• Journal of Microbiology and Biotechnology
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• 제30권12호
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• pp.1835-1842
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• 2020

Ergosterol, an essential constituent of membrane lipids of yeast, is distributed in both the cell membrane and intracellular endomembrane components such as vacuoles. Honokiol, a major polyphenol isolated from Magnolia officinalis, has been shown to inhibit the growth of Candida albicans. Here, we assessed the effect of honokiol on ergosterol biosynthesis and vacuole function in C. albicans. Honokiol could decrease the ergosterol content and upregulate the expression of genes related with the ergosterol biosynthesis pathway. The exogenous supply of ergosterol attenuated the toxicity of honokiol against C. albicans. Honokiol treatment could induce cytosolic acidification by blocking the activity of the plasma membrane Pma1p H+-ATPase. Furthermore, honokiol caused abnormalities in vacuole morphology and function. Concomitant ergosterol feeding to some extent restored the vacuolar morphology and the function of acidification in cells treated by honokiol. Honokiol also disrupted the intracellular calcium homeostasis. Amiodarone attenuated the antifungal effects of honokiol against C. albicans, probably due to the activation of the calcineurin signaling pathway which is involved in honokiol tolerance. In conclusion, this study demonstrated that honokiol could inhibit ergosterol biosynthesis and decrease Pma 1p H+-ATPase activity, which resulted in the abnormal pH in vacuole and cytosol.

• Journal of Microbiology and Biotechnology
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• 제28권7호
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• pp.1086-1093
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• 2018

Honokiol, a bioactive compound isolated from the cone and bark of Magnolia officinalis, has been shown to have various activities including inhibition of the growth of Candida albicans. We investigated the roles of the Hsp90-calcineurin pathway in the antifungal activity of honokiol. The pharmacologic tool was employed to evaluate the effects of Hsp90 and calcineurin in the antifungal activity of honokiol. We also evaluated the protective effects of the calcineurin inhibitor cyclosporin A (CsA) on honokiol-induced mitochondrial dysfunction by the fluorescence staining method. The Hsp90 inhibitor potentiated the antifungal activity of honokiol. A C. albicans strain with the calcineurin gene deleted displayed enhanced sensitivity to honokiol. However, co-treatment with calcineurin inhibitor CsA attenuated the cytotoxic activity of honokiol due to the protective effect on mitochondria. Our results provide insight into the action mechanism of honokiol.

• BMB Reports
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• 제42권9호
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• pp.574-579
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• 2009

The regulatory effects of honokiol on the cellular responses of macrophages and monocytes were evaluated. Specifically, we investigated the effects of honokiol with respect to lipopolysaccharide (LPS)-induced cytotoxicity, LPS- or phorbol-12-myristate-13-acetate (PMA)-mediated morphological changes, and relevant events (FITC-dextran-induced phagocytic uptake). Honokiol blocked the LPS-induced cytotoxicity of RAW264.7 cells in a dose-dependent manner. In addition, honokiol appeared to block the production of cytotoxic cytokines such as interleukin (IL)-$1{\beta}$ and tumor necrosis factor (TNF)-$\alpha$, nitric oxide (NO), and reactive oxygen species (ROS). Moreover, honokiol strongly prevented the morphological changes in RAW 264.7 and U937 cells that were induced by LPS and PMA. The surface levels of marker proteins, which are up-regulated under the morphological changes of RAW264.7 and U937 cells, were also diminished. The data presented here strongly suggest that the honokiol modulates various cellular responses managed by macrophages and monocytes.

• 생명과학회지
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• 제20권10호
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• pp.1443-1450
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• 2010

