Uses And Pharmacology(PART II)

Diabetes
In vitro and animal data

Other pharmacologic activity
Antioxidant

In vitro and animal studies document potent antioxidant activity for magnolol and honokiol in protecting against myocardial and cerebral ischemia by inhibiting neutrophil infiltration and reactive oxygen species production. 48 , 49 , 50

Magnolol and honokiol have weak activity against HIV-1 in human peripheral blood mononuclear cells. 51

Extracts of M. officinalis may have benzodiazepine -like activity as documented by a strong affinity on the benzodiazepine -binding site of the gamma aminobutyric acid (GABA) receptor . Honokiol also interacts with the GABA receptor and exhibited activity similar to that of diazepam . 8 , 52

Magnolol inhibited expression of monocyte chemoattractant protein-1 in vascular smooth muscle cells, which contributes to the development of atherosclerosis and re-stenosis. 53 Magnolol also induced apoptosis 53 and inhibited cell viability in TNF-alpha cytokine 54 -stimulated vascular smooth muscle cells. Magnolol's antioxidant activity appears to also play a role in preventing atherosclerotic vascular disease. 55 , 56 Antiplatelet activity relaxes vascular smooth muscle by releasing endothelium-derived relaxing factor and inhibiting calcium influx through voltage-gated calcium channels. 57

Magnolol may stimulate corticosterone secretion by the adrenal gland, a mechanism similar to the action of exogenous glucocorticoids in the treatment of asthma. 58

Honokiol reduced the infarct zone, duration of ventricular tachycardia, and ventricular fibrillation in coronary ligated rats. 59 The cardioprotective effect may be associated with increased nitric oxide synthesis. 60

Honokiol inhibited hydrogen peroxide–induced apoptosis in human lens epithelial cells by modulating various signaling pathways in cataract formation. 61

Honokiol and magnolol blocked calcium-dependent uterine oscillatory contractions in rat uterus. 5The mechanism may be associated with blocking receptor-operated cation and voltage-operated calcium channels. 5

Magnolol reduced acetaminophen-induced liver damage in rats by inhibiting lipid peroxidation and formation of reactive oxygen species. 6 Honokiol reversed the effects of induced alcoholic fatty liver in rats by inhibiting lipid accumulation or fatty acid synthesis. 62

Honokiol and magnolol inhibited excitatory amino acid-evoked cation signals and N -methyl-D-aspartate acid (NMDA)–induced seizures. 63 Honokiol was more selective in blocking the NMDA receptor and demonstrated greater inhibition against NMDA-induced seizures.

Magnolol prevented hypotension, bradycardia, and multiple organ failure induced by lipopolysaccharide in rats. 64 Potential mechanisms of action include: reducing the plasma TNF-alpha and nitrate/nitrite concentrations, suppressing organ superoxide anion level, and suppressing the blood coagulation cascade and expression of inflammatory genes.

Dosage

MBE is commercially available in the United States and throughout Europe, as documented by Internet search engines. Dosage varies depending on the condition treated, with weight loss products containing MBE available mostly in powder form. Several strengths are available for Relora , a patented blend marketed as “a natural stress management supplement” that includes MBE. Dosing recommendations include taking a 300?mg capsule of Relora 2 to 3 times per day. A small, randomized, controlled study treated patients with one 60?mg tablet of MBE daily to help relieve menopausal symptoms. 45

Pregnancy/Lactation

Avoid use during pregnancy and lactation because of limited clinical data. An animal study documented that honokiol and magnolol blocked calcium-dependent uterine oscillatory contractions in rat uterus. 5

Interactions

Drug-herb interactions are documented, and caution is advisable in patients self-medicating with MBE. Magnolol may interact with acetaminophen ; one study documented reduced acetaminophen -induced liver damage in rats. 6 Additive adverse reactions with antiplatelet medications may occur in patients also self-medicating with magnolol. 57 MBE and honokiol may interact with benzodiazepines . 8 , 52 Magnolol may stimulate corticosterone secretion 58 or increase steroid medication concentrations. 65 MBE may cause excess sleepiness, vertigo, and dizziness in patients taking muscle relaxants .

Adverse Reactions

No adverse dermatologic effects were documented with topical application of magnolol and honokiol. 14 In one small clinical trial, a patient dropped out because of a number of adverse reactions, including heartburn, shaking hands, perilabial numbness, sexual dysfunction, and thyroid dysfunction. 46

Toxicology

Dietary administration of MBE in rats at doses of up to 480 mg/kg in a 21-day study and 240 mg/kg in a 90-day study resulted in no clinically important toxicity. 7 Some sources document the development of progressive interstitial renal fibrosis in patients consuming an herbal blend containing M. officinalis . 66 , 67 In vitro studies demonstrate no genotoxic effects from MBE in chromosomal aberration assays. 68 One study documented that magnolol in liver graft preservation enhanced apoptotic events under cold preservation instead of preserving hepatocyte integrity. 69

