Magnolia extract is effective for the chemoprevention of oral cancer through its ability to inhibit mitochondrial respiration at complex I.

BACKGROUND: Magnolia extract (ME) is known to inhibit cancer growth and metastasis in several cell types in vitro and in animal models. However, there is no detailed study on the preventive efficacy of ME for oral cancer, and the key components in ME and their exact mechanisms of action are not clear. The overall goal of this study is to characterize ME preclinically as a potent oral cancer chemopreventive agent and to determine the key components and their molecular mechanism(s) that underlie its chemopreventive efficacy. METHODS: The antitumor efficacy of ME in oral cancer was investigated in a 4-nitroquinoline-1-oxide (4NQO)-induced mouse model and in two oral cancer orthotopic models. The effects of ME on mitochondrial electron transport chain activity and ROS production in mouse oral tumors was also investigated. RESULTS: ME did not cause detectable side effects indicating that it is a promising and safe chemopreventive agent for oral cancer. Three major key active compounds in ME (honokiol, magnolol and 4-O-methylhonokiol) contribute to its chemopreventive effects. ME inhibits mitochondrial respiration at complex I of the electron transport chain, oxidizes peroxiredoxins, activates AMPK, and inhibits STAT3 phosphorylation, resulting in inhibition of the growth and proliferation of oral cancer cells. CONCLUSION: Our data using highly relevant preclinical oral cancer models, which share histopathological features seen in human oral carcinogenesis, suggest a novel signaling and regulatory role for mitochondria-generated superoxide and hydrogen peroxide in suppressing oral cancer cell proliferation, progression, and metastasis. Video abstract.

Portulaca oleracea extracts protect human keratinocytes and fibroblasts from UV-induced apoptosis.

Portulaca oleracea extracts, known as Ma Chi Hyun in the traditional Korean medicine, show a variety of biomedical efficacies including those in anti-inflammation and anti-allergy. In this study, we investigate the protective activity of the P. oleracea extracts against UVB-induced damage in human epithelial keratinocytes and fibroblasts by several apoptosis-related tests. The results suggest that P. oleracea extracts have protective effects from UVB-induced apoptosis.

Pharmacokinetics and metabolism of 4-O-methylhonokiol in rats.

The purpose of this study was to characterize the pharmacokinetics and metabolism of 4-O-methylhonokiol in rats. The absorption and disposition of 4-O-methylhonokiol were investigated in male Sprague-Dawley rats following a single intravenous (2 mg/kg) or oral (10 mg/kg) dose. Its metabolism was studied in vitro using rat liver microsomes and cytosol. 4-O-Methylhonokiol exhibited a high systemic plasma clearance and a large volume of distribution. The oral dose gave a peak plasma concentration of 24.1±3.3 ng/mL at 2.9±1.9 h and a low estimated bioavailability. 4-O-Methylhonokiol was rapidly metabolized and converted at least in part to honokiol in a concentration-dependent manner by cytochrome P450 in rat liver microsomes, predicting a high systemic clearance consistent with the pharmacokinetic results. It was also shown to be metabolized by glucuronidation and sulfation in rat liver microsomes and cytosol, respectively. 4-O-Methylhonokiol showed a moderate permeability with no apparent vectorial transport across Caco-2 cells, suggesting that intestinal permeation process is not likely to limit its oral absorption. Taken together, these results suggest that the rapid hepatic metabolism of 4-O-methylhonokiol could be the major reason for its high systemic clearance and low oral bioavailability.

Inhibitory effects of Saururi chinensis extracts on melanin biosynthesis in B16F10 melanoma cells.