Honokiol은 작은 분자량을 갖는 중국의 약초인 'Magnolia officinalis'에서 추출한 리간드로서 중국과 일본에서 전통 의약제로 사용되어 왔다. 이전 연구에서는 honokiol이 다양한 종류의 암에서anti-angiogenic, anti-invasive, anti-proliferative activities 등의 다양한 효과가 있는 것으로 알려져 있다. 우리는 이전 연구에서 Nitric oxide donor인 sodium nitroprusside (SNP)에 의해서 토끼 무릎관절연골세포에서 세포사멸이 일어나는 것을 보고하였다. 본 연구에서는 무릎 연골세포에서 NO에 의해 유도되는 세포사멸이 honokiol 처리농도에 의존적으로 억제되는 것을 세포형태, MTT assay, Western blot analysis 그리고 FACS를 통해 확인할 수 있었다. 또한, honokiol은 SNP에 의해 유도되는 p53의 발현 및 pro-caspase-3의 활성 저해, DNA fragmentation을 억제하였다. Honokiol에 의한 세포사멸 억제는 PI-3K의 특정 저해제인 LY294002를 SNP와 honokiol과 함께 처리하였을 때 세포의 사멸이 증가하는 것을 확인할 수 있었다. 이는 honokiol이 PI-3K/AKT pathway를 통하여 NO가 유도하는 세포사멸을 억제하는 것을 의미한다.

• Molecules and Cells
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• 제37권5호
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• pp.383-388
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• 2014

Renal cell carcinoma (RCC) is associated with a high frequency of metastasis and only few therapies substantially prolong survival. Honokiol, isolated from Magnolia spp. bark, has been shown to exhibit pleiotropic anticancer effects in many cancer types. However, whether honokiol could suppress RCC metastasis has not been fully elucidated. In the present study, we found that honokiol suppressed renal cancer cells' metastasis via dual-blocking epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties. In addition, honokiol inhibited tumor growth in vivo. It was found that honokiol could upregulate miR-141, which targeted ZEB2 and modulated ZEB2 expression. Honokiol reversed EMT and suppressed CSC properties partly through the miR-141/ZEB2 axis. Our study suggested that honokiol may be a suitable therapeutic strategy for RCC treatment.

• Journal of Microbiology and Biotechnology
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• 제29권4호
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• pp.538-547
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• 2019

The aim of the present study was to evaluate the effects of two well-known natural antioxidants, vitamin C (VC) and vitamin E (VE), on the antifungal activity of honokiol against Candida albicans. The broth microdilution method was employed to test the antifungal activities of honokiol with or without antioxidants in the medium against C. albicans strain. Intracellular reactive oxygen species and lipid peroxidation were determined by fluorescence staining assay. Mitochondrial dysfunction was assessed by detecting the mitochondrial DNA and the mitochondrial membrane potential. We observed that VC could significantly potentiate the antifungal activities of honokiol while VE reduced the effectiveness of honokiol against C. albicans. In addition, VC accelerated honokiol-induced mitochondrial dysfunction and inhibited glycolysis leading to a decrease in cellular ATP. However, VE could protect against mitochondrial membrane lipid peroxidation and rescue mitochondrial function after honokiol treatment. Our research provides new insight into the understanding of the action mechanism of honokiol and VC combination against C. albicans.

• 한국양봉학회지
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• 제34권2호
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• pp.131-136
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• 2019

Recently, number of honeybees (Apis mellifera) has visibly decreased because they are vulnerable to some diseases like American foulbrood disease. American foulbrood disease, which is caused by Paenibacillus larvae, is emerged as great cause of decrease in number of honeybees. After antibiotic-resistant strain emerged, it is now more difficult to treat those pathogens successfully. Researches on finding alternative antibacterial compound are ongoing. In this study, we examined the antibacterial effect of honokiol on P. larvae. Honokiol showed great antibacterial effect with minimum inhibitory concentration of 12.5 ㎍/mL and minimum bactericidal concentration of 50 ㎍/mL. An agar diffusion test also confirmed the anti-Paenibacillus larvae activity of honokiol with an inhibitory zone of 9±0.5 mm. Since honokiol is known to interact membrane of some bacteria, we measured 260 nm absorbing particles, which could be induced by leakage of cells, and confirmed that the leakage of P. larvae occurred in dose-dependent manners. However, result of crystal violet assay suggested that honokiol has only mild anti-biofilm formation effect on P. larvae, which means honokiol controls the bacteria by inducing the bursting of membrane. Finally, an additive effect of honokiol with tetracycline and terramycin was found using a checkerboard assay with a fractional inhibitory concentration index value of 0.5.

