Kang, Young Eun;Choi, Kyeong-Mi;Park, Eunjin;Jung, Won-Beom;Jeong, Heejin;Yoo, Hwan-Soo
Journal of Life Science
/
v.27
no.3
/
pp.289-294
/
2017
Diabetes mellitus is associated with insulin resistance, which leads to down-regulation of insulin signaling and the decreased glucose uptake. Adipocytes are sensitive to insulin, and closely implicated in insulin resistance and diabetes. Insulin stimulates differentiation of preadipocytes to adipocytes, and increases glucose transport. Allium species have been used as traditional medicine and health-promoting foods. Allium hookeri (A. hookeri) is reported to improve the pancreatic ${\beta}-cell$ damage and exhibit pancreatic anti-inflammatory activity in streptozotocin-induced diabetic rats. We investigated whether A. hookeri extract (AHE) may stimulate glucose uptake in adipocytes through increasing insulin sensitivity. AHE enhanced fat accumulation, a differentiation biomarker, under the partial induction of differentiation by insulin. $PPAR{\gamma}$, a transcription factor highly expressed in adipocytes, promotes adipocyte differentiation and insulin sensitivity. AHE increased the differentiation of preadipocytes through up-regulation of $PPAR{\gamma}$. The activation of $PPAR{\gamma}$ increases the GLUT4 expression during adipocyte differentiation. GLUT4 is responsible for glucose uptake into the adipocytes. AHE increased the expression of GLUT4 in adipocytes, and subsequently enhanced the insulin-stimulated glucose uptake. These results suggest that AHE promotes adipocyte differentiation through activation of $PPAR{\gamma}$, and leads to enhance glucose uptake in adipocytes along with GLUT4 up-regulation. Thus, AHE may be effective for the insulin-sensitizing and anti-diabetic activities.
Background: Nowadays, the encapsulation of cytotoxic chemotherapeutic agents is attracting interest as a method for drug delivery. We hypothesized that the efficiency of helenalin might be maximized by encapsulation in ${\beta}$-cyclodextrin nanoparticles. Helenalin, with a hydrophobic structure obtained from flowers of Arnica chamissonis and Arnica Montana, has anti-cancer and anti-inflammatory activity but low water solubility and bioavailability. ${\beta}$-Cyclodextrin (${\beta}$-CD) is a cyclic oligosaccharide comprising seven D-glucopyranoside units, linked through 1,4-glycosidic bonds. Materials and Methods: To test our hypothesis, we prepared ${\beta}$-cyclodextrin-helenalin complexes to determine their inhibitory effects on telomerase gene expression by real-time polymerase chain reaction (q-PCR) and cytotoxic effects by colorimetric cell viability (MTT) assay. Results: MTT assay showed that not only ${\beta}$-cyclodextrin has no cytotoxic effect on its own but also it demonstrated that ${\beta}$-cyclodextrin-helenalin complexes inhibited the growth of the T47D breast cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of ${\beta}$-cyclodextrin-helenalin complexes increased. Conclusions: ${\beta}$-Cyclodextrin-helenalin complexes exerted cytotoxic effects on T47D cells through down-regulation of telomerase expression and by enhancing Helenalin uptake by cells. Therefore, ${\beta}$-cyclodextrin could be superior carrier for this kind of hydrophobic agent.
Background : The pathogenesis of acute inflammatory demyelinating polyradiculoneuropathy (AIDP), Guillain Barre syndrome (GBS) is not clear, but it has been known that the immune mechanisms play an important role. Authors performed this study to establish an animal model of experimental allergic neuritis (EAN) by immunizing the myelin components of peripheral nerves and to understand the electrophysiological and histopathological features as well as the ${CD_5}^+$ B-lymphocyte changes in peripheral bloods in the EAN models. Methods : Lewis rats weighing 150-200 gm were injected subcutaneously in soles two times with total myelin, P0, P1, or P2 proteins purified from the bovine cauda eguina. The EAN induction was assessed by evaluating clinical manifestations. The electrophysiological and histopathological features were studied as routine methods. The ${CD_5}^+$ Blymphocytes were double stained using monoclonal FITC conjugated anti-rat CD45RA and R-PE conjugated anti-rat ${CD_5}^+$ antibodies and calculated using a fluorescence activated cell sorter (FACS). Results : The EAN animal models were established. In two out of five, in one out of two, in none out of three, and in none out of one Lewis rats injected with purified total myelin, P0, P1, P2 proteins respectively, They showed slow spontaneous motor activity and weak resistance against pulling back by tails. The typical electrophysiological and histologic findings in total protein and P0 induced EAN animal models were the decreased conduction velocity, the decreased compound muscle action potential (CMAP) amplitude and the dispersion phenomenon. The perivascular infiltrates of lymphocytes with focal demyelinating process were found in light microscopy. The ${CD_5}^+$ B-lymphocyte expression in three EANs were 2.38%, 3.50% 2.50%, which were not significantly increased, compared with those in normal controls. Conclusion : The EAN animal models were successfully established by injecting the total myelin and P0 myelin and they showed electrophysiological and histological features typical of demyelinating process. However they did not show an increased expression of ${CD_5}^+$ B-lymphocyte in peripheral bloods which could be indirect evidence of humoral autoimmunity.