Saururus chinensis has been used in folk medicine in Korea for the treatment of edema, jaundice, gonorrhea, and several inflammatory diseases. Saururi chinensis extracts (SCE) have demonstrated anti-inflammatory and anti-oxidant activities, as well as anti-asthmatic, antihypertensive, anti-angiogenic, and therapeutic activities for atopic dermatitis. However, the inhibitory activity of SCE on the melanogenesis signaling pathway is not completely understood. This study examined the effects of SCE on the melanogenesis signaling pathway activated by α-melanocyte-stimulating hormone (α-MSH). We found that SCE inhibited melanin production in a dose-dependent manner without causing cytotoxicity in B16F10 cells. Interestingly, SCE decreased α-MSH-induced tyrosinase activity in B16F10 cells but did not inhibit tyrosinase activity under cell-free conditions. The results of this study indicate that SCE may reduce pigmentation by way of an indirect, nonenzymatic mechanism. We also found that SCE decreased α-MSH-induced microphthalmia-associated transcription factor (MITF) and tyrosinase expression and induced the activation of extracellular signal-regulated kinase (ERK). These results suggest that the depigmenting effect of SCE may result from downregulation of MITF and tyrosinase expression due to increased ERK activity. Thus, our results provide evidence that SCE might be useful as a potential skin-whitening agent.

Promotion effect of norgalanthamine, a component of Crinum asiaticum, on hair growth.

This study was conducted to evaluate the effect of Crinum asiaticum, a plant native to Jeju Island, Korea, on the promotion of hair growth. When rat vibrissa follicles were treated with a 95% ethanol (EtOH) extract of C. asiaticum, the hair-fiber lengths of the vibrissa follicles increased significantly. In addition, after daily topical application of the EtOH extract of C. asiaticum onto the back of C57BL/6 mice, anagen progression of the hair shaft was induced. Moreover, the extract increased the proliferation of immortalized vibrissa dermal papilla cells. When the vibrissa follicles in the anagen phase were treated with the extract, immunohistochemical analysis revealed that the extract was found to increase the expression of proliferating cell nuclear antigen (PCNA) in the bulb region of the 7-day cultured follicles. In particular, norgalanthamine, a principal of the extract, showed activity that increased the hair-fiber lengths of vibrissa follicles and the proliferation of dermal papilla cells. These results suggest that norgalanthamine, a principal of C. asiaticum, has the potential to promote hair growth via the proliferation of dermal papilla.

Anti-wrinkle activity of Platycarya strobilacea extract and its application as a cosmeceutical ingredient.

In order to investigate the potential of Platycarya strobilacea fruit extract as an active ingredient for cosmetics, we measured their free-radical scavenging activity, elastase inhibitory activity, the expression of MMP-1 (matrix metalloproteinase-1), and type I collagen synthesis in normal human fibroblast cells. To isolate the main component compounds from P. strobilacea fruit extract, we purified the extract through solvent fractionation, column chromatography, and recrystallization. The component compounds were identified as ellagic acid and 4-O-xyloside of ellagic acid (ellagic acid 4-O-xylopyranoside). P. strobilacea fruit extract and ellagic acid increased the expression of type I collagen mRNA in a dose-dependent manner (up to 37% and 41% at 20 microg/ml and 1.0 microg/ml, respectively), comparable to that of ascorbic acid (up to 39% at 500 muM). A clinical study of measurements using visual evaluation and image analysis showed a statistically significant difference (p < 0.05) between the effects of the test and placebo products. This result suggests that P. strobilacea fruit extract could be used as an active ingredient for antiaging cosmetics.

Neurite outgrowth effect of 4-O-methylhonokiol by induction of neurotrophic factors through ERK activation.

