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Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness

التفاصيل البيبلوغرافية
العنوان: Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness
المؤلفون: Xiaoning Yan, Jie Liu, Meixia Zhu, Lirong Liu, Yijun Chen, Yinhuan Zhang, Menghan Feng, Zhixin Jia, Hongbin Xiao
المصدر: Pharmaceutical Biology, Vol 59, Iss 1, Pp 1540-1550 (2021)
بيانات النشر: Taylor & Francis Group, 2021.
سنة النشر: 2021
المجموعة: LCC:Therapeutics. Pharmacology
مصطلحات موضوعية: rhodiola crenulata, lactate, glycolysis, oxidative phosphorylation, Therapeutics. Pharmacology, RM1-950
الوصف: Context Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba (Crassulaceae) is used to prevent and treat acute mountain sickness. However, the mechanisms underlying its effects on the central nervous system remain unclear. Objective To investigate the effect of Rhodiola crenulata on cellular metabolism in the central nervous system. Materials and methods The viability and Hif-1α levels of microglia and neurons at 5% O2 for 1, 3, 5 and 24 h were examined. We performed the binding of salidroside (Sal), rhodiosin, tyrosol and p-hydroxybenzyl alcohol to Hif-1α, Hif-1α, lactate, oxidative phosphorylation and glycolysis assays. Forty male C57BL/6J mice were divided into control and Sal (25, 50 and 100 mg/kg) groups to measure the levels of Hif-1α and lactate. Results Microglia sensed low oxygen levels earlier than neurons, accompanied by elevated expression of Hif-1α protein. Salidroside, rhodiosin, tyrosol, and p-hydroxybenzyl alcohol decreased BV-2 (IC50=1.93 ± 0.34 mM, 959.74 ± 10.24 μM, 7.47 ± 1.03 and 8.42 ± 1.63 mM) and PC-12 (IC50=6.89 ± 0.57 mM, 159.28 ± 8.89 μM, 8.65 ± 1.20 and 8.64 ± 1.42 mM) viability. They (10 μM) reduced Hif-1α degradation in BV-2 (3.7-, 2.5-, 2.9- and 2.5-fold) and PC-12 cells (2.8-, 2.8-, 2.3- and 2.0-fold) under normoxia. Salidroside increased glycolytic capacity but attenuated oxidative phosphorylation. Salidroside (50 and 100 mg/kg) treatment increased the protein expression of Hif-1α and the release of lactate in the brain tissue of mice. Conclusions These results suggest that Sal induces metabolic reprogramming by regulating the Hif-1α signalling pathway to activate compensatory responses, which may be the core mechanism underlying the effect of Rhodiola crenulata on the central nervous system.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1388-0209
1744-5116
13880209
Relation: https://doaj.org/toc/1388-0209; https://doaj.org/toc/1744-5116
DOI: 10.1080/13880209.2021.1992449
URL الوصول: https://doaj.org/article/bf04b79c3f4946db93b1d340243ae105
رقم الأكسشن: edsdoj.bf04b79c3f4946db93b1d340243ae105
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:13880209
17445116
DOI:10.1080/13880209.2021.1992449