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Steel Magnolia (Bark): The Power of Honokiol

Sept 21, 2023 | Written by Scott Sherr, MD | Reviewed by Marion Hall

Have you ever heard of honokiol and its potential therapeutic benefits? If your answer is no, then this article is for you!

Honokiol is a natural compound derived from the bark and seed cones of the Magnolia tree. It has a long history of use in traditional medicine, particularly in East Asia. It has gained significant attention in recent years due to its potential therapeutic properties, especially as an allosteric modulator of GABA receptors.

Honokiol's History

The synthesis of honokiol began in the 1990s when researchers started exploring its chemical structure and properties. Through various extraction and purification techniques, scientists were able to isolate and synthesize honokiol in a laboratory setting. This breakthrough allowed for further investigation into its potential applications.

How Honokiol Works

One of the key mechanisms of honokiol is its interaction with GABA receptors in the brain. GABA receptors are responsible for regulating the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which plays a crucial role in reducing neuronal excitability.

It is believed that honokiol acts as a positive allosteric modulator of GABA receptors, meaning that it enhances the receptor's response to GABA. This interaction can lead to increased GABAergic neurotransmission, promoting relaxation and reducing anxiety.

Furthermore, honokiol has been found to increase the activity of the enzyme glutamic acid decarboxylase (GAD), which is responsible for synthesizing GABA. By increasing GAD activity, honokiol can potentially boost GABA production, further enhancing its calming effects.

Several studies have investigated the interaction between honokiol and GABA receptors. One study published in Neuropharmacology found that honokiol increased GABAergic neurotransmission in the hippocampus, a brain region involved in memory and emotions. Another study published in Psychopharmacology demonstrated that honokiol exerted anxiolytic effects through its interaction with GABA receptors.

In addition to its effects on GABA receptors, honokiol also interacts with other receptors in the brain, such as those of serotonin and dopamine. These interactions contribute to its anxiolytic, antidepressant, and neuroprotective properties.

The more active form of honokiol, dihydrohonokiol beta (DHHB), has similar effects to honokiol but has a greater affinity for the allosteric site on the GABA receptor.

Honokiol's Benefits

Several clinical studies have investigated the potential therapeutic benefits of honokiol in both humans and animals. These studies have shown promising results in various areas, such as:

Anxiety and Stress Reduction

A study published in the Journal of Ethnopharmacology found that honokiol exhibited anxiolytic effects in mice, reducing anxiety-like behaviors. Another clinical trial conducted on humans showed that honokiol supplementation reduced anxiety symptoms and improved overall well-being.

Anticancer Properties

Research has demonstrated that honokiol possesses potent anticancer properties. It has been found to inhibit the growth of various cancer cells, including breast, lung, prostate, and colon cancer. Honokiol's ability to induce apoptosis (programmed cell death) and inhibit angiogenesis (formation of new blood vessels) makes it a promising candidate for cancer treatment.

Neuroprotective Effects

Studies have shown that honokiol has neuroprotective effects, making it potentially beneficial for neurodegenerative disorders such as Alzheimer's and Parkinson's disease. It has been found to protect neurons from oxidative stress, reduce inflammation, and enhance cognitive function.

Honokiol Safety

Despite honokiol's many benefits, several studies have also highlighted its potential drawbacks. These studies suggest that at very high doses, honokiol may have potential neurotoxicity, raising concerns about its impact on the nervous system. Beyond that, at elevated concentrations, honokiol may lead to gastrointestinal disturbances and hepatotoxicity, potentially causing liver damage.

These findings emphasize the importance of carefully considering dosages and monitoring honokiol's use in clinical applications to mitigate potential adverse reactions. As with any medicinal compound, make sure to do your research and ask your doctor before use to avoid negative reactions with any medications you may currently be taking!


Honokiol shows great potential as a natural compound with various therapeutic benefits, especially as a positive allosteric modulator of the GABA receptor. Because when there is more GABA, the brain is more relaxed, less stressed, calms (and sleeps) easier, and much more. 

Have you tried honokiol? Would you like to? Then check out Tro Zzz, our buccal troche formulated for sleep, which has honokiol as one of its main ingredients!



  1.  Liou KT, Lin SM, Huang SS, Chih CL, Tsai SK. Honokiol ameliorates cerebral infarction from ischemia-reperfusion injury in rats. Planta Med. 2003;69(2):130-134. doi: 10.1055/s-2003-37707
  2. Sarrica A, Kirika N, Romeo M, Salmona M, Diomede L. Safety and Toxicology of Magnolol and Honokiol. Planta Med. 2018;84(16):1151-1164. doi: 10.1055/a-0642-1966
  3. Chen XR, Lu R, Dan HX, Liao G, Zhou M, Li XY, Ji N. Honokiol: A promising small molecular weight natural agent for the growth inhibition of oral squamous cell carcinoma cells. Int. J. Oral Sci. 2011;3(10):34-42. doi: 10.4248/IJOS11014
  4. Woodbury A, Yu SP, Wei L, García P. Neuro-modulating effects of honokiol: a review. Front Neurol. 2013;4:130. Published 2013 Sep 11. doi: 10.3389/fneur.2013.00130
  5. Xu Y et al. Honokiol improves cognitive impairment by inhibiting ferroptosis and activating the Nrf2/ARE signaling pathway in a mouse model of Alzheimer's disease. Journal of Molecular Neuroscience 2019;68(2):263-275.

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