Magnolia officinalis

Magnolia officinalis is a Traditional Chinese Medicine known for its neuroprotective and relaxing properties, being used to treat depression and anxiety as well as acting as a slight sedative. It may also possess anti-cancer effects in higher doses.

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Magnolia Officinalis is a plant from the Magnolia species of plants which share a set of similar compounds. Two of them, known as Honokiol and Magnolol, are seen as the active ingredients.

Magnolia plants tend to be significantly cancer protective, and show protective effects on the liver and the brain via fighting inflammation and oxidation. They have also been linked to anti-depressant and anxiety reducing effects.

One of the compounds, Honokiol, is currently in trials for usage as an adjunct treatment for cancer therapy.

Benefits can be found with drinking Magnolia teas, known as Saiboku-to, although the tea should be consumed with meals due to the fat-solubility of the active ingredients.

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Also Known As

Saiboku-to, Magnolia Bark Extract, Honokiol, Magnolol


Do Not Confuse With

Moringa oleifera


Things to Note

  • Enemas of magnolia officinalis bark appear to result in higher circulating levels of bioactives than oral ingestion[1]

Is a Form of


Goes Well With

  • Ginger (ginger enhances the antidepressive effects of magnolia officinalis)
  • Pinellia ternata (synergistically antidepressive)

Stacks Part Of increased usefulness


Caution Notice

Examine.com Medical Disclaimer

The dosage of magnolia officinalis to take varies on goal. For those related to GABA (including anxiety, sedation, stress, and epilepsy) an oral dose of 0.2mg/kg in mice appears effective and suggests very lose doses (5-10 mg) are effective in humans.

For those goals related to learning or depression, higher doses may be required. This usually means 15-30mg/kg in rats, and suggests a human dose of:

  • 160-330 mg for a 150lb person
  • 220-440 mg for a 200lb person
  • 270-550 mg for a 250lb person

The above doses refer to the total neolignans (usually magnolol plus honokiol), which are usually at 1-10% of a basic bark extract unless otherwise concentrated.


The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Magnolia officinalis has in your body, and how strong these effects are.
GradeLevel of Evidence
ARobust research conducted with repeated double blind clinical trials
BMultiple studies where at least two are double-blind and placebo controlled
CSingle double blind study or multiple cohort studies
DUncontrolled or observational studies only
Level of Evidence
EffectChange
Magnitude of Effect Size
Scientific ConsensusComments
CDental Health

Notable

An improvement in dental health is noted with gum containing magnolia bark, which outperforms that of Xylitol in regards to reducing acid, plaque, and gum bleeding


Disagree? Join the Magnolia officinalis Discussion

Table of Contents:


Edit1. Sources and Composition

1.1. Sources

Magnolia officinalis (of the family magnoliaceae) is a Traditional Chinese Medicine also commonly referred to as Houpu Magnolia, Kara-koboku,[2] or Magnolia bark since the bark of the tree is the main active ingredient. It is known as a component of two popular compound medications, Saiboku-to or Chai Po Tang (containing the formulation known as minor bupleurum with additional magnolia[3]) and Banxia-houpu (Ginger, the rhizome of pinellia ternata, Poria cocos, and Perilla frutescens[4]) for lung health and depression, respectively. A related herb, magnolia obovata (Wa-koboku)[2] has similar properties as magnolia officinalis.

The bark has traditionally been used for medicinal purposes of cognitive diseases and in particular those related to depression, anxiety, and convulsions.[5]

1.2. Composition

The bark of magnolia officinalis tends to contain:

  • The biphenolic neolignans known as Honokiol[6][7] and Magnolol,[7][6][8] two biphenolic compounds that are commonly seen as the main active ingredients
  • Related biphenolics such as Magnoloside A[9] and 4-0-Methylhonokiol[10]
  • (S)-magnoflorine (alkaloid) and (S)-4-keto-magnoflorine[11]
  • (R)-magnocurarine (alkaloid) and (R)-3,4-dehydromagnocurarine[11]
  • N-feruloylputrescine (trans and cis isomers)[11]
  • N-methylbulbocapine[11]
  • N-methyloxocylonine[11]
  • (S)-tembetarine (alkaloid)[11]
  • (R)-oblongine (alkaloid)[11]
  • (R)-asimilobine (alkaloid)[11]
  • Lotusine[11]
  • Nornuciferine[11]
  • Reticuline[11]
  • Roemerine,[11] Lirinidine,[11] Nandigerine,[11] and Anonaine[11]
  • Beta-eudesmol[9]
  • Syringin[12][13] and its related glycosides[14]
The main bioactives in Magnolia officinalis are the two biphenolic compounds known as Honokiol and Magnolol

