Recent experimental research has connected magnolia with a transcription factor that is termed the body’s ‘major regulator of cellular antioxidant defence’— nuclear factor erythroid-derived 2-related factor 2 (Nrf2).
A traditional Chinese medicine herb used for stress and anxiety, the mechanism of action for Magnolia officinalis has until now been unclear, despite scientific data supporting its use in nervous system complaints.
The recently revealed connection is an important finding, as it is known that inflammation and oxidative stress are linked to neurological complaints, such as depression.
The active phenolic ingredients in magnolia, honokiol and magnolol, have been attributed to its success in promoting neuroprotection and alleviating anxiety and depressive symptoms. Honokiol, in particular, has been shown to preserve Na+/K+-ATPase activity, phosphorylate pro-survival factors, preserve the mitochondria, and modulate GABA; however, it also prevents glucose, reactive oxygen species (ROS) and inflammatory mediated damage.
Nrf2 is crucial for antioxidant cell support, and knowing the beneficial effect of magnolia on neurological health, researchers hypothesised its effect may be due to the activation of Nrf2. Using various biochemical procedures, researchers were able to demonstrate that magnolia induced Nrf2 activity by destabilising the inhibitory protein, Keap-1, which then allows Nrf2 to translocate to the cell nucleus and activate cellular stress response genes. With HPLC fractionation, they were also able to identify that this action was due to the active phytochemicals in magnolia: honokiol, magnolol and 4-methoxy honokiol.
Another experimental study, which confirmed that persistent oxidative stress increases depression vulnerability, revealed low brain-derived neurotrophic factor (BDNF) prevented Nrf2 activation and consequently prevented the activation of antioxidant enzymes. This resulted in sustained oxidative stress; however, activating Nrf2 restored homeostasis and reversed the vulnerability to depression.
The ability to induce Nrf2 activation provides an indirect antioxidant effect, regulating both basal and inducible expression of cell protectant enzymes. While direct antioxidants, like vitamin C and E, are important, they are consumed in redox reactions and need to be regularly supplied or produced. The activation of Nrf2 produces protective proteins and antioxidant enzymes, which are highly efficient, have long durations of action and half-lives (which means they do not need to be constantly made), and are able to restore endogenous antioxidants, such as CoQ10.
Activation of the Nrf2 pathway by magnolia may even increase the body’s ability to defend against future oxidative stress. ‘Research has shown that transiently activating the Nrf2-pathway through an intake of dietary phytochemicals in the absence of oxidative stressors leads to a robust defense against xenobiotic and oxidative cellular attack.’
- Rajgopal A, Missler SR, Scholten JD. Magnolia officinalis (Hou Po) bark extract stimulates the Nrf2-pathway in hepatocytes and protects against oxidative stress. J Ethnopharmacol2016;193:657-662. [Abstract]
- Liu CS, Adibfar A, Herrmann N, et al. Evidence for inflammation-associated depression. Curr Top Behav Neurosci 2017;31:3-30. [Abstract]
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- Bouvier E, Brouillard F, Molet J, et al. Nrf2-dependent persistent oxidative stress results in stress-induced vulnerability to depression. Mol Psychiatry 2016;00:1-13. [Full text]
- Houghton CA, Fassett RG, Coombes JS. Sulforaphane and other nutrigenomic Nrf2 activators: Can the clinician’s expectation be matched by the reality? Oxid Med Cell Longev. 2016;2016:7857186. [Full text]