• Food Science and Biotechnology
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• 제18권5호
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• pp.1204-1211
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• 2009

Hericium erinaceus is an edible mushroom used as a medicinal food in Asian countries. In this study, the chemopreventive effects of H. erinaceus mycelia hot water extract (HEW) were evaluated. HEW remarkably induced the luciferase activity of the antioxidant response element (ARE), located in the promoter region of phase 2 and antioxidant genes and regulated by nuclear factor E2-related factor 2 (Nrf2). The up-regulation of ARE activity by HEW corresponded with the induction of Nrf2 and the antioxidant enzyme, hemeoxygenase-1. The inhibition of cyclooxygenase-2 (COX-2) activity is a promising effective approach in cancer chemoprevention, and HEW prominently suppressed COX-2 protein expression in HepG2 cells. Furthermore, HEW showed anti-inflammatory activity by modulating inflammatory mediators such as nitric oxide (NO), inducible NO synthase, tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, and the transcription factor, nuclear factor-${\kappa}B$, in lipopolysaccharide-stimulated RAW 264.7 cells. These results suggest that H. erinaceus possessed anti-tumor and anti-inflammatory effects via the modulation of Nrf2/ARE and inflammatory signaling pathways, and may therefore have potential use as a natural chemopreventive agent.

• Journal of Microbiology and Biotechnology
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• 제18권7호
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• pp.1308-1316
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• 2008

Propionibacterium acnes is known to playa pivotal role in the pathogenesis of acne vulgaris. CBT-SL5 is one of the antimicrobial peptides from Enterococcus faecalis SL5, and it has shown antimicrobial activity against P. acnes. The aim of this study was to investigate the anti-inflammatory effect of CBT-SL5 on the inflammation induced by P. acnes in cultured human keratinocyes. Cultured human keratinocytes derived from neonatal foreskin were treated with heat-killed P. acnes to induce inflammation, and then various concentrations of CBT-SL5 were added to the P. acnes-treated keratinocytes. The mRNA expression and protein secretion of interleukin (IL)-8, an inflammation marker, was analyzed by real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. We also analyzed the nuclear factor-kappa B (NF-$\kappaB$) p65 translocation by performing immunofluorescent staining. P. acnes treatment up regulated the IL-8 mRNA expression in the keratinocytes, and this was brought about through both toll-like receptor (TLR)2 and TLR4. At the concentrations of 10, 50, and 100 ng/ml, CBT-SL5 significantly down regulated the P. acnes-induced IL-8 mRNA expression and protein production (p<0.05). At 6 hand 12 h of the treatment, CBT-SL5 significantly suppressed the P. acnes-induced IL-8 mRNA expression. Secretion of IL-8 protein was significantly reduced at 24 h. The functional inhibitory activity of CBT-SL5 was shown by CBT-SL5 suppressing the P. acnes-induced NF-$\kappaB$ translocation from the cytoplasm to the nucleus. These results demonstrated that CBT-SL5 suppressed the P. acnes-induced IL-8 expression in keratinocytes. Therefore, CBT-SL5 may be a novel anti-inflammatory treatment for acne.

• 한국어류학회지
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• 제23권1호
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• pp.61-69
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• 2011

멸종위기 어류 미호종개(Cobitis choii)로부터 중금속해독 단백질(metallothionein) 유전자를 분리, 클로닝하고 중금속 및 고온 스트레스에 대한 전사 발현 특정을 분석하였다. 미호종개 metallothionein는 gDNA, mRNA 및 아미노산 서열 모두에서 경골 어류 MT들의 구조적 특징을 잘 보전하고 있었으며, 생물정보분석을 통해 미호종개 MT 유전자 5'-upstream 영역은 중금속 조절, 면역 반응 및 온도 반응에 관여하는 다양한 전사 조절인자들의 부착 위치들을 포함하는 것으로 관찰되었다. 카드뮴(Cd), 구리(Cu), 니켈(Ni), 망간(Mn) 및 아연(Zn)을 이용한 침지 노출 실험(0.5 및 $1.0\;{\mu}M$; 24시간)에서 미호종개 MT mRNA 발현은 구리 및 카드뮴 처리군에서 가장 많이 유도되었고($1.0\;{\mu}M$ Cu 처리군에서 최대 10배), 망간 처리군에서는 비교적 적은 양의 MT 발현이 유도된 반면(2배), 아연 및 니켈 노출 군에서는 유의적인 MT 발현의 증감이 관찰되지 않았다. 또한 미호종개 MT 전사 발현은 고온 자극 ($25^{\circ}C$로부터 $31^{\circ}C$까지 증가)에도 민감하게 반응하는 것으로 나타나, $31^{\circ}C$ 도달시점에서 $25^{\circ}C$ 초기 MT mRNA 발현 수준보다 9배 높은 mRNA 발현이 관찰되었다. 본 연구 결과는 MT 기반의 유전자 발현 분석을 이용함으로써, 향후 멸종위기 어류 미호종개의 스트레스 반응 연구에 유용한 기초 자료를 제공할 수 있다고 기대된다.

