Uses And Pharmacology(PART I)

Magnolia Bark Extract Uses and Pharmacology 

Scientific Name(s): Magnolia officinalis Rehd. et Wils. Family: Magnoliaceae. 

Common Name(s): Magnolia bark , “Hu-bak” (Korea)，Hou Pu(China)

History

MBE has been used for over 1,000?years as a folk medicine in Asia. 4 , 5 In traditional Asian medicine, MBE has been prescribed for treating acute pain, headaches, diarrhea, allergies, asthma, and gynecological disorders. It has also been used to treat fever, anxiety, nervous disorders, depression, muscular pain, abdominal fullness, constipation, and thrombotic stroke. 6 ,7 , 8 , 9 In Chinese and Japanese folk medicine, MBE has been used to treat bronchitis and emphysema. 10

Chemistry

Magnolol and honokiol are the 2 primary active phenolic constituents of MBE. 1 , 2 , 3

Antibacterial In vitro data

In an agar dilution study, honokiol and magnolol inhibited (minimum inhibitory concentration [MIC]?= 25?mcg/mL) the growth of periodontal pathogens Actinobacillus actinomycetemcomitans , Porphyromonas gingivalis , Prevotella intermedia , Micrococcus luteus , and Bacillus subtilis , 11and were less potent than tetracycline. MBE, honokiol, and magnolol were all effective against killing bacteria responsible for halitosis and formation of dental caries (ie, Streptococcus mutans ). 11 , 12 , 13 The MIC ranged from 8?to 31 mcg/mL for magnolol, honokiol, and MBE against Porphyromonas gingivalis , Fusobacterium nucleatum , and S. mutans . Mint candies containing MBE 0.2% reduced oral bacteria by 99.9% within 5?minutes of treatment. Similar antibacterial activity was demonstrated with MBE chewing gum. 12 The antibacterial activity of MBE may include nonionic surface agent activity leading to disruption of the cell membrane and lipid protein interface. 13

Honokiol and magnolol inhibited the growth of acne-causing bacteria Propionibacterium acnes and Propionibacterium granulosum . 14 Both phenolic compounds also reduced inflammation by inhibiting the secretion of interleukin-8 and tumor necrosis factor alpha (TNF-alpha) induced by P. acnes . A human skin irritation test in 30 healthy patients demonstrated no adverse effects from topical application of the phenolic compounds.

MBE may also have antimicrobial activity against Helicobacter pylori . 12

Anti-inflammatory In vitro and animal data

Magnolol reduced swelling and inflammation in edema induced by carrageenan, compound 48/80, polymyxin B, and reversed passive Arthus reaction in mice. 15 When compared with dexamethasone, magnolol did not increase glycogen levels in the liver. The mechanism of action appears to involve reducing the levels of eicosanoid mediators rather than affecting glucocorticoid activity or steroid hormone activity from the adrenal gland. 15 , 16

In mice, honokiol and magnolol reduced inflammatory pain by blocking the inflammatory mediators substance P and prostaglandin E2, and the neurotransmitter glutamate. 17 Honokiol inhibited several signal transduction cascades (eg, protein kinase?C, mitogen-activated protein kinase, nuclear transcription factor kappa-B) involved with regulating inflammatory mediator and gene expression. 18

Alzheimer disease In vitro and animal data

Magnolol and honokiol exhibited central depressant effects by producing sedation, ataxia, muscle relaxation, and a loss of the righting reflex in young chicks. 19 The compound 4-O-methylhonokiol (4-O-MH) promoted neurite outgrowth in a concentration-dependent manner in cultured embryonic neuronal cells. The compound also increased expression of neurotrophins, which are believed to promote neurite outgrowth. 20 An ethanol extract of M. officinalis and 4-O-MH suppressed beta amyloid peptide (eg, Aβ1–42)–induced memory impairment in mice, perhaps by inhibiting neuronal cell death, and increased reactive oxygen species expression. 21The compound 4-O-MH may also inhibit activation of the mitogen-activated protein kinase (MAP kinase) pathway, which is important in neuronal cell death. 22 An ethanol extract of M. officinalis and 4-O-MH improved memory impairment induced by scopolamine in a dose-dependent manner. 23

