Xiaobo Wang1, Ya Hou1, Qiuyue Li2, Xuanhao Li3, Wenxiang Wang4, Xiaopeng Ai4, Tingting Kuang2, Xiaorui Chen4, Yi Zhang2, Jing Zhang5, Yao Hu6, Xianli Meng7. 1. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; Interdisciplinary Laboratory of Exercise and Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China. 2. Ethnic Medicine College, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China. 3. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; Ethnic Medicine College, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China. 4. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China. 5. Ethnic Medicine College, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China. Electronic address: 31649123@qq.com. 6. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; Interdisciplinary Laboratory of Exercise and Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China. Electronic address: 392402056@qq.com. 7. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China. Electronic address: xlm999@cdutcm.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola crenulata, a traditional Tibetan medicine, has shown promise in the treatment of hypobaric hypoxia (HH)-induced brain injury. However, the underlying mechanisms remain unclear. This study investigated the protective effects of R. crenulata aqueous extract (RCAE) on HH-induced brain injury in rats. MATERIALS AND METHODS: An animal model of high-altitude hypoxic brain injury was established in SD rats using an animal decompression chamber for 24 h. Serum and hippocampus levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and lactate dehydrogenase (LDH) were then determined using commercial biochemical kits. Neuron morphology and vitality were also evaluated using H&E and Nissl staining, and TUNEL staining was used to examine apoptosis. Gene and protein expression of HIF-1α, microRNA 210, ISCU1/2, COX10, Apaf-1, cleaved Caspase-3, Caspase-3, Bax, Bcl-2, and Cyto-c were determined by western blot, immunohistochemical and qRT-PCR analysis. RESULTS: RCAE administration attenuated HH-induced brain injury as evidenced by decreased levels of MDA, LDH, and GSSG, increased GSH and SOD, improvements in hippocampus histopathological changes, increased cell vitality and ATP level, and reduced apoptotic cell numbers. RCAE treatment also enhanced HIF-1α, ISCU1/2, COX10, and Bcl-2 protein expression, while dramatically inhibiting expression of Apaf-1, Bax, Cyto-c, and cleaved Caspase-3. Treatment also increased gene levels of HIF-1α, microRNA 210, ISCU1/2, and COX10, and decreased Caspase-3 gene production. CONCLUSIONS: RCAE attenuated HH-induced brain injury by regulating apoptosis and mitochondrial energy metabolism via the HIF-1α/microRNA 210/ISCU1/2 (COX10) signaling pathway.
ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola crenulata, a traditional Tibetan medicine, has shown promise in the treatment of hypobaric hypoxia (HH)-induced brain injury. However, the underlying mechanisms remain unclear. This study investigated the protective effects of R. crenulata aqueous extract (RCAE) on HH-induced brain injury in rats. MATERIALS AND METHODS: An animal model of high-altitude hypoxic brain injury was established in SD rats using an animal decompression chamber for 24 h. Serum and hippocampus levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and lactate dehydrogenase (LDH) were then determined using commercial biochemical kits. Neuron morphology and vitality were also evaluated using H&E and Nissl staining, and TUNEL staining was used to examine apoptosis. Gene and protein expression of HIF-1α, microRNA 210, ISCU1/2, COX10, Apaf-1, cleaved Caspase-3, Caspase-3, Bax, Bcl-2, and Cyto-c were determined by western blot, immunohistochemical and qRT-PCR analysis. RESULTS: RCAE administration attenuated HH-induced brain injury as evidenced by decreased levels of MDA, LDH, and GSSG, increased GSH and SOD, improvements in hippocampus histopathological changes, increased cell vitality and ATP level, and reduced apoptotic cell numbers. RCAE treatment also enhanced HIF-1α, ISCU1/2, COX10, and Bcl-2 protein expression, while dramatically inhibiting expression of Apaf-1, Bax, Cyto-c, and cleaved Caspase-3. Treatment also increased gene levels of HIF-1α, microRNA 210, ISCU1/2, and COX10, and decreased Caspase-3 gene production. CONCLUSIONS: RCAE attenuated HH-induced brain injury by regulating apoptosis and mitochondrial energy metabolism via the HIF-1α/microRNA 210/ISCU1/2 (COX10) signaling pathway.