• Nutrition Research and Practice
• /
• v.10 no.3
• /
• pp.265-273
• /
• 2016

BACKGROUND/OBJECTIVES: The inhibitory effect of Hijikia fusiforme (HF) extracts on degenerative osteoarthritis was examined in primary cultured rat cartilage cells and a monosodium iodoacetate (MIA)-induced osteoarthritis rat model. MATERIALS/METHODS: In vitro, cell survival and the expression of matrix metalloproteinases (MMPs), collagen type I, collagen type II, aggrecan, and tissue inhibitor of metalloproteinases (TIMPs) was measured after $H_2O_2$ ($800{\mu}M$, 2 hr) treatment in primary chondrocytes. In vivo animal study, osteoarthritis was induced by intra-articular injection of MIA into knee joints of rats, and then RH500, HFE250 and HFE500 were administered orally once a day for 28 days. To determine the anti-inflammatory effects of HFE, nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) expression were measured. In addition, real-time PCR was performed to measure the genetic expression of MMPs, collagen type I, collagen type II, aggrecan, and TIMPs. RESULTS: In the in vitro assay, cell survival after $H_2O_2$ treatment was increased by HFE extract (20% EtOH). In addition, anabolic factors (genetic expression of collagen type I, II, and aggrecan) were increased by HFE extract (20% EtOH). However, the genetic expression of MMP-3 and 7, known as catabolic factors were significantly inhibited by treatment with HFE extract (20% EtOH). In the in vivo assay, anabolic factors (genetic expression of collagen type I, II, aggrecan, and TIMPs) were increased by oral administration of HFE extract. However, the genetic expression of MMP-3 and 7, known as catabolic factors, and production of NO and $PGE_2$ were significantly inhibited by treatment with oral administration of HFE extract. CONCLUSION: HFE extract inhibited articular cartilage degeneration through preventing extracellular matrix degradation and chondrocyte injury.

• Journal of Chest Surgery
• /
• v.35 no.6
• /
• pp.407-419
• /
• 2002

Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by progressive accumulation of lipids, cells, and extracellular matrix. Matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases(TIMPS) contribute to vascular matrix remodeling in atherosclerosis, and some cytokines may play role in the synthesis or activation of MMPs or TIMPs. Material and Method： We produced experimental atherosclerotic plaques in 9 rabbits by atherogenic hypercholesterol diet for 12 weeks, and 10 other rabbits were used as control group with standard laboratory chow, At that time, 19 rabbits were sacrificed and aorta, coronary arteries and blood specimens were prepared. The expressions of MMP-9, TIMP-2 and interleukin(IL)-18, and the bioactivity of IL-6 were investigated with H&E stain, immunohistochemical stain, immunoblotting(Western blot analysis), and bioassay. Result： Serum cholesterol in the experimental group increased up to 1258$\pm$262 mg/dL(control group： 41$\pm$7 mg/dL). All experimental group showed well-developed atherosclerotic plaques in aorta and coronary artery. The expression of MMP-9 in aorta and coronary artery of the experimental group showed significant increase than that of the control group by immunohistochemistry. Among the experimental group, complicated lesions with intimal rupture or complete luminal occlusion, demonstrated stronger expression of MMP-9. Interestingly, there was no difference in expression of TIMP-2 between the experimental and the control group. These findings were confirmed by Western blot analysis. The bioassay revealed significant up-regulation of serum bioactivity of IL-6 in the experimental group(4819.60$\pm$2021.25 IU/$m\ell$) compared to that of IL-6 in the control group(27.20 $\pm$ 12.19 IU/$m\ell$). IL-18 was expressed in all atherosclerotic plaques, whereas little or no expression was detected in the control group. Conclusion： The increased MMP-9 expression along with the unchanged TIMP-2 expression seem to be contributory factors in extracellular matrix degradation in atherosclerosis. Focal overexpression of MMP-9 may promote plaque destabilization and cause complications of atherosclerotic plaques such as thrombosis with/without acute coronary syndrome. Elevation of IL-6 and IL-18 may be more than just markers of atherosclerosis but actual participants in lesion development. Identification of critical regulatory pathway is important to improve the understanding of the cellular and molecular basis of atherosclerosis and may open the way for novel therapeutic strategies.

