• Nutrition Research and Practice
• /
• 제17권5호
• /
• pp.917-933
• /
• 2023

BACKGROUND/OBJECTIVES: As peanuts germinate, the content of the components beneficial to health, such as resveratrol, increases within the peanut sprout. This study examined whether the ethanol extract of peanut sprout tea (PSTE) inhibits breast cancer growth and metastasis. MATERIALS/METHODS: After orthotopically injecting 4T1 cells into BALB/c mice to induce breast cancer, 0, 30, or 60 mg/kg body weight/day of PSTE was administered orally. Angiogenesis-related protein expression in the tumors and the degree of metastasis were analyzed. 4T1 and RAW 264.7 cells were co-cultured, and reverse transcription polymerase chain reaction was performed to measure the crosstalk between breast cancer cells and macrophages. RESULTS: PSTE reduced tumor growth and lung metastasis. In particular, PSTE decreased matrix metalloproteinase-9, platelet endothelial cell adhesion molecule-1, vascular endothelial growth factor-A, F4/80, CD11c, macrophage mannose receptor, macrophage colony-stimulating factor, and monocyte chemoattractant protein 1 expression in the tumors. Moreover, PSTE prevented 4T1 cell migration, invasion, and macrophage activity in RAW 264.7 cells. PSTE inhibited the crosstalk between 4T1 cells and RAW 264.7 cells and promoted the macrophage M1 subtype while inhibiting the M2 subtype. CONCLUSIONS: These results suggest that PSTE blocks breast cancer growth and metastasis to the lungs. This may be because the PSTE treatment inhibits the crosstalk between mammary cancer cells and macrophages and inhibits the differentiation of macrophages into the M2 subtype.

• IMMUNE NETWORK
• /
• 제21권6호
• /
• pp.42.1-42.20
• /
• 2021

Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

• Journal of Microbiology and Biotechnology
• /
• 제33권11호
• /
• pp.1484-1494
• /
• 2023

NUC1 (Nutraceutical compound 1) is an ethanol extract composed of a formulation based on medicinal herbs traditionally used for the treatment of arthritis in Korea and China. This study investigated the therapeutic effects of NUC1 on osteoarthritis (OA). The protective effect of NUC1 on OA was tested in a rabbit model of collagenase-induced arthritis (CIA) for 4 weeks. Results were compared among four groups (n = 9 per group): the normal group (untreated), the CIA group (vehicle control), the NUC1 group (CIA rabbits treated with 200 mg/kg NUC1), and the JOINS group (positive control, CIA rabbits treated with 200 mg/kg JOINS tablet). NUC1 significantly inhibited NO production (p < 0.05 at 125 ㎍/ml, p < 0.01 at 250 ㎍/ml, and p < 0.001 at 500 ㎍/ml) and iNOS expression in macrophages, in a concentration-dependent manner. NUC1 also inhibited the release and protein expression of MMP-1, 3, and 13, in TNF-α-induced chondrosarcoma cells in a concentration-dependent manner. In vivo, the MMP-1 and MMP-3 levels in synovial fluids were significantly (p < 0.05) lower in NUC1 group (77.50 ± 20.56 and 22.50 ± 7.39 pg/ml, respectively) than in the CIA group (148.33 ± 68.58 and 77.50 ± 20.46 pg/ml, respectively). Also, in histopathological, NUC1 ameliorated articular cartilage damage in OA by increasing the abundance of chondrocytes and proteoglycan in the articular cartilage. Thus, NUC1 showed promise as a potential therapeutic agent, and it can be generalized to a broader study population in different OA animal models.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제31권5호
• /
• pp.399-408
• /
• 2005

In the progression of the Temporomandibular Joint Disorder(TMD), not only deformation and perforation of disc occur. But also fibrotic adhesion and inflammatory changes to the retrodiscal tissue can be seen in addition to the condylar degenerative change (e.g. osteoarthritis). However, the correct diagnosis,?planning for appropriate treatment, and prediction of prognosis are limited, because there are no means to stage the progression of the disorder. In this study relative signal intensity of retrodiscal tissue in MRI and the synovial fluid concentration of matrix metalloproteinase-2 (MMP-2), MMP-9, and Interleukin-6(IL-6) in the 23 temporomandibular joints(TMJ), from 17 patients with TMD were evaluated as a possible diagnostic marker. The relative signal intensity of retrodiscal tissue was referenced to brain gray matter with same region of interest(ROI) size. The concentrations of MMP-2, MMP-9, and IL-6 were evaluated by Enzyme Linked Immunosorbent Assay (ELISA). The collected data were compared with condylar degenerative change, joint effusion and disc position observed in MRI. The relative signal intensity of the retrodiscal tissue was increased significantly when degenerative changes were present. In addition, there was significantly high signal intensity in the presence of a disc displaced without reduction. The concentration of IL-6 was significantly increased when condylar degenerative change was no observed. And there were no changes in the levels of IL-6 according to disc position and joint effusion measurement. Moreover, there were no significant relevance between the concentration of total MMP-2 and active MMP-9 in synovial fluid, relative to degenerative changes in the mandibular condyle, to joint effusion, and to disc position observed on MRI images. In conclusion, the relative signal intensity of the retrodiscal tissue can be regarded as a mean of diagnosing the procession of TMD in a non-invasive manner. But more additional studies are required for the levels of MMP-2. MMP-9, and IL-6 to determine their potentials as a diagnostic marker for TMD.

