Active Components of Rosa laevigata Michx. Isolated Using Activity-Guided Methods Based on LC-MS/MS for Treating Alzheimer's Disease through Multitarget Mechanisms

Pinyi Gao; Yan Cheng; Xingxing Si; Jialuo Li; Wenchao Zhang; Lixin Zhang; Lingzhi Li; Xuegui Liu; Danqi Li

doi:10.1002/slct.202300675

Active Components of Rosa laevigata Michx. Isolated Using Activity-Guided Methods Based on LC-MS/MS for Treating Alzheimer's Disease through Multitarget Mechanisms

Pinyi Gao^*
, Yan Cheng
, Xingxing Si
, Jialuo Li
, Wenchao Zhang
, Lixin Zhang
, Lingzhi Li
, Xuegui Liu
, Danqi Li

^*Kontaktforfatter

Institut for Fysik, Kemi og Farmaci

Shenyang University of Chemical Technology
Shenyang Pharmaceutical University
Syddansk Universitet

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstract

Rosa laevigata Michx., a member of the Rosaceae family, is a famous traditional Chinese medicine and edible food in Asian countries. The major active ingredient is triterpenoid, which has anti-Alzheimer's Disease (AD), antioxidant and neuroprotection properties. However, the properties of “multi-component structure” and “multi-directional target” make it impossible to explain the molecular mechanism by conventional ways. The present study aimed to predict the multi-target mechanisms of triterpenoids in R. laevigata against AD using high performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometer (HPLC-Q-TOF MS) approach, network pharmacology analysis, dynamics simulation (MDs) and validation of the predicted results with straight-target tests as well as neuroprotection model. Firstly, bioassay-guided fractionation of R. laevigata integrated with LC-MS/MS analysis of the most prospective enriched fractions in terms of anti-AD efficacy was commenced. Subsequently, multi-level network model of “multi components-multi-targets-multiple pathways” was established based on the identification of 69 triterpenoids. Complementarily, 64 AD-related targets were identified through various databases. Network structure analysis illuminated that the intricate pharmacological mechanisms improving cognitive dysfunction of AD was superiorly combined with the crucial targets of APP, APOE, VEGFA, IL1B, MAPT, PSEN1 and BACE and further regulation of principal pathways as HIF-1 and Calcium signaling pathways. In addition, AChE, BChE and BACE inhibitory activities in vitro showed that nine compounds exhibited potential inhibitory activities. The neuroprotective effects also had a similar effect on H₂O₂-induced SH-SY5Y cell injury. The results show that R. laevigata and its bioactive triterpenoids can pave the way for potential application as inhibitors for treatment of AD.

Originalsprog	Engelsk
Artikelnummer	e202300675
Tidsskrift	ChemistrySelect
Vol/bind	8
Udgave nummer	27
ISSN	2365-6549
DOI	https://doi.org/10.1002/slct.202300675
Status	Udgivet - 20. jul. 2023

Bibliografisk note

Funding Information:
This work was supported by the National Natural Science Foundation of China (81703377), Young Top Talents in “Xingliao Talent Program” (XLYC2007168) of Liaoning province of P. R. China, Young and Middle‐aged Scientific and Technological Innovation Talents in Shenyang (RC210148) of Liaoning province of P. R. China, Foundation (2021‐MS‐258) from the Project of Science and Technology Department of Liaoning province of P. R. China, the grants from the China Scholarship Council (CSC202008210156; CSC202008210032), Foundation (No. LJKZ0438; No. LJKZ0469) from the Project of Education Department of Liaoning Province of P. R, Foundation (2022YQ008) from the Excellent youth promotion project of Shenyang University of Chemical Technology.This work was financially supported by the Foundation from the Project of Science and Technology Department of Liaoning province of P. R. China [No. 2023JH2/101600021].

Funding Information:
This work was supported by the National Natural Science Foundation of China (81703377), Young Top Talents in “Xingliao Talent Program” (XLYC2007168) of Liaoning province of P. R. China, Young and Middle-aged Scientific and Technological Innovation Talents in Shenyang (RC210148) of Liaoning province of P. R. China, Foundation (2021-MS-258) from the Project of Science and Technology Department of Liaoning province of P. R. China, the grants from the China Scholarship Council (CSC202008210156; CSC202008210032), Foundation (No. LJKZ0438; No. LJKZ0469) from the Project of Education Department of Liaoning Province of P. R, Foundation (2022YQ008) from the Excellent youth promotion project of Shenyang University of Chemical Technology.This work was financially supported by the Foundation from the Project of Science and Technology Department of Liaoning province of P. R. China [No. 2023JH2/101600021].