• Molecules and Cells
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• 제42권11호
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• pp.810-819
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• 2019

For physiological or pathological understanding of bone disease caused by abnormal behavior of osteoclasts (OCs), functional studies of molecules that regulate the generation and action of OCs are required. In a microarray approach, we found the suppression of tumorigenicity 5 (ST5) gene is upregulated by receptor activator of nuclear $factor-{\kappa}B$ ligand (RANKL), the OC differentiation factor. Although the roles of ST5 in cancer and ${\beta}-cells$ have been reported, the function of ST5 in bone cells has not yet been investigated. Knockdown of ST5 by siRNA reduced OC differentiation from primary precursors. Moreover, ST5 downregulation decreased expression of NFATc1, a key transcription factor for osteoclastogenesis. In contrast, overexpression of ST5 resulted in the opposite phenotype of ST5 knockdown. In immunocytochemistry experiments, the ST5 protein is colocalized with Src in RANKL-committed cells. In addition, ST5 enhanced activation of Src and Syk, a Src substrate, in response to RANKL. ST5 reduction caused a decrease in RANKL-evoked calcium oscillation and inhibited translocation of NFATc1 into the nucleus. Taken together, these findings provide the first evidence of ST5 involvement in positive regulation of osteoclastogenesis via Src/Syk/calcium signaling.

• 한국약용작물학회지
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• 제24권3호
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• pp.228-236
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• 2016

Background: Sedum takesimense Nakai has been used as folk medicine in Korea. The present study aimed to determine the biological activity of S. takesimense by investigating the anti-inflammatory effects of S. takesimense water extract (SKLC) on the lipopolysaccharide-induced inflammatory response in RAW 264.7 cells. Methods and Results: Cytotoxicity of SKLC on RAW 264.7 cells was determinded by performing MTS assay was found to have no cytotoxic effect on RAW 264.7 cells at a concentration range of $62-500{\mu}g/m{\ell}$. Further, pretreatment of SKLC inhibited lipopolysaccharide-induced nitric oxide (NO) production in a dose-dependent manner. To determined the inhibitory mechanisms of SKLC on inflammatory mediators, we assessed the inducible nitric oxide synthase (iNOS) and cyclooxygnease-2 (COX-2) pathways. The activities of these pathways were decreased in a dose-dependent manner by SKLC. The production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin $(IL)-1{\beta}$, and IL-6 were also reduced. Conclusions: These results suggest that the down regulation of iNOS, COX-2, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 expression by SKLC are mediated by the down regulation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity, a transcription factor necessary for pro-inflammatory mediators. This might be the mechanism underlying the anti-inflammatory effects of SKLC.

• Asian-Australasian Journal of Animal Sciences
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• 제19권10호
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• pp.1399-1403
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• 2006

A total of 80 cows, including 40 top mastitis resistant and 40 top mastitis susceptible animals as Group I and Group II, were selected from a population of 520 cows based on clinical mastitis occurrence. PCR-SSCP analysis on four fragments within the 5'region and two fragments of Exons 4,15 of bovine lactoferrin (bLF) revealed that four fragments-P1,P4,E4,E15-had polymorphisms which totally included six base mutations, and only two of them had significant differences in allele frequencies between resistant and susceptible groups, P1 (53.7% vs. 70.0%, p<0.05) and P4 (55.0% vs. 68.8%, p<0.05). Further study on these two promising markers combined with the milk performance traits of cows demonstrated that their selection would result in higher fat percentage (p<0.05), lower Somatic Cell Score (SCS) (p<0.05) and Clinical Mastitis Residuals (CMR) (p<0.01) indicating higher mastitis resistance and lower milk yield (p<0.05). The putative transcription factor binding sites in the 5'region were also studied by using MatInspector 7.2.2 software, and two signal pathways regulating the expression of bLF including the NF-${\kappa}B$ pathway and nuclear hormone receptor pathway were predicted.