Like many plants, the exact composition of the plant differs based on growing conditions and species.[15][16]

1.3. Structure and Properties

The two primary active compounds in Magnolia officinalis are known as Honokiol and Magnolol; two biphenolic structural isomers known as 'neolignans' that exert similar effects in the body.[17][18] They were first noted in plants of the Magnolia family, in teas (known as saiboku-to) used historically to treat asthma and anxiety.[19]


Edit2. Pharmacology

2.1. Serum

Magnolol and Honokiol are known to be highly hydrophobic, making free magnolol and honokiol floating in serum without a transport unlikely. They have been shown in vitro to readily associate with serum albumin, [20] which may be its transport in vivo.

2.2. Metabolism

After oral administration, the component Syringin can be metabolized to Sinapic Acid.[13]

Magnolol either leaves the urine intact or it is metabolized into 3-{2',6-dihydroxy-5'-(2-propenyl){1,1'-biphenyl}-3-yl}-(E)-2-propenoic acid or dihydroxydihydromagnolol (DHHM), which retains some bioactivity.[13]

2.3. Excretion

After ingestion of Saiboku-to (herbal mixture of 10 ingredients, one of which is magnolia officinalis), free magnolol can be found in the urine as well as 8,9-dihydroxydihydromagnolol (DDM).[21] Excretion of these compounds begins after 1-3 hours, and afterwards the rate of excretion declines with a half-life of 1-2 hours.[21]

Elimination half-life does not seem to differ much when comparing a bolus injection against a continual infusion[22] nor does it seem to change significantly when comparing a 2mg/kg dose against 5mg/kg and 10mg/kg.[23]

2.4. Neural

Magnolol can readily pass the blood brain barrier in vivo and reaches levels four times higher in the brain when compared to serum; it shows no real preference as to where in the brain it gets deposited, being quite evenly distributed in measured areas.[23]

Honokiol also appears to effectively cross the Blood Brain Barrier, although the ratios of blood to brain concentrations were not four-fold higher but fluctuated in the 1.29-2.72-fold range.[24]


Edit3. Neurology

3.1. GABAergic Neurotransmission

GABAA receptors have a benzodiazepine binding site, and both honokiol and magnolol appear to be positive allosteric modulators (reducing the amount of a ligand required to activate the receptor).[25] Honokiol (5uM) is able to reduce the EC50 of GABA in binding to these receptors from 200-450nM down to 39-79nM and the same concentration of magnolol reduces the EC50 down to 78-89nM.[25] In a set amount of 200nM GABA, honokiol and magnolol have EC50 values at 0.25-0.61uM and 1.1-1.6uM reaching 22-33% and 34-47% respectively[25] and they have failed to inherently influence neuronal activity when not in the presence of an agonist.[26]

This positive allosteric modulation affects both synaptic and extrasynaptic receptors[26] and when looking at mutations of the GABAA it appears that the site of interaction differs from common neurosteroids, anesthetics, Alcohol, and picrotoxin.[26][27]

Similar to K36 from Scutellaria baicalensis, the neolignans from magnolia officinalis appear to be positive allosteric modulators of the benzodiazepine receptor and are able to enhance the signalling of ligands (activators) of the GABAA receptor despite not inherently activating them

20µM magnolol in vitro appears to enhance the density of GABAA receptors with an α type subunit, without affecting β nor γ type subunits or GAD65/67 (required for GABA synthesis).[28] This increase in the subunit has been noted elsewhere with 4-O-methylhonokiol (oral intake of 0.5mg/kg in mice) and diazepam.[10]

Magnolol appears to be able to increase the overall expression of GABAA receptors with alpha type subunits. This may be biologically relevant following oral ingestion

This positive allosteric modulation is thought to underlie benefits of magnolia officinalis to epilepsy,[29] and anxiety,[10] and sedation.[30][28] It has been noted to be relevant following oral ingestion of doses as low as 0.2mg/kg in mice (enhancing phenobarbital induced sleep).[28]

