Honokiol is a polyphenol found in many varieties of Magnolia and is well-known in traditional medicines. Traditionally, it is used for several purposes including sleep, stress, and inflammation. The molecule has a strong lipophilic property, which allows it to readily cross the blood-brain barrier and the blood-cerebrospinal fluid barrier. Developing medicines that are able to cross these barriers is always an obstacle in treating brain and nervous system diseases. That is why diseases such as amyotrophic lateral sclerosis (ALS) are so difficult to treat. Currently, there are not many drugs approved by the FDA for treatment of ALS, and their effects are quite limited.
Why Honokiol, Why Now?
Previously, studies have reported neuroprotective effects of honokiol in multiple animal models of several nervous system diseases. However, none of those previous studies were specifically dealing with ALS. Therefore, a recent study took a look at its impact on a model of ALS.
The first part of this study was done in vitro, using mouse motor neuron cells with known genetic mutations consistent with ALS, to test the effects of honokiol. The studies showed that honokiol has a strong antioxidant capacity. Treating cells with honokiol protected them from oxidative stress and alleviated neurotoxicity.
Two separate in vivo studies were also done. These experiments used a transgenic mouse model. The first animal study tested the behavior and survival of the animals during the disease progression, from the onset up to the end-stage. This part of the study showed the honokiol treatment led to improved motor functions and extended the animals’ lifespans.
The second animal study looked at biochemical and histological analyses after chemical treatment from 11 to 18 weeks. Data collected in this part of the study indicates that honokiol treatment activates the NRF2/GSH pathway and improves mitochondrial function, reversing the degeneration of cells and muscle atrophy.
While honokiol is the main bioactive component of Magnolia, there are also several other bioactive components. Two of these are 4-O-Methylhonokiol and Magnolol. Further research with these components may help to increase the understanding of ALS. On the whole, the positive results found in this study appear to be quite promising. Unquestionably, the search for a cure for this devastating disease must continue.
Zhou Y, Tang J, Lan J, et al. Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis. Acta Pharm Sin B. 2023 Feb;13(2):577-597. doi: 10.1016/j.apsb.2022.07.019. PMID: 36873166