• Journal of Ginseng Research
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• 제47권2호
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• pp.183-192
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• 2023

Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H₂S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

• 생명과학회지
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• 제20권9호
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• pp.1332-1338
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• 2010

사람 신경모세포종 세포주 SH-SY5Y에서 Fenretinide (FenR)에 의한 GD3합성효소(hST8Sia I)의 발현증가기작을 규명하게 위하여 hST8Sia I의 프로모터 활성을 조사해 본 결과 -1146에서 -646영역에서 FenR에 의한 활성증가를 나타내었다. 또한 부위특이적 변이의 분석은 -731에서 -722영역에 위치한 전사인자 NF-kB 결합부위가 hST8Sia I의 FenR에 의한 활성증가에 중요하게 관여하고 있음을 나타내었다. FenR에 의한 hST8Sia I 유전자의 발현유도에 포함된 신호전달기작을 전사인자 단백질의 항체를 이용하여 조사해 본 결과 FenR처리에 의해 세포질에서는 인산화된 AKT단백질 수준의 증가가 관찰되었고 핵내에서는 NF-kB의 p65단백질의 증가가 관찰되었다. 이러한 결과들은 FenR에 의한 hST8Sia I 유전자의 발현증가는 AKT신호전달경로에 의해 활성화된 NF-kB의 핵내로 이동하여 hST8Sia I 유전자의 프로모터에 결합함으로서 전사가 촉진되어 일어난다는 것을 나타낸다.

• Nutrition Research and Practice
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• 제16권6호
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• pp.685-699
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• 2022

BACKGROUND/OBJECTIVES: Platycodon grandiflorum (PG) has long been known as a medicinal herb effective in various diseases, including bronchitis and asthma, but is still more widely used for food. Fermentation methods are being applied to increase the pharmacological composition of PG extracts and commercialize them with high added value. This study examines the hydrolyzed and fermented PG extract (HFPGE) fermented with Lactobacillus casei in RAW 264.7 cells, and investigates the effect of amplifying the immune and the probable molecular mechanism. MATERIALS/METHODS: HFPGE's total phenolic, flavonoid, saponin, and platycodin D contents were analyzed by colorimetric analysis or high-performance liquid chromatography. Cell viability was measured by the MTT assay. Phagocytic activity was analyzed by a phagocytosis assay kit, nitric oxide (NO) production by a Griess reagent system, and cytokines by enzyme-linked immunosorbent assay kits. The mRNA expressions of inducible nitric oxide synthase (iNOS) and cytokines were analyzed by reverse transcription-polymerase chain reaction, whereas MAPK and nuclear factor (NF)-κB activation were analyzed by Western blots. RESULTS: Compared to PGE, HFPGE was determined to contain 13.76 times and 6.69 times higher contents of crude saponin and platycodin D, respectively. HFPGE promoted cell proliferation and phagocytosis in RAW 264.7 cells and regulated the NO production and iNOS expression. Treatment with HFPGE also resulted in increased production of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, C-X-C motif chemokine ligand10, granulocyte-colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-1, and the mRNA expressions of these cytokines. HFPGE also resulted in significantly increasing the phosphorylation of NF-κB p65, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. CONCLUSIONS: Taken together, our results imply that fermentation and hydrolysis result in the extraction of more active ingredients of PG. Furthermore, we determined that HFPGE exerts immunostimulatory activity via the MAPK and NF-κB signaling pathways.

• Korean Journal of Acupuncture
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• 제37권2호
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• pp.63-75
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• 2020

Objectives : Osteoporosis is the most common bone disease and osteoporosis fracture is the leading cause of decreased life. Bisphosphonate and selective estrogen receptor modulators are the best choice of treatment for osteoporosis. However, when used for a long time, they increase the probability of side effect such as osteonecrosis of the jaw. Thus, it is crucial to develop alternative medicine to treat osteoporosis. Gentianae Macrophyllae Radix, a herbal medicine, is mainly to treat rheumatoid arthritis. However, the effect of the water extract of Gentianae Macrophyllae Radix (w-GM) on osteoporosis has not been investigated. Thus, we examine whether w-GM can inhibit osteoclast differentiation and bone resorption on receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL)-treated RAW 264.7 cells. In this study, RAW 264.7 cells were used as an osteoclast differentiation model by treating them with RANKL. Methods : RAW 264.7 cells were used to determine the effect of w-GM on osteoclast differentiation and bone resorption. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells, TRAP activity and pit formation assay were examined. In addition, protein expressions were measured by western blot and mRNA expressions were analyzed by reverse transcription polymerase chain reaction. Results : Treatment with w-GM inhibited the number of TRAP-positive cells, TRAP activity and pit area. In addition, w-GM decreased protein expression such as mitogen-activated protein kinase, NF-κB, c-Fos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). It also inhibited the mRNA levels such as c-Fos, NFATc1, TRAP, NF-κB, calcitonin receptor and cathepsin K in RANKL-treated RAW 264.7 cells. Conclusions : These results suggest that w-GM has inhibitory effects via osteoclast differentiation, thus it could be a new medication for osteoporosis.