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crenulata and its active metabolites can inhibit the NF-B/NLRP3 pathway to reduce HH-induced brain oxidative stress damage, inflammatory responses, and BBB damage, which are attributed to improved energy metabolism and the anti-inflammatory M2 microglial phenotype ( Rhodiola crenulata and salidroside can exert anti-hypoxia neuroprotective effects by inhibiting neuronal apoptosis, maintaining BBB integrity, increasing tight junction proteins claudin-1, ZO-1, and occludin, and improving mitochondrial morphology and function, possibly through activation of the AMPK/Sirt1 signaling pathway ( Rhodiola crenulata extracts exert antioxidant effects by scavenging lipid peroxidation products (e.g., MDA) and enhancing SOD activity, regulating cell apoptosis and mitochondrial energy metabolism through the HIF-1/microRNA 210/ISCU1/2 (COX10) signaling pathway, and inhibiting caspase-3 activation to improve brain tissue energy metabolism disorders to alleviate HH-induced brain damage (Wang et al., 2019)
