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      Drug Design, Development and Therapy (submit here)

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      Focus on Notoginsenoside R1 in Metabolism and Prevention Against Human Diseases

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          Abstract

          Notoginsenoside (NG)-R1 is one of the main bioactive compounds from Panax notoginseng (PN) root, which is well known in the prescription for mediating the micro-circulatory hemostasis in human. In this article, we mainly discuss NG-R1 in metabolism and the biological activities, including cardiovascular protection, neuro-protection, anti-diabetes, liver protection, gastrointestinal protection, lung protection, bone metabolism regulation, renal protection, and anti-cancer. The metabolites produced by deglycosylation of NG-R1 exhibit higher permeability and bioavailability. It has been extensively verified that NG-R1 may ameliorate ischemia-reperfusion (IR)-induced injury in cardiovascular and neuronal systems mainly by upregulating the activity of estrogen receptor α-dependent phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor erythroid-2-related factor 2 (NRF2) pathways and downregulating nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. However, no specific targets for NG-R1 have been identified. Expectedly, NG-R1 has been used as a main bioactive compound in many Traditional Chinese Medicines clinically, such as Xuesaitong, Naodesheng, XueShuanTong, ShenMai, and QSYQ. These suggest that NG-R1 exhibits a significant potency in drug development.

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          Absorption and disposition of ginsenosides after oral administration of Panax notoginseng extract to rats.

          Houfu Liu, Junling Yang, Feifei Du … (2009)
          Panax notoginseng (Sanqi) is a cardiovascular herb containing ginsenosides that are believed to be responsible for the therapeutic effects of Sanqi. The aim of this study was to evaluate rat exposure to ginsenosides after oral administration of Sanqi extract and to identify the key factors affecting their absorption and disposition. Ginsenosides were administered to rats, either in the form of Sanqi extract or as pure chemicals. The ginsenosides Ra(3), Rb(1), Rd, Re, Rg(1), and notoginsenoside R(1) were the major saponins present in the herbal extract. Systemic exposure to ginsenosides Ra(3), Rb(1), and Rd after oral administration of the extract was significantly greater than that to the other compounds. Considerable colonic deglycosylation of the ginsenosides occurred, but the plasma levels of deglycosylated metabolites were low in rats. Poor membrane permeability and active biliary excretion are the two primary factors limiting systemic exposure to most ginsenosides and their deglycosylated metabolites. In contrast with other ginsenosides, biliary excretion of ginsenosides Ra(3) and Rb(1) was passive. Meanwhile, the active biliary excretion of ginsenoside Rd was significantly slower than that of other saponins. Slow biliary excretion, inefficient metabolism, and slow renal excretion resulted in long-circulating and thus relatively high exposure levels for these three ginsenosides. For these reasons, plasma ginsenosides Ra(3), Rb(1), and Rd were identified as pharmacokinetic markers for indicating rat systemic exposure to Sanqi extract. This is a systematic investigation of the absorption and disposition of ginsenosides from an herb, the information gained from which is important for linking Sanqi administration to its medicinal effects.
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            Protective Effects of Panax Notoginseng Saponins on Cardiovascular Diseases: A Comprehensive Overview of Experimental Studies

            Xiaochen Yang, Xingjiang Xiong, Heran Wang … (2014)
            Panax notoginseng saponins (PNS) are one of the most important compounds derived from roots of the herb Panax notoginseng which are traditionally used as a hemostatic medicine to control internal and external bleeding in China for thousands of years. To date, at least twenty saponins were identified and some of them including notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were researched frequently in the area of cardiovascular protection. However, the protective effects of PNS on cardiovascular diseases based on experimental studies and its underlying mechanisms have not been reviewed systematically. This paper reviewed the pharmacology of PNS and its monomers Rb1, Rg1, and R1 in the treatment for cardiovascular diseases.
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              Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress- related signaling pathways

              Yingli Yu, Guibo Sun, Yun-ya Luo … (2016)
              Background: Recent reports suggested the involvement of oxidative stress- and endoplasmic reticulum stress (ERS)-associated pathways in the progression of ischemia/reperfusion (I/R) injury. Notoginsenoside R1 (NGR1) is a novel saponin isolated from P. notoginseng, which has a history of prevention and treatment of cardiovascular diseases. Objective: We aimed to examine the cardioprotective effects of NGR1 on I/R-induced heart dysfunction ex vivo and in vitro. Methods: H9c2 cadiomyocytes were incubated with NGR1 for 24 h and exposed to hypoxia/reoxygenation. Isolated rat hearts were perfused by NGR1 for 15 min and then subjected to global ischemia/reperfusion. Hemodynamic parameters were monitored as left ventricular systolic pressure (LVSP), heart rate, and maximal rate of increase and decrease of left ventricular pressure (±dP/dt max/min). Results: NGR1 pretreatment prevents cell apoptosis and delays the onset of ERS by decreasing the protein expression levels of ERS-responsive proteins GRP78, P-PERK, ATF6, IRE, and inhibiting the expression of pro-apoptosis proteins CHOP, Caspase-12, and P-JNK. Besides, NGR1 scavenges free radical, and increases the activity of antioxidase. NGR1 inhibits Tunicamycin-induced cell death and cardic dysfunction. Conclusion: We elucidated the significant cardioprotective effects of NGR1 against I/R injuries, and demonstrated the involvement of oxidative stress and ERS in the protective effects of NGR1.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): DDDT
                Journal ID (pmc): dddt
                Title: Drug Design, Development and Therapy
                Publisher: Dove
                ISSN (Electronic): 1177-8881
                Publication date (Electronic): 07 February 2020
                Publication date Collection: 2020
                Volume: 14
                Pages: 551-565
                Affiliations
                [1 ]School of Chinese Materia Medica, Beijing University of Chinese Medicine , Beijing, People’s Republic of China
                [2 ]College of Pharmacy, Gannan Medical University , Ganzhou, Jiangxi, People’s Republic of China
                [3 ]Department of Clinical Research Center, The First Affiliated Hospital of Gannan Medical University , Ganzhou, Jiangxi, People’s Republic of China
                Author notes
                Correspondence: Shouying Du School of Chinese Materia Medica, Beijing University of Chinese Medicine , 11 North 3rd Ring East Road, Chaoyang District, Beijing, People’s Republic of ChinaTel +86 17812165051Fax +86 10 64286231 Email dumenzidi123@163.com
                Author information
                http://orcid.org/0000-0002-1748-0990
                http://orcid.org/0000-0002-9063-8117
                http://orcid.org/0000-0002-2390-3857
                http://orcid.org/0000-0001-7788-8130
                http://orcid.org/0000-0001-6058-2629
                http://orcid.org/0000-0001-5552-7828
                http://orcid.org/0000-0003-3827-3277
                Article
                Publisher ID: 240511
                DOI: 10.2147/DDDT.S240511
                PMC ID: 7012233
                PubMed ID: 32103897
                SO-VID: e122c531-e394-4831-8fc7-ab2d1886d946
                Copyright © © 2020 Liu et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 29 November 2019
                Date accepted : 28 January 2020
                Page count
                Figures: 3, Tables: 1, References: 102, Pages: 15
                Categories
                Subject: Review

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: notoginsenoside (ng)-r1,panax notoginseng,micro-circulatory hemostasis,permeability,bioavailability
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: notoginsenoside (ng)-r1, panax notoginseng, micro-circulatory hemostasis, permeability, bioavailability

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