• Natural Product Sciences
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• v.18 no.1
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• pp.16-21
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• 2012

Honokiol, a naturally occurring neolignan mainly found in Magnolia species, has been shown to have the anti-angiogenic, anti-invasive and cancer chemopreventive activities, but the molecular mechanism of actions has not been fully elucidated yet. In the present study, we investigated the effect of honokiol on the growth inhibitory activity in cultured SNU-638 human gastric cancer cells. We found that honokiol exerted potent antiproliferative activity against SNU-638 cells. Honokiol also arrested the cell cycle progression at the G0/G1 phase and induced the apoptotic cell death in a concentration-dependent manner. The cell cycle arrest was well correlated with the downregulation of Rb, cyclin D1, cyclin A, cyclin E, and CDK4 expression, and the induction of cyclin-dependent kinase inhibitor p27. The increase of sub-G1 peak by honokiol was closely related to the induction of apoptosis, which was evidenced by the induction of DNA fragmentation, the cleavage of poly(ADPribose) polymerase, and the sequential activation of caspase cascade. These findings suggest the cell cycle arrest and induction of apoptosis might be one possible mechanism of actions for the anti-proliferative activity of honokiol in human gastric cancer cell.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.328-335
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• 2008

This study was undertaken to investigate whether honokiol could enhance the pentobarbitalinduced sleeping behaviors through $\gamma$-aminobutyric acid (GABA) receptor $Cl^-$ channel activation. Thirty minutes after the oral administration of honokiol, mice were received sodium pentobarbital (42 mg/kg, i.p.). The time elapsed from pentobarbital injection to the loss of the righting reflex was taken as sleeping latency. The time elapsed between the loss and voluntary recovery of the righting reflex was considered as the total sleeping time. Western blot technique and $Cl^-$ sensitive fluorescence probe were used to detect the expression of $GABA_A$ receptor subunits and $Cl^-$ influx in the primary cultured cerebellar granule cells. Honokiol (0.1 and 0.2 mg/kg) prolonged the sleeping time induced by pentobarbital (42 mg/kg) in a dosage-dependent manner. Honokiol (20 and 50 ${\mu}M$) increased $Cl^-$ influx in primary cultured cerebellar granule cells, and selectively increased the $GABA_A$ receptor $\alpha$-subunit expression, but had no effect on the abundance of $\beta$ or $\gamma$-subunits. Chronic treatment with 20 ${\mu}M$ honokiol in primary cultured cerebellar neurons did not affect the abundance of GAD65/67. The results suggested that honokiol could potentiate pentobarbital-induced sleeping through $GABA_A$ receptor $Cl^-$ channel activation.

• Mass Spectrometry Letters
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• v.4 no.2
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• pp.34-37
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• 2013

Honokiol and magnolol, the major bioactive neolignans of magnolia officinalis, are the most important constituents of the crude drug prescriptions that are used in the therapy of neuroses and various nervous disorders. There have been limited reports on the effects of neolignoid compounds on human cytochrome P450 activity. Therefore, the inhibitory effects of honokiol and magnolol on seven human cytochrome P450 s were evaluated in human liver microsomes. Honokiol and magnolol showed the most potent inhibition of CYP1A2-mediated phenacetin O-deethylase activity ($IC_{50}$ values of 3.5 and 5.4 mM, respectively) among the seven P450s tested. These in vitro data indicate that neolignan compounds can inhibit the activity of CYP1A2 and suggest that these compounds should be examined for potential pharmacokinetic drug interactions in vivo.

• Natural Product Sciences
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• v.11 no.2
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• pp.89-91
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• 2005

Effect of the neolignans, honokiol (1) and magnolol (2), isolated from Magnoliae Cortex on mushroom tyrosinase activity was investigated in vitro using L-tyrosine as a substrate. Honokiol (1) inhibited tyrosinase activity significantly in a concentration-dependent manner, on the other hand, magnolol (2) did not show tyrosinase inhibitory effect. Honokiol exhibited tyrosinase inhibitory effect with $IC_{50}$ value of $67.9\;{\mu}M$, and proved to act as a non-competitive inhibitor by the analysis of Lineweaver-Burk plot.