• Journal of Periodontal and Implant Science
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• 제23권1호
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• pp.145-158
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• 1993

The oral microbiota such as P. gingivalis, P. intermedia and A. actinomycetemcomitans play a primary role in the initiation and progression of the periodontal disease. The purpose of this study was to evaluate the antimicrobial effects and inhibitory effects of honokiol and magnolol on the bacterial collagenase activity, cytotoxicity and cytokine production of periodontopathic microorganisms. The antimicrobial activities of honokiol and magnolol was evaluted with minimum inhibition concentration. Honokiol was more active than magnolol, but less than chlorhexidine on antimicrobial activity. The inhibitory effects of magnolol and honokiol on the collagenolytic activity and cytotoxicity were evaluated using a Collagenokit CLN-100 and rapid colorimetric assay (MTT method) for cellular growth and survival of gingival fibroblast and periodontalligament cell and $[^3H]-thymidine$ incorporation for the gingival epithelial cell. The inhibitory effects on the collagenolytic activity was the highest in chlorhexidine, and the lowest in magnolol. Magnolol had the lowest cytotoxic effect and chlorhexidine had the highest. The inhibitory effects on cytokine production was evaluated using $interleukin-1{\beta}$ ELISA kit (Cistron Biotech.), IL-6, $TNF-{\alpha}$ ELISA kit (Genzyme) and inhibitory effects were higher than bacterial LPS and there is no difference among the honokiol, magnolol and chlorhexidine. From these results, the antimicrobial and antienzymatic activities of honokiol and magnolol were seemed to inhibit bacterial growth and enzyme activities with lesser cytotoxic activities. Therefore, it was suggested that honokiol and magnolol are very effective antimicrobial agents on periodontal pathogens.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.270-276
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• 2008

In this study we investigated the effects of Magnolia Bark (MB) extract and its constituents, such as honokiol and magnolol, on gastritis in rats and the growth of human gastric cancer cells. The MB extract, honokiol, and magnolol showed the acid-neutralizing capacities, the antioxidant activities, and the inhibitory effect on the growth of Helicobacter pylori (H. pylori.) at the dose of $50\;{\mu}g/ml$ and over, which is equivalent to that of ampicillin ($100\;{\mu}g/ml$). Honokiol and magnolol had no significant cytotoxicity to human gastric caner cells (AGS and SNU638). However, the MB extract had cytotoxic activity against AGS gastric cancer cell. The MB extract, honokiol, and magnolol significantly inhibited HCI-ethanol-induced gastric lesions without clear change of mucus content. In pylorus ligated rats, honokiol significantly decreased the volume of gastric secretion and gastric acid output, and increased the pH. Magnolol increased the mucus content to almost the same as the control group at oral doses of 50 mg/kg. Therefore, we could guess that antigastritic action of honokiol and magnolol may be associated with the antioxidant activities, acid-neutralizing capacities, inhibition of secretion in gastric acid, and anti-H. pylori action. From these results, we could suggest that MB extract and its constituents, such as honokiol and magnolol, may be useful for the treatment and/or protection of gastritis.

• Natural Product Sciences
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• 제19권2호
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• pp.155-159
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• 2013

Honokiol, a naturally occurring neolignan mainly found in Magnolia species, has exhibited a potential anti-proliferative activity in human cancer cells. However, the growth inhibitory activity against hepatocellular carcinoma cells and the underlying molecular mechanisms has been poorly determined. The present study was designed to examine the anti-proliferative effect of honokiol in SK-HEP-1 human hepatocellular cancer cells. Honokiol exerted anti-proliferative activity with cell-cycle arrest at the G0/G1 phase and sequential induction of apoptotic cell death. The cell-cycle arrest was well correlated with the down-regulation of checkpoint proteins including cyclin D1, cyclin A, cyclin E, CDK4, PCNA, retinoblastoma protein (Rb), and c-Myc. The increase of sub-G1 peak by the higher concentration of honokiol ($75{\mu}M$) was closely related to the induction of apoptosis, which was evidenced by decreased expression of Bcl-2, Bid, and caspase-9. Hohokiol was also found to attenuate the activation of signaling proteins in the Akt/mTOR and ERK pathways. These findings suggest that the anti-proliferative effect of honokiol was associated in part with the induction of cell-cycle arrest, apoptosis, and dow-nregulation of Akt/mTOR signaling pathways in human hepatocellular cancer cells.