Compounds isolated from Magnolia officinalis such as magnolol, honokiol and obovatol exhibit several pharmacological effects on CNS including depressant, anxiolytic and anticonvulsant effects, as well as neuroprotective effects against chemical and heat damages. Recently, honokiol was found to have a neurotrophic effect in fetal rat cortical neurons. In the present study, we show that 4-O-methylhonokiol, a novel compound from Magnolia officinalis, promotes neurite outgrowth in a concentration- dependent manner in rat embryonic neuronal cells. In parallel with the neurite outgrowth activity, the expression of neurite outgrowth marker proteins is also increased by treatment with 4-O-methylhonokiol. We also found that 4-O-methylhonokiol promotes the release of NGF and BDNF into cell culture medium. In addition, lower concentration of 4-O-methylhonokiol (1 and 2 lM) further enhanced neurite outgrowth and expression of neurite outgrowth marker proteins in the presence of NGF (50 ng/ml) or BDNF (10 ng/ml). Subsequently, we found that 4-O-methylhonokiol activates ERK in a concentration- dependent manner. However, the neurite outgrowth activity and the NGF and BDNF release induced by 4-O-methylhonokiol are suppressed by an ERK-specific inhibitor. These results suggest that 4-O-methylhonokiol has the ability to induce neurite outgrowth via the increase of neurotrophic factor levels through ERK activation.

Inhibitory effects of an aqueous extract of Cornus kousa Burg. leaves on TNF-alpha-induced chemokine expression and monocyte adhesion to human colonic epithelial cells.

An aqueous extract of Cornus kousa Burg. leaves (ACK) that contained high amount of polyphenols showed significant antioxidant activity against diphenylpicrylhydrazyl (DPPH) radicals and TNF-alpha-generated reactive oxygen species. ACK at concentrations of 10 and 50 microg/mL significantly inhibited TNF-alpha-induced adhesion of U937 pre-monocytic cells to HT-29 colon epithelial cells in a concentration-dependent manner. The reduced adhesion by ACK correlated with the suppressed expressions of monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8, the major inflammatory bowel disease (IBD)-associated chemokines. Moreover, ACK significantly suppressed TNF-alpha-induced translocation of redox-sensitive nuclear factor (NF)-kappaB as well as degradation of cytosolic I-kappaBalpha. The effective concentrations of ACK were much lower than that of 5-aminosalicylic acid (3.06 mg/mL), which is an active metabolite of sulfasalazine, a well-known drug used in the treatment of IBD. The results indicate that ACK may provide a potential benefit for the prevention and treatment of inflammatory diseases such as IBD.

Anti-wrinkle activity of ziyuglycoside I isolated from a Sanguisorba officinalis root extract and its application as a cosmeceutical ingredient.

In order to investigate the potential of a Sanguisorba officinalis root extract as an active ingredient for wrinkle-care cosmetics, we measured its free radical scavenging activity, elastase inhibitory activity, expression of MMP-1 (matrix metalloprotease-1) in vitro, and type I collagen synthesis in normal human fibroblast cells. To isolate the main components from the S. officinalis root extract, we purified the extract by solvent fractionation, column chromatography, and recrystallization. The active component was identified as ziyuglycoside I by a spectroscopic analysis. Ziyuglycoside I increased the expression of type I collagen in a dose-dependent manner (by up to 71.3% at 50 muM). A clinical study of a formulation containing ziyuglycoside I, which involved visual evaluation and image analysis, showed a significantly different effect (p<0.05) of the test formulation from that of the placebo. This result suggests that ziyuglycoside I isolated from S. officinalis root extract could be used as an active ingredient for cosmetics.

Anti-inflammatory activity of Crinum asiaticum Linne var. japonicum extract and its application as a cosmeceutical ingredient.

