Magnolol

266.34

266.33

001E35HGVF

293099

DTXSID0044076

2907299090

40.5

5

White powder; Bitter aroma

1.1±0.1 g/cm3

103 °C

178-180 °C @ Press: 1 Torr

184.5±21.9 °C

1.602

In water, 1.24 mg/L at 25 deg C (est)

2-8°C

4.37X10-7 mm Hg at 25 deg C (est)

LD50 orl-mus: 2200 mg/kg BRXXAA #5135746

Henry's Law constant = 9.41X10-12 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 1.12X10-10 cu cm/molec-sec at 25 °C (est)|Ozone radical reaction rate constant = 2.4X10-17 cu cm/molec-sec at 25 °C (est)

UN 3077

3

37/38-41-51/53

26-39-61

DV5105500

N

P261-P273-P280-P305 + P351 + P338

H315-H318-H335-H411

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

|Danger|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P273, P280, P302+P352, P304+P340, P305+P351+P338, P310, P312, P321, P332+P313, P337+P313, P362, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 70 companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Three neolignans, known as magnolol, honokiol and the new monoterpenylmagnolol, were isolated from the bark of Magnolia officinalis ... . The MeOH extract of this plant and magnolol exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two stage carcinogenesis test...|Magnolol has been reported to strongly inhibit the mutagenicity induced by indirect mutagens in the Ames test as well as the clastogenicity induced by benzo(a)pyrene (B(a)P) in the mice micronucleus test. Here, ... the inhibitory effect of magnolol on the DNA damage induced by 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) /was evaluated/ in various organs using the mice alkaline single cell gel electrophoresis (SCG) assay. Animals were treated with a single oral administration of magnolol (0.01, 0.1, 1, 10, and 100 mg/kg), followed by a single intraperitoneal injection of Trp-P-2 (10 mg/kg). The liver, lung, and kidney were removed at 3 hr after treatment and used in SCG assay. The results indicated that magnolol inhibited Trp-P-2-induced DNA damage in various organs. To elucidate the mechanism of this inhibitory effect against Trp-P-2, we investigated the inhibitory effect of magnolol on in vivo CYP1A2 activity using the zoxazolamine paralysis test. Magnolol significantly prolonged zoxazolamine paralysis time and showed an inhibitory effect on in vivo CYP1A2 activity. These results indicate that magnolol has an inhibitory effect on the DNA damage induced by Trp-P-2 in various organs in vivo. This inhibitory mechanism is considered due to in vivo CYP1A2 inhibition.|... The in vivo anti-clastogenic effect of magnolol against clastogenicity induced by B(a)P was evaluated using the micronucleus test in mice. Animals were treated with an oral administration of magnolol (1, 10, and 100 mg/kg) at -24, 0, 24, 48, 72, and 96 hr before a single intraperitoneal injection of B(a)P. Peripheral blood specimens were prepared 48 h after administration of B(a)P, and analyzed by the acridine orange (AO) technique. The results indicated that magnolol inhibited clastogenicity induced by B(a)P at various administration times. In order to elucidate the mechanism behind this effect, we measured the activity of the detoxifying enzymes [UDP-glucuronosyltransferase (UGT) and glutathione-S-transferase (GST)] and antioxidative enzymes [superoxide dismutase (SOD) and catalase] in the liver when treated with an oral administration of magnolol at various administration times. Its effect on clastogenicity created by exposure to oxidative DNA damage-inducing X-ray irradiation was also evaluated using the micronucleus test in mice. Results showed that magnolol increased the activity of both UGT and SOD enzymes, and also inhibited the clastogenicity induced by X-ray irradiation. Magnolol had an anti-clastogenic effect on B(a)P in the micronucleus test as well as an anti-mutagenic effect on indirect mutagens in the Ames test. The anti-clastogenic effect of magnolol was also suggested by the increases in UGT and SOD enzyme activity, and by the attenuation of oxidative damage induced by X-ray irradiation.|... Anti-mutagenic activity of magnolol against mutagenicity induced by direct mutagens [1-nitropyrene (1-NP), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)] and indirect mutagens [2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), benzo(a)pyrene (B(a)P), 2-aminoanthracene (2-AA) and 7,12-dimethylbenz[a]anthracene (DMBA)] were investigated using the bacterial mutagenicity test (Ames test). Results show that magnolol strongly inhibits mutagenicity induced by indirect mutagens, but does not affect direct mutagens. To elucidate the mechanism of this effect against indirect mutagens, effect of magnolol on CYP1A1- and CYP1A2-related enzyme activities of ethoxyresorufin-O-deethylase (EROD) and methoxyresorufin-O-demethylase (MROD) were investigated. Magnolol strongly and competitively suppressed these enzyme activities, suggesting it inhibited mutation induced by indirect mutagens through suppression of CYP1A1 and CYP1A2 activity.|A23187-induced pleurisy in mice was used to investigate the anti-inflammatory effect of magnolol, a phenolic compound isolated from Chinese medicine Hou p'u (cortex of Magnolia officinalis). A23187-induced protein leakage was reduced by magnolol (10 mg/kg, ip), indomethacin (10 mg/kg, ip) and BW755C (30 mg/kg, ip). A23187-induced polymorphonuclear (PMN) leukocyte infiltration in the pleural cavity was suppressed by magnolol and BW755C, while enhanced by indomethacin. Like BW755C, magnolol reduced both prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels in the pleural fluid of A23187-induced pleurisy, while indomethacin reduced PGE2 but increased LTB4 formation. In the rat isolated peripheral neutrophil suspension, magnolol (3.7 uM) and BW755C (10 microM) also suppressed the A23187-induced thromboxane B2 (TXB2) and LTB4 formation. These results suggest that magnolol, like BW755C, might be a dual cyclo-oxygenase and lipoxygenase inhibitor. The inhibitory effect of magnolol on the A23187-induced pleurisy is proposed to be, at least partly, dependent on the reduction of the formation of eicosanoids mediators in the inflammatory site.

