Salidroside protects pulmonary artery endothelial cells against hypoxia-induced apoptosis via the AhR/NF-κB and Nrf2/HO-1 pathways.

Autor: Lei W; TAAHC-GDMU Biomedical and Health Joint R&D Center, The Provincial and Ministerial Co-founded Collaborative Innovation Center for R&D in Tibet Characteristic Agriculture and Animal Husbandry Resources, The Center for Xizang Chinese (Tibetan) Medicine Resource, Joint Laboratory for Tibetan Materia Medica Resource Scientific Protection and Utilization, Tibetan Medical Research Center of Tibet, Tibet Agriculture and Animal Husbandry University, Nyingchi, Tibet, PR China; Guangdong Provincial Engineering Technology Research Center for Molecular Diagnosis and Innovative Drugs Translation of Cardiopulmonary Vascular Diseases, University Joint Laboratory of Guangdong Province and Macao Region on Molecular Targets and Intervention of Cardiovascular Diseases, GDMU-TAAHC Biomedical and Health Joint R&D Center, Department of Precision Laboratory, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, PR China., Chen MH; Guangdong Provincial Engineering Technology Research Center for Molecular Diagnosis and Innovative Drugs Translation of Cardiopulmonary Vascular Diseases, University Joint Laboratory of Guangdong Province and Macao Region on Molecular Targets and Intervention of Cardiovascular Diseases, GDMU-TAAHC Biomedical and Health Joint R&D Center, Department of Precision Laboratory, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, PR China; Laboratory of Cardiovascular Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, PR China., Huang ZF; Laboratory of Cardiovascular Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, PR China., Chen XY; Laboratory of Cardiovascular Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, PR China., Wang JX; TAAHC-GDMU Biomedical and Health Joint R&D Center, The Provincial and Ministerial Co-founded Collaborative Innovation Center for R&D in Tibet Characteristic Agriculture and Animal Husbandry Resources, The Center for Xizang Chinese (Tibetan) Medicine Resource, Joint Laboratory for Tibetan Materia Medica Resource Scientific Protection and Utilization, Tibetan Medical Research Center of Tibet, Tibet Agriculture and Animal Husbandry University, Nyingchi, Tibet, PR China; Laboratory of Cardiovascular Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, PR China., Zheng J; Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, Wisconsin, USA., Zhu YZ; State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, PR China., Lan XZ; TAAHC-GDMU Biomedical and Health Joint R&D Center, The Provincial and Ministerial Co-founded Collaborative Innovation Center for R&D in Tibet Characteristic Agriculture and Animal Husbandry Resources, The Center for Xizang Chinese (Tibetan) Medicine Resource, Joint Laboratory for Tibetan Materia Medica Resource Scientific Protection and Utilization, Tibetan Medical Research Center of Tibet, Tibet Agriculture and Animal Husbandry University, Nyingchi, Tibet, PR China. Electronic address: lanxiaozhong@xza.edu.cn., He Y; TAAHC-GDMU Biomedical and Health Joint R&D Center, The Provincial and Ministerial Co-founded Collaborative Innovation Center for R&D in Tibet Characteristic Agriculture and Animal Husbandry Resources, The Center for Xizang Chinese (Tibetan) Medicine Resource, Joint Laboratory for Tibetan Materia Medica Resource Scientific Protection and Utilization, Tibetan Medical Research Center of Tibet, Tibet Agriculture and Animal Husbandry University, Nyingchi, Tibet, PR China; Guangdong Provincial Engineering Technology Research Center for Molecular Diagnosis and Innovative Drugs Translation of Cardiopulmonary Vascular Diseases, University Joint Laboratory of Guangdong Province and Macao Region on Molecular Targets and Intervention of Cardiovascular Diseases, GDMU-TAAHC Biomedical and Health Joint R&D Center, Department of Precision Laboratory, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, PR China; Laboratory of Cardiovascular Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, PR China. Electronic address: heyuan@gdmu.edu.cn.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Jun; Vol. 128, pp. 155376. Date of Electronic Publication: 2024 Jan 18.
DOI: 10.1016/j.phymed.2024.155376
Abstrakt: Background: The apoptosis of pulmonary artery endothelial cells (PAECs) is an important factor contributing to the development of pulmonary hypertension (PH), a serious cardio-pulmonary vascular disorder. Salidroside (SAL) is a bioactive compound derived from an herb Rhodiola, but the potential protective effects of SAL on PAECs and the underlying mechanisms remain elusive.
Purpose: The objective of this study was to determine the role of SAL in the hypoxia-induced apoptosis of PAECs and to dissect the underlying mechanisms.
Study Design: Male Sprague-Dawley (SD) rats were subjected to hypoxia (10% O 2 ) for 4 weeks to establish a model of PH. Rats were intraperitoneally injected daily with SAL (2, 8, and 32 mg/kg/d) or vehicle. To define the molecular mechanisms of SAL in PAECs, an in vitro model of hypoxic cell injury was also generated by exposed PAECs to 1% O 2 for 48 h.
Methods: Various techniques including hematoxylin and eosin (HE) staining, immunofluorescence, flow cytometry, CCK-8, Western blot, qPCR, molecular docking, and surface plasmon resonance (SPR) were used to determine the role of SAL in rats and in PAECs in vitro.
Results: Hypoxia stimulation increases AhR nuclear translocation and activates the NF-κB signaling pathway, as evidenced by upregulated expression of CYP1A1, CYP1B1, IL-1β, and IL-6, resulting in oxidative stress and inflammatory response and ultimately apoptosis of PAECs. SAL inhibited the activation of AhR and NF-κB, while promoted the nuclear translocation of Nrf2 and increased the expression of its downstream antioxidant proteins HO-1 and NQO1 in PAECs, ameliorating the hypoxia-induced oxidative stress in PAECs. Furthermore, SAL lowered right ventricular systolic pressure, and decreased pulmonary vascular remodeling and right ventricular hypertrophy in hypoxia-exposed rats.
Conclusions: SAL may attenuate the apoptosis of PAECs by suppressing NF-κB and activating Nrf2/HO-1 pathways, thereby delaying the progressive pathology of PH.
Competing Interests: Declaration of competing interest Authors declare no conflict of interest.
(Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
Databáze: MEDLINE
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