Cancer In vitro and animal data

Honokiol induced apoptosis and inhibited angiogenesis via the Bcl-2 and caspase-3 pathway in ovarian tumor cells. 24 Honokiol increased apoptotic DNA fragmentation in cultured human prostate cancer cells irrespective of their androgen responsiveness or p53 status and inhibited growth of an androgen-independent p53 mutant cell line xenograft in mice without causing weight loss or any other adverse reactions. 25 Magnolol inhibited growth and induced apoptosis, and G1- and G2/M phase cell cycle arrest in human urinary bladder cancer 5637 cells by activating extracellular signaling. 26 Magnolol inhibited growth of human malignant melanoma A375-S2 cells by both the death receptor pathway and the mitochondrial pathway. 27 Honokiol reduced cell survival and inhibited growth in human chondrosarcoma cells, a malignant primary bone tumor.28 The anticancer activity involves mitochondria dysfunction and induced cell death mediated by increased endoplasmic reticulum stress, eventually resulting in apoptosis. Honokiol induced apoptosis and inhibited HeLa cell proliferation through many proteins and multiple pathways. 29

Magnolol induced apoptosis in human lung cancer CH27 cells through activation of signaling pathways responsible for cell death, including regulation of the Bcl-2 family proteins and release of cytochrome c from mitochondria into the cytosol, leading to activation of the caspase cascade.30

Magnolol and honokiol exhibited cytostatic rather than cytotoxic effects on HL-60 leukemia cells. Both compounds also enhanced vitamin D3 and all- trans -retinoic acid induced HL-60 leukemic cell differentiation. 31

Magnolol suppressed growth of cultured human U373 malignant glioblastoma cells by inhibiting DNA synthesis and activating apoptosis. Magnolol is able to cross the blood brain barrier, as documented by pharmacokinetic studies in rats. 32

Honokiol alone inhibited the growth of human lung cancer A549 in lung carcinoma models, and when combined with cisplatin, enhanced antitumor efficacy by increasing apoptosis and inhibition of angiogenesis. 33 Honokiol inhibited several human breast cancer cell lines, as well as drug-resistant breast cancer cell lines. The mechanism involved inhibition of cell proliferation, induced cell cycle arrest, and apoptosis. Honokiol also enhanced the proapoptotic activity of lapatinib or rapamycin in her-2 over-expressed or low-expressed breast cancer models. 34

Honokiol-hydrogel reduced the number of pleural tumor foci and prolonged survival time in malignant pleural effusion–bearing mice when compared with controls. The mechanism involved inhibition of angiogenesis, and histological analysis of the pleural tumors revealed application of the gel increased the rate of apoptosis. 35

Depression
In vitro and animal data

A mixture of honokiol and magnolol at 20 and 40 mg/kg inhibited stress-induced decreases of serotonin in the frontal cortex, hippocampus, striatum, hypothalamus, and nucleus accumbens in mice. The mixture also increased serotonin metabolite levels in the frontal cortex, striatum, and nucleus accumbens at 40 mg/kg. Honokiol and magnolol also reduced elevated corticosterone concentrations and normalized hypothalamic–pituitary–adrenal hyperactivity and reduced platelet adenylyl cyclase activity by upregulating the cyclic adenosine monophosphate pathway. 36

Experimentally induced depression in mice was inhibited by magnolol and its metabolite hydroxydihydromagnolol. 37 An ethanol extract of a traditional Chinese medicine containing M. officinalis exhibited antidepressant effects in mice similar to the effects of fluoxetine. 38 In a stress-induced model in rats, the combination of honokiol, magnolol, and ginger oil exhibited antidepressant effects. Honokiol and magnolol increased serotonin levels in numerous brain regions, while ginger reduced gastric mucosa cholecystokinin and serum gastrin levels. 39