Bibliography

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2. Shen CC, Ni CL, Shen YC, et al. Phenolic constituents from the stem bark of Magnolia officinalis . J Nat Prod . 2009;72(1):168-171.
3. Tong, ZK, Zeng YR & Si JP. Variation, heredity and selection of effective ingredients in Magnolis officinalis of different provenances. J Forestry Res . 2002;13(1):7-11.
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5. Lu YC, Chen HH, Ko CH, Lin YR, Chan MH. The mechanism of honokiol-induced and magnolol-induced inhibition on muscle contraction and Ca2+ mobilization in rat uterus. Naunyn Schmiedebergs Arch Pharmacol . 2003;368(4):262-269.
6. Chen YH, Lin FY, Liu PL, et al. Antioxidative and hepatoprotective effects of magnolol on acetaminophen -induced liver damage in rats. Arch Pharm Res . 2009;32(2):221-228.
7. Liu Z, Zhang X, Cui W, et al. Evaluation of short-term and subchronic toxicity of magnolia bark extract in rats. Regul Toxicol Pharmacol . 2007;49(3):160-171.
8. Squires RF, Ai J, Witt MR, Kahnberg P, et al. Honokiol and magnolol increase the number of [3H] muscimol binding sites three-fold in rat forebrain membranes in vitro using a filtration assay, by allosterically increasing the affinities of low-affinity sites. Neurochem Res . 1999;24(12):1593-1602.
9. Jeong SI, Kim YS, Lee MY, et al. Regulation of contractile activity by magnolol in the rat isolated gastrointestinal tracts. Pharmacol Res . 2009;59(3):183-188.
10. Konoshima T, Kozuka M, Tokuda H, et al. Studies on inhibitors of skin tumor promotion, IX. Neolignans from Magnolia officinalis . J Nat Prod . 1991;54(3):816-822.
11. Ho KY, Tsai CC, Chen CP, Huang JS, Lin CC. Antimicrobial activity of honokiol and magnolol isolated from Magnolia officinalis . Phytother Res . 2001;15(2):139-141.
12. Greenberg M, Urnezis P, Tian M. Compressed mints and chewing gum containing magnolia bark extract are effective against bacteria responsible for oral malodor. J Agric Food Chem . 2007;55(23):9465-9469.
13. Greenberg M, Dodds M, Tian M. Naturally occurring phenolic antibacterial compounds show effectiveness against oral bacteria by a quantitative structure-activity relationship study. J Agric Food Chem . 2008;56(23):11151-11156.
14. Park J, Lee J, Jung E, et al. In vitro antibacterial and anti-inflammatory effects of honokiol and magnolol against Propionibacterium sp. Eur J Pharmacol . 2004;496(1-3):189-195.
15. Wang JP, Hsu MF, Raung SL, Chen CC, Kuo JS, Teng CM. Anti-inflammatory and analgesic effects of magnolol. Naunyn Schmiedebergs Arch Pharmacol . 1992;346(6):707-712.
16. Wang JP, Ho TF, Chang LC, Chen CC. Anti-inflammatory effect of magnolol, isolated from Magnolia officinalis , on A23187-induced pleurisy in mice. J Pharm Pharmacol . 1995;47(10):857-860.
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19. Watanabe K, Watanabe H, Goto Y, Yamaguchi M, Yamamoto N

Magnolol reduced metabolic parameters common in diabetic nephropathy, such as blood glucose, plasma insulin, sorbitol, and advanced glycation end products in an experimental type 2 diabetes rat model. Magnolol also attenuated upregulation of renal transforming growth factor beta?1, which plays a key role in the pathogenesis of diabetic nephropathy, and reduced expression of extracellular matrix protein as type IV collagen. 40 In mature adipocytes, magnolol improved insulin sensitivity by increasing basal and insulin stimulated glucose uptake through peroxisome proliferator-activated receptors. 41 KIOM-4, a plant extract obtained from M. officinalis , protected pancreatic beta cells against streptozotocin-induced oxidative damage. 42KIOM-4 induced a rate-limiting enzyme through the extracellular regulated kinase pathway, which resulted in cytoprotection against diabetic conditions and increased insulin release from the pancreas. Another plant extract combination containing M. officinalis , KIOM-79, inhibited xylose-induced lens opacity. 43 KIOM-79 also protected human lens epithelial-B3 cells from the toxic effects of high glucose levels by inhibiting transforming growth factor beta, which is involved in the pathophysiology of ocular damage. An antioxidant mechanism may be involved with KIOM-79, protecting against oxidative stress-induced apoptosis in diabetic retinopathy. 44

Menopause
Clinical data
 

A small, controlled, randomized, multicenter study examined the effects of 2 formulations, one containing magnolia bark extract (60?mg) and magnesium (50?mg), in symptomatic menopausal women with sleep or mood alterations. The magnolia extract and magnesium combination appeared to be effective in reducing psychoaffective and sleep disturbances from menopause.45 A small pilot study examined the effects on body weight from a dietary supplement containing extracts of M. officinalis and Phellodendron amurense in 28 premenopausal women. 46 The supplement reduced evening cortisol levels and may have improved systolic blood pressure as well as perceived stress. Another randomized, placebo-controlled trial indicated that the same dietary supplement may reduce mild transitory anxiety in premenopausal women. 47