LD50 Mouse oral 2200 mg/kg /from table/

Magnolol and honokiol, biphenyl compounds, were isolated as anti-emetic principles from the methanolic extract of Magnolia obovata bark(1). Magnolia bark extract (MBE) is an extract of the dried stem, root, or branch bark of magnolia trees(2).

Magnolol's production and use as a traditional medicine(1) may result in its release to the environment through various waste streams(SRC).

Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. (See all compounds classified as Anti-Arrhythmia Agents.)|Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. (See all compounds classified as Platelet Aggregation Inhibitors.)|Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)

To investigate the relationship between magnolol and the clinical effects of Saiboku-To, urinary magnolol excretion was compared in responders and non-responders under long-term Saiboku-To treatment. The clinical outcome of the Saiboku-To treatment was evaluated in nine asthmatic patients at 52 weeks after the onset of the treatment, using individual fluctuation of asthmatic points obtained from the patients' diary cards. Three patients whose clinical conditions were improved by the treatment were termed responders and six others were termed non-responders. The difference in the amounts of the total magnolol excreted were not significant; however, free (or non-conjugated) amounts of magnolol excreted in the responders were 7 times those in the non-responders (P < 0.05). These results suggest that the magnolol might be responsible for the therapeutic effect of Saiboku-To, indicating practical bioavailability in the responders.

Magnolol has known human metabolites that include (2S,3S,4S,5R)-3,4,5-trihydroxy-6-[2-(2-hydroxy-5-prop-2-enylphenyl)-4-prop-2-enylphenoxy]oxane-2-carboxylic acid.