Platycodon grandiflorum A. De Candolle (Korean name, ‘Doraji’) is a perennial plant containing various triterpenoid saponins. The roots of this plant have traditionally been used as a food material in Korea. Here, we prepared a fermented P. grandiflorum extract (PG). Although it was previously reported that P. grandiflorum A. extract has a variety of physiological functionalities, including anti-inflammatory and anti-oxidant activities, little is known about its vascular functions. In this study, we executed a series of experiments to identify the effect of PG on endothelial cells. PG at a high concentration (100 μg/ml) was found to induce cell detachment, whereas PG at a low concentration (0.1 μg/ml) appeared to promote cell proliferation and migration in bovine aortic endothelial cells. The cell detachment induced by the high concentration was not associated with cell death, such as apoptosis, necrosis, and autophagy. In addition, we found that PG at the high concentration formed a small vesicular structure called an endothelial microparticle (EMP). The EMP was prepared by centrifugal fractionation and determined with flow cytometry and a microscope. Interestingly, PG-induced cell detachment was found to be mediated by EMP. We furthermore determined that PG at the low concentration activated Akt, a crucial cell-signaling molecule, and then controlled cell proliferation and migration. Overall, our findings suggest that PG at low doses maintains vascular stability by promoting endothelial cell proliferation, and enhances the efficacy of wound healing by cell proliferation and migration activity.
Journal of the Society of Cosmetic Scientists of Korea
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v.31
no.3
s.52
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pp.219-236
/
2005
Glycolic acid, an alpha-hydroxy acid derived from fruit and milk sugars, has been commonly used as a cosmetic ingredient since it was known to have photo-protective, anti-inflammatory effects, and anti-oxidant effect in UV-irradiated skin. However, little has been know about the functional role of glycolic acid on UV-induced skin cell proliferation. It was previously found that glycolic acid inhibited UV-induced skin tumor development in hairless mouse. As a possible mechanism of glycolic acid on the UV-induced skin tumor development, the ability of glycolic acid to inhibit the UVB-induced cell growth and possible mechanisms were investigated. Glycolic acid treatment attenuated the UV-induced cell proliferation and apoptotic cell death in the skin. In vitro study, glycolic acid inhibited the UVB-induced cell growth and apoptotic death through inhibiting caspase-3 activity. These results suggest that glycolic acid may exert the Inhibitory effect on the UVB-induced skin tumor development by regulating cell growth and apoptotic cell death.
It has been previously described that transcription factor early growth response gene product 1 (EGR-1) functions as a tumor suppressor gene. This study was conducted to demonstrate that EGR-1 induction by phytochemical apigenin and its derivative isovitexin can mediate the growth suppression of the intestinal epithelial tumor cells. Apigenin and isovitexin induced EGR-1 gene expression both in the dose and time-dependent manners. Moreover the induction was relatively late around 9-12 hr after treatment of HCT-116 cells, while several anti-inflammatory agent such as NSAIDS and catechins elicit the ECR-1 gene expression at much earlier time about 1-3 hr after treatment. In terms of signal transduction, ERK1/2 was critical for apigenin-induced EGR-1 gene expression and its promoter activation. When EGR-1 gene expression was blocked with EGR-1 small interference RNA, the cytotoxicity of apigenin in the human epithelial cells was attenuated, suggesting the involvement of EGR-1 in the anti-tumoric activity of apigenin. To link the EGR-1 induction to EGR-1-regulated gene products in colon cancer, NSAID-Activated Gene 1 (NAG-1) was demonstrated to be elevated by apigenin and isovitexin at 24-48 hr after treatment. Taken together, apigenin-activated ERK1/2 mediated EGR-1 gene induction, which was associated with suppression of the cellular viability by apigenin compound.