This interaction with the GABAA receptor is biologically relevant to supplementation of magnolia officinalis, and occurs at doses low enough to be attained with oral intake of standard doses of the supplement

3.2. Glutaminergic Neurotransmission

Honokiol has the ability to prevent NMDA-induced Ca2+ influx into neurons while Magnolol has a more general prevention of Ca2+ influx by NMDA and other means. Both compounds were ineffective in preventing KCl induced Na2+ influx.[31] These effects were shown to increase the NMDA-induced seizure threshold, and may help protect against NMDA-induced seizures.[31] Some active ingredients of Magnolia Bark may also suppress adrenaline secretion from adrenal glands.[32]

Both biphenolic compounds may be anti-glutaminergic

3.3. Cholinergic Neurotransmission

The neolignans (magnolol and honokiol) appear to increase the affinity of muscarine to its receptor (the muscarinic acetylcholine receptors) due to allosterically modifying low affinity receptors to a higher binding capacity, thus causing a greater amount of overall binding.[25] Honokiol and magnolol were both effective, and increased binding 3.2-fold and 2.8-fold (respectively) in rat forebrains and 71% and 64% (respectively) in the cerebellum.[25]

The neolignans appear to positively modulate muscarinic acetylcholine receptors similar to how they influence GABAA receptors

An increase in potassium-evoked acetylcholine release as been noted with honokiol at 10uM (magnolol at 10uM not effective)[33] and later observed in vivo with a direct cerebral infusion of 100uM, although in this instance both honokiol (165.5%) and magnolol (237.86%) were effective in releasing acetylcholine in free moving rats.[34]

4-O-methylhonokiol appears to be a very potent inhibitor of acetylcholinesterase, with an IC50 value of 12nM in vitro.[35] This appears to be biologically relevant with 0.75-1.5mg/kg oral ingestion of 4-O-methylhonokiol or 5-10mg/kg of a methanolic extract of magnolia officinalis.[35]

The neolignans appear to enhance acetylcholine release, which occurs in living creatures; relevance to oral supplementation is not known but honokiol appears somewhat promising due to the low concentration required

In SAMP8 mice (research model of neurological aging and Alzheimer's), oral ingestion of honokiol (1mg/kg but not 0.1mg/kg) and magnolol (10mg/kg but not 1mg/kg) prevented learning deficits associated with preventing a decline in cholinergic function (assessed via ChAT-positive cells in the rat brain).[36] The memory impairment induced by scopolamine is also fully prevented with 4-O-methylhonokiol (0.75-1.5mg/kg) and a methanolic extract of magnolia officinalis (5-10mg/kg), which was attributed to the acetylcholinesterase inhibiting properties of 4-O-methylhonokiol.[35]

The neolignans appear to be neuroprotective in general, and this spills over into cholinergic neurons which appear to be preserved during aging and toxin exposure

3.4. Dopaminergic Neurotransmission

Magnolia officinalis has been found to interact with the dopamine transporter (39% inhibition at 10μg/mL) and to associate with the D5 dopamine receptor (11-64% ligand displacement at 10-100μg/mL) and no influence on the other dopamine receptors (D1, D2S, D3, D4.4).[37] It is not clear if magnolia is an agonist or antagonist at the D5 receptor.[37]

A potential inhibition of the dopamine transporter associated with magnolia officinalis, and although most dopamine receptors do not interact with the extrac tthe D5 receptor may slightly

There appear to be neuroprotective effects of magnolol as 10-20mg/kg intraperitoneal injections for two weeks (alongside the 6-OHDA neurotoxin 30m after the first dose) is able to normalize behavioural alterations when measured on day 15; 1mg/kg appeared to be effective as well.[38]

The standard neuroprotective effects of magnolol appear to extend to dopaminergic neurons

3.5. Adenosinergic Neurotransmission

A carbon dioxide extract of magnolia officinalis appears to have affinity for the adenosine A1 receptor in vitro with a Ki of 9.2+/-1.1μg/mL.[37]

3.6. Serotonergic Neurotransmission

Magnolia officinalis has been found to associate with the serotonin transporter, although whether this was inhibition or not (and the degree of potency at 100μg/mL) was not established.[37]

