Honokiol & Magnolol (Magnolia species)

Various species of the Magnolia plant have a long history of use in traditional medicine throughout Southeast Asia, China and Japan. Constituents of Magnolia are becoming widely studied in the U.S. due to their many potential benefits.

 

Honokiol and Magnolol, the major bioactive constituents of Magnolia bark, are believed to have therapeutic potential in the treatment of neuropathic and inflammatory pain, anxiety, cerebrovascular injury, epilepsy, and cognitive disorders including Alzheimer’s disease. Additionally, Honokiol has neuroprotective properties and improves mitochondrial bioenergetics.

 

See also:

Palmitoylethanolamide (PEA)

Mitochondrial Dysfunction

Traumatic Brain Injury

 

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Honokiol and Magnolol (Magnolia species)

 

More than 250 different constituents have been isolated from the cones, bark, flowers, and leaves of  different Magnolia species including Magnolia officinalis (M. officinalis), M. obovata and M. grandiflora. Of these constituents, honokiol (named after “Honoki”, a Japanese name for M. obovata) and magnolol are the most studied and have the best evidence for clinical benefits.

 

State of Research

Despite well-documented uses of Magnolia in traditional Chinese and Japanese medicine for literally thousands of years and a large number of preclinical laboratory and animal studies, there are practically no clinical studies published in English. 

 

Safety

The biological and pharmacological activities of magnolol and honokiol have been extensively investigated.  Studies indicate that concentrated magnolia bark extract has no mutagenic and genotoxic potential and no serious adverse effects have been identified for concentrated extract > 240 mg/kg /day. Magnolol and honokiol are metabolized by glucuronidation with a relatively quick clearance, but interaction with pharmaceutical active agents or other herbal constituents is possible. Trials of concentrated magnolia bark extract for up to 1 year did not report adverse effects. Over the recent years different food safety authorities have evaluated magnolol and honokiol and considered them safe.

 

Use of Magnolia in Traditional Chinese and Japanese Medicine

Magnolia bark has been used as a constituent of multiple traditional Chinese formulas including “Banxia Houpo Tang,”  “Xiao Zhengai Tang,” “Ping Wei San,” and “Shenmi Tang.” In China, Houpo is still a component used in modern clinical prescriptions. In Japan, two prescriptions containing Magnolia bark, Hange- Koboku-To (Japanese name for Banxia Houpo Tang) and Saiboku-To, are also still in use in modern clinical practice.

 

Magnolia Bark

Herbal preparations containing Magnolia bark extractions are typically used as ingredients in both dietary supplements with doses ranging from 200 to 800 mg/d per person, and cosmetic products. Magnolia bark has a very wide range of applications in Chinese and Japanese traditional medicines for the treatment of anxiety, depression, nervous disorders, asthma, and allergic disease, as well for the alleviation of headaches, muscular pain, and fever.

 

 M. officinalis is also commonly used in traditional Chinese medicine for treating GI disorders including irritable bowel syndrome, abdominal pain, bloating, nausea, vomiting, diarrhea, and constipation probably through an its antispasmodic effect that results in relaxation of GI tract smooth muscles.

 

Magnolia Flowers

The Magnolia flower bud is used almost exclusively for the treatment of sinus congestion and sinus headaches, and is taken orally or applied topically.

 

Conditions with Evidence of Benefit with Honokiol and/or Magnolol

  1. Neuropathic and inflammatory pain
  2. Anxiety & Depression
  3. Neurodegenerative disorders including Alzheimer’s disease
  4. Mitochondria Support

 

Neuropathic and Inflammatory Pain

Honokiol and magnolol decrease neuropathic and inflammatory pain. The mechanisms by which they affect pain suggests that the pain benefits of honokiol related to neuroinflammation are greater than magnolol. Neuroinflammation occurs via the activation of microglia in response to inflammatory stimuli with subsequent microglial release of proinflammatory agents (cytokines and prostaglandins), including TNF alpha, IL-6, and COX-2. A lab study in 2012 showed that honokiol reduces inflammation in brain tissue by down-regulating transcription factors that control the activation of overactive microglia, thus inhibiting the release of these inflammatory agents. Additional mechanisms include actions on glutamate-, NMDA-, CHPG-, PGE2- and substance P-induced pain.