Publisher Copyright:
© 2023 Wiley-VCH GmbH.

Finansiering

This work was supported by the National Natural Science Foundation of China (81703377), Young Top Talents in “Xingliao Talent Program” (XLYC2007168) of Liaoning province of P. R. China, Young and Middle‐aged Scientific and Technological Innovation Talents in Shenyang (RC210148) of Liaoning province of P. R. China, Foundation (2021‐MS‐258) from the Project of Science and Technology Department of Liaoning province of P. R. China, the grants from the China Scholarship Council (CSC202008210156; CSC202008210032), Foundation (No. LJKZ0438; No. LJKZ0469) from the Project of Education Department of Liaoning Province of P. R, Foundation (2022YQ008) from the Excellent youth promotion project of Shenyang University of Chemical Technology.This work was financially supported by the Foundation from the Project of Science and Technology Department of Liaoning province of P. R. China [No. 2023JH2/101600021]. This work was supported by the National Natural Science Foundation of China (81703377), Young Top Talents in “Xingliao Talent Program” (XLYC2007168) of Liaoning province of P. R. China, Young and Middle-aged Scientific and Technological Innovation Talents in Shenyang (RC210148) of Liaoning province of P. R. China, Foundation (2021-MS-258) from the Project of Science and Technology Department of Liaoning province of P. R. China, the grants from the China Scholarship Council (CSC202008210156; CSC202008210032), Foundation (No. LJKZ0438; No. LJKZ0469) from the Project of Education Department of Liaoning Province of P. R, Foundation (2022YQ008) from the Excellent youth promotion project of Shenyang University of Chemical Technology.This work was financially supported by the Foundation from the Project of Science and Technology Department of Liaoning province of P. R. China [No. 2023JH2/101600021].

Dokumenter og links

10.1002/slct.202300675

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Tjek adgangen til materialet i Syddansk Universitetsbiblioteks søgemaskine

Citationsformater

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title = "Active Components of Rosa laevigata Michx. Isolated Using Activity-Guided Methods Based on LC-MS/MS for Treating Alzheimer's Disease through Multitarget Mechanisms",

abstract = "Rosa laevigata Michx., a member of the Rosaceae family, is a famous traditional Chinese medicine and edible food in Asian countries. The major active ingredient is triterpenoid, which has anti-Alzheimer's Disease (AD), antioxidant and neuroprotection properties. However, the properties of {\textquotedblleft}multi-component structure{\textquotedblright} and {\textquotedblleft}multi-directional target{\textquotedblright} make it impossible to explain the molecular mechanism by conventional ways. The present study aimed to predict the multi-target mechanisms of triterpenoids in R. laevigata against AD using high performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometer (HPLC-Q-TOF MS) approach, network pharmacology analysis, dynamics simulation (MDs) and validation of the predicted results with straight-target tests as well as neuroprotection model. Firstly, bioassay-guided fractionation of R. laevigata integrated with LC-MS/MS analysis of the most prospective enriched fractions in terms of anti-AD efficacy was commenced. Subsequently, multi-level network model of {\textquotedblleft}multi components-multi-targets-multiple pathways{\textquotedblright} was established based on the identification of 69 triterpenoids. Complementarily, 64 AD-related targets were identified through various databases. Network structure analysis illuminated that the intricate pharmacological mechanisms improving cognitive dysfunction of AD was superiorly combined with the crucial targets of APP, APOE, VEGFA, IL1B, MAPT, PSEN1 and BACE and further regulation of principal pathways as HIF-1 and Calcium signaling pathways. In addition, AChE, BChE and BACE inhibitory activities in vitro showed that nine compounds exhibited potential inhibitory activities. The neuroprotective effects also had a similar effect on H2O2-induced SH-SY5Y cell injury. The results show that R. laevigata and its bioactive triterpenoids can pave the way for potential application as inhibitors for treatment of AD.",

keywords = "Alzheimer's Disease, HPLC-Q-TOF MS, Molecular docking, Network pharmacology, Neuroprotective effects",