• 동의생리병리학회지
• /
• 제27권6호
• /
• pp.782-788
• /
• 2013

Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae), colloquially known "Gujulcho" in Korea, has been used in traditional medicine for the treatment of various diseases, including cough, common cold, bladder-related disorders, gastroenteric disorders, hypertension, and inflammatory diseases, such as pneumonia, bronchitis, pharyngitis, and rheumatoid arthritis (RA) However, the effect of Chrysanthemum zawadskii var. latilobum on breast cancer invasion is unknown. In this study, we investigated the inhibitory effect of Chrysanthemum zawadskii var. latilobum extract (CZE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in MCF-7 cells. CZE were not cytotoxic up to 100 ${\mu}g/ml$ concentration in the MCF-7 cell line. CZE decreased MMP-9 expression. TPA substantially increased NF-${\kappa}B$ DNA binding activity. Pre-treatment with CZE inhibited TPA-stimulated NF-${\kappa}B$ binding activity and NF-${\kappa}B$ related protein expression. To identify invasion ability of MCF-7 cells decreased by CZE, we used martrigel invasion assay. As a result, it is significantly decreased cell invasion. These results indicate that CZE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the NF-${\kappa}B$ pathway in MCF-7 cells. Chrysanthemum zawadskii var. latilobum may have potential value in restricting breast cancer metastasis.

• KSBB Journal
• /
• 제24권5호
• /
• pp.425-431
• /
• 2009

본 연구에서는 U-251-MG 세포를 이용하여 증식, 이동, 침윤 및 단백질분해효소의 분비에 미치는 PSA와 HGF의 효과를 확인하였다. 그 결과, PSA siRNA에 의해 U-251-MG 세포의 증식은 약 37% 억제되었으나, HGF 처리 (10 ng/mL)에 의해 증식이 약 1.4배 증가되었다. PSA siRNA에 의한 U-251-MG 세포의 이동은 약 60%가 억제되었으나, HGF 처리에 의해 이동이 약 1.3배 증가되었다. 또한, PSA siRNA에 의해 U-251-MG 세포의 침윤이 약 67% 억제되었으나 HGF 처리에 의해 세포의 침윤이 약 4.3배 증가되었다. PSA siRNA처리에 의해 MMP-2의 분비는 약 25%, MMP-9의 분비는 약 20% 억제되었으며, HGF에 의해 PSA siRNA에 의해 억제된 MMP-2 및 MMP-9의 분비가 약 2.8배 및 3.5배 증가되었다. HGF 처리에 의해 플라스민의 분비량은 약 14배 증가되었고, PSA를 억제한 U-251-MG 세포에 HGF를 처리한 결과, 플라스민의 분비가 약 1.6배 증가하였다. 또한, PSA siRNA에 의해 MMP-2의 발현은 유의할만한 변화가 없었으나, MMP-9의 발현은 약 85% 억제되었다. PSA를 억제시킨 U-251-MG 세포에 HGF를 처리한 결과, MMP-2의 발현은 약 5.7배, MMP-9의 발현은 약 6.3배 증가되었다. 한편, MMPs의 광범위 억제제인 BB-94 처리에 의해 U-251-MG 세포의 증식, 이동 및 침윤이 유의할만하게 억제 된 것은 MMP-2 및 MMP-9이 U-251-MG 세포의 증식, 이동 및 침윤에 관여할 것임을 시사해준다.

• 생명과학회지
• /
• 제28권8호
• /
• pp.945-954
• /
• 2018

오메가-3 지방산(오메가-3)은 수종의 암에 대해 종양형성 억제 및 침윤이 억제됨이 알려져 있다. 그러나 혀의 편평세포암 세포에서 내인성 오메가-3에 의한 침윤 및 종양형성 억제 대한 연구가 명확하게 보고된 바 없다. 이에 본 연구는 혀의 편평세포암 세포에서 ${\omega}3$-fatty acid desaturase의 유전자 발현이 침윤 및 종양형성에 미치는 영향을 규명하였다. 먼저 SCC-4 및 SCC-9세포의 침윤능은 오메가-3인 DHA 처리에 의해 억제 됨을 확인 하였다. DHA 처리 후 MMP-9 및 MMP-2 활성이 감소 되었을 뿐만 아니라 그 promoter의 reporter 활성도 억제하였다. 또한 COX-2 및 VEGF promoter 활성 뿐만 아니라 NF-kB 활성도 DHA에 의해 억제 되었다. SCC-9의 ${\omega}3$-desaturase 유전자 stable 세포(fSCC-9sc)의 세포증식 및 colony formation이 억제 되었으며, in vivo 동물실험에서 fSCC-9sc 세포의 종양형성능은 현저히 억제 되었고, 면역형광염색법을 이용한 fSCC-9sc 세포의 종양 조직에서의 TUNEL 양성세포는 대조군인 fSCC-9cc 세포에 비해 현저히 증가하였다. 이상의 결과로 오메가-3는 인체 혀의 편평세포암 세포의 침윤 뿐만 아니라 종양형성을 억제하여 항암작용을 나타낼 수 있으며 따라서 오메가-3는 인체 혀의 편평암의 예방 및 치료에 유용하게 사용될 수 있으리라 생각된다.

