• Journal of Life Science
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• v.29 no.10
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• pp.1096-1103
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• 2019

Neuroinflammation is mediated by the activation of microglia and has been implicated in the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Therefore, the inhibition of neuroinflammation may be an effective solution to treat these brain disorders. Protaetia brevitarsis seulensis is an insect belonging to the order Coleoptera and inhabits Korea, China, Japan and Siberia. P. brevitarsis seulensis is an edible insect that can be consumed as a protein source for humans. It has been reported that P. brevitarsis seulensis contains useful bioactive substances for hepatoprotection and improving blood circulation, such as indole alkaloids. Microglia cells are the main source of proinflammatory cytokines and nitric oxide (NO) in the central nervous system, which Perform neuroimmune, inflammatory, and other neurobilogical functions. In this study, we investigated the anti-neuroinflammatory effects of P. brevitarsis seulensis ethanol extract (PBE) in activated microglia cells treated with lipopolysaccgarude (LPS, 100 ng/ml). As a result, PBE significantly inhibited NO production without cytotoxicity and decreased the expression levels of inducible NO synthase and cyclooxygenase-2. In addition, the production of inflammatory cytokine secreted by LPS was also reduced by PBE. These results suggest that PBE could be a good source of functional substances to prevent neuroinflammation and neurodegenerative diseases.

• Journal of Life Science
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• v.30 no.12
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• pp.1078-1084
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• 2020

Protaetia brevitarsis seulensis is an insect belonging to the order Coleoptera. This insect is reported to contain large amounts of physiologically active substances useful for liver protective effect and improvements in blood circulation as well as a broad source of edible protein. Antimicrobial peptides (AMPs) are found in a variety of species, from microorganisms to mammals, and play an important role in the innate immune systems of living things. Microglia are the main source of proinflammatory cytokines and nitric oxide (NO) in the central nervous system. Activated microglia secrete large amounts of neuroinflammatory mediators (e.g., TNF-α, NO, and ROS), which are the main cause of neuronal cell death. In the present study, we investigated the inhibitory effect of Protaetiamycine 6 (PKARKLQKLSAYKTTLRN-NH2), an AMP derived from Protaetia brevitarsis seulensis, on LPS-induced neuroinflammation in BV-2 microglia. Protaetiamycine 6 significantly inhibited NO production without cytotoxicity and decreased the expression levels of inducible NO synthase and cyclooxygenase-2. In addition, Protaetiamycine 6 also reduced the production of neuroinflammatory cytokines on activated BV-2 microglia. These results suggest that Protaetiamycine 6 could be a good source of functional substance to prevent neuroinflammation and neurodegenerative diseases.

• Journal of Applied Biological Chemistry
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• v.61 no.2
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• pp.141-150
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• 2018

In this study, the inflammation of ethanol extracts from Caryopteris incana (CI) and fermented C. incana (FCI) on induced to lipopolysaccharide with Raw 264.7 cell was tested. The composition profile of L. plantarum was changed by fermentation, and confirmed by HPLC analysis. We performed the 3-[4,5-dimethylthiazol]-2-yl]-2,5-diphenyltetrazolium bromide assay to evaluate the toxicity of CI and FCI extracts. In cell viability, cell toxicity was not shown at 5, 10 and $15{\mu}g/mL$ of CI extracts and 10, 20, 30 and $40{\mu}g/mL$ of FCI extracts. The results of inducible nitric oxide synthase and cyclooxygenase-2 protein production were confirmed to be inhibitory in a concentration-dependent manner, respectively. Additionally, protein expression of nitric oxide and prostaglandin $E_2$ by CI and FCI extracts were also inhibited in a concentration-dependent manner. In the result of pro-inflammatory cytokine, $15{\mu}g/mL$ concentration of CI extracts was showed tumar necrosis factor $(TNF)-{\alpha}$ (57.3%), interleukin (IL)-6 (35.2%), and $IL-1{\beta}$ (48.0%), respectively. And $40{\mu}g/mL$ of FCI extracts was showed $TNF-{\alpha}$ (34.6%), IL-6 (32.1%), and $IL-1{\beta}$ (30.0%), respectively. These results suggest that FCI extracts showed better effect of anti-inflammatory than CI extracts. Therefore, it was found that both CI and FCI can be used as an excellent material for the development of new anti-inflammatory resource.

