Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness
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 i...
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2021
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oai:doaj.org-article:bf04b79c3f4946db93b1d340243ae1052021-11-11T14:23:41ZSalidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness1388-02091744-511610.1080/13880209.2021.1992449https://doaj.org/article/bf04b79c3f4946db93b1d340243ae1052021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2021.1992449https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context 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.Xiaoning YanJie LiuMeixia ZhuLirong LiuYijun ChenYinhuan ZhangMenghan FengZhixin JiaHongbin XiaoTaylor & Francis Grouparticlerhodiola crenulatalactateglycolysisoxidative phosphorylationTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 59, Iss 1, Pp 1540-1550 (2021) |
| institution |
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| collection |
DOAJ |
| language |
EN |
| topic |
rhodiola crenulata lactate glycolysis oxidative phosphorylation Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
rhodiola crenulata lactate glycolysis oxidative phosphorylation Therapeutics. Pharmacology RM1-950 Xiaoning Yan Jie Liu Meixia Zhu Lirong Liu Yijun Chen Yinhuan Zhang Menghan Feng Zhixin Jia Hongbin Xiao Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness |
| description |
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. |
| format |
article |
| author |
Xiaoning Yan Jie Liu Meixia Zhu Lirong Liu Yijun Chen Yinhuan Zhang Menghan Feng Zhixin Jia Hongbin Xiao |
| author_facet |
Xiaoning Yan Jie Liu Meixia Zhu Lirong Liu Yijun Chen Yinhuan Zhang Menghan Feng Zhixin Jia Hongbin Xiao |
| author_sort |
Xiaoning Yan |
| title |
Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness |
| title_short |
Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness |
| title_full |
Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness |
| title_fullStr |
Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness |
| title_full_unstemmed |
Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness |
| title_sort |
salidroside orchestrates metabolic reprogramming by regulating the hif-1α signalling pathway in acute mountain sickness |
| publisher |
Taylor & Francis Group |
| publishDate |
2021 |
| url |
https://doaj.org/article/bf04b79c3f4946db93b1d340243ae105 |
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