• Journal of Ginseng Research
• /
• v.44 no.3
• /
• pp.496-505
• /
• 2020

Background: Panax ginseng is a marvelous herbal remedy for all ailments of body. That may be why it is called Panax, which means "cure for all". Melanin is a pigment that gives color to our skin; however, increased melanin production can lead to tumor formation. Human exposure to ultraviolet B radiation has increased extensively owing to the increased sunlight due to global warming. Consequently, a phenomenon called photoaging has been observed for all skin colors and types. As a result of this phenomenon, a set of enzymes called matrix metalloproteinases, which serve as degradation enzymes for extracellular matrix proteins, mainly collagen, is increased, causing depletion of collagen and resulting in early wrinkle formation. Methods: Therefore, in our study, we used the murine melanoma cell line B16/F10 to study the inhibition of melanogenesis by Korean Red Ginseng (KRG) extract in vitro and HRM-2 hairless mice exposed to artificial ultraviolet B to examine the efficacy of KRG in vivo. We prepared a 3% red ginseng extract cream and evaluated its effects on human skin. Results: Our results demonstrated that KRG induced potent suppression of tyrosinase activity and melanin production in B16/F10 cells; moreover, it reduced the transcription and translation of components involved in the melanin production pathway. In the in vivo experiments, KRG potently suppressed the expression of matrix metalloproteinases, reduced wrinkle formation, and inhibited collagen degradation. On human skin, ginseng cream increased skin resilience and skin moisture and enhanced skin tone. Conclusion: Therefore, we conclude that KRG is an excellent skin whitening and antiaging product.

• ALGAE
• /
• v.29 no.4
• /
• pp.355-366
• /
• 2014

Fucoxanthin is known to be an effective cell proliferation inhibitor with anti-tumor and anti-angiogenic activities. However, there is a lack of data regarding the biological effects of cis isomers of fucoxanthin. To assess the potential therapeutic properties of 9'-cis-(6'R) fucoxanthin (FcA), and 13-cis and 13'-cis-(6'R) fucoxanthin complex (FcB) isolated from Sarggassum siliquastrum, we investigated their inhibitory effects on matrix metalloproteinases (MMPs) in phorbol 12-myristate 13-acetate (PMA)-induced human fibrosarcoma (HT1080) cells. FcA and FcB reduced MMP-2 and MMP-9 protein and mRNA levels, as well as the migration of these cells, in a dose-dependent manner. Additionally, FcA and FcB increased levels of MMPs inhibition factors such as tissue inhibitor of metalloproteinase-1. FcA and FcB significantly inhibited the transcriptional activity of nuclear factor ${\kappa}B$ (NF-${\kappa}B$) and by inhibiting c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases. Our results demonstrate that suppression of the NF-${\kappa}B$, JNK, and p38 signaling pathways may inhibit PMA-induced MMP-2 and MMP-9 activity. Therefore, FcA and FcB may be useful in noninvasive therapeutic strategies against fibrosarcoma metastasis.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2003.05a
• /
• pp.41-42
• /
• 2003

Matrix metalloproteinases (MMPs) inhibitors were screened from Metasequoia glyptostroboides and one potent inhibitor, dihydrohinokiflavone (DHHF), a biflavonoid, was selected. DHHF inhibited proliferation of HT1080, human fibrosarcoma cells in a dose-dependent manner. Noncytotoxic levels of DHHF dramatically decreased MMP-9 and MMP-2 production in unistimulated cells, but did not change the level of tissue inhibited of metalloproteinase (TIMP)-1, an inhibitor of MMP-9.(omitted)

• Tuberculosis and Respiratory Diseases
• /
• v.52 no.5
• /
• pp.453-462
• /
• 2002

Background : Matrix metalloproteinases(MMPs) are a large family of proteolytic enzymes, which are involved in the degradation of many different components of the extracellular matrix. There is increasing evidence indicating that individual MMPs have important roles in tumor invasion by inactivating the MMPs. In this study, the correlation between MMPs and TIMPs expression, and the clinical outcome was investigated. Materials and Methods : Immunohistochemical staining of MMP-2, 9 and TIMP-1,2 were performed on paraffin-embedded tumor sections from 74 resected primary non-small cell lung cancers. Results : In 74 patients, MMP-2, MMP-9, TIMP-1, and TIMP-2 immunoreactivity was demonstrated in 24(34%), 19(26%) and 32(43%) of the paraffin-embedded tumors, respectively. The median survival of the MMP-2 positive cases was significantly shorter than that of the negative cases(20 vs 34 months). The median survival of the TIMP-2 positive cases was also was significantly longer than that of the negative cases (34 vs 18 months). The MMP-2, and MMP-9 expression level had a positively correlation with a more advanced stage and lymph node metastasis. There was inverse correlation between TIMP-2 expression and tumor invasion. The median survival of the MMP-2 negative/TIMP-2 positive cases was higher than that of the other cases. Conclusion : These results suggest that tumor invasion and lymph node metastasis are closely related to MMP-2 and MMP-9 expression. There was an inverse correlation between TIMP-2 and MMP-9 expression, and tumor invasion.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.304.2-304.2
• /
• 2002

