• Journal of Life Science
• /
• v.21 no.6
• /
• pp.796-804
• /
• 2011

Microglia are central nervous system (CNS)-resident professional macrophages that function as the principal immune cells responding to pathological stimulations in the CNS. Activation of microglia, induced by various pathogens, protects neurons and maintains homeostasis in the CNS, but severe activation causes inflammatory responses secreting various neurotoxic molecules such as nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines. Allium fistulosum, a member of the onion family, is mainly cultivated for consumption, as well as medicinal use in Oriental medicine. It has been reported that A. fistulosum has various biological effects such as anti-oxidant, anti-platelet aggregation, anti-fungus and anti-cholesterol synthesis, however there has been no research about the anti-inflammatory effects of A. fistulosum extracts. In this study, it was undertaken to explore the functions of A. fistulosum as a suppressor of neuronal inflammation by using BV2 microglia cells. As a result, it was found that four kinds of extracts of A. fistulosum effectively reduced the expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) at both mRNA and protein levels, and also attenuated pro-inflammatory cytokines such as tumor necrosis alpha (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and interleukin-6 (IL-6) at the mRNA level in BV2 stimulated by lipopolysaccharide (LPS). In addition, the extracts of A. fistulosum attenuated the release of NO markedly, as well as resulting in slight decreases of TNF-${\alpha}$ and IL-6 production, the effects of which were most significant when treated with ethyl alcohol extract from the whole A. fistulosum. In conclusion, the data indicated that the anti-inflammatory actions of A. fistulosum against BV2 microglia cells is through the down-regulation of iNOS, COX2 and pro-inflammatory cytokines such as TNF-${\alpha}$ and IL-6, and these effects are expected to help in the protection of nerve tissues by suppressions of neuronal inflammation in various neurodegenerative diseases.

• Journal of Life Science
• /
• v.19 no.12
• /
• pp.1802-1807
• /
• 2009

Platycodin D, a major component of Platycodi radix, is known to have various activities including anti-inflammatory, anti-hyperlipidemic, anti-tumor activities and others. Recently, it was reported that platycodin D inhibits fat accumulation and adipogenesis. The aim of this study was to investigate whether various adipogenic regulators are modulated by platycodin D treatment during the adipogenesis of 3T3-L1 cells. mRNA levels of terminal markers of adipogenesis such as ADIPOQ (adiponectin) and GLUT (glucose transporter) 4, which were quantified by real time PCR, were decreased by platycodin D treatment. mRNA expression of PPAR (peroxisome proliferator-activated receptor) $\gamma$ and C/EBP (CCAAT/enhaner binding protein) $\alpha$, which are central transcription factors of adipogenesis, were also decreased by platycodin D treatment. To elucidate the detailed molecular mechanism of platycodin D-induced inhibition of adipogenesis, we analyzed mRNA expression of upstream regulators of PPAR$\gamma$ and C/EPB$\alpha$. mRNA levels of the pro-adipogenic regulators, KROX20 and KLF (Kruppel-like factor) 15 were markedly down-regulated by platycodin D treatment. On the other hand, mRNA expression of CHOP (C/EBP homologous protein), an anti-adipogenic regulator, was significantly up-regulated by platycodin D treatment. mRNA levels of other pro-adipogenic regulators, C/EBP$\beta$ and C/EPB$\delta$, were not affected by platycodin D treatment, and another anti-adipogenic regulator, C/EBP$\gamma$ was also not affected by platycodin D treatment. Taken together, these results suggest that platycodin D-induced inhibition of adipogenesis is mediated by gene interactions including the down-regulation of pro-adipogenic regulators, KROX20 and KLF15, and the up-regulation of an anti-adipogenic regulator, CHOP.

