2′-O-Galloylhyperin Isolated From Pyrola incarnata Fisch. Attenuates LPS-Induced Inflammatory Response by Activation of SIRT1/Nrf2 and Inhibition of the NF-κB Pathways in Vitro and Vivo

2′-O-galloylhyperin, a major compound of Pyrola incarnata Fisch., possesses a variety of biological and pharmacological activities, including anti-oxidative and anti-inflammatory activities. Nevertheless, the underlying molecular mechanisms of 2′-O-GH in microbial infection and sepsis are not clear....

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Main Authors: Peng Wang, Chang Gao, Na Guo, Sun-Dong Zhang, Wei Wang, Li-Ping Yao, Jing Zhang, Thomas Efferth, Yu-Jie Fu
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-06-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2018.00679/full
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author Peng Wang
Chang Gao
Na Guo
Sun-Dong Zhang
Wei Wang
Li-Ping Yao
Jing Zhang
Thomas Efferth
Yu-Jie Fu
Yu-Jie Fu
author_facet Peng Wang
Chang Gao
Na Guo
Sun-Dong Zhang
Wei Wang
Li-Ping Yao
Jing Zhang
Thomas Efferth
Yu-Jie Fu
Yu-Jie Fu
author_sort Peng Wang
collection DOAJ
description 2′-O-galloylhyperin, a major compound of Pyrola incarnata Fisch., possesses a variety of biological and pharmacological activities, including anti-oxidative and anti-inflammatory activities. Nevertheless, the underlying molecular mechanisms of 2′-O-GH in microbial infection and sepsis are not clear. In this study, we investigated the anti-inflammatory effects of 2′-O-GH. We found that 2′-O-GH significantly reduced the production of TNF-α, IL-6, and nitric oxide (NO), suppressed the expression levels of iNOS, blocked the translocation of NF-κB from the cytosol to nucleus, and decreased the MAPK activation in LPS-activated RAW 264.7 cells. 2′-O-GH also enhanced the nuclear translocation of Nrf2 and up-regulated the expression of heme oxygenase-1 (HO-1) and SIRT1. In addition, the administration of 2′-O-GH attenuated the TNF-α and IL-6 production in the serum, infiltration of inflammatory cells, liver tissue damage, and the mortality rate of LPS-challenged mice. Moreover, 2′-O-GH significantly upregulated Nrf2 and SIRT1 expression and inhibited the inflammatory responses in the liver of septic mice. The collective data indicate that 2′-O-GH could potentially be a novel functional food candidate in the treatment of sepsis.
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spelling doaj.art-8b12aa5f6576483795a91519cb85d97a2022-12-22T01:34:34ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-06-01910.3389/fphar.2018.006793680492′-O-Galloylhyperin Isolated From Pyrola incarnata Fisch. Attenuates LPS-Induced Inflammatory Response by Activation of SIRT1/Nrf2 and Inhibition of the NF-κB Pathways in Vitro and VivoPeng Wang0Chang Gao1Na Guo2Sun-Dong Zhang3Wei Wang4Li-Ping Yao5Jing Zhang6Thomas Efferth7Yu-Jie Fu8Yu-Jie Fu9Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, ChinaDepartment of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaKey Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, ChinaKey Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, ChinaKey Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, ChinaKey Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, ChinaKey Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, ChinaInstitute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, GermanyKey Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, ChinaBeijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing, China2′-O-galloylhyperin, a major compound of Pyrola incarnata Fisch., possesses a variety of biological and pharmacological activities, including anti-oxidative and anti-inflammatory activities. Nevertheless, the underlying molecular mechanisms of 2′-O-GH in microbial infection and sepsis are not clear. In this study, we investigated the anti-inflammatory effects of 2′-O-GH. We found that 2′-O-GH significantly reduced the production of TNF-α, IL-6, and nitric oxide (NO), suppressed the expression levels of iNOS, blocked the translocation of NF-κB from the cytosol to nucleus, and decreased the MAPK activation in LPS-activated RAW 264.7 cells. 2′-O-GH also enhanced the nuclear translocation of Nrf2 and up-regulated the expression of heme oxygenase-1 (HO-1) and SIRT1. In addition, the administration of 2′-O-GH attenuated the TNF-α and IL-6 production in the serum, infiltration of inflammatory cells, liver tissue damage, and the mortality rate of LPS-challenged mice. Moreover, 2′-O-GH significantly upregulated Nrf2 and SIRT1 expression and inhibited the inflammatory responses in the liver of septic mice. The collective data indicate that 2′-O-GH could potentially be a novel functional food candidate in the treatment of sepsis.https://www.frontiersin.org/article/10.3389/fphar.2018.00679/fullNF-κBSIRT1anti-inflammation2′-O-galloylhyperinNrf2
spellingShingle Peng Wang
Chang Gao
Na Guo
Sun-Dong Zhang
Wei Wang
Li-Ping Yao
Jing Zhang
Thomas Efferth
Yu-Jie Fu
Yu-Jie Fu
2′-O-Galloylhyperin Isolated From Pyrola incarnata Fisch. Attenuates LPS-Induced Inflammatory Response by Activation of SIRT1/Nrf2 and Inhibition of the NF-κB Pathways in Vitro and Vivo
Frontiers in Pharmacology
NF-κB
SIRT1
anti-inflammation
2′-O-galloylhyperin
Nrf2
title 2′-O-Galloylhyperin Isolated From Pyrola incarnata Fisch. Attenuates LPS-Induced Inflammatory Response by Activation of SIRT1/Nrf2 and Inhibition of the NF-κB Pathways in Vitro and Vivo
title_full 2′-O-Galloylhyperin Isolated From Pyrola incarnata Fisch. Attenuates LPS-Induced Inflammatory Response by Activation of SIRT1/Nrf2 and Inhibition of the NF-κB Pathways in Vitro and Vivo
title_fullStr 2′-O-Galloylhyperin Isolated From Pyrola incarnata Fisch. Attenuates LPS-Induced Inflammatory Response by Activation of SIRT1/Nrf2 and Inhibition of the NF-κB Pathways in Vitro and Vivo
title_full_unstemmed 2′-O-Galloylhyperin Isolated From Pyrola incarnata Fisch. Attenuates LPS-Induced Inflammatory Response by Activation of SIRT1/Nrf2 and Inhibition of the NF-κB Pathways in Vitro and Vivo
title_short 2′-O-Galloylhyperin Isolated From Pyrola incarnata Fisch. Attenuates LPS-Induced Inflammatory Response by Activation of SIRT1/Nrf2 and Inhibition of the NF-κB Pathways in Vitro and Vivo
title_sort 2 o galloylhyperin isolated from pyrola incarnata fisch attenuates lps induced inflammatory response by activation of sirt1 nrf2 and inhibition of the nf κb pathways in vitro and vivo
topic NF-κB
SIRT1
anti-inflammation
2′-O-galloylhyperin
Nrf2
url https://www.frontiersin.org/article/10.3389/fphar.2018.00679/full
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