 

Animal studies indicate that early exposure to pain in neonates alters normal neuronal connections and causes anatomic, electrophysiological, and molecular changes that manifest as neurologic and behavioral deficits later in childhood, adolescence, and even adulthood. These changes can lead to long-term decreases in thresholds for pain and stress. It has been speculated that a similar mechanism explains the development of neuropsychiatric problems (anxiety, depression, learning disabilities, and chronic pain) in humans born prematurely, since these infants are typically exposed to multiple needlesticks and other painful procedures including catheterization, circumcision, and chest tube placement.

 

A 2018 study showed that honokiol prevents and reduces both acute and chronic pathological pain-induced deteriorations in neonatal rats. Additional research is needed for this promising means of treating pain in the neonate.

Anxiety & Depression

The bark of M. officinalis is one of the most important traditional herbal medicines in China and Japan used to treat clinical depression and anxiety-related disorders. The oldest known traditional Chinese medicine book, Shennong Bencao Jing, mentions this tranquilizing action. Traditional Japanese Kampo preparations, such as Hange-Koboku-To, Yoku-Kan-san, Saiboku-To, and Kami-Kihi-To, that incorporate M. officinalis have been historically prescribed for clinical depression, anxiety-related disorders and insomnia. In addition to magnolol and honokiol, other M. officinalis constituents that possess pharmacological effects on the nervous systems include the terpenes β-eudesmol and pinenes.

 

Honokiol reduces anxiety at low doses. This can be partially attributed to its interaction with  GABA-A receptors, the same target of benzodiazepines and other anxiolytics. In fact, the injection of flumazenil blocks the anxiolysis from honokiol as it does Valium (diazepam). Honokiol may also alter the brain’s synthesis of GABA, an inhibitory neurotransmitter in the brain.

 

Neurodegenerative disorders including Alzheimer’s disease

Because honokiol can cross the blood-brain barrier and into the cerebrospinal fluid, it is bioavailable to brain and central nervous system. Multiple studies have provided evidence for the neuroprotective effect of honokiol in the central nervous system due to its potent antioxidant activity and suppression of  excitotoxicity related to reduction in neuroinflammation.

 

In addition, recent studies suggest that honokiol can reduce neurotoxicity resulting from the build-up   β-amyloid (Aβ) plaque in Alzheimer’s disease. It has been suggested that there may also be a potential benefit for honokiol in traumatic brain injury (TBI) for prevention of chronic traumatic encephalopathy (CTE).

See: Traumatic Brain Injury

 

Mitochondrial Support

Honokiol is a Sirtuin-3 (SIRT3) activator, an agent that increases mitochondrial functions including antioxidant and energy production. Recent evidence suggests a critical role of reduced SIRT3 activity in the progression of several metabolic and neurodegenerative diseases, including Alzheimer’s disease. A recent study showed that by enhancing SIRT3 expression, honokiol significantly increases antioxidant activity and reduces reactive oxygen species (ROS) generation and lipid peroxidation. Other conditions that are related to mitochondrial dysfunction include fibromyalgia and diabetic peripheral neuropathy.

 

 

References

Honokiol – Availability

 

Honokiol & Magnolol – Overview

  1. Neuro-modulating effects of honokiol – a review – 2013
  2. Biological activity and toxicity of the Chinese herb Magnolia officinalis Rehder & E. Wilson (Houpo) and its constituents – 2017
  3. The Pharmacokinetics and Tissue Distribution of Honokiol and its Metabolites in Rats. – PubMed – NCBI – 2016
  4. Effects of magnolol and honokiol derived from traditional Chinese herbal remedies on gastrointestinal movement – 2014
  5. Magnolol and honokiol account for the anti-spasmodic effect of Magnolia officinalis in isolated guinea pig ileum. – PubMed – NCBI – 2008
  6. Comparative pharmacokinetics and brain distribution of magnolol and honokiol after oral administration of Magnolia officinalis cortex extract and i… – PubMed – NCBI – 2015
  7. [Effects of storage time on magnolol and honokiol contents in bark of Magnolia officinalis]. – PubMed – NCBI – 2008
  8. Is there a potential of misuse for Magnolia officinalis compounds:metabolites? – PubMed – NCBI – 2017
  9. Safety and Toxicology of Magnolol and Honokiol. – PubMed – NCBI – 2018
  10. Neuroprotective effects of honokiol: from chemistry to medicine. – PubMed – NCBI – 2017
  11. Honokiol for the Treatment of Neonatal Pain and Prevention of Consequent Neurobehavioral Disorders – 2018
  12. Herbal Medicine for Anxiety, Depression and Insomnia – 2015
  13. Honokiol Research Review – 2013
  14. Potential use of Magnolia officinalis bark polyphenols in the treatment of cannabis dependence. – PubMed – NCBI
  15. Magnolia Extract, Magnolol, and Metabolites – Activation of Cannabinoid CB2 Receptors and Blockade of the Related GPR55 – 2013
  16. Kampo Medicine – Evaluation of the Pharmacological Activity of 121 Herbal Drugs on GABAA and 5-HT3A Receptors – 2016