• Journal of Life Science
• /
• v.29 no.12
• /
• pp.1305-1313
• /
• 2019

Licochalcone (LC), isolated from the roots of Glycyrrhiza inflata has multiple pharmacological effects including anti-inflammatory and anti-tumor activities. To date, Licochalcone C (LCC) has induced apoptosis and inhibited cell proliferation in oral and bladder cancer cells, but lung cancer has not yet been studied. In addition, no study reported LCC-induced autophagy in cancer until now. The present study was designed to investigate the effect of LCC on gefitinib-sensitive and -resistant lung cancer cells and elucidate the mechanism of its action. The 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay data showed that LCC significantly inhibited cell viability in non-small cell lung cancer (NSCLC) HCC827 (gefitinib-sensitive) and HCC827GR (gefitinib-resistant) cell lines. Interestingly, Annexin V/7-aminoactinomycin D double staining and cell cycle analysis showed an apoptosis rate within about 20% at the highest concentration of LCC. LCC induced G2/M arrest by reducing the expression of the cell cycle G2/M related proteins cyclin B1 and cdc2 in NSCLC cell lines. Treatment of LCC also induced autophagy by increasing the expression of the autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3) and the protein autophagy-related gene 5 involved in the autophagy process. In addition, LCC increased the production of reactive oxygen species (ROS), and the cell viability was partially restored by treatment with the ROS inhibitor N-acetyl-L-cysteine. In western blotting analysis, the expression of cdc2 was increased and LC3 was decreased by the simultaneous treatment of NAC and LCC. These results indicate that LCC may contribute to anti-tumor effects by inducing ROS-dependent G2/M arrest and autophagy in NSCLC. In conclusion, LCC treatment may be useful as a potential therapeutic agent against NSCLC.

• Korean Journal of Food Science and Technology
• /
• v.46 no.2
• /
• pp.198-204
• /
• 2014

Ultraviolet B (UV-B) irradiation is a negative factor that induces skin damage, inflammation, and aging. UVB irradiation induces the inflammatory response through interleukin (IL)-6 and IL-8 expression in keratinocytes. In addition, it induces the production of reactive oxygen species (ROS) and the activation of matrix metalloproteinase-1 (MMP-1), which plays an important role in collagen 1 degradation in the extracellular matrix. We investigated the antiaging effects of five kinds of berry in human skin keratinocyte (HaCaT) cells using juice of black raspberry (Rubus occidentalis), blueberry wild (Vacciniun angustifolium) and cultivar (Vacciniun corymbosum), black chokeberry (Aronia melanocarpa (Michx.) Elliott), and mulberry (Morus abla). HaCaT cells irradiated with UV-B exhibited increased ROS generation, as well as IL-6, IL-8, and MMP-1 gene expression, when compared to the control cells that were not irradiated with UV-B. However, pre-treatment of berry juice before UV-B irradiation significantly down-regulated the UV-B-induced ROS generation and inflammatory cytokine and MMP-1 expression. The results suggest that all berries have anti-aging effects including lowering inflammatory cytokine levels, ROS generation, and MMP-1 expression in HaCaT cells during UV-B irradiation.

• Journal of Life Science
• /
• v.26 no.1
• /
• pp.34-41
• /
• 2016

Black chokeberries (scientific name Aronia melanocarpa) have been reported to have major effects due to anti-oxidant, anti-inflammatory, and anti-cancer capabilities. In this study, we investigated the anti- wrinkle effects of A. melanocarpa, including collagenase inhibition effects and their molecular biological mechanisms, such as oxidative stress-induced matrix metalloproteinase (MMP), mitogen-activated protein (MAP) kinase, and activator protein (AP)-1 expression and/or phosphorylation. In collagenase inhibition activity, the ethyl acetate fraction of black chokeberry (AE) was 77.2% at a concentration of 500 μg/ml, which was a significant result compared to that of Epigallocatechin gallate (positive control, 83.9% in 500 μg/ml). In the reactive oxygen species (ROS) assay, the AE produced 78% of ROS in 10 μg/ml and 70% of ROS in 75 μg/ml, which was a much lower percentage than the ROS production of H₂O₂-induced CCRF S-180II cells. In the MTT assay, cell viability was increased dose-dependently with AE in H₂O₂-induced cells. In protein expression by western blot assay, the AE suppressed the expression and phosphorylation of MMPs (MMP-1, -3, -9), MAPK (ERK, JNK, and p38), and AP-1 (c-Fos and c-Jun), and expressed the pro-collagen type I in H₂O₂-induced cells. These results suggest that black chokeberries have anti-wrinkle and collagen-production effects, and they may be used in applications for material development in the functional food and cosmetic industries.

