Neuroprotective Effects of a New Derivative of Chlojaponilactone B against Oxidative Damaged Induced by Hydrogen Peroxide in PC12 Cells

A new sesquiterpenoid (<b>1</b>) was obtained by hydrogenating Chlojaponilactone B. The structure of <b>1</b> was elucidated according to a combination of NMR, HRESIMS, and NOE diffraction data. The treatment of H<sub>2</sub>O<sub>2</sub> in a PC12 cel...

Cijeli opis

Bibliografski detalji
Glavni autori: Shaoxia Ye, Qiyin Wen, Longping Zhu, Chunguo Qian, Depo Yang, Zhimin Zhao
Format: Članak
Jezik:English
Izdano: MDPI AG 2022-09-01
Serija:Molecules
Teme:
Online pristup:https://www.mdpi.com/1420-3049/27/18/6049
_version_ 1827658297183830016
author Shaoxia Ye
Qiyin Wen
Longping Zhu
Chunguo Qian
Depo Yang
Zhimin Zhao
author_facet Shaoxia Ye
Qiyin Wen
Longping Zhu
Chunguo Qian
Depo Yang
Zhimin Zhao
author_sort Shaoxia Ye
collection DOAJ
description A new sesquiterpenoid (<b>1</b>) was obtained by hydrogenating Chlojaponilactone B. The structure of <b>1</b> was elucidated according to a combination of NMR, HRESIMS, and NOE diffraction data. The treatment of H<sub>2</sub>O<sub>2</sub> in a PC12 cell model was used to evaluate the antioxidant activity of <b>1</b>. An MMT assay showed that <b>1</b> had no cytotoxicity to the PC12 cell and rescued cell viability from the oxidative damage caused by H<sub>2</sub>O<sub>2</sub>. The treatment of <b>1</b> stabilized the mitochondria membrane potential (MMP), which decreased the intracellular ROS level and reduced cell apoptosis in the oxidative stress model. The activities of antioxidant enzyme superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the content of intracellular glutathione (GSH) were significantly enhanced after the treatment of <b>1</b>. In addition, the results of qRT-PCR showed that <b>1</b> treatment minimized the cell injury by H<sub>2</sub>O<sub>2</sub> via the up-regulation of the expression of nuclear factor erythroid 2 (Nrf2) and its downstream enzymes Heme oxygenase 1 (HO-1), glutamate cysteine ligase-modifier subunit (GCLm), and NAD(P)H quinone dehydrogenase 1 (Nqo1). Based on the antioxidant activity of <b>1</b>, we speculated its potential as a therapeutic agent for some diseases induced by oxidative damage.
first_indexed 2024-03-09T22:59:47Z
format Article
id doaj.art-257e7af2cf75459684a5dcd4581a31ab
institution Directory Open Access Journal
issn 1420-3049
language English
last_indexed 2024-03-09T22:59:47Z
publishDate 2022-09-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj.art-257e7af2cf75459684a5dcd4581a31ab2023-11-23T18:03:24ZengMDPI AGMolecules1420-30492022-09-012718604910.3390/molecules27186049Neuroprotective Effects of a New Derivative of Chlojaponilactone B against Oxidative Damaged Induced by Hydrogen Peroxide in PC12 CellsShaoxia Ye0Qiyin Wen1Longping Zhu2Chunguo Qian3Depo Yang4Zhimin Zhao5School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaA new sesquiterpenoid (<b>1</b>) was obtained by hydrogenating Chlojaponilactone B. The structure of <b>1</b> was elucidated according to a combination of NMR, HRESIMS, and NOE diffraction data. The treatment of H<sub>2</sub>O<sub>2</sub> in a PC12 cell model was used to evaluate the antioxidant activity of <b>1</b>. An MMT assay showed that <b>1</b> had no cytotoxicity to the PC12 cell and rescued cell viability from the oxidative damage caused by H<sub>2</sub>O<sub>2</sub>. The treatment of <b>1</b> stabilized the mitochondria membrane potential (MMP), which decreased the intracellular ROS level and reduced cell apoptosis in the oxidative stress model. The activities of antioxidant enzyme superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the content of intracellular glutathione (GSH) were significantly enhanced after the treatment of <b>1</b>. In addition, the results of qRT-PCR showed that <b>1</b> treatment minimized the cell injury by H<sub>2</sub>O<sub>2</sub> via the up-regulation of the expression of nuclear factor erythroid 2 (Nrf2) and its downstream enzymes Heme oxygenase 1 (HO-1), glutamate cysteine ligase-modifier subunit (GCLm), and NAD(P)H quinone dehydrogenase 1 (Nqo1). Based on the antioxidant activity of <b>1</b>, we speculated its potential as a therapeutic agent for some diseases induced by oxidative damage.https://www.mdpi.com/1420-3049/27/18/6049sesquiterpeneneuroprotectionPC12 cellsROSNrf2
spellingShingle Shaoxia Ye
Qiyin Wen
Longping Zhu
Chunguo Qian
Depo Yang
Zhimin Zhao
Neuroprotective Effects of a New Derivative of Chlojaponilactone B against Oxidative Damaged Induced by Hydrogen Peroxide in PC12 Cells
Molecules
sesquiterpene
neuroprotection
PC12 cells
ROS
Nrf2
title Neuroprotective Effects of a New Derivative of Chlojaponilactone B against Oxidative Damaged Induced by Hydrogen Peroxide in PC12 Cells
title_full Neuroprotective Effects of a New Derivative of Chlojaponilactone B against Oxidative Damaged Induced by Hydrogen Peroxide in PC12 Cells
title_fullStr Neuroprotective Effects of a New Derivative of Chlojaponilactone B against Oxidative Damaged Induced by Hydrogen Peroxide in PC12 Cells
title_full_unstemmed Neuroprotective Effects of a New Derivative of Chlojaponilactone B against Oxidative Damaged Induced by Hydrogen Peroxide in PC12 Cells
title_short Neuroprotective Effects of a New Derivative of Chlojaponilactone B against Oxidative Damaged Induced by Hydrogen Peroxide in PC12 Cells
title_sort neuroprotective effects of a new derivative of chlojaponilactone b against oxidative damaged induced by hydrogen peroxide in pc12 cells
topic sesquiterpene
neuroprotection
PC12 cells
ROS
Nrf2
url https://www.mdpi.com/1420-3049/27/18/6049
work_keys_str_mv AT shaoxiaye neuroprotectiveeffectsofanewderivativeofchlojaponilactonebagainstoxidativedamagedinducedbyhydrogenperoxideinpc12cells
AT qiyinwen neuroprotectiveeffectsofanewderivativeofchlojaponilactonebagainstoxidativedamagedinducedbyhydrogenperoxideinpc12cells
AT longpingzhu neuroprotectiveeffectsofanewderivativeofchlojaponilactonebagainstoxidativedamagedinducedbyhydrogenperoxideinpc12cells
AT chunguoqian neuroprotectiveeffectsofanewderivativeofchlojaponilactonebagainstoxidativedamagedinducedbyhydrogenperoxideinpc12cells
AT depoyang neuroprotectiveeffectsofanewderivativeofchlojaponilactonebagainstoxidativedamagedinducedbyhydrogenperoxideinpc12cells
AT zhiminzhao neuroprotectiveeffectsofanewderivativeofchlojaponilactonebagainstoxidativedamagedinducedbyhydrogenperoxideinpc12cells