Crinum asiaticum Linne var. japonicum has long been used as a rheumatic remedy, as an anti-pyretic and as an anti-ulcer treatment, and for the alleviation of local pain and fever in Korea and Malaysia. In order to investigate the possibility of Crinum asiaticum Linne var. japonicum extract as a cosmetic ingredient, we measured its anti-inflammatory effect by its inhibition of iNOS (inducible nitric oxide synthase) and the release of PGE2, IL-6, and IL-8. We also measured its anti-allergic effect by its inhibition of beta-hexosamidase release. An HPLC experiment after extraction with 95% EtOH at pH 3.5 showed that Crinum asiaticum Linne var. japonicum was mainly composed of lycorine (up to 1%), a well-known immunosuppressor. The content of lycorine varied, depending on the type of plant tissue analyzed and the extraction method. In an anti-inflammatory assay for inhibition of nitric oxide formation on lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells, the ethanol extract of Crinum asiaticum showed an inhibitory activity of NO production in a dose-dependent manner (IC50 = 58.5 microg/ml). Additional study by RT-PCR demonstrated that the extract of Crinum asiaticum significantly suppressed the expression of the iNOS gene. Moreover, the extract of Crinum asiaticum did not show any cytotoxicity, but did show a cell proliferation effect against LPS (a 10 approximately 60% increase in cell viability). In an assay to determine inhibition of the H2O2-activated release of PGE2, IL-6, and IL-8 in human normal fibroblast cell lines, the release of PGE2 and IL-6 was almost completely inhibited above concentrations of 0.05% and 1%, respectively. Moreover, the release of IL-8 was completely inhibited over the entire range of concentration (>0.0025%). In order to investigate the skin-sensitizing potentials of the extract of Crinum asiaticum, a human clinical test was performed after repeated epicutaneous 48-h applications under an occlusive patch (RIPT). The repeated and single cutaneous applications of Crinum asiaticum Linne var. japonicum extract under the occlusive patch did not provoke any cumulative irritation and sensitization reactions. The result showed that the extract of Crinum asiaticum Linne var. japonicum has a sufficient anti-inflammatory effect. Therefore, Crinum asiaticum Linne var. japonicum extract may be useful for development as an ingredient in cosmetic products.

A novel microbial technique for producing high-quality sophorolipids from horse oil suitable for cosmetic applications.

Horse oil contains linoleic, palmitoleic and unsaturated fatty acids that are similar to those in human skin, and may therefore be an ideal substance from which to isolate biosurfactants for cosmetic products to improve human skin quality. Herein, an innovative approach was developed to synthesise sophorolipids from horse oil by hydrolysis, followed by fermentation using the yeast Candida bombicola. The yield of sophorolipids from direct fermentation of horse oil and hydrolysed horse oil was 40.6 ± 1.3 g l-1 and 58.4 ± 1.8 g l-1 respectively. To further increase the yield, 30-40 g l-1 glucose was added in a fed-batch fermentation process to maintain the pH between 4.0 and 4.5, resulting in a conversion yield of 71.7 ± 0.8 g l-1 . The purity and structure of the synthesised sophorolipids were analysed by ultra-performance liquid chromatography-mass spectrometry and nuclear magnetic resonance. An in vitro human dermal fibroblast model was used as a surrogate for human skin to measure elastase inhibition activity. Antiwrinkle properties of isolated sophorolipids were better than those of horse oil or hydrolysed horse oil in several in vitro assays. Furthermore, no cytotoxicity was observed at a concentration of 50 µg ml-1 , and wound-healing capacity was evident in a cell culture model. Additionally, the synthesised sophorolipids attenuated lipopolysaccharide-induced expression of inflammatory cytokines in macrophages, and efficiently inhibited several strains of bacteria and yeast. In conclusion, fed-batch fermentation of hydrolysed horse oil is a novel and efficient approach for producing high-quality and high-yield sophorolipids that exhibit great potential as cosmetic ingredients.

Enhanced bioavailability of soy isoflavones by complexation with beta-cyclodextrin in rats.

