• BMB Reports
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• 제41권12호
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• pp.858-862
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• 2008

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a zinc-dependent proteinase found in cholesterol-rich lipid rafts on the plasma membrane. MT1-MMP hydrolyzes extracellular matrix (ECM) proteins, activates pro-matrix metalloproteinase-2 (proMMP-2) and plays an important role in ECM remodeling, cancer cell migration and metastasis. The role of caveolin-1, an integral protein of caveolae, in the activation of MT1-MMP remains largely unknown. Here, we show that the expression of caveolin-1 attenuates the activation of proMMP-2, reduces proteolytic cleavage of ECM and inhibits cell migration. We utilized the cytoplasmic tail domain deletion (${\Delta}CT$) or the E240A mutant of MT1-MMP. Co-expression of caveolin-1 with the wild-type or the ${\Delta}CT$ MT1-MMP decreased the proMMP-2 activation and inhibited collagen degradation and cell migration. Caveolin-1 had no effect on the catalytically inert E240A MT1-MMP. Our findings suggest that caveolin-1 is essential in the down-regulation of MT1-MMP activity by promoting internalization from the cell surface.

• Journal of Ginseng Research
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• 제44권3호
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• pp.496-505
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• 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.

• 한국자원식물학회지
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• 제30권3호
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• pp.272-279
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• 2017

EP was obtained through 20% ethanol extraction of Pueraria lobata root, and the fermented form of EP, FEP, was prepared from the EP after incubating with Lactobacillus rhamnosus vitaP1. There was no significant toxicity by EP and FEP up to $1000{\mu}g/ml$ in NIH-3T3, HaCaT, and B16F10 cells. In addition to antioxidant potentials of EP and FEP determined by DPPH and ABST assays, we confirmed increase of procollagen type I and elastin synthesis by supplementation of the EP and FEP at the concentration of $50{\mu}g/ml$ using ELISA kits. The protein expression levels of matrix metalloprotease (MMP)-1, -3, and -9, those are involved in the degradation of collagen or other skin matrix proteins, were remarkably suppressed while their inhibitory protein metallopeptidase inhibitor 1 (TIMP-1) was greatly up-regulated by supplementation of the EP and FEP at a concentration of $50{\mu}g/ml$. Taken together, both EP and FEP supplementation could be involved in the suppression of the skin wrinkle formation through inhibiting degradation of collagen and stimulating the synthesis of collagen and elastin. The results showed that the anti-wrinkle potential of the EP and FEP will be a promising candidate for developing cosmeceutical compounds or products.

• International Journal of Advanced Culture Technology
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• 제7권4호
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• pp.125-136
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• 2019

The radish skin and radish greens are an edible part of the radish. But they are removed before eating the radish and used as a byproduct or an animal feed material because of their tough and rough texture. Melanin is a pigment that gives colour to our skin. But increased production of melanin can turn into benign or malignant tumours. These days due to global warming, the amount of Ultra violet (UVB) rays has been extensively increased with sunlight. Due to this, a phenomenon called exogenous photo aging is widely observed for all skin colour and types. As a result of this phenomenon, a set of enzymes called matrix metalloproteinases (MMP's) that serves as degradation enzymes for extracellular matrix proteins mainly collagen is increased, causing depletion in collagen and resulting in early wrinkles formation. Therefore in our study we used the murine melanoma cell line B16/F10 to study the melanogenesis inhibition by Heated radish extract (HRE) in vitro and we used HRM-2 hair less mice exposed to artificial UVB for checking the efficacy of Heated radish extract in vivo. Furthermore, we prepared a 3% Heated radish extract (HRE) cream and checked its effects on human skin. Our results have clearly demonstrated that Heated radish extract (HRE) have potently suppressed the tyrosinase activity and melanin production in B16/F10 cells. It had also reduced the expression of components involved in melanin production pathway both transcriptionally and transitionally. In in vivo studies, HRE had potently suppressed the expression of MMP's and reduced the wrinkle formation and inhibited collagen degradation. Moreover, on human skin, ginseng cream increased the resilience, skin moisture and enhanced the skin tone. Therefore in light of these findings, we conclude that HRE is an excellent skin whitening and antiaging product.

• Journal of Periodontal and Implant Science
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• 제50권1호
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• pp.14-27
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• 2020