• Journal of Life Science
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• v.22 no.1
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• pp.41-48
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• 2012

Bee venom (BV) has been used in medicine to treat a variety of diseases including arthritis, rheumatism, and various cancers. Recent reports indicate that BV has anti-angiogenic effects, but the precise molecular mechanism underlying the effects of BV against colorectal cancer remains to be elucidated. We examined the effects of BV and its major components (melittin and apamin) on tumor angiogenesis and found that BV significantly decreased protein levels of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), an important factor involved in angiogenesis and tumor progression, in human colorectal carcinoma HCT116 cells. BV also suppressed the transcription of HIF-$1{\alpha}$ under hypoxia, leading to a decrease in the expression of vascular endothelial growth factor (VEGF), a major target gene of HIF-$1{\alpha}$. We also found that these effects were mainly elicited by apamin, but not melittin. BV specifically inhibited the phosphorylation of ERK1/2 without changing the total levels of this protein, but had no effect on kinases of p38/JNK and AKT. Our results suggest that BV may inhibit human colorectal cancer progression and angiogenesis by inhibiting HIF-$1{\alpha}$ and VEGF expression, thereby providing a novel potential mechanism for the anticancer action of BV.

• Tuberculosis and Respiratory Diseases
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• v.66 no.3
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• pp.178-185
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• 2009

Background: Epigallocatechin-3-gallate (EGCG) is the major catechin in green tea, and has shown antiproliferative, antiangiogenic, antimetastatic and cell cycle pertubation activity in various tumor models. Hypoxia can be induced because angiogenesis is insufficient for highly proliferating cancer. Hypoxia-inducible factor-1$\alpha$ (HIF-1$\alpha$) and its downstream target, vascular endothelial growth factor (VEGF), are important for angiogenesis, tumor growth and metastasis. The aim of this study was to determine how hypoxia could cause changes in the cellular phenomena and microenvironment in a non-small cell culture system and to examine the effects of EGCG on a HIF-1$\alpha$ and VEGF in A549 cell line. Methods: A549 cells, a non-small cell lung cancer cell line, were cultured with DMEM and 10% fetal bovine serum. A decrease in oxygen tension was induced using a hypoxia microchamber and a $CO_2-N_2$ gas mixture. Gas analysis and a MTT assay were performed. The A549 cells were treated with EGCG (0, 12.5, 25, 50 ${\mu}mol/L$), and then examined by real-time-PCR analysis of HIF-1$\alpha$, VEGF, and $\beta$-actin mRNA. Results: Hypoxia reduced the proliferation of A549 cells from normoxic conditions. EGCG inhibited HIF-1$\alpha$ transcription in A549 cells in a dose-dependent manner. Compared to HIF-1$\alpha$, VEGF was not inhibited by EGCG. Conclusion: HIF-1$\alpha$ can be inhibited by EGCG. This suggests that targeting HIF-1$\alpha$ with a EGCG treatment may have therapeutic potential in non-small cell lung cancers.

• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.191-199
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• 2005

Background: Though infections of Helicobacter pylori (H. pylori) are closely associated with activation of host angiogenesis, the underlying mechanisms, as well as the strategy for its prevention, have not been identified. Here, we investigated a causal role of H. pylori infection in angiogenesis of gastric mucosa and a potent inhibitory effect of a gastric proton pump inhibitor (PPI) on the gastropathy. Materials and Methods: A comparative analysis of CD 34 expression in tissues obtained from 20 H. pylori-associated gastritis and 18 H. pylori-negative gastritis patients was performed. Expression of $HIF-1{\alpha}$ and VEGF were tested by using RT-PCR. To evaluate the direct effect of H. pylori infection on differentiation of endothelial HUVEC cells, we carried out an in vitro angiogenesis assay. Results: H. pyfori-associated gastritis tissues showed significantly higher density of $CD34^+$ blood vessels than did H. pylori-negative gastritis tissues, and the levels were well correlated with expressions of $HIF-1{\alpha}$. Conditioned media from H. pylori-infected gastric mucosal cells stimulated a tubular formation of HUVEC cells. We also found a significant inhibitory effect of PPI, an agent frequently used for H. pylori eradication, on H. pylori-induced angiogenesis. This drug effectively inhibited the phosphorylation of MAP kinase ERK1/2, which is a principal signal for H. pylori-induced angiogenesis. Conclusion: The fact that PPls can down-regulate H. pylori-induced angiogenesis suggest that anti-angiogenic treatment using PPI may be a preventive approach for H. pylori-associated carcinogenesis.