• Journal of Korea Foresty Energy
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• v.20 no.2
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• pp.1-8
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• 2001

The 90% methanol extracts of eight magnoliaceae plants were collected and tested the cytotoxicity against SK-OV-3 and SiHa cells. Also six pure compounds such as magnonol, honokiol, dihydroxybiphenyl ether, linodenine, anonaine, asimilobine which were previously isolated from Magnolia obovata Thunb. were evaluated the cytotoxicities and their mechanism study using the Lactate dehydrogenase assay(LDH) and FACScan analysis system. Of the tested six compounds, magnonol, honokiol, dihydroxybiphenyl ether showed high cytotoxicities against human cancer cell lines, SK-OV-3 and SiHa cells. In addition, one of the plausible mechanisms of their antitumor activities suggested that they could induce the early stage of apoptosis. For the quantitative analysis, the methanol extractives were fractionated with chloroform, ethylacetate, $H_2O$ and then the ethylacetate fraction was chromatographed on silica gel using n-Hexane ; Acetone(4:1, v/v) as eluent. This fraction was subjected for the quantitative analysis in the HPLC system. The result suggested that the methanol extractives of Magnolia obovata Thunb. contained with magnonol, honokiol, dihydroxybiphenyl ether, 0.9%, 0.3% and 0.24%, respectively.

• Archives of Pharmacal Research
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• v.13 no.1
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• pp.117-119
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• 1990

A combination of magnolol or honokiol with lysozyme isolated from the egg white of the Korean Ogol fowl (Korean natural monument No.265) exhibited synergistic effect of bactericidal activity against a typical cariogenic bacterium, Streptococcus mutans OMZ 176. The synergistic ratio increased with time dependence.

• Archives of Pharmacal Research
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• v.8 no.2
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• pp.85-89
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• 1985

It was revealed that magnolol and honokiol isolated from the stem bark of Magnolia obovata, had potent antibacterial activity against Bacillus anthracis. A quantitative analytical method of magnolol and honokiol by HPLC has been established, and the amounts of the two components in the dried stem bark of M. obovata were 1, 94% and 0.44%, respectively.

• Korean Journal of Pharmacognosy
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• v.31 no.4
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• pp.407-411
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• 2000

Antibacterial activities of magnolol (MGL) and honokiol (HKL) in combination with four representative antibiotics-amoxicillin (AMPC), oxytetracyclin (OTC), gentamicin (GM) and chloramphenicol (CAP)-were evaluated against four bacterial strains. When tested by disk-plate method, five out of eight combinations such as HKL-AMPC, HKL-CAP, MGL- AMPC, MGL-OTC, and MGL-CAP showed additive to synergistic interaction against gram- negative bacterium Salmonella typhimureum. Of these, MGL-AMPC combination turned out to be antagonistic against Sarcina lutea and Bacillus thurungiensis. Against these two grain-positive bacteria, only HKL-GM combination showed additivity to synergism. All the other combinations showed no interactions. Despite these results, however, no synergism was observed in checkerboard titration assay.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.5.1-5.14
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• 2018

Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). Sirtuin 3 (SIRT3), a sirtuin family protein located in mitochondria, is essential for mitochondrial homeostasis; however, the role of SIRT3 in the process of IVDD has remained elusive. Here, we explored the expression of SIRT3 in IVDD in vivo and in vitro; we also explored the role of SIRT3 in senescence, apoptosis, and mitochondrial homeostasis under oxidative stress. We subsequently activated SIRT3 using honokiol to evaluate its therapeutic potential for IVDD. We assessed SIRT3 expression in degenerative nucleus pulposus (NP) tissues and oxidative stress-induced nucleus pulposus cells (NPCs). SIRT3 was knocked down by lentivirus and activated by honokiol to determine its role in oxidative stress-induced NPCs. The mechanism by which honokiol affected SIRT3 regulation was investigated in vitro, and the therapeutic potential of honokiol was assessed in vitro and in vivo. We found that the expression of SIRT3 decreased with IVDD, and SIRT3 knockdown reduced the tolerance of NPCs to oxidative stress. Honokiol ($10{\mu}M$) improved the viability of NPCs under oxidative stress and promoted their properties of anti-oxidation, mitochondrial dynamics and mitophagy in a SIRT3-dependent manner. Furthermore, honokiol activated SIRT3 through the AMPK-PGC-$1{\alpha}$ signaling pathway. Moreover, honokiol treatment ameliorated IVDD in rats. Our study indicated that SIRT3 is involved in IVDD and showed the potential of the SIRT3 agonist honokiol for the treatment of IVDD.

• YAKHAK HOEJI
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• v.41 no.4
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• pp.407-413
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• 1997

Magnolol and honokiol, the main components of Magnoliae Cortex, were isolated and used as the standard substances for the analysis. In order to determine the contents of magnolol and honokiol in Magnoliae Cortex originated from Korea, China and Japan, both HPLC and HPTLC methods are applied and compared with each other. The components were separated on C8 column with acetonitrile-water-acetic acid (50:50:1) in HPLC and detected at UV 294nm. The components separated on HPTLC precoated silica gel plate with chloroform-methanol (9:1) were detected directly on the plate at 254nm. The contents of magnolol and honokiol in Magnoliae Cortex were in the wide range of 0.01~2.8% and 0.005~0.8%, respectively, according to their purchase places. It is also applicable to the quality control of various preparation from Magnoliae Cortex.