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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-01-01
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| Series: | Pharmaceutical Biology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/13880209.2021.1992449 |
| _version_ | 1818821127026245632 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T23:03:14Z |
| format | Article |
| id | doaj.art-bf04b79c3f4946db93b1d340243ae105 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-18T23:03:14Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-bf04b79c3f4946db93b1d340243ae1052022-12-21T20:48:32ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162021-01-015911540155010.1080/13880209.2021.19924491992449Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sicknessXiaoning Yan0Jie Liu1Meixia Zhu2Lirong Liu3Yijun Chen4Yinhuan Zhang5Menghan Feng6Zhixin Jia7Hongbin Xiao8School of Chinese Materia Medica, Beijing University of Chinese MedicineResearch Center of Chinese Medicine Analysis and Transformation, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineResearch Center of Chinese Medicine Analysis and Transformation, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineResearch Center of Chinese Medicine Analysis and Transformation, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineContext 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.http://dx.doi.org/10.1080/13880209.2021.1992449rhodiola crenulatalactateglycolysisoxidative phosphorylation |
| spellingShingle | 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 Pharmaceutical Biology rhodiola crenulata lactate glycolysis oxidative phosphorylation |
| title | 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_short | 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 |
| topic | rhodiola crenulata lactate glycolysis oxidative phosphorylation |
| url | http://dx.doi.org/10.1080/13880209.2021.1992449 |
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