Honokiol improves cognitive impairment in APP/PS1 mice through activating mitophagy and mitochondrial unfolded protein response

Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis

“…ALS is a fatal neurodegenerative disease characterized by the loss of the upper and lower MNs in the brain and spinal cord with no current effective treatments, although riluzole and edaravone have been approved in clinic. Honokiol is a pleiotropic compound isolated from the plant of Magnolia grandiflora , and has been reported to display neuroprotective effects on several CNS diseases, such as ischemic stroke, Alzheimer's disease and Parkinson's disease, due to its potent antioxidation, anti-excitotoxicity, mitochondrial protection and anti-neuroinflammation 28 , 33 , 45 , 46 , 47 , 48 , 49 . However, whether honokiol has a beneficial function in ALS is unknown.…”

“…Honokiol was reported to display therapeutic activity on the motor deficits and neuronal degeneration in Parkinson's disease by decreasing oxidative stress and inflammation 32 . In addition, honokiol was shown a beneficial effect on the cognitive impairment in APP/PS1 via ameliorating the mitochondrial dysfunction 33 . Honokiol alleviated brain edema and neurobehavioral deficits after subarachnoid hemorrhage through increasing mitochondrial fusion thus maintaining mitochondrial morphology, protecting mitochondrial function, and promoting neural survival 34 .…”

Sirtuins as potential therapeutic targets for mitigating OxInflammation in typical Rett syndrome: plausible mechanisms and evidence

“…Thanks to its safety and tolerability up to 5 g/day in healthy individuals (Patel et al 2011), the natural compound resveratrol may represent a promising candidate for further testing in clinical trials of neurodegenerative disorders and, maybe, for starting in vitro and pre-clinical studies in RTT. Honokiol, a poly-phenolic molecule and SIRT3 activator, even showed neuroprotective properties, enhanced antioxidant activity and mitochondrial function, through activating mitophagy and mtUPR in animal models of Alzheimer's and Parkinson's diseases (Chen et al 2018, Hou et al 2022, which makes this compound another likely candidate to be investigated in trying to counteract mitochondrial alterations typical of RTT.…”

Regulation of Mitophagy by Sirtuin Family Proteins: A Vital Role in Aging and Age-Related Diseases

“…Importantly, a recent study found that mitochondrial debris released from microglia can trigger the A1 astrocytic response, resulting in the propagation of the inflammatory response and neuronal cell death, linking dysfunctional mitochondria and glial cells in the brain and suggesting a potential new intervention for neurodegeneration (Joshi et al, 2019 ). Interestingly, a recent ad study showed that Honokiol (HKL, an extract from bark of Magnolia) can improve the activity of SIRT3 and improve the synaptic damage, mitophagy and mitochondrial dysfunction of hippocampal neurons in a SIRT3 dependent manner, thus exerting anti-AD effect (Hou et al, 2022 ).…”