• KSBB Journal
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• v.24 no.4
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• pp.327-333
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• 2009

The antioxidant and anti-inflammatory activities of ethanol extract of Malus micromalus were studied in vitro. Ethanol extract of M. micromalus showed scavenging effects on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide (NO) radicals. In addition, ethanol extract of M. micromalus inhibited the generation of superoxide anion ($O_2^-$) radical and uric acid by xanthine oxidase. We also investigated the effect of ethanol extract of M. micromalus on NO production in a lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. Ethanol extract of M. micromalus significantly inhibited NO production and this inhibitory action was not due to the cytotoxicity. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was markedly down-regulated by ethanol extract of M. micromalus. These results indicate that the inhibitory action of ethanol extract of M. micromalus on NO production in LPS-stimulated macropages might be due in part to abrogation of iNOS and COX-2 protein induction. Taken together, this study suggests that ethanol extract of M. micromalus could contribute to the chemoprevention and therapy of oxidative stress and inflammation.

• Journal of Life Science
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• v.29 no.11
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• pp.1218-1226
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• 2019

The white-spotted flower chafer Protaetia brevitarsis seulensis is a medicinally beneficial and important edible insect species. We previously performed an in silico analysis of the Protaetia brevitarsis seulensis transcriptome to identify putative antimicrobial peptides and then tested their antimicrobial and hemolytic activities. These peptides had potent antimicrobial activities against bacteria and yeast without inducing hemolysis. In the present study, the cationic antimicrobial peptide, protaetiamycine 2, was selected for further assessment of its anti-inflammatory properties in mouse macrophage Raw264.7 cells. Protaetiamycine 2 treatment of Raw264.7 cells suppressed LPS-induced nitric oxide production and reduced the expression of inducible nitric oxide synthase and cyclooxygenase-2, as determined by real-time PCR and western blotting. The expression of proinflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) was also attenuated through the MAPKs and $NF-{\kappa}B$ signaling. We also confirmed that protaetiamycine 2 bound to bacterial cell membranes by a specific interaction with LPS. Collectively, these data obtained from LPS-induced Raw264.7 cells indicated that protaetiamycine 2 could have both antimicrobial and anti-inflammatory properties.

• Korean Journal of Food Science and Technology
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• v.54 no.1
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• pp.43-51
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• 2022

Regulation of the hair follicle cycle in association with dermal papilla cells is one of the most interesting targets for promoting hair regrowth. In this study, we examined whether steam-dried Betula platyphylla extracts (BPE) promote hair growth by upregulating in vitro and in vivo responses of dermal papilla cells. The data showed that BPE3 contained high amounts of phenolic compounds with higher antioxidant effects and increased hair growth-related genes, including fibroblast growth factor7 and Wnt7b, in dermal papilla cells. Notably, BPE3 effectively enhanced the formation of hair follicles by increasing FGF7, Wnt7b, and vascular endothelial growth factor in C57BL/6N dorsal skins. Additionally, BPE3 significantly decreased the expression of inflammatory repertoires, inducible nitric oxide synthase, interleukin-6, and cyclooxygenase 2. Several small molecules, such as betulin and unsaturated fatty acids, support the pharmacological activity of BPE3. In conclusion, BPE3 effectively promoted hair growth by activating dermal papilla cells and enhancing hair follicle cycles by attenuating the inflammatory environment in the scalp.

• Korean Journal of Food Science and Technology
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• v.50 no.5
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• pp.535-542
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• 2018

The current study investigated the beneficial effects of 15 essential oils isolated from tree branches, leaves, and flowers. Among these oils, clove bud and Illicium anisatum oils showed the most potent anti-oxidant effects on 1,1-diphenyl-2-picrylhydrazyl and 2,2'azinbis-(3-ethyl-benzothiazoline-6-sulfonic acid) radical scavenging activities. Next, we evaluated the antibacterial effects of 15 essential oils on Staphylococcus aureus, Listeria monocytogenes, Escherichia coli O157:H7, Salmonella typhimurium, and Streptococcus mutans. Clove bud significantly decreased growth of 5 bacterial strains. In addition, clove bud, Magnolia kobus, Picea abies and Chamaecyparis obtuse significantly reduced growth of the fungi, Aspergillus fumigatus, Aspergillus ochraceus, Candida albicans and Trichophyton rubrum. Additionally, clove bud also remarkably reduced the expression of cyclooxygenase-2 and inducible NO synthase in lipopolysaccharide-activated RAW264.7 cells. These results indicate that essential oils isolated from trees, which exhibit antioxidant, antibacterial, antifungal and anti-inflammatory properties, may be potentially useful in the development of cosmetic ingredients.