The effects of honokiol and magnolol, two major bioactive constituents of the bark of Magnolia officinalis, on Ca(2+) and Na(+) influx induced by various stimulants were investigated in cultured rat cerebellar granule cells by single-cell fura-2 or SBFI microfluorimetry. Honokiol and magnolol blocked the glutamate- and KCl-evoked Ca(2+) influx with similar potency and efficacy, but did not affect KCl-evoked Na(+) influx. However, honokiol was more specific for blocking NMDA-induced Ca(2+) influx, whereas magnolol influenced with both NMDA- and non-NMDA activated Ca(2+) and Na(+) influx. Moreover, the anti-convulsant effects of these two compounds on NMDA-induced seizures were also evaluated. After honokiol or magnolol (1 and 5 mg/kg, ip) pretreatment, the seizure thresholds of NMRI mice were determined by tail-vein infusion of NMDA (10 mg/mL). Data showed that both honokiol and magnolol significantly increased the NMDA-induced seizure thresholds, and honokiol was more potent than magnolol. These results demonstrated that magnolol and honokiol have differential effects on NMDA and non-NMDA receptors, suggesting that the distinct therapeutic applications of these two compounds for neuroprotection should be considered.|Magnolol inhibited phorbol 12-myristate 13-acetate (PMA)-activated rat neutrophil aggregation in a concentration-dependent manner with an IC50 (concentration resulting in 50% inhibition) of 24.2 +/- 1.7 uM. Magnolol suppressed the enzyme activity of neutrophil cytosolic and rat brain protein kinase C (PKC) over the same range of concentrations at which it inhibited the aggregation. Magnolol did not affect PMA-induced cytosolic PKC-alpha and -delta membrane translocation or trypsin-treated rat-brain PKC activity, but attenuated [3H]phorbol 12,13-dibutyrate binding to neutrophil cytosolic PKC. These results suggest that the inhibition of PMA-induced rat neutrophil aggregation by magnolol is probably attributable, at least in part, to the direct suppression of PKC activity through blockade of the regulatory region of PKC.|Magnolol, a substance purified from the bark of Magnolia officialis, inhibits cell proliferation and induces apoptosis in a variety of cancer cells. The aim of this study was to study the effects of magnolol on CGTH W-2 thyroid carcinoma cells. After 24 hr treatment with 80 u M magnolol in serum-containing medium, about 50% of the cells exhibited apoptotic features and 20% necrotic features. Cytochrome-c staining was diffused in the cytoplasm of the apoptotic cells, but restricted to the mitochondria in control cells. Western blot analyses showed an increase in levels of activated caspases (caspase-3 and -7) and of cleaved poly (ADP-ribose) polymerase (PARP) by magnolol. Concomitantly, immunostaining for apoptosis inducing factor (AIF) showed a time-dependent translocation from the mitochondria to the nucleus. Inhibition of either PARP or caspase activity blocked magnolol-induced apoptosis, supporting the involvement of the caspases and PARP. In addition, magnolol activated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and inactivated Akt by decreasing levels of phosphorylated PTEN and phosphorylated Akt. These data suggest that magnolol promoted apoptosis probably by alleviating the inhibitory effect of Akt on caspase 9. Furthermore, inhibition of PARP activity, but not of caspase activity, completely prevented magnolol-induced necrosis, suggesting the notion that it might be caused by depletion of intracellular ATP levels due to PARP activation. These results show that magnolol initiates apoptosis via the cytochrome-c/caspase 3/PARP/AIF and PTEN/Akt/caspase 9/PARP pathways and necrosis via PARP activation.|The mis-regulation of nuclear factor-kappa B (NF-kappaB) signal pathway is involved in a variety of inflammatory diseases that leds to the production of inflammatory mediators. /These/ studies using human U937 promonocytes cells suggested that magnolol ... differentially down-regulated the pharmacologically induced expression of NF-kappaB-regulated inflammatory gene products MMP-9, IL-8, MCP-1, MIP-1alpha, TNF-alpha. Pre-treatment of magnolol blocked TNF-alpha-induced NF-kappaB activation in different cell types as evidenced by EMSA. Magnolol did not directly affect the binding of p65/p50 heterodimer to DNA. Immunoblot analysis demonstrated that magnolol inhibited the TNF-alpha-stimulated phosphorylation and degradation of the cytosolic NF-kappaB inhibitor IkappaBalpha and the effects were dose-dependent. Mechanistically, a non-radioactive IkappaB kinases (IKK) assay using immunoprecipitated IKKs protein demonstrated that magnolol inhibited both intrinsic and TNF-alpha-stimulated IKK activity, thus suggesting a critical role of magnolol in abrogating the phosphorylation and degradation of IkappaBalpha. The involvement of IKK was further verified in a HeLa cell NF-kappaB-dependent luciferase reporter system. In this system magnolol suppressed luciferase expression stimulated by TNF-alpha and by the transient transfection and expression of NIK (NF-kappaB-inducing kinase), wild type IKKbeta, constitutively active IKKalpha and IKKbeta, or the p65 subunit. Magnolol was also found to inhibit the nuclear translocation and phosphorylation of p65 subunit of NF-kappaB. In line with the observation that NF-kappaB activation may up-regulate anti-apoptotic genes, it was shown in U937 cells that magnolol enhanced TNF-alpha-induced apoptotic cell death. /The/ results suggest that magnolol or its derivatives may have potential anti-inflammatory actions through IKK inactivation.