Neuroprotective effect of acetoxypachydiol against oxidative stress through activation of the Keap1-Nrf2/HO-1 pathway

doi:10.1186/s12906-024-04474-6

科研成果详情

题名	Neuroprotective effect of acetoxypachydiol against oxidative stress through activation of the Keap1-Nrf2/HO-1 pathway
作者	Qi, Yu1; Liu, Ge 2; Jin, Shengjie1; Jian, Rong1; Zou, Ziqiang1; Wang, Chenjing1; Zhang, Yuanlong1; Zhao, Min 3; Zhu, Haoru1; Yan, Pengcheng1
发表日期	2024-04-25
发表期刊	BMC Complementary Medicine and Therapies 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Acetoxypachydiol Neuroprotective effect Keap1-Nrf2/HO-1 pathway Oxidative stress
其他关键词	PROTEIN-PROTEIN INTERACTION ; BROWN ALGA ; ANTIOXIDANT ; DITERPENES ; MECHANISM ; INJURY
摘要	Background Excessive oxidative stress in the brain is an important pathological factor in neurological diseases. Acetoxypachydiol (APHD) is a lipophilic germacrane-type diterpene extracted as a major component from different species of brown algae within the genus Dictyota. There have been no previous reports on the pharmacological activity of APHD. The present research aims to explore the potential neuroprotective properties of APHD and its underlying mechanisms.Methods The possible mechanism of APHD was predicted using a combination of molecular docking and network pharmacological analysis. PC12 cells were induced by H2O2 and oxygen-glucose deprivation/reoxygenation (OGD/R), respectively. Western blot, flow cytometry, immunofluorescence staining, and qRT-PCR were used to investigate the antioxidant activity of APHD. The HO-1 inhibitor ZnPP and Nrf2 gene silencing were employed to confirm the influence of APHD on the signaling cascade involving HO-1, Nrf2, and Keap1 in vitro.Results APHD exhibited antioxidant activity in both PC12 cells subjected to H2O2 and OGD/R conditions by downregulating the release of LDH, the concentrations of MDA, and ROS, and upregulating SOD, GSH-Px, and GSH concentrations. APHD could potentially initiate the Keap1-Nrf2/HO-1 signaling cascade, according to the findings from network pharmacology evaluation and molecular docking. Furthermore, APHD was observed to increase Nrf2 and HO-1 expression at both mRNA and protein levels, while downregulating the protein concentrations of Keap1. Both Nrf2 silencing and treatment with ZnPP reversed the neuroprotective effects of APHD.Conclusions APHD activated antioxidant enzymes and downregulated the levels of LDH, MDA, and ROS in two cell models. The neuroprotective effect is presumably reliant on upregulation of the Keap1-Nrf2/HO-1 pathway. Taken together, APHD from brown algae of the genus Dictyota shows potential as a candidate for novel neuroprotective agents.
资助项目	National Natural Science Foundation of China[82204608];Wenzhou Municipal Science and Technology Bureau[2022Y1461];Crosswise Project[KJHX2303];Wenzhou Medical University[604091809];
出版者	BMC
ISSN	2662-7671
EISSN	2662-7671
卷号	24 期号:1
DOI	10.1186/s12906-024-04474-6
页数	14
WOS类目	Integrative & Complementary Medicine
WOS研究方向	Integrative & Complementary Medicine
WOS记录号	WOS:001209747000001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	38664646
SCOPUSEID	2-s2.0-85191448940
通讯作者地址	[Zhu, Haoru]School of Traditional Chinese Medicine,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China ; [Yan, Pengcheng]School of Traditional Chinese Medicine,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
Scopus学科分类	Complementary and Alternative Medicine
SCOPUS_ID	SCOPUS_ID:85191448940
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/212502
专题	第二临床医学院、附属第二医院、育英儿童医院_中医系药学院（分析测试中心）
通讯作者	Zhu, Haoru; Yan, Pengcheng
作者单位	1.School of Traditional Chinese Medicine,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 2.Department of pharmacy,Yongkang First People’s Hospital Affiliated to Hangzhou Medical College,Yongkang,321300,China; 3.School of Pharmaceutical Sciences,Wenzhou Medical University,Chashan University Town,Ouhai District, Zhejiang,Wenzhou,325035,China
第一作者单位	温州医科大学
通讯作者单位	温州医科大学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Qi, Yu,Liu, Ge,Jin, Shengjie,et al. Neuroprotective effect of acetoxypachydiol against oxidative stress through activation of the Keap1-Nrf2/HO-1 pathway[J]. BMC Complementary Medicine and Therapies,2024,24(1).
APA	Qi, Yu., Liu, Ge., Jin, Shengjie., Jian, Rong., Zou, Ziqiang., ... & Yan, Pengcheng. (2024). Neuroprotective effect of acetoxypachydiol against oxidative stress through activation of the Keap1-Nrf2/HO-1 pathway. BMC Complementary Medicine and Therapies, 24(1).
MLA	Qi, Yu,et al."Neuroprotective effect of acetoxypachydiol against oxidative stress through activation of the Keap1-Nrf2/HO-1 pathway".BMC Complementary Medicine and Therapies 24.1(2024).