In order to improve the solubility and bioavailability of a soy isoflavone extract (IFE), inclusion complexes (IFE-beta-CD) of the isoflavone extract with beta-cyclodextrin (beta-CD) were prepared and studied for their solubility and bioavailability. The aqueous solubility of the complexes of IFE with beta-CD (2.0 mg/ml) was about 26 times that of IFE itself (0.076 mg/ml). The same dosages of IFE and IFE-beta-CD were orally administered to SD rats (Sprague-Dawley) on an isoflavone glycoside (IFG) basis (daidzin, genistin and glycitin), and the plasma concentrations of daidzein, genistein and glycitein were measured over time to estimate the average AUC (area under the plasma concentration versus time curve) of the isoflavones. After the oral administration, the AUC values for daidzein, genistein and glycitein were 340, 11 and 28 microg x min/ml, respectively. In contrast, the respective AUC values after the administration of IFE-beta-CD were 430, 20 and 48 microg x min/ml. The bioavailability of daidzein in IFE-beta-CD was increased to 126% by the formation of inclusion complexes with beta-CD, compared with that in IFE. Furthermore, the bioavailability of genistein and glycitein in IFE-beta-CD formulation was significantly higher by up to 180% and 170%, respectively, compared with that of IFE p=0.008 and p=0.028, respectively). These results show that the absorption of IFE could be improved by the complexation of IFE with beta-CD (IFE-beta-CD).

Inhibitory effects of natural plants of Jeju Island on elastase and MMP-1 expression.

In order to search for new active cosmetic ingredients of natural origin, we screened about 60 plants collected from Jeju Island, which is located in the southernmost part of the Republic of Korea. We investigated their free radical scavenging activity, elastase inhibition activity, and reduction of MMP-1 mRNA expression for the development of anti-aging ingredients as raw materials for use in cosmetics. In the free radical scavenging capacity assay, 12 extracts, including Typha orientalis (seed) and Torreya nucifera (leaf), showed significant free radical scavenging activity (up to SC(50)<30 microg/ml). Among these extracts, Nymphaea tetragona (rhizome) extract showed the highest free radical scavenging activity (SC(50)=4.7 microg/ml). In the anti-elastase inhibition assay, seven extracts, including Typha orientalis (seed) and Persicaria hydropiper (whole plant), showed high inhibitory activity (>50% at 100 mug/ml). Among these extracts, Persicaria hydropiper (whole plant) extract showed the highest elastase inhibition activity (IC(50) = 46.7 mug/ml). In the MMP-1 expression assay using RT-PCR, Typha orientalis (seed), Pyrrosia hastata (root), and Capsicum annum (whole plant) showed slightly lower inhibition activity than EGCG, which was used as a control. Furthermore, four extracts, including Persicaria hydropiper (whole plant), Filipendula glaberrima (root), Nymphaea tetragona (root), and Camellia japonica (leaf), completely inhibited the expression of MMP-1 in human fibroblast cells. The results showed that four of the 60 plant extracts may hold potential for use as natural active ingredients for anti-aging cosmetics.

Effect of isosecotanapartholide isolated from Artemisia princeps Pampanini on IL­33 production and STAT­1 activation in HaCaT keratinocytes.

The present study aimed to investigate the anti­inflammatory effect and mechanism of action of isosecotanapartholide (ISTP), isolated from Artemisia princeps Pampanini extract (APE). The effects of ISTP and APE on the proliferation of human keratinocytes following stimulation by tumor necrosis factor­α/interferon­Î³ were assessed. ISTP and APE downregulated the expression levels of signal transducer and activator of transcription­1 (STAT­1), and reduced interleukin­33 (IL­33) production. ISTP and APE inhibited the mRNA expression levels of thymus and activation­regulated chemokine (TARC/CCL17) in a dose­dependent manner. Western blot analysis demonstrated that ISTP and APE dose­dependently inhibited protein expression levels of intercellular adhesion molecule­1 and phosphorylation of STAT­1. The results of the present study indicate that ISTP may inhibit TARC/CCL17 production in human epidermal keratinocytes via the STAT­1 signaling pathway and may be associated with the inhibition of IL­33 production. The current study indicated that ISTP is an active component in APE and may be a potential therapeutic agent for the treatment of inflammatory skin disorders.

4-O-Methylhonokiol Protects HaCaT Cells from TGF-ß1-Induced Cell Cycle Arrest by Regulating Canonical and Non-Canonical Pathways of TGF-ß Signaling.