author = "Pinyi Gao and Yan Cheng and Xingxing Si and Jialuo Li and Wenchao Zhang and Lixin Zhang and Lingzhi Li and Xuegui Liu and Danqi Li",

note = "Funding Information: This work was supported by the National Natural Science Foundation of China (81703377), Young Top Talents in {\textquotedblleft}Xingliao Talent Program{\textquotedblright} (XLYC2007168) of Liaoning province of P. R. China, Young and Middle‐aged Scientific and Technological Innovation Talents in Shenyang (RC210148) of Liaoning province of P. R. China, Foundation (2021‐MS‐258) from the Project of Science and Technology Department of Liaoning province of P. R. China, the grants from the China Scholarship Council (CSC202008210156; CSC202008210032), Foundation (No. LJKZ0438; No. LJKZ0469) from the Project of Education Department of Liaoning Province of P. R, Foundation (2022YQ008) from the Excellent youth promotion project of Shenyang University of Chemical Technology.This work was financially supported by the Foundation from the Project of Science and Technology Department of Liaoning province of P. R. China [No. 2023JH2/101600021]. Funding Information: This work was supported by the National Natural Science Foundation of China (81703377), Young Top Talents in {\textquotedblleft}Xingliao Talent Program{\textquotedblright} (XLYC2007168) of Liaoning province of P. R. China, Young and Middle-aged Scientific and Technological Innovation Talents in Shenyang (RC210148) of Liaoning province of P. R. China, Foundation (2021-MS-258) from the Project of Science and Technology Department of Liaoning province of P. R. China, the grants from the China Scholarship Council (CSC202008210156; CSC202008210032), Foundation (No. LJKZ0438; No. LJKZ0469) from the Project of Education Department of Liaoning Province of P. R, Foundation (2022YQ008) from the Excellent youth promotion project of Shenyang University of Chemical Technology.This work was financially supported by the Foundation from the Project of Science and Technology Department of Liaoning province of P. R. China [No. 2023JH2/101600021]. Publisher Copyright: {\textcopyright} 2023 Wiley-VCH GmbH.",

year = "2023",

month = jul,

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doi = "10.1002/slct.202300675",

language = "English",

volume = "8",

journal = "ChemistrySelect",

issn = "2365-6549",

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T1 - Active Components of Rosa laevigata Michx. Isolated Using Activity-Guided Methods Based on LC-MS/MS for Treating Alzheimer's Disease through Multitarget Mechanisms

AU - Gao, Pinyi

AU - Cheng, Yan

AU - Si, Xingxing

AU - Li, Jialuo

AU - Zhang, Wenchao

AU - Zhang, Lixin

AU - Li, Lingzhi

AU - Liu, Xuegui

AU - Li, Danqi

N1 - Funding Information: This work was supported by the National Natural Science Foundation of China (81703377), Young Top Talents in “Xingliao Talent Program” (XLYC2007168) of Liaoning province of P. R. China, Young and Middle‐aged Scientific and Technological Innovation Talents in Shenyang (RC210148) of Liaoning province of P. R. China, Foundation (2021‐MS‐258) from the Project of Science and Technology Department of Liaoning province of P. R. China, the grants from the China Scholarship Council (CSC202008210156; CSC202008210032), Foundation (No. LJKZ0438; No. LJKZ0469) from the Project of Education Department of Liaoning Province of P. R, Foundation (2022YQ008) from the Excellent youth promotion project of Shenyang University of Chemical Technology.This work was financially supported by the Foundation from the Project of Science and Technology Department of Liaoning province of P. R. China [No. 2023JH2/101600021]. Funding Information: This work was supported by the National Natural Science Foundation of China (81703377), Young Top Talents in “Xingliao Talent Program” (XLYC2007168) of Liaoning province of P. R. China, Young and Middle-aged Scientific and Technological Innovation Talents in Shenyang (RC210148) of Liaoning province of P. R. China, Foundation (2021-MS-258) from the Project of Science and Technology Department of Liaoning province of P. R. China, the grants from the China Scholarship Council (CSC202008210156; CSC202008210032), Foundation (No. LJKZ0438; No. LJKZ0469) from the Project of Education Department of Liaoning Province of P. R, Foundation (2022YQ008) from the Excellent youth promotion project of Shenyang University of Chemical Technology.This work was financially supported by the Foundation from the Project of Science and Technology Department of Liaoning province of P. R. China [No. 2023JH2/101600021]. Publisher Copyright: © 2023 Wiley-VCH GmbH.