Injections of magnolol (25-100mg/kg) have been found to inhibit serotonin release in rats which results in a reduction in colonic temperature and metabolic rate (thought to be indicative of sedation), and this is overcome with the addition of 5-HT2 agonists.[39] This is thought to be due to an inhibition of serotonin release, as although magnolol does not inherently influence serotonin release it can inhibit potassium-invoked serotonin release in the concentration range of 1-100μM via a mechanism not related to the serotonin receptors.[40]

Appears to interact with the serotonin transporter (unknown manner) but it can also inhibit serotonin release from neurons, resulting in an anti-serotonergic effect

Magnolia officinalis has been noted to be an agonist at the 5-HT1B receptor (102% activation at 100μg/mL) and an antagonist at the 5-HT6 receptor, although other tested serotonin receptors (5-HT1A, 5-HT4E, 5-HT7) did not associated with magnolia extract.[37] The activation at the 5-HT1B receptor appeared weak, as coincubation with a Ziziphus jujuba extract (inhibited this receptor slightly) prevented magnolia from acting.[37]

The interactions with serotonin receptors appear somewhat weak and may not be practically relevant for oral supplementation of the extract

When administered to rats subject to tests of depression, 15-30mg/kg of a mixture of the two main neolignans failed to modify serotonin concentrations at baseline but greatly prevented the decrease in serotonin following stress testing with a somewhat comparable potency to 7mg/kg fluoxetine (more potent in the striatum and NAc, less in the PFC, equal in other brain regions).[5] This potency was replicated elsewhere with 30mg/kg[41] and 15mg/kg may be as effective as 30mg/kg when paired with 39mg/kg Ginger oil (pairing 30mg/kg magnolia with ginger oil does not exceed its own potency).[41]

The alterations in serotonin seem with depression seem to be normalized with oral intake of neolignans with a potency comparable to SSRIs, although the mechanisms underlying this effect are not known. Ginger appears to make lower doses more efficient without increasing maximal potency

3.7. Sedation

The sedative effects of Magnolia (Magnolol and Honokiol) was first noted in 1983 when anxiolytic and relaxing effects were seen in animals given Magnolia Officinalis.[42]

It appears that magnolol can enhance phenobarbital induced sleep time (0.2mg/kg oral intake)[28] and 5-25mg/kg intraperitoneal injections of magnolol itself can induce sleep (reduce sleep latency, increase REM and non-REM sleep duration) via the GABAA receptor, as blocking this receptor abolishes the effects.[30]

Sedation has been noted with magnolol in isolation, and it appears to augment phenobarbital induced sleep at a very low dose that is easily attainable with supplements. These occur in instances where the rats were going to rest regardless and can be interpreted as aiding the passage of sleep

In studies assessing locomotion as a side effect (GABAA agonists tend to induce sleepiness at improper times as a side-effect), oral ingestion of 4-O-methylhonokiol sufficient to cause anxiolysis does not impair locomotion.[10]

In studies where sleep is not being encouraged, isolated neolignans from magnolia officinalis do not appear to cause sedative-like side-effects

3.8. Anxiety

Neolignans from the magnolia family are commonly used for anxiety reduction[18] in part due to the GABAA interactions; benzodiazepines (acting via this receptor) are known to be a therapy for anxiety[43] and the two neolignans from magnolia officinalis (honokiol and magnolol) are known to interact with these receptors both in vitro[25] and in vivo[2] at doses that are feasible with oral supplementation (0.2-0.5mg/kg oral ingestion in mice).

A third less researched neolignan, 4-O-methylhonokiol, also appears to confer anxiolytic effects in isolation via the GABAA receptor.[10]

The neolignans of magnolia officinalis are thought to possess anxiolytic effects due to their interactions with the GABAA receptor

Supplementation of honokiol at 0.2mg/kg in mice appears to be effective in reducing anxiety.[2]

Oral ingestion of 0.5mg/kg isolated 4-O-methylhonokiol (but not 0.1-0.25mg/kg) to mice appears to confer anxiolytic properties with a potency comparable to the reference drug of 2mg/kg diazepam, although trending to be less potent.[10] This was abolished with a GABAA receptor antagonist, and unlike the reference drug of diazepam the neolignan was not associated with a reduction in locomotion.[10]

The anxiolytic effect appears to extend to rodents

3.9. Stress

In rats subject to depressive stress testing, 15-30mg/kg of a mixture of neolignans daily for two weeks appears to be able to prevent the increase in corticosterone at both doses.[5]

A combination nutraceutical called Relora (A mixture of Magnolia and Phellodendron amurense) has shown efficacy in reducing perceived stress and can acutely reduce anxiety at a thrice daily dose of 250mg, although it doesn't appear to potent in reducing overall anxiety in healthy women.[44] The anti-anxiety and destressing effects of Magnolia appear to be more potent in post-menopausal women[45][46] but the nutrient cofounds in these human studies make direct comparisons difficult.