4-O-methylhonokiol, a neolignan compound from Magnolia Officinalis, has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-ß (TGF-ß) signal pathway has an essential role in the regression induction of hair growth, the effect of 4-O-methylhonokiol on the TGF-ß signal pathway has not yet been elucidated. We thus examined the effect of 4-O-methylhonokiol on TGF-ß-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4-O-methylhonokiol, TGF-ß1-induced G1/G0 phase arrest and TGF-ß1-induced p21 expression were decreased. Moreover, 4-O-methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-ß1-induced canonical pathway. We observed that ERK phosphorylation by TGF-ß1 was significantly attenuated by treatment with 4-O-methylhonokiol. 4-O-methylhonokiol inhibited TGF-ß1-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-ß1-induced noncanonical pathway. These results indicate that 4-O-methylhonokiol could inhibit TGF-ß1-induced cell cycle arrest through inhibition of canonical and noncanonical pathways in human keratinocyte HaCaT cell and that 4-O-methylhonokiol might have protective action on TGF-ß1-induced cell cycle arrest.

Cosmeceutical properties of polysaccharides from the root bark of Ulmus davidiana var. japonica.

In Korea and China, Ulmus davidiana var. japonica has been used as a traditional oriental medicine for the treatment of difficulty in urination, skin inflammation, etc. In order to investigate the potential of a polysaccharide extract from Ulmus davidiana var. japonica as a cosmetic ingredient, we measured its moisturizing effect, photo-induced cytotoxicity, and anti-inflammatory effect. After hydrolysis, HPLC experiments showed that the composition of the polysaccharide extract was mainly rhamnose, galactose, and glucose. The molecular weight of the obtained Ulmus davidiana root extract was 20,000. The intrinsic viscosity was 90 dl/g. In a moisturizing test conducted through the measurement of water loss in a desiccator and of moisture content with a Corneometer CM820, Ulmus davidiana root extract showed almost the same moisturizing effect as hyaluronic acid. In an assay for inhibition of the H(2)O(2)-activated release of PGE2, IL-6, and IL-8 in normal human fibroblast cell lines, Ulmus davidiana root extract showed an inhibitory activity of PGE2 release in a dose-dependent manner (up to 85.9% at a concentration of 0.1%). The percent inhibition of the release of IL-6 was in the range of 45.6% to 64.5% (H(2)O(2) was used as the positive control). Moreover, the release of IL-8 was completely inhibited in the entire concentration range (>0.0025%). In a test of recovery from photo-induced damage after UVA irradiation (3 J/cm(2)), the cell recovery of human fibroblasts increased to levels two times higher than that of the positive control, which was UVA-damaged cells in the absence of Ulmus davidiana root extract (up to 60.2% at 3.0% of Ulmus davidiana root extract). In a photo-induced cytotoxicity assay in the presence of promethazine as a photosensitizer, Ulmus davidiana root extract showed approximately 48% of the increased cell viability of the control. Therefore, Ulmus davidiana root extract may be useful for the development of a cosmetic ingredient.

Polyethylenimine with acid-labile linkages as a biodegradable gene carrier.

Polyethylenimine (PEI) is a gene carrier with high transfection efficiency. However, PEI has high cytotoxicity, which depends on its molecular weight. To reduce the cytotoxicity, degradable PEIs with acid-labile imine linkers were synthesized with low molecular weight PEI1.8K (1.8 kDa) and glutadialdehyde. The molecular weights of the synthesized acid-labile PEIs were 23.7 and 13 kDa, respectively. The half-life of the acid-labile PEI was 1.1 h at pH 4.5 and 118 h at pH 7.4, suggesting that the acid-labile PEI may be rapidly degraded into nontoxic low molecular weight PEI in acidic endosome. In a gel retardation assay, plasmid DNA (pDNA) was completely retarded at a 3:1 N/P (nitrogen of polymer/phosphate of DNA) ratio. The zeta potential of the polyplexes was in the range of 46.1 to 50.9 mV and the particle size was in the range of 131.8 to 164.6 nm. In vitro transfection assay showed that the transfection efficiency of the acid-labile PEIs was comparable to that of PEI25K. In toxicity assay, the acid-labile PEI was much less toxic than PEI25K, due to the degradation of acid-labile linkage. Therefore, the acid-labile PEIs may be useful for the development of a nontoxic polymeric gene carrier.