• Journal of Life Science
• /
• v.27 no.2
• /
• pp.247-266
• /
• 2017

Cordyceps is a traditional Chinese medicinal herb well-known in China, Korea and Japan since B.C. 2,000. The original entomopathogenic fungus, Cordyceps sinensis belonging to the genus Cordyceps could not be found inside Korean peninsula due to the absence of the host insect for the corresponding entomogenous fungus. The development of artificial production methods of Korean type Cordyceps using the silkworm Bombyx mori as in vivo culture medium for the the entomopathogenic fungus Paecilomyces tenuipes is the first, and wonderful occasion in the research history of insect industry of this global world. The aim of this article is to review the historical research background, mass-production methods, and pharmacological effects of the silkworm-dongchunghacho (Paecilomyces tenuipes) which is a newly developed Korean medicinal insect-borne mushroom, and another non-insect-borne medicinal mushroom (Cordyceps militaris and Cordyceps pruinosa). Their biological actions include anti-tumor, immunostimulating, anti-fatigue, anti-stress, anti-oxidant, anti-aging, anti-diabetic, anti-inflammatory, anti-thrombosis, hypolipidaemic and insecticidal effects. The bioactive principles are protein-bound polysaccharides (hexose, hexosamin), cordycepin, D-manitol, acidic polysaccharide etc. Protein-bound polysaccharides and n-butanol fractions were demonstrated to show a significant anti-tumor activities but did not show a cytotoxicities. D-mannitol exhibited a significant prolongation of the life span in tumor bearing mice. Ergosterol did not show an efficient anti-tumor activity, but showed a significant phagocytosis enhancing activity. Anti-tumor activity of silkworm-dongchunghacho might be attributed to immuno-stimulating activities rather than cytotoxic effects [164]. Also this review comprises the breeding of Dongchunghacho varieties, optimization of culture conditions, improvement of learning and memory by Dongchunghacho, application of them as foods and chemical constituents.

• Journal of Life Science
• /
• v.27 no.2
• /
• pp.155-163
• /
• 2017

Mori Folium, the leaf of Morus alba, is a traditional medicinal herb that shows various pharmacological activities such as antiinflammatory, antidiabetic, antimelanogenesis, antioxidant, antibacterial, antiallergic, and immunomodulatory activities. However, the mechanisms of their inhibitory effects on adipocyte differentiation and adipogenesis remain poorly understood. In the present study, we investigated the inhibition of adipocyte differentiation and adipogenesis by ethanol extracts of Mori Folium (EEMF) in 3T3-L1 preadipocytes. Treatment with EEMF suppressed the terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner, as confirmed by a decrease in the lipid droplet number and lipid content through Oil Red O staining. EEMF significantly reduced the accumulation of cellular triglyceride, which is associated with a significant inhibition of pro-adipogenic transcription factors, including sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-${\gamma}$ ($PPAR{\gamma}$), and CCAAT/enhancer-binding proteins ${\alpha}$ ($C/EBP{\alpha}$) and ${\beta}$ ($C/EBP{\beta}$). In addition, EEMF potentially downregulated the expression of adipocyte-specific genes, including adipocyte fatty acid binding protein (aP2) and leptin. Furthermore, EEMF treatment effectively increased the phosphorylation of the AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC); however, treatment with a potent inhibitor of AMPK, compound C, significantly restored the EEMF-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results together indicate that EEMF has preeminent effects on the inhibition of adipogenesis through the AMPK signaling pathway, and further studies will be needed to identify the active compounds in Mori Folium.