In persons who suffer from stress-related eating, the Relora combination has been shown to suppress weight gain that is due to stress eating.[47] Similar to Rhodiola Rosea, this is due to a negation of stress eating as these herbs do not inherently possess fat burning potential.

3.10. Depression

A mixture of neolignans from magnolia officinalis (1.6:1 honokiol:magnolol) at 15-30mg/kg oral ingestion for two weeks is able to induce antidepressant effects in rats with a potency comparable (nonsignificantly exceeding) 15mg/kg fluoxetine, an SSRI, when taken at 30mg/kg.[5] This has been noted elsewhere, although the potency of 15mg/kg neolignans can exceed 30mg/kg when paired with Ginger oil (39mg/kg) due to synergism.[41]

In rodents, supplementation of the neolignans from magnolia officinalis appear to exert antidepressive effects

A study conducted in rats with unpredictable chronic stress found that one component of Magnolia, Magnolol, was able to rescue negative changes in serotonergic signalling and BNDF associated with depression[48] and has been replicated in three other rat models of depression.[5] These anti-depression effects are seen at dosages ranging from 20-40mg/kg bodyweight in rats (3.2-6.4mg/kg human) and seem to be synergistically enhanced by Ginger consumption.[41][49]

3.11. Menopausal Symptoms

Two studies currently on Magnolia Officinalis have been conducted in menopausal women, mean ages of around 53 for both studies and slightly overweight BMI on average.[45][46] Although both studies are confounded with coingested nutrients, it appears that Magnolia Officinalis can alleviate insomnia, irritability, anxiety, depression and loss of libido assocaited with menopause.[45]


Edit4. Interactions with Glucose Metabolism

4.1. Mechanisms

Magnolol has been noted to inhibit AGE formation with an IC50 of 65.22μM (more potent than aminoguanidine at 498.12μM) and direct inhibitory effects on the aldose reductase enzyme from rat lens with an IC50 of 24.14μM.[50]

A reduction in AGE formation has been confirmed in diabetic rats fed 100mg/kg magnolol for 13 weeks[51] and streptozotocin induced diabetic mice.[52] Lens opacity has also been confirmed to be reduced, suggesting therapeutic benefits against retinopathy.[53]

Magnolol appears to be able to inhibit the aldose reductase enzyme, which inhibits AGE formation and may reduce the side-effects typically associated with diabetes (retinopathy, neuropathy, nephropathy, etc.)

4.2. Diabetic Nephropathy

Magnolia officinalis appears to be traditionally used for the treatment of diabetes in Korean traditional medicine.[51]

Supplementation of 100mg/kg magnolol daily for 13 weeks in diabetic rats was able to restore insulin function and reduce urinary protein with a potency comparable to 50mg/kg aminoguanidine, while it appeared more effective in reducing AGE formation yet less potent at reducing fasting glucose.[51]

Magnolol appears to be able to reduce urinary proteins in diabetic rats, suggesting a kidney protective effect


Edit5. Obesity and Fat Mass

5.1. Mechanisms

PPAR is an acronym for Peroxisomal Proliferator-Activated Receptor, of which one of the three subsets (PPARγ) is the molecular target of some antidiabetic drugs (thiazolidinediones) as it is expressed in high levels in adipose tissue[54] and upon activation causes insulin sensitization;[55] a side-effect of high PPARγ activation, however, is fat gain as this receptor also positively mediates adipogenesis.[56] It is thought that partial agonists such as balaglitazone,[57] MBX-102/JNJ39659100,[58] or N-Acetylfarnesylcysteine[59] possess the antihyperglycemic properties without the fat gain; as neolignans appear to be ligands for this receptor in general[60] both magnolol and honokiol have been investigated.

