HH-A, a honokiol derivative, alleviates hypoxic brain injury in the animal ischemic model by interacting with hemoglobin.

Exposure to hypoxic conditions can result in significant brain damage, such as that experienced during an ischemic stroke. Thus, finding ways to mitigate ischemia/hypoxia-induced brain tissue damage is a critical issue that needs addressing. HH-A, a derivative of honokiol, has demonstrated potent pharmacological activities and medicinal properties in treating brain ischemia/reperfusion injury. However, its effect on anti-hypoxic responses during stroke remains largely unexplored. In the present study, we subjected male Sprague-Dawley rats to 24 h of hypoxia (oxygen content at 11%) or to 7 d of permanent middle cerebral artery occlusion. We discovered that both 1 mg/kg (i.v.) and 40 mg/kg (i.g.) of HH-A elevated arterial oxygen saturation after 24 h of hypoxia and significantly reduced the infarct volume after 7 d of ischemia. Furthermore, fluorescence staining with hypoxyprobe-1 indicated that HH-A significantly mitigated the severity of hypoxia in brain tissue. Hematoxylin and eosin staining, along with neuronal nuclei immunofluorescent staining, further revealed that HH-A curbed the death of brain cells. To identify potential protein partners of HH-A, we used a molecular fishing approach based on surface plasmon resonance technology. A high binding affinity was detected between HH-A and the hemoglobin subunit beta, with an estimated binding free energy of -8.7 kcal/mol. These findings suggested that HH-A was capable of enhancing hypoxia tolerance and alleviating brain injury caused by ischemia. [ABSTRACT FROM AUTHOR]