In central nervous system. matrix metalloproteinases (MMPs) are produced by neuron as well as glia and implicated in physiological events such as neurite outgrowth and myelination etc. In addition. MMPs also contribute to the pathogenesis of several CNS diseases such as multiple sclerosis, Alzheimer's disease and malignant glioma. In spite of their functional importance, little is known about the signal transduction pathways leading to the induction of MMPs in CNS. Here. we investigated whether the activation of Erk(1/2) is involved in the induction of MMP-9 in LPS-stimulated primary astrocytes. (omitted)

• The Journal of Internal Korean Medicine
• /
• v.42 no.1
• /
• pp.1-10
• /
• 2021

Objective: This study was conducted to investigate the effect of Chaenomelis Fructus (CF) water extract on thioacetamide (TAA)-treated rats. Methods: Rats were divided into five groups: one normal group (n=8) and four with TAA-induced hepatic injury. These treatment groups were administered distilled water (n=8); silymarin 100 mg/kg (n=8); CF 100 mg/kg (n=8); and CF 200 mg/kg (n=8). In the TAA groups, the acute liver injury was induced via IP injection (200 mg/kg), and the silymarin and CF extract were then orally administered for three days. Subsequently, serum levels of GOT, GPT, and ammonia were confirmed as well as protein expressions using liver tissue. Results: In the liver injury-induced rats, CF administration reduced tissue damage and serum levels of GOT, GPT, and ammonia. In addition, CF increased the anti-oxidant proteins Nrf2, Keap1, HO-1, and catalase and significantly regulated matrix metalloproteinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2). Conclusions: In this animal model of liver injury induced by TAA, CF extract is determined to have a hepatoprotective effect by increasing anti-oxidant proteins that relieve damage and by regulating the expression of matrix metalloproteinases.

• Analytical Science and Technology
• /
• v.24 no.2
• /
• pp.135-141
• /
• 2011

MMPs (Matrix metalloproteinases) are enzymes playing an important role to turnover and remodel main protein compositions of extracellular matrix. MMP-2 and MMP-9 of MMPs having a catalytic domain which is apart from a hemopexin-like domain part, are different from the other MMPs pertaining fibronectinlike domain close to hemopexin-like domain. It was reported that the development of MMP-9 restrainer can prevent the transfer of liver cancer. In this study, MMP-9 restrainers were extracted and purified from Hovenia dulcis Thunberg. The each fractionary part was examined to investigate the inhibitory effect on MMPs. Three compounds, compound A and B eluted with ethyl acetate (EA) and compound C with methanol, were identified by $^1H$ and $^{13}C$ NMR, GC/MS, and FT-IR. Compound A is considered as a kind of catechine type compound having a benzene ring substituted by hydroxyl and methoxyl groups. Compound B and C are nobiletin type compound pertaining a carbonyl group. Compound A, B and C showed 76%, 66% and 71% of inhibition effect on MMP-9 at 1.0% concentration, respectively. Compound A showed the best inhibition effect on MMP-9.

• YAKHAK HOEJI
• /
• v.48 no.2
• /
• pp.165-170
• /
• 2004

The production of matrix metalloproteinases (MMPs) by the UV irradiated skin fibroblast and the degradation of extracellular matrix (ECM) by these enzymes is known as one of the main reasons of photoaging. In this paper, to investigate the relationship between aging and Selaginella tamariscina extract (STE), we investigated the effects of antioxidant and expression of UVA-induced MMP-1 in human dermal fibroblasts. STE was found to show scavenging activities of radicals and reactive oxygen species (ROS) with the $IC_{50}$/ values of 65.1 $\mu\textrm{g}$/$m\ell$ against 1,1-diphenyl-2-picrylhydrazyl(DPPH) radical and 40.9 $\mu\textrm{g}$/$m\ell$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. UVA induced MMP expression was reduced 75.5% by treatment with STE, and MMP-1 mRNA expression was reduced in a dose-dependent manner. Therefore STE was able to significantly inhibition of MMP expression in protein and mRNA level. All these results suggested that STE may act as an anti-aging agent by antioxidation and reducing UVA-induced MMP-1 production.