Notoginsenoside R1 activates the Ang2/Tie2 pathway to promote angiogenesis

Zhong, Jincheng; Lu, Weijin; Zhang, Jiayan; Huang, Maohua; Lyu, Wen-Yu; Ye, Geni; Deng, Lijuan; Chen, Minfeng; Yao, Nan; Li, Yong; Liu, Guanping; Liang, Yunfei; Fu, Jingwen; Zhang, Dongmei; Ye, Wen‐Cai

doi:10.1016/j.phymed.2020.153302

Cited by 21 publications

(14 citation statements)

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“…Notoginsenoside R1 (NR) is a characteristic component of traditional Chinese medicine Panax notoginseng, which have been clinically used to treat cardiovascular and cerebral vascular diseases in China due to its good effect in controlling internal and external bleeding, improving blood stasis and reducing blood pressure ( Wang et al, 2016 ; Yang et al, 2020 ). Numerous studies have reported that notoginsenoside R1 can inhibit inflammation, apoptosis and oxidative stress and promote angiogenesis ( Jia et al, 2014 ; Zhao et al, 2020 ; Zhong et al, 2020 ). Therefore, GP and NR can alleviate the occurrence and development of AS.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

Cheng

et al. 2021

Front. Pharmacol.

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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.

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Section: Introductionmentioning

confidence: 99%

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

Liu

Cheng

et al. 2021

Front. Pharmacol.

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“…Vinylstannane 25 can be coupled with 2-iodomethylacrylate under non-basic conditions to deliver des-hydroxy-isolindenatriene (26b). Liu claims to have formed lindenatriene itself by lactone ring opening of 24 with methoxide; however, the compound which Liu assigns as des-hydroxylindenatriene (26a) produces 1 H and 13 C NMR spectra matching Snyder and Eagan's deshydroxy-iso-lindenatriene exactly.…”

Section: Resultsmentioning

confidence: 99%

“…Liu's data allowed us to assign nearly all of the 1 H and 13 C resonances of the Diels-Alder product (compound 27a or b; see SI for full characterization). Due to the characteristic chemical shift of the ketone carbonyl carbon in the 13 C NMR spectrum (and the large geminal coupling constants it imparts on its α-protons), the assignments of C1, C2 and C3 by HMBC were straightforward. These assignments led to the first indication that structure 27a might be incorrect: C3 correlates to the protons of methyl 19 and methyl 20, easily identified by their integrations and differentiated by chemical shift.…”

Section: Resultsmentioning

confidence: 99%

“…Further corroborating this reassignment is the 2D NMR data for a Diels-Alder product reported by Liu and coworkers. 16a A distinct set of diagnostic resonances possess cross-peaks to both aliphatic methyls, including an olefin 13 C resonance and the single all-carbon quaternary 13 C resonance. Strong cross-peaks would be unlikely for a 5-6 bond distance between the methyl hydrogens and 13 C nuclides in question and more consistent with a 2-3 bond distance.…”

Section: Resultsmentioning

confidence: 99%

“…Since the discovery of 1 in C. serratus, 1i this sesquiterpenoid dimer has been found in 7 other members of the Chloranthus genus: C. japonicas, 7 C. multistachys, 8 C. fortunei, 2, 9 C. spicatus, 10 Sarcandra glabra (Chloranthaceae family), 11 C. sessilifolius, 12 and C. henryi. 13 Despite the number of potential targets available and the decades that have passed since their original discovery, there have been only two reports of successful syntheses of lindenane sesquiterpenoid dimers of the [4+2] variety. 14 Significant effort towards the efficient synthesis of lindane monomers has been expended by Baldwin, Fenlon, Lee and Liu and Nan.…”

Section: Introductionmentioning

confidence: 99%

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Reanalysis of lindenatriene, a building block for the synthesis of lindenane oligomers

2019

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Lindenane oligomers isolated from Chloranthus pose significant challenges for chemical synthesis. The structure of a proposed biosynthetic monomer, lindenatriene, was recently called into question. Its attempted synthesis produced a compound whose 1 H NMR spectrum differed significantly from the spectrum of a monomer produced by oligomer pyrolysis. Here we propose that the original structural assignment after pyrolysis was correct and instead the spectra of synthetic materials were misinterpreted. Reanalysis of 2D NMR data suggest that lindenatriene isomerizes (formal [1,7]-hydrogen shift) upon treatment with base.

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Effects of notoginsenoside R1 on attenuating depressive behavior induced by chronic stress in rats through induction of PI3K/AKT/NF‐κB pathway

Zhan

2021

Drug Development Research

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Chronic unpredictable mild stress (CUMS) can cause a series of depressive symptoms in depression patients. Recently, notoginsenoside R1 (NGR1) has been reported to play crucial roles in the anti‐inflammatory, antioxidant, and anti‐apoptotic. However, the role and mechanisms of NGR1 in improving symptoms of depressive behavior remain unknown. Evaluating and identifying its value and exploring the mechanisms of NGR1 on CUMS‐induced depressive behavior were the aims of this study. Here, rats were separated into five different groups and treated with or without different concentrations of the NGR1. Then, the body weight, sucrose preference rate, immobility time, crossing number, rearing number, and grooming number were determined to evaluate the effect of NGR1 on improving the depressive behavior of CUMS rats. Subsequently, the morphology of hippocampal neurons and protein expression of brain‐derived neurotrophic factor in each group were examined by hematoxylin and eosin staining and western blot to show the neuroprotective effects of NGR1. Furthermore, the mRNA and protein expression of TNF‐α, IL‐6, and IL‐1β were also detected by quantitative polymerase chain reaction (qPCR) and enzyme‐linked immunosorbent assay to verify the anti‐inflammatory effects of NGR1 on CUMS rats. In addition, the cell apoptosis‐related proteins were examined to reveal that NGR1 can inhibit cell apoptosis in CUMS rats. Moreover, it was confirmed that NGR1 attenuated the symptoms of depressive behavior by mediated PI3K/Akt/NF‐κB pathway. Together, this study shows that NGR1 improves depressive behavior induced by chronic stress in rats through activation of PI3K/AKT/NF‐κB pathway.

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Notoginsenoside R1 activates the Ang2/Tie2 pathway to promote angiogenesis

Cited by 21 publications

References 68 publications

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

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

Reanalysis of lindenatriene, a building block for the synthesis of lindenane oligomers

Effects of notoginsenoside R1 on attenuating depressive behavior induced by chronic stress in rats through induction of PI3K/AKT/NF‐κB pathway

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