Activation of the PPARγ receptor appears to reduce insulin resistance although it promotes fat gain, and since the structural class of molecules that magnolol and honokiol belong to (the neolignans) appear to associate with this receptor they have been investigated

Honokiol appears to be a partial agonist of PPARγ with an EC50 of 3.9µM, which reaches up to two-fold activation; significantly weaker than the reference drug of pioglitazone (300nM reaces 12-fold activation).[61] Despite the differences in potency, honokiol at 3-10µM is able to enhance glucose uptake to a similar degree as 3-10µM pioglitazone (without influencing fat cell differentiation) and 100mg/kg honokiol is comparable to 10mg/kg pioglitazone over 35 days in diabetic mice in reducing blood glucose despite honokiol not being associated with fat gain.[61]

Honokiol can activate both the PPARα and PPARβ/δ receptors as well, albeit requiring a 3-4 fold higher concentration to reach EC50 values.[61] Additionally, honokiol has been associated with causing fat gain in adipocytes elsewhere in the 10-30µM range[62] which was thought to be due to the methodology of the study.[61]

Partial agonists of the PPARγ receptor appear to be able to preserve the antidiabetic effects of this receptor without activating the pro-obesogenic effects, and honokiol appears to be a partial agonist

PPARs need to form heterodimers with receptors known as RXRα (molecular targets of vitamin A)[63] and magnolol appears to be a dual agonist of RXRα (EC50 of 10.4µM[64]) and PPARγ (EC50 of 17.7µM[64] and 1-10µM causing a 1.2-1.3 fold increase[65]).[64] This dual agonism caused a preferential induction of the PPRE (response element) which is mediated by the aforementioned RXRα:PPARγ dimer rather than the RXRE (response element) mediated by a RXRα:RXRα homodimer.[64]

It has been noted to enhance adipocyte differentiation in vitro[65] and 13 weeks of supplementation at 100mg/kg has been noted to reduce symptoms of diabetic nephropathy in rats.[51]

Magnolol also appears to be a PPARγ agonist, with a potency lesser than honokiol but also having affinity towards RXRα

5.2. Weight Gain

In mice given a high fat diet with added magnolol or honokiol (0.02% of the diet) appeared to reduce fat gain in white adipose tissue associated with less inflammatory changes and an increased metabolic rate.[66]


Edit6. Skeleton and Bone Mass

6.1. Dental Health

Periodontitis is a relatively common inflammatory dental condition[67] where oral bacteria such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans release PGE2 (an inflammatory prostaglandin)[68][69] and cause an inflammatory reaction in cells that is associated with an increase in RANKL and reduction in osteoprotegerin (OPG), as RANKL activates the NF-kB receptor.[70].

Oral supplementation (gavage) of 100mg/kg magnolol for nine days to rats appears to reduce bone loss induced by ligature-induced periodontitis (despite not influencing bone density in rats not subject to ligature) associated with suppressing RANKL expression, although even in the presence of RANKL magnolol could suppress its actions.[71]

Beyond the antiinflammatory mechanisms, magnolol (and honokiol) appear to exert antibacterial properties against a variety of bacteria known to cause periodontitis, although with less potency than the reference drugs tetracycline and chlorhexidine.[72][73] The IC50 is approximately 100μM.[71]

The neolignans magnolol and honokiol may be beneficial for oral health and treating periodontitis via their bone health effects as well as anti-bacterial effects


Edit7. Inflammation and Immunology

7.1. Macrophages

Magnolol appears to cause a reduction in intracellular lipids in macrophages at 40-60mM (but not 20mM), which appears to be related to a reduction in adipose differentiation-related protein (ADRP) expression but not from a cAMP/PKA pathway.[74]

May reduce intracellular lipid accumulation, but appears to occur at a very high concentration that may not be practically relevant


Edit8. Interactions with Cancer Metabolism

8.1. Mechanisms

Once in the body, Honokiol can exert potent anti-oxidant effects against hydroxyl radicals (most likely) due to allyl groups on the compound structure.[75][76] This may be used to explain the more significant anti-oxidant abilities of Honokiol over Magnolol, due to greater activity of the allyl formations on the Honokiol molecule relative to the Magnolol molecule.[77][78]

