaling pathway and its downstream signals. Our results confirmed that the GN combination could improve blood lipid levels and plaque formation in ApoE ^-/- mice fed with a high-fat diet (HFD), inhibit the secretion of serum inflammatory factors and oxidative stress factors. It also decreased the expression of pyrin domain containing protein 3 (NLRP3) inflammasome-related protein and Bax/Bcl2/caspase-3 pathway-related proteins. At the same time, the GN combination could also inhibit the H₂O₂-induced inflammatory response and apoptosis of human umbilical vein endothelial cells (HUVECs), which is mainly related to the activation of the AMPK/mTOR pathway by GN combination, which in turn induces the activation of Nrf2/HO-1 signal. In addition, the above phenomenon could be significantly reversed by dorsomorphin. Therefore, our experiments proved for the first time that the GN combination can effectively inhibit AS inflammation and apoptosis by activating the AMPK/mTOR/Nrf2 signaling pathway to inhibit the NLRP3 inflammasome and Bax/Bcl2/caspase-3 pathway.

SUBMITTER: Liu X

PROVIDER: S-EPMC8293676 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Geniposide alleviates non-alcohol fatty liver disease via regulating Nrf2/AMPK/mTOR signalling pathways.

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2022-08-12 | PXD032814 | Pride

Notoginsenoside R1 attenuates cardiac dysfunction in endotoxemic mice: an insight into oestrogen receptor activation and PI3K/Akt signalling.

Project description:BACKGROUND AND PURPOSE: Notoginsenoside R1 (NG-R1), a novel phytoestrogen isolated from Panax notoginseng, is believed to have anti-inflammatory, anti-oxidative and anti-apoptotic properties. However, its cardioprotective properties and underlying mechanisms are largely unknown. Here we have assessed the contribution of the anti-inflammatory effects of NG-R1 to the amelioration of septic cardiac dysfunction and inflammation in mice. EXPERIMENTAL APPROACH: We assessed cardiac function in mice by echocardiography. We studied the protein or mRNA levels of some inflammatory factors, apoptotic factors and oestrogen receptors (ERs) in heart tissues upon stimulation with bacterial LPS, NG-R1 or some pharmacological inhibitors. KEY RESULTS: Six hours after LPS administration (10 mg·kg(-1) , i.p.) cardiac function was decreased, an effect attenuated by NG-R1 pretreatment (25 mg·kg(-1) ·d(-1) , i.p.). NG-R1 also improved the imbalance between iNOS and eNOS, prevented activation of NF-?B and the subsequent myocardial inflammatory and apoptotic responses in endotoxemic mice. The effects of NG-R1 were closely associated with activation of the oestrogen receptor ER? and of PI3K/PKB (Akt) signalling, as characterized by NG-R1-induced preservation in ER?, phospho-Akt, phospho-GSK3? and I-?B?, and of cardiac function that was partially blocked by selective inhibitors of ER? or PI3K. However, NG-R1 had no effect on LPS-activated TLR-4. CONCLUSIONS AND IMPLICATIONS: NG-R1 is a promising compound for protecting the heart from septic shock, possibly via the activation of ER? and PI3K/Akt signalling. This mechanism produces blockade of NF-?B activation and attenuation of the pro-inflammatory state and apoptotic stress in the myocardium.

| S-EPMC3605881 | biostudies-other

Notoginsenoside R1 Ameliorates Diabetic Retinopathy through PINK1-Dependent Activation of Mitophagy.

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