Frontiers in pharmacology · 2026
Carnosic acid alleviates high-altitude cerebral edema by suppressing oxidative stress and microglia activation-induced neuroinflammation.
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Gao Junlan, Che Ningwei, Yu Jian
Аннотация
BACKGROUND: Oxidative stress and neuroinflammation constitute key pathological contributors to high-altitude cerebral edema (HACE). Carnosic acid (CA) exerts important roles in neurodegeneration and brain injury, but its function in HACE remains elusive.
METHODS: High-altitude hypobaric hypoxic (HH)-mimicked HACE rats were administered carnosic acid. The effects on hematological parameter changes, blood-brain barrier (BBB) permeability, energetic metabolism disorder, cognitive and motor impairment, oxidative stress, and microglia-mediated neuroinflammation were explored. The function of carnosic acid in microglia-mediated damage to astrocytes and endothelial cells under hypoxia was investigated.
RESULTS: Carnosic acid dose-dependently normalized aberrant hematological parameter changes, brain water content, and histopathological changes in HH-mimicked HACE rats. Moreover, HH conditions enhanced BBB permeability and BBB-related aquaporin 4 (AQP4) expression and decreased BBB-related occludin and zonula occludens-1 (ZO-1) expression, which were reversed after carnosic acid. Carnosic acid alleviated energetic metabolism disorder and improved cognitive and motor impairment in HACE rats. Carnosic acid attenuated HH-evoked oxidative stress by inhibiting reactive oxygen species (ROS) and malondialdehyde levels and increased antioxidant glutathione and superoxide dismutase levels. Carnosic acid suppressed HH-induced microglia activation and pro-inflammatory response. Additionally, aberrant activation of the NF-κB-NLRP3 inflammasome axis in HACE rats was also inhibited by carnosic acid. Carnosic acid inhibited hypoxia-induced pro-inflammatory microglia activation by the NF-κB-NLRP3 pathway. Moreover, carnosic acid also attenuated hypoxia-activated microglia-induced AQP4 expression in astrocytes and damage to the endothelial tight junction.
CONCLUSION: Carnosic acid may attenuate the pathological progression of HACE by restraining oxidative stress and microglia activation-induced neuroinflammation via the NF-κB-NLRP3 axis, supporting it as a promising neuroprotective intervention for HACE.
METHODS: High-altitude hypobaric hypoxic (HH)-mimicked HACE rats were administered carnosic acid. The effects on hematological parameter changes, blood-brain barrier (BBB) permeability, energetic metabolism disorder, cognitive and motor impairment, oxidative stress, and microglia-mediated neuroinflammation were explored. The function of carnosic acid in microglia-mediated damage to astrocytes and endothelial cells under hypoxia was investigated.
RESULTS: Carnosic acid dose-dependently normalized aberrant hematological parameter changes, brain water content, and histopathological changes in HH-mimicked HACE rats. Moreover, HH conditions enhanced BBB permeability and BBB-related aquaporin 4 (AQP4) expression and decreased BBB-related occludin and zonula occludens-1 (ZO-1) expression, which were reversed after carnosic acid. Carnosic acid alleviated energetic metabolism disorder and improved cognitive and motor impairment in HACE rats. Carnosic acid attenuated HH-evoked oxidative stress by inhibiting reactive oxygen species (ROS) and malondialdehyde levels and increased antioxidant glutathione and superoxide dismutase levels. Carnosic acid suppressed HH-induced microglia activation and pro-inflammatory response. Additionally, aberrant activation of the NF-κB-NLRP3 inflammasome axis in HACE rats was also inhibited by carnosic acid. Carnosic acid inhibited hypoxia-induced pro-inflammatory microglia activation by the NF-κB-NLRP3 pathway. Moreover, carnosic acid also attenuated hypoxia-activated microglia-induced AQP4 expression in astrocytes and damage to the endothelial tight junction.
CONCLUSION: Carnosic acid may attenuate the pathological progression of HACE by restraining oxidative stress and microglia activation-induced neuroinflammation via the NF-κB-NLRP3 axis, supporting it as a promising neuroprotective intervention for HACE.