S. W. Lim;S. W. Jung;Kim, Bora;H. C. Ryoo;Lee, S. H.;S. K. Ahn
Proceedings of the SCSK Conference
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2003.09b
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pp.108-109
/
2003
Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromerol, prunol and malol, are pentacyclic triterpenoid compounds which naturally occur in a large number of vegetarian foods, medicinal herbs, and plants. They may occur in their free acid form or as aglycones for triterpenoid saponins, which are comprised of a triterpenoid aglycone, linked to one or more sugar moieties. Therefore UA and ON A are similar in pharmacological activity. Lately scientific research, which led to the identification of UA and ONA, revealed that several pharmacological effects, such as antitumor, hepatoprotective, anti-inflammatory, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. To clarify the effects of UA and ONA on skin barrier recovery, both flank skin of 8-12 weeks hairless mice were topically treated with samples (2mg/ml) after tape stripping, then measured recovery rate using TEWL on hairless mice. The recovery rate increased in UA and ONA treated groups at 6h more than 20% compared to vehicle treated group (p <0.05). For verifying the effects of UA and ONA on normal epidermal barrier, hydration and TEWL were measured for 1 and 3 weeks after UA and ONA applications (2mg/ml per day). We also investigated the features of epidermis and dermis using electron microscopy (EM) and light microscopy (LM). Both samples increased hydration compared to Vehicle group from 1 week without TEWL alteration (p<0.005). EM examination using Ru04 and OsO4 fixation revealed that secretion and numbers of lamellar bodies and complete formation of lipid bilayers were most prominent (ONA$\geq$UA>Vehicle). LM finding showed that stratum corneum was slightly increased and especially epidermal thickening and flattening was observed (UA>ONA>Vehicle). Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber increasing by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory experiments were also confirmed in vivo findings. This result suggested that the effects of UA and ONA related to not only skin barrier but also collagen and elastic fibers. Taken together, UA and ONA can be relevant candidates to improve barrier function and pertinent agents for cosmetic applications.
Phellinus baumii has been used in traditional oriental medicine for the treatment of various cancer types, such as lung cancer, ovarian cancer and malignant melanoma. It has strong anti-cancer, anti-inflammatory and antioxidant activities due to its polysaccharides including glucan, schizophyllan, heteroglycan and lentinan, as well as its polyphenolics such as protocatechuic acid, caffeic acid, coumaric acid. ${\beta}$-Glucan and polyphenolics may be the most important activ ecompounds in P. baumii. Therefore, researchers have focused on these two compounds to improve their contents in extracts. In this study, P. baumii was extracted with hot-water and ethanol at different pH conditions, and their ${\beta}$-glucan contents, antioxidant activity and antioxidant contents were determined. Extraction yield was highest for the 60% ethanol extract at pH 4. The ${\beta}$-glucan contents of the hot-water extract at pH 7 was higher than those of the ethanol extracts. The antioxidant contents and antioxidant activities of the ethanol extracts were higher than those of the hot-water extracts. Extraction with 60% ethanol at pH 7 was appropriate with respect to the antioxidant capacities.
Bee venom is used to treat inflammatory diseases in Korean traditional medicine and has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in bee venom-induced apoptosis are still uncharacterized in human lung cancer cells. In the present study, we investigated the effects of bee venom on the apoptosis of A549 human lung epithelial cancer cells. Treatment of bee venom inhibited the cell viability and induced apoptosis in a concentration-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometry analysis. Bee venom-induced apoptosis in A549 cells was associated with a marked inhibition of anti-apoptotic Bcl-2 expression without significant changes in the levels of Bax and Bcl-xL. Bee venom treatment also inhibited the levels of IAP family members such as cIAP-1 and cIAP-2 and induced the proteolytic activation of caspase-3 and caspase-9. Although further studies are needed, the present results suggest that apoptotic signals evoked by bee vemon in A549 cancer cells may converge caspases activation through a down-regulation of Bcl-2 rather than an up-regulation of Bax. These findings provide important insights into the possible molecular mechanisms of the anti-cancer activity of bee vemon in human cancer cells.
The fermented red ginseng by microorganism is known to increase pharmacological activity in vivo. To evaluate the bioavailablity of red ginseng fermented by probiotics, we conducted the pharmacokinetic study of ginsenoside Rb1, Rd and total ginsenosides (TG, ginsenosides Rb1 + Rd + Rg1 + F2 + Rg3 + compound K) in BALB/C mice. The AUC value of ginsenoside Rb1 in mice serum administered with 600mg/kg drugs showed 21.93 ± 14.68 ng·h/mL (RGw, water extract), 275.211 ± 110.04 ng·h/mL (RGe, 50% ethanol extract) and 404.91 ± 162.57 ng·h/mL (fRGe, fermented red ginseng extract). Analysis of ginsenoside Rd also showed a higher ACU value in fRGe than in RGw or RGe. And the AUC value of total ginsenosides in mice serum treated with 600 mg/kg were observed 42.12 ± 23.44 ng·h/mL (RGw), 321.44 ± 133.5 ng·h/mL (RGe) and 537.33 ± 229.01 ng·h/mL (fRGe), respectively. Cmax value of ginsenoside Rb1 in mice administered with 600mg/kg were observed 3.67 ± 3.34 ng/mL (RGw), 23.27 ± 8.81 ng/mL (RGe) and 25.52 ± 7.29 ng/mL (fRGe). These results can be considered that the fermented red ginseng has more bioavailability than that of unfermented red ginseng. In quantitative analysis of the inflammation-related cytokines IL-1β and TNF, no significant difference was found between the fermented red ginseng (fRGe) and the red ginseng (RGe).
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