PY - 2023/7/20

Y1 - 2023/7/20

N2 - Rosa laevigata Michx., a member of the Rosaceae family, is a famous traditional Chinese medicine and edible food in Asian countries. The major active ingredient is triterpenoid, which has anti-Alzheimer's Disease (AD), antioxidant and neuroprotection properties. However, the properties of “multi-component structure” and “multi-directional target” make it impossible to explain the molecular mechanism by conventional ways. The present study aimed to predict the multi-target mechanisms of triterpenoids in R. laevigata against AD using high performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometer (HPLC-Q-TOF MS) approach, network pharmacology analysis, dynamics simulation (MDs) and validation of the predicted results with straight-target tests as well as neuroprotection model. Firstly, bioassay-guided fractionation of R. laevigata integrated with LC-MS/MS analysis of the most prospective enriched fractions in terms of anti-AD efficacy was commenced. Subsequently, multi-level network model of “multi components-multi-targets-multiple pathways” was established based on the identification of 69 triterpenoids. Complementarily, 64 AD-related targets were identified through various databases. Network structure analysis illuminated that the intricate pharmacological mechanisms improving cognitive dysfunction of AD was superiorly combined with the crucial targets of APP, APOE, VEGFA, IL1B, MAPT, PSEN1 and BACE and further regulation of principal pathways as HIF-1 and Calcium signaling pathways. In addition, AChE, BChE and BACE inhibitory activities in vitro showed that nine compounds exhibited potential inhibitory activities. The neuroprotective effects also had a similar effect on H2O2-induced SH-SY5Y cell injury. The results show that R. laevigata and its bioactive triterpenoids can pave the way for potential application as inhibitors for treatment of AD.

AB - Rosa laevigata Michx., a member of the Rosaceae family, is a famous traditional Chinese medicine and edible food in Asian countries. The major active ingredient is triterpenoid, which has anti-Alzheimer's Disease (AD), antioxidant and neuroprotection properties. However, the properties of “multi-component structure” and “multi-directional target” make it impossible to explain the molecular mechanism by conventional ways. The present study aimed to predict the multi-target mechanisms of triterpenoids in R. laevigata against AD using high performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometer (HPLC-Q-TOF MS) approach, network pharmacology analysis, dynamics simulation (MDs) and validation of the predicted results with straight-target tests as well as neuroprotection model. Firstly, bioassay-guided fractionation of R. laevigata integrated with LC-MS/MS analysis of the most prospective enriched fractions in terms of anti-AD efficacy was commenced. Subsequently, multi-level network model of “multi components-multi-targets-multiple pathways” was established based on the identification of 69 triterpenoids. Complementarily, 64 AD-related targets were identified through various databases. Network structure analysis illuminated that the intricate pharmacological mechanisms improving cognitive dysfunction of AD was superiorly combined with the crucial targets of APP, APOE, VEGFA, IL1B, MAPT, PSEN1 and BACE and further regulation of principal pathways as HIF-1 and Calcium signaling pathways. In addition, AChE, BChE and BACE inhibitory activities in vitro showed that nine compounds exhibited potential inhibitory activities. The neuroprotective effects also had a similar effect on H2O2-induced SH-SY5Y cell injury. The results show that R. laevigata and its bioactive triterpenoids can pave the way for potential application as inhibitors for treatment of AD.

KW - Alzheimer's Disease

KW - HPLC-Q-TOF MS

KW - Molecular docking

KW - Network pharmacology

KW - Neuroprotective effects

U2 - 10.1002/slct.202300675

DO - 10.1002/slct.202300675

M3 - Journal article

AN - SCOPUS:85165451063

SN - 2365-6549

VL - 8

JO - ChemistrySelect

JF - ChemistrySelect

IS - 27

M1 - e202300675

ER -

Active Components of Rosa laevigata Michx. Isolated Using Activity-Guided Methods Based on LC-MS/MS for Treating Alzheimer's Disease through Multitarget Mechanisms

Abstract

Bibliografisk note

Finansiering

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Fingeraftryk

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