|For more Mechanism of Action (Complete) data for MAGNOLOL (10 total), please visit the HSDB record page.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/GENOTOXICITY/ The aim is to investigate the effect of Magnolol preserved H460 cells from an oxidative agent tert-butylhydroperoxide (TBHP)-induced cell death. Magnolol augmented cell survival ratio after TBHP challenged. ... DNA damage, detected by the Comet assay, was diminished after treatment of Magnolol. The cells viability decreased after treatment with 0.15 mM TBHP for 24 hr, accompanied by inducing apoptotic death of the cells. Cytotoxicity and apoptosis induced by TBHP were significantly inhibited or attenuated after pretreatment with 20 uM Magnolol. Magnolol contributes to the cells survival through downregulated the p53 phosphorylation and PTEN expression, and upregulated Akt phosphorylation. Taken together, Magnolol was effective against DNA single strand breaks (SSB) formation, cytotoxicity and lipid peroxidation induced by TBHP, and its effects on p53 phosphorylation, PTEN and Akt phosphorylation were due to its antioxidative function, and partially via a p53 dependent mechanism in this protective effects.|/ALTERNATIVE and IN VITRO TESTS/ Magnolol, isolated from the stem bark of Magnolia officnalis, was found to inhibit proliferation of human HL-60 cells and Jurkat T leukemia cells via inducing apoptosis in a dose- and time-dependent manner. By contrast, magnolol did not cause apoptosis in neutrophils and peripheral blood mononuclear cells of healthy donors. Apoptosis was determined by detection of DNA fragmentation in gel electrophoresis, morphological alternations by flow cytometry, quantification of phosphatidylserine externalization by Annexin V labeling and oligonucleosomal DNA content by TUNEL labeling. Activation of caspase-9, -3 and -2, and the proteolytic cleavage of poly(ADP-ribose) polymerase were found during apoptosis induced by magnolol. In addition, both pan-caspase and selective caspase-9 inhibitor blocked magnolol-induced apoptosis. The apoptosis could also be partially attenuated by caspase-3 and -2 inhibitors. Magnolol induced the reduction of mitochondrial transmembrane potential and the release of cytochrome c into cytoplasm. In conclusion, our findings indicate that magnolol-induced apoptotic signaling is carried out through mitochondria alternations to caspase-9 and that then the downstream effector caspases are activated sequentially...|/ALTERNATIVE and IN VITRO TESTS/ Magnolol (MG) and honokiol (HK) ... were found to enhance HL-60 cell differentiation initiated by low doses of 1,25-dihydroxyvitamin D3 (VD3) and all-trans-retinoic acid (ATRA). Cells expressing membrane differentiation markers CD11b and CD14 were increased from 4% in non-treated control to 8-16% after being treated with 10-30 microM MG or HK. When added to 1 nM VD3, MG or HK increased markers expressing cells from approximately 30% to 50-80%. When either MG or HK was added to 20 nM ATRA, only CD11b, but not CD14, expressing cells were increased from 9% to 24-70%. Under the same conditions, adding MG or HK to VD3 or ATRA treatment further enlarged the G0/G1 cell population and increased the expression of p27(Kip1), a cyclin-dependent kinase inhibitor. Pharmacological studies using PD098059 (a MEK inhibitor), SB203580 (a p38 MAPK inhibitor) and SP600125 (a JNK inh ibitor) suggested that the MEK pathway was important for VD3 and ATRA-induced differentiation and also its enhancement by MG or HK, the p38 MAPK pathway had a inhibitory effect and the JNK pathway had little influence.|/ALTERNATIVE and IN VITRO TESTS/ The effect of magnolol on ionic currents was studied in cultured smooth muscle cells of human trachea with the aid of the patch clamp technique. In whole cell current recordings magnolol reversibly increased the amplitude of K+ outward currents. The increase in outward current caused by magnolol was sensitive to inhibition by iberiotoxin (200 nM) or paxilline (1 microM) but not by glibenclamide (10 uM). In inside out patches, magnolol added to the bath did not modify single channel conductance but effectively enhanced the activity of large conductance Ca2+ activated K+ (BK(Ca)) channels. Magnolol increased the probability of these channel openings in a concentration dependent manner with an EC50 value of 1.5 uM. The magnolol stimulated increase in the probability of channels opening was independent of internal Ca2+. The application of magnolol also shifted the activation curve of BK(Ca) channels to less positive membrane potentials. The change in the kinetic behaviour of BK(Ca) channels caused by magnolol in these cells is the result of an increase in dissociation and gating constants. ... These results provide evidence that, in addition to the presence of antioxidative activity, magnolol is potent in stimulating BK(Ca) channel activity in tracheal smooth muscle cells. The direct stimulation of these BK(Ca) channels by magnolol may contribute to the underlying mechanism by which it acts as an anti-asthmatic compound.|For more Human Toxicity Excerpts (Complete) data for MAGNOLOL (8 total), please visit the HSDB record page.

5,5'-diallyl-2,2'-dihydroxybiphenyl

Bioreactive constituent of Magnoliae Cortex, the bark of Magnolia officinalis, Rehd. et Wils., Magnoliaceae, known in Chinese traditional medicine as houpo, or of M. Obovata, Thnb., called wakoboku in Japanese ... Anti-inflammatory and analgesic effects ... CNS depressant effects

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