• Journal of Ginseng Research
• /
• v.33 no.4
• /
• pp.367-377
• /
• 2009

Halitosis is a generally accepted marker of diseases in the oral cavity and of systemic and gastrointestinal disorders. Based on these authors' previous findings (that (1) there is a close association between H. pylori infection and halitosis; (2) Korea red ginseng may suppress the colonization of H. pylori, fight H. pylori-induced cytotoxicity, and impose significant anti-inflammatory actions in patients with chronic gastritis; and (3) H. pylori infection is linked with the generation of significant levels of volatile sulfur compounds (VSCs), and the levels of VSCs correlate significantly with H. pylori-associated mucosal damages), in the current study, the authors documented the molecular mechanisms of Korea red ginseng's efficacy in ameliorating halitosis. When the RAW 264.7 cells were treated with the $H_2S$ releasing compound NaHS, the mRNA expression of cystathionine ${\gamma}$-lyase (CSE), IL-6, COX-2, and iNOS were more significantly induced compared with the vehicle-treated group. The cytoskeletal components of ezrin's and moesin's mRNA expressions were elevated by NaHS treatment accompanied by the activation of MAPK, p38, and ERK. Korea red ginseng pretreatment reduced both the NaHS-induced CSE expression and the proinflammatory genes (e.g., IL-6, COX-2, and iNOS) in a concentration-dependent manner. The ERM expression and the phosphorylation of p38 were also significantly reduced by Korea-red-ginseng pretreatment. Overall, Korea red ginseng pretreatment imposed significant anti-inflammatory effects through the downregulation of the NaHS-triggered proinflammatory gene expression, CSE, and ERM mRNA expression. Korea red ginseng could thus be said to be a key remedy of halitosis and to be effective in relieving gastric inflammation.

• Journal of Life Science
• /
• v.25 no.7
• /
• pp.801-809
• /
• 2015

Homotypic cell adhesion (homotypic aggregation) in activated monocytes plays a central role in physiological and pathological processes including inflammatory responses, differentiation and migration. The extract of the Prunus mume Sieb. et Zucc. fruit (Maesil) has potential benefits to human health; such as anti-viral, anti-microbial, and anti-cancer activities. Indeed, Maesil extract may modulate inflammatory responses via interference with homotypic aggregation in monocytes. In the present study, the molecular mechanisms underpinning the therapeutic efficacy of Maesil extract in inflammatory diseases were investigated. It was found that Maesil extract inhibited homotypic aggregation in lipopolysaccharide (LPS)-activated monocytes. This was mediated by reduction of nitric oxide (NO) production, partly via inhibition of inducible nitric oxide synthase (iNOS) expression in LPS-activated THP-1 cells. It was confirmed that NO inhibition is a key mechanism in Maesil induced blockade of monocyte aggregation through identification of reversal of this inhibitory effect by the NO-producing agent S-nitroso-N-acetyl penicillamine (SNAP). In addition, Maesil extract significantly attenuated LPS-induced IκB-α phosphorylation and NF-κB translocation into the nucleus. In conclusion, Maesil extract exerts anti-inflammatory effects via inhibition of homotypic aggregation of LPS-activated monocytes through mechanisms involving the suppression of NO production and NF-κB activity, suggesting Maesil extract as a potential therapeutic candidate for the prevention and treatment of chronic inflammatory diseases.

• Journal of Life Science
• /
• v.21 no.4
• /
• pp.561-567
• /
• 2011

This study was performed to evaluate the anti-inflammatory and antioxidant activities of methanol extract from natural products. Cell viability was determined by MTT assay. The production of NO and TNF-${\alpha}$ were measured by Griess assay and enzyme-linked immunosorbent assay (ELISA). In order to effectively screen for anti-inflammatory agents, we first examined the inhibitory effects of 24 natural products on the production of lipopolysaccharide (LPS)-induced nitric oxide (NO) in RAW 264.7 cells. Three extracts of Terminalia chebula Retz., Lavandula spica L., and Dalbergia odorifera T. significantly inhibited NO production. The three extracts significantly decreased production of NO in a dose-dependent manner. Terminalia chebula Retz. decreased TNF-${\alpha}$ production. Antioxidative effects of the three extracts were measured based on polyphenol and flavonoid contents and DPPH radical scavenging activity assay. The three extracts showed high polyphenol contents as well as strong DPPH scavenging activities. In particular, Terminalia chebula Retz. contained the highest polyphenol and flavonoid levels of 616 and $96\;{\mu}g/mg$, respectively, compared to Lavandula spica L. and Dalbergia odorifera T. As DPPH radical scavensing activities, RC50 values of Terminalia chebula Retz. were $2.09\;{\mu}g/ml$.