Cosmeceutical properties of levan produced by Zymomonas mobilis.

Levan, a polysaccharide that can be produced by both plants and microorganisms, is a sugar polymer composed of fructose, with beta-2,6 linkages. Here, we have attempted to assess the possible use of levan produced by Zymomonas mobilis as a cosmeceutical ingredient. In service of this goal, we assessed a host of levan's properties, including its moisturizing effects, cell cytotoxicity, cell proliferation effects, and anti-inflammation effects. Levan exhibited a moisturizing effect that was almost exactly the same as that evidenced by hyaluronic acid, as well as a similar cell proliferation effect in human fibroblast and keratinocyte cell lines. Moreover, in our cell proliferation test, which was conducted using bio-artificial skin constructed via 3-dimensional (3-D) culture after the induction of primary skin inflammation with 0.05% sodium lauryl sulfate (SLS), cell viability in the presence of levan (0.01 mg/ml, 0.05 mg/ml) was determined to be higher than cell viability in the absence of levan. In our anti-inflammation test, which was also conducted using 3-D artificial skin, and which involved the measurement of a quantity of secreted interleukin-1alpha (IL-1alpha), a pre-inflammatory mediator induced by SLS, we determined that the quantity of IL-1alpha in the 3-D artificial skin treated with 0.01 mg/ml and 0.05 mg/ml of levan was less than that registered in a skin sample that had been treated only with SLS. In this study, we determined that levan exerted an anti-inflammatory effect against inflammatory reactions to skin irritants, and also that levan exerted a cell-proliferative effect in bio-artificial skin, thereby indicating its potential applicability as a cosmeceutical agent.

Magnolia bioactive constituent 4-O-methylhonokiol prevents the impairment of cardiac insulin signaling and the cardiac pathogenesis in high-fat diet-induced obese mice.

In obesity, cardiac insulin resistance is a putative cause of cardiac hypertrophy and dysfunction. In our previous study, we observed that Magnolia extract BL153 attenuated high-fat-diet (HFD)-induced cardiac pathogenic changes. In this study, we further investigated the protective effects of the BL153 bioactive constituent, 4-O-methylhonokiol (MH), against HFD-induced cardiac pathogenesis and its possible mechanisms. C57BL/6J mice were fed a normal diet or a HFD with gavage administration of vehicle, BL153, or MH (low or high dose) daily for 24 weeks. Treatment with MH attenuated HFD-induced obesity, as evidenced by body weight gain, and cardiac pathogenesis, as assessed by the heart weight and echocardiography. Mechanistically, MH treatment significantly reduced HFD-induced impairment of cardiac insulin signaling by preferentially augmenting Akt2 signaling. MH also inhibited cardiac expression of the inflammatory factors tumor necrosis factor-α and plasminogen activator inhibitor-1 and increased the phosphorylation of nuclear factor erythroid-derived 2-like 2 (Nrf2) as well as the expression of a Nrf2 downstream target gene heme oxygenase-1. The increased Nrf2 signaling was associated with decreased oxidative stress and damage, as reflected by lowered malondialdehyde and 3-nitrotyrosine levels. Furthermore, MH reduced HFD-induced cardiac lipid accumulation along with lowering expression of cardiac fatty acid translocase/CD36 protein. These results suggest that MH, a bioactive constituent of Magnolia, prevents HFD-induced cardiac pathogenesis by attenuating the impairment of cardiac insulin signaling, perhaps via activation of Nrf2 and Akt2 signaling to attenuate CD36-mediated lipid accumulation and lipotoxicity.