In vitro studies on Honokiol indicate that it may exert apoptosis via decreasing phosphorylation of the MAPK pathway, Akt, and C-Src[79][77] which ultimately suppress nuclear NF-kB signalling.[80] These upstream mechanisms of action seem to induce apoptosis in pathological cells more than normal cells[81] and does so in the presence of the normally inhibitory factors IGF-1 and IL-6.[77][82][83]

Honokiol can exert actions against tumor development on its own, but works synergistically with other anti-cancer interventions[84] perhaps through inhibiton of NF-kB.[77][85] Honokiol has also been shown in one instance to reverse multidrug resistance and perhaps the ABCC transporter gene, two major means of drug efflux.[86] These mechanisms suggest that Honokiol or M.officinalis can potentiate anti-cancer treatment options.

Its suspected to act vicariously through the heat-shock protein Grp94, found on the endoplasmic reticulum of cells.[77][87]

The benefits of Honokiol have been noted with colonic cancer cell lines[88], breast cancer cell lines[89], gastric tumors[87], prostate[90] and a model of lung and bladder cancer cells.[91] When its water-insolubility is overcome with pegylated liposomes it shows some promise in treating ovarian cancer as an adjunct treatment.[92] This same modification potentially increases potency in other cell lines where benefits are seen without, such as lung.[93][94]

Beyond the inhibiting effects of Honokiol on TNF-a induced upstream phosphorylation of intermediates that ultimately reduces NF-kB, Holokiol also may exert apoptotic effects in cells via inducing cyclosporin D expression which increases mitochondrial membrane permeability and oxidation.[95]

8.2. Tumorogenesis

Honokiol, in particular, appears to be effective in reducing or alleviating tumor growth and occurrence in vitro[88][96][97][98] and in vivo.[24]


Edit9. Nutrient-Nutrient Interactions

9.1. Ginger

Ginger appears to be used alongside magnolia officinalis in Traditional Chinese Medicine for the purpose of depression and cognitive disorders alongside a few other herbs, the combination being known as Banxia-Houpu.[99][100]

While magnolia officinalis itself appears to exert anti-depressive effects, ginger is ineffective yet the addition of 14mg/kg ginger oil appears to augment the anti-depressive effects of magnolia officinalis.[49] This has been replicated elsewhere[41] and is thought to be due to a synergistic increase in serotonin,[41] although it seems that while adding 39mg/kg ginger oil to 15mg/kg neolignans can make said neolignans as effective as 30mg/kg adding ginger oil to the higher dose does not augment its potency.[41]

Although ginger itself does not have anti-depressant properties, it appears to augment the antidepressant effects of magnolia officinalis in a synergistic manner. This synergism seems to be due to ginger making low doses of magnolia more effective, but does not appear to increase the maximal potency of magnolia neolignans

9.2. Pinelliae Rhizome

Another component of Banxia-Houpu alongside both ginger and magnolia offcinalis is Pinellia Rhizome (root of pinellia ternata) and while it also appears to have inherent anti-depressant effects it works synergistically with magnolia officinalis in exerting them.[101] This has been noted elsewhere where the combination of 15mg/kg magnolia neolignans paired with 16-32mg/kg pinellia ternata rhizome was able to preserve noradrenaline concentrations in stressed rats; in this sense, since the neolignans were inactive while pinellia was weakly active the synergism seems to be from the neolignans potentiating the effects of pinellia.[41]

Pinelliae Rhizome appears to have antidepressant properties that are synergistic with the antidepressant properties of magnolia officinalis. This may be due to weak effects on serotonin (magnolia) and noradrenaline (pinellia) with the coingestion causing a mutual synergism on both neurotransmitters

References

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  3. Naito A, Satoh H, Sekizawa K. Asthma as well as anxiety improved by the Kampo extract Saiboku-to. Eur J Intern Med. (2005)
  4. Luo L, et al. Antidepressant effects of Banxia Houpu decoction, a traditional Chinese medicinal empirical formula. J Ethnopharmacol. (2000)
  5. Xu Q, et al. Antidepressant-like effects of the mixture of honokiol and magnolol from the barks of Magnolia officinalis in stressed rodents. Prog Neuropsychopharmacol Biol Psychiatry. (2008)
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(Common misspellings for Magnolia officinalis include magnolea, manolia, magnola, manola, honokeol, honokol, magnol, magnlol, saibokuto, saiboto)

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