Purpose: To overcome several drawbacks of chemically-crosslinked collagen membranes, modification processes such as ultraviolet (UV) crosslinking and the addition of biphasic calcium phosphate (BCP) to collagen membranes have been introduced. This study evaluated the efficacy and biocompatibility of BCP-supplemented UV-crosslinked collagen membrane for guided bone regeneration (GBR) in a rabbit calvarial model. Methods: Four circular bone defects (diameter, 8 mm) were created in the calvarium of 10 rabbits. Each defect was randomly allocated to one of the following groups: 1) the sham control group (spontaneous healing); 2) the M group (defect coverage with a BCP-supplemented UV-crosslinked collagen membrane and no graft material); 3) the BG (defects filled with BCP particles without membrane coverage); and 4) the BG+M group (defects filled with BCP particles and covered with a BCP-supplemented UV-crosslinked collagen membrane in a conventional GBR procedure). At 2 and 8 weeks, rabbits were sacrificed, and experimental defects were investigated histologically and by micro-computed tomography (micro-CT). Results: In both micro-CT and histometric analyses, the BG and BG+M groups at both 2 and 8 weeks showed significantly higher new bone formation than the control group. On micro-CT, the new bone volume of the BG+M group (48.39±5.47 ㎣) was larger than that of the BG group (38.71±2.24 ㎣, P=0.032) at 8 weeks. Histologically, greater new bone area was observed in the BG+M group than in the BG or M groups. BCP-supplemented UV-crosslinked collagen membrane did not cause an abnormal cellular reaction and was stable until 8 weeks. Conclusions: Enhanced new bone formation in GBR can be achieved by simultaneously using bone graft material and a BCP-supplemented UV-crosslinked collagen membrane, which showed high biocompatibility and resistance to degradation, making it a biocompatible alternative to chemically-crosslinked collagen membranes.

• 한국식품영양과학회지
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• 제46권7호
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• pp.857-867
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• 2017

본 연구는 저분자 해양성 콜라겐과 GABA 생성 L. brevis CFM20의 섭취 시 다양한 인체 장내 조건에 의한 유산균의 사멸과 콜라겐의 분해를 최소화하고자 진행되었다. 유산균과 저분자 해양성 콜라겐의 안정성을 향상하기 위하여 alginate와 chitosan을 이용하여 이중코팅캡슐을 제조하였다. L. brevis CFM20의 온도별 생육특성을 분석하여 캡슐화에 유리한 배양온도를 조사한 결과 $37^{\circ}C$에서 배양한 균의 대수기가 가장 빠르고 GABA양 또한 $400{\mu}g/mL$로 가장 높은 수치를 나타내어 생육속도에서 가장 유리한 것으로 나타났다. Calcium-alginate bead 법으로 캡슐을 제조한 결과 1~2 mm 사이의 일정한 구형의 캡슐을 제조하였으며, chitosan을 이용하여 이중코팅캡슐을 제조한 결과 캡슐의 크기가 감소하였고 외형적으로도 더욱 단단해짐을 확인하였다. 제조된 이중코팅캡슐을 CLSM과 SEM을 이용하여 관찰한 결과, chitosan 코팅을 한 이중코팅캡슐의 표면이 alginate와의 가교결합에 의해 더욱 치밀해짐을 확인하였다. 체내 위와 장내 조건에서 시간에 따른 이중코팅캡슐의 L. brevis CFM 20 생균수를 분석한 결과 캡슐화한 경우 균의 감소가 더디어 더 안정하다고 판단하였다. 이중코팅캡슐을 체내 위와 장내 조건에서 시간에 따른 GABA와 hydroxyproline의 용출량을 분석한 결과 두 경우 모두 위 조건에서는 낮은 수치를 나타내었고 장내 조건에서는 시간이 지남에 따라 급격하게 증가한 것을 확인하였다. 동물실험 결과 콜라겐 섭취군이 비섭취군에 비해 체중증가량, 혈청 지질 농도 등이 적은 것을 확인하였고, 혈액 내 hydroxyproline 함량, 진피의 피부조직 밀도가 더 높은 것으로 관찰되었다. 본 연구에서 개발된 이중코팅캡슐을 섭취하는 경우 위에서는 안정한 상태였다가 장에 도달한 후 붕해됨으로 인하여, 유산균, GABA, 콜라겐 및 키토산의 작용으로 인체에 유익한 효과를 기대할 수 있을 것으로 생각된다.

• Biomolecules & Therapeutics
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• 제7권2호
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• pp.112-120
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• 1999

The protective actions of ambroxol, rutin, glutathione and harmaline on oxidative damages of various tissue components were compared. The mechanisms by which they prevent oxidative tissue damages were explored. Lipid peroxidation of liver microsomes induced by combinations of $Fe^{2+}$ and ascorbate or $Fe^{+3}$, ADP and NADPH was inhibited by $50\; \muM$ of rutin, ambroxol, harmaline and glutathione. Ambroxol ($100\; \muM$) inhibited the degradation of hyaluronic acid by $Fe^{2+}$, $H_2O$_2$ and ascorbate, and it was greater than that of harmaline, whereas hyaluronic acid degradation was not prevented by rutin and glutathione. The compounds used ($100\; \muM$) did not protect the degradation of cartilage collagen by xanthine and xanthine oxidase. Rutin, glutathione and harmaline decreased the degradation of IgG by xanthine and xanthine oxidate, while ambroxol did not attenuate degradation of IgG. Glutathione showed a scavenging action on $H_2O_2$. The compounds all showed scavenging actions on hydroxyl radical. Ambroxol and harmaline exhibited quenching effects en singlet oxygen. In conclusion, ambroxol, rutin, glutathione and harmaline may exert protective effects differently on tissue components against oxidative attack depend on kind of tissue component and free radical.