• 한국식품영양과학회지
• /
• 제42권4호
• /
• pp.550-555
• /
• 2013

본 연구에서는 한방이화주의 피부 생리기능 활성을 알아보기 위해 70% EtOH 추출물의 피부 미백, 주름 개선 및 항염증 효과를 조사하였다. HEE은 tyrosinase 활성 억제 및 tyrosine을 기질로 melanin이 형성되는 pathway에 관여하는 주요한 인자인 TRP-1과 TRP-2를 저해하는 작용 기전을 통해 피부 색소침착의 주요 원인 물질인 melanin 생합성을 농도 의존적으로 저해하는 것을 확인하였다. HEE은 피부 진피 내 피부 탄력을 유지하는 elastin을 분해하는 효소인 elastase의 활성을 저해하였고, 피부의 keratinocyte가 생성 분비하는 MMP-2와 MMP-9의 단백질 발현과 proteolytic 활성을 억제하여 노화에 따른 피부 주름 생성 억제할 수 있는 가능성을 확인하였다. 또한 세포 독성 없이 LPS에 의해 유도된 염증 반응을 50% 저해하는 HEE의 농도($IC_{50}$)는 $24.9{\mu}g/mL$이며, $50{\mu}g/mL$ 농도로 처리하였을 때 염증 반응 저해 효과가 70%로 높은 효과를 가지는 것을 확인하였다. 이상의 결과를 종합하면 HEE의 피부 미백, 주름 개선 및 항염증에 우수한 효과를 나타내고 있으므로 기능성 화장품의 주요한 소재로 이용 가치가 높을 것으로 사료된다.

• Journal of Ginseng Research
• /
• 제32권1호
• /
• pp.39-47
• /
• 2008

본 실험은 홍삼 혼합물 (KTNG0345)을 이용한 주름 예방 및 개선효과가 있는 건강기능 식품을 개발하기 위한 기초자료로 활용하기 위하여 시료를 경구투여한 무모생쥐의 피부조직 으로부터 MMP-3의 발현양상과 작용 메커니즘을 연구하였다. MMP-3의 발현정도는 농도 의존적으로 현저한 감소를 나타내었으며, 유전자와 단백질 모두에서 동일한 양상을 보였다. PAK는 변화가 없었지만, p38, p-p38 그리고 c-Jun, p-c-Jun 을 통계적으로 유의하게 감소시킴으로써 MMPs의 발현 감소를 가져온 것으로 보인다. 뿐만 아니라 자외선에 의한 $TNF-{\alpha}$의 생성 또는 유입을 억제함으로써 $TNF-{\alpha}$ receptor에 의해 매개되는 신호전달 경로를 둔화시켜 MMPs의 발현을 감소시킨 것으로 보인다. 이렇게 KTNG0345는 복합적인 활성으로 작용하여 주름생성 억제 활성을 보이는 것으로 판단된다.

• Journal of Ginseng Research
• /
• 제32권1호
• /
• pp.48-56
• /
• 2008

Chronic ultraviolet (UV) exposure is the major cause of photoaging that causes skin wrinkling, roughness, dryness, laxity, and pigmentation. Recently, increasing efforts are being made to understand the relationship between foods and skin health. Ginsenosides are present in ginseng (Ginseng Radix Rubra) extract, and are known to have biomedical properties, such as, anti-oxidant and anti-inflammatory effects. In this study, we investigated whether KTNG0345 prepared from red ginseng extracts delivered orally reduces skin wrinkling and ultraviolet B (UVB)-induced wrinkle formation in hairless mouse skin. KTNG0345 was administrated orally to the mice (5 times a week) during the period of UVB-irradiation (3 times a week) for 8 weeks at three different doses of 300 mg/kg, 500 mg/kg and 1000 mg/kg (w/v). UV doses were increased weekly by 1 MED (1MED = 75 $mJ/cm^2)$ up to 4 MED and then maintained at this level. After the 8-week administration period, it was found that orally administered KTNG0345 significantly inhibited UVB-induced wrinkle formation in a dose-dependent manner. Increases in skin thickness caused by UVB were prevented by KTNG0345. Moreover, it also significantly inhibited matrix metalloproteinases (MMP) -13 and MMP-9 expressional inductions by UVB. In addition, KTNG0345 was observed to prevent UVB-induced water loss of epidermis in hairless mouse skin. Our results demonstrate that orally administered KTNG0345 has anti-wrinkling effects in hairless mouse skin, and suggest that dietary red ginseng and herbal mixture may be considered a functional beauty food for preventing UVB-induced skin wrinkles.