 

Honokiol & Magnolol – Anxiety and Depression

  1. Neuro-modulating effects of honokiol – a review – 2013
  2. Combined administration of the mixture of honokiol and magnolol and ginger oil evokes antidepressant-like synergism in rats – 2009
  3. Biological activity and toxicity of the Chinese herb Magnolia officinalis Rehder & E. Wilson (Houpo) and its constituents – 2017
  4. The natural products magnolol and honokiol are positive allosteric modulators of both synaptic and extra-synaptic GABA-A receptors – 2012
  5. Is there a potential of misuse for Magnolia officinalis compounds:metabolites? – PubMed – NCBI – 2017
  6. The anxiolytic effect of two oriental herbal drugs in Japan attributed to honokiol from magnolia bark. – PubMed – NCBI
  7. Herbal Medicine for Anxiety, Depression and Insomnia – 2015 Orofacial pain management – current perspectives – 2014
  8. Modulation of GABAA-receptors by honokiol and derivatives: subtype selectivity and structure-activity relationship. – PubMed – NCBI – 2011
  9. Honokiol Exerts Antidepressant Effects in Rats Exposed to Chronic Unpredictable Mild Stress by Regulating Brain Derived Neurotrophic Factor Level a… – PubMed – NCBI – 2018

Honokiol & Magnolol – Mitochondrial Dysfunction

  1. SIRT3_activator_Honokiol_attenuates_b-Amyloid_by modulating amyloidogenic pathway – 2017

Honokiol & Magnolol – Neurodegenerative Diseases

  1. Neuro-modulating effects of honokiol – a review – 2013
  2. Effects of magnolol and honokiol derived from traditional Chinese herbal remedies on gastrointestinal movement – 2014
  3. Neuroprotective effects of honokiol against beta-amyloid-induced neurotoxicity via GSK-3β and β-catenin signaling pathway in PC12 cells. – PubMed – NCBI – 2016
  4. Comparative pharmacokinetics and brain distribution of magnolol and honokiol after oral administration of Magnolia officinalis cortex extract and i… – PubMed – NCBI – 2015
  5. Neuroprotective effects of honokiol: from chemistry to medicine. – PubMed – NCBI – 2017
  6. SIRT3_activator_Honokiol_attenuates_b-Amyloid_by modulating amyloidogenic pathway – 2017

 

Honokiol & Magnolol – Pain

  1. Neuro-modulating effects of honokiol – a review – 2013
  2. Antinociceptive actions of honokiol and magnolol on glutamatergic and inflammatory pain – 2009
  3. Effects of honokiol and magnolol on acute and inflammatory pain models in mice. – PubMed – NCBI – 2007
  4. Honokiol for the Treatment of Neonatal Pain and Prevention of Consequent Neurobehavioral Disorders – 2018
  5. Orofacial pain management – current perspectives – 2014
  6. Honokiol-Rich Magnolia officinalis Bark Extract Attenuates Trauma-Induced Neuropathic Pain – 2023

Honokiol & Magnolol – Endocannabinoid System

  1. The Natural Product Magnolol as a Lead Structure for the Development of Potent Cannabinoid Receptor Agonists – 2016
  2. Magnolia Extract, Magnolol, and Metabolites – Activation of Cannabinoid CB2 Receptors and Blockade of the Related GPR55 – 2013

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