• 대한한의학회지
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• 제23권4호
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• pp.98-104
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• 2002

Objectives: Calpain, a calcium-dependent cysteine proteinase, may be one of the proteolytic enzymes that mediate cartilage degradation associated with rheumatoid arthritis. The object of this study is to ascertain immunohistochemically whether calpain is present in the inflamed joints of collagen-induced arthritis of rats, and examine the effect of Cortex Acanthopanacis Senticosi on the expression of calpain. Methods: Male Lewis rats, around 200g of body weight, were immunized with bovine type II collagen. After 3 weeks from first immunization, rats were divided into arthritic control (n=6) group and Cortex Acanthopanacis Senticosi-treated (n=6) group. Non-immunized rats served as the normal (n=6) group. All animals were sacrificed at 15 days post-treatment and tibiotarsal joints were removed. Calpain immunohistochemistry was performed on the midsagittal section of the tibiotarsal joint. Results: All animals of the control and treated groups showed ankylosing osteoarthritis. However, the animals of the treated group showed alleviation in the fibrous ankylosis, destruction of articular cartilage and destruction of subchondral bony tissue compared with the animals of the control group. Calpain was expressed in the chondrocyte lacunae of growing articular cartilage, in the skeletal muscle fibers, in the peripheral nerves, and in the vessel walls around the joints of all groups. In the control and treated groups, calpain was also expressed in proliferating synovial epithelia, subsynovial stroma cells, surface of articular cartilage, and fibrous pannus around destructive subchondral bony tissue. However, the expression density of calpain in the treated group was diminished compared with the control group, especially in surface of articular cartilage and fibrous pannus. Conclusions: These observations indicated that calpain plays an important role in the destruction of cartilage and bone in collagen-induced arthritis of rats, and also indicated that Cortex Acanthopanacis Senticosi inhibits the development of arthritis by decreasing the expression of calpain.

• Journal of Periodontal and Implant Science
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• 제53권3호
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• pp.207-217
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• 2023

Purpose: Non-crosslinked and crosslinked collagen membranes are known to exhibit distinct degradation characteristics, resulting in contrasting orientations of the adjacent tissues and different biological processes. The aim of this study was to conduct a histomorphometric assessment of non-crosslinked and crosslinked collagen membranes regarding neovascularization, tissue integration, tissue encapsulation, and biodegradation. Methods: Guided bone regeneration was performed using either a non-crosslinked (BG) or a crosslinked collagen membrane (CM) in 15 beagle dogs, which were euthanized at 4, 8, and 16 weeks (n=5 each) for histomorphometric analysis. The samples were assessed regarding neovascularization, tissue integration, encapsulation, the remaining membrane area, and pseudoperiosteum formation. The BG and CM groups were compared at different time periods using nonparametric statistical methods. Results: The remaining membrane area of CM was significantly greater than that of BG at 16 weeks; however, there were no significant differences at 4 and 8 weeks. Conversely, the neovascularization score for CM was significantly less than that for BG at 16 weeks. BG exhibited significantly greater tissue integration and encapsulation scores than CM at all time periods, apart from encapsulation at 16 weeks. Pseudoperiosteum formation was observed in the BG group at 16 weeks. Conclusions: Although BG membranes were more rapidly biodegraded than CM membranes, they were gradually replaced by connective tissue with complete integration and maturation of the surrounding tissues to form dense periosteum-like connective tissue. Further studies need to be performed to validate the barrier effect of the pseudoperiosteum.

• Natural Product Sciences
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• 제13권4호
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• pp.289-294
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• 2007

Ethanolic extract (50% v/v) and alkaloid fraction of Tylophora indica leaves were examined for lysosomal enzyme inhibitory activity in adjuvant-induced arthritic rats. The alkaloid fraction showed statistically significant inhibition of arthritic lesions (p < 0.05) from day 18, (p < 0.025) from day 20 and (p < 0.001) from day 21 onwards in the adjuvant-induced arthritis, which was comparable to the response of standard drug Indomethacin. The ethanolic extract was less significant than the alkaloidal fraction in inhibition of arthritis. Alkaloid fraction showed significant (p < 0.001) inhibitory effect on the lysosomal enzyme activities in adjuvantinduced arthritic rats. It also significantly prevented decrease in collagen levels and synovial damage observed during arthritis and also inhibited increase in urinary excretion levels of collagen degradation products like hydroxyproline, hexosamine, hexuronic acid, etc. Both ethanolic extract as well as the alkaloid fraction, however, did not show any significant activity in normal nonarthritic rats. The ethanolic extract and the alkaloid fraction may thus be able to inhibit the progress of inflammation and inhibit the destructive activity of lysosomal enzymes on structural macromolecules like collagen etc. in the synovial capsule in joints during arthritic states. They may thus prevent synovial damage observed during arthritis.