• International Journal of Industrial Entomology and Biomaterials
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• v.46 no.2
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• pp.60-66
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• 2023

Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases and is more common in older and obese individuals. Silkworm male pupae exerts tonic effects by increasing testosterone secretion and the forced swimming time and muscle ratio increased in mice consuming silkworm pupae, which may be beneficial to the older population. Therefore, it will be beneficial to investigate the effects of silkworm pupal extracts (SPE) on OA. To confirm this effect, we prepared SPE in different solvents, and their ability to attenuate matrix metalloproteinases (MMPs) and inflammatory mediators (interleukin-6 [IL-6], interleukin-8 [IL-8] and tumor necrosis factor-α [TNF-α]) were evaluated in an interleukin-1β (IL-1β)-induced SW1353 human chondrosarcoma cell line. 70% ethanolic SPE outperformed the other solvents, reducing MMP-1 and MMP-3 expression by up to 53% and 13%, respectively. Further experiments were performed using 70% ethanolic SPE from three distinct pupation stages in males and females. SPE treatment alleviated MMP-1 expression (43.9-47.4%) regardless of pupation stage and sex. Among the inflammatory mediators, 70% ethanolic SPE alleviated IL-6 and TNF-α levels, and the concentrations thereof were lowest in the early-stage male SPE-treated group (43.15% and 56.74%, respectively). In conclusion, 70% ethanolic SPE may prevent IL-1β-induced osteoarthritis by inhibiting MMPs and inflammatory cytokines. Therefore, SPE is a potential therapeutic agent for the treatment of OA.

• Journal of Microbiology and Biotechnology
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• v.33 no.11
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• pp.1484-1494
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• 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.

• 순환기질환의공학회:학술대회논문집
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• 2006.10a
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• pp.10-13
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• 2006

Inflammation plays an important role in the progression of atherosclerosis and plaque destabilization converting a chronic process into an acute disorder with ensuing thromboembolism. Current therapeutic effective in preventing atherosclerosis and stroke such as statins, ASS and RAS inhibitors my exert part of their effects by modulating inflammatory responses in the vessel walls. As alternative approaches, discovery to find having inhibitory action of MMP activity, COX-2, macrophage infiltration, such as APE1/ref-1 and fusion technology for cell permeable protein may provide a new antiatherosclerotic therapy in the future.

• Journal of Acupuncture Research
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• v.28 no.3
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• pp.111-119
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• 2011

목적 : 이 연구는 봉독이 세포자멸사 관련 단백질의 발현 조절을 통하여 세포자멸사를 유도하고 전립선 암세포주인 DU-145 세포의 성장을 억제하는지를 확인하고 해당 기전을 살펴보고자 하였다. 방법 : 봉독을 처리한 후 DU-145의 세포자멸사를 관찰하기 위해 TUNEL staining assay를 시행하였으며, 세포자멸사 조절단백질의 변동 관찰에는 western blot analysis를 시행하였다. 결과 : DU-145 세포에 봉독을 처리한 후, 세포자멸사의 유발, 세포자멸사 관련 단백질의 발현에 미치는 영향을 관찰하여 다음과 같은 결과를 얻었다. 1. DU-145 세포에서 봉독을 처리한 후 세포자멸사가 유도되어 세포성장이 억제되었다. 2. 세포자멸사 관련 단백질 중 분리된 pro-apoptotic proteins인 PARP, caspase-3, caspase-9은 유의한 증가를 나타내었다. 3. 세포자멸사 관련 단백질 중 분리된 anti-apoptotic proteins인 Bcl-2, p-AKT, XIAP, cIAP2는 유의한 감소를, MMP2, MMP13은 유의한 증가를 나타내었다. 결론 : 이상의 결과는 봉독이 인간 전립선 암세포주인 DU-145의 세포자멸사를 유발함으로써 전립선암세포 증식억제 효과가 있음을 입증한 것으로 전립선암의 예방과 치료에 대한 효과적인 치료제 개발에 도움이 될 것으로 기대된다.

• Korean Journal of Pharmacognosy
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• v.38 no.1
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• pp.62-66
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• 2007

Ethanol extract from Salvia miltiorrhiza (SME) was tested for breast cancer chemoprevention and metastasis by measuring the activites of cytochrome P45O 1A1, aromatase, ornithine decarboxylase (ODC), and matrix metalloproteinase (MMP)-9. SME significantly inhibited cytochrome P45O 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity in a dose-dependent manner in a concentration range of 100${\sim}$l,200 ${\mu}g/ml$ (p<0.01). Microsomal aromatase (estrogen synthase) activity was suppressed 54.9%${\sim}$77.5% by the SME at concentration of 600${\sim}$l,200 ${\mu}g/ml$. ODC activity induced by 12-O-tet-radecanoylphorbol-13-acetate (TPA) was significantly reduced by the SME 900 and 1,200 ${\mu}g/ml$ (p<0.05) in MCF-7 breast cancer cells. In addition, SME (900 and 1,200 ${\mu}g/ml$) markedly inhibited MMP-9 activity, a key role in cancer metastasis. Therefore, SME is worth further investigation with respect to breast cancer chemoprevention or therapy.

• Journal of Acupuncture Research
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• v.26 no.3
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• pp.49-58
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• 2009

목적 : 본 연구는 봉약침의 주요성분인 멜리틴이 전립선 암세포주인 DU-145 세포성장에 어떤 영향을 미치는지를 알아보기 위하여 시행하였다. 방법 : 멜리틴이 DU-145의 성장에 미치는 영향을 알아보기 위한 cell viability 측정으로는 WST-1 assay를, 세포자멸사의 관찰에는 DAPI(4,6-diamidino-2-phenylindole)와 TUNEL staining assay를 시행하였으며, 세포자멸사 조절단백질(calpain, Bax, caspase-3, -9, cleaved caspase-3, cleavaged PARP, cleaved caspase-9, Bcl-2, XIAP, cIAP2, Akt, p-Akt, MMP-2, MMP-13)의 관찰을 위하여 western blot analysis를 시행하였다. 결과 : 1. DU-145 세포에서 멜리틴을 처리한 후 세포자멸사가 유도되어 세포성장이 억제되었다. 2. 세포자멸사 관련 단백질 중 분리된 caspase-3, caspase-9은 유의한 증가를, Bcl-2, p-Akt, XIAP, cXIAP는 유의한 감소를 나타내었다. 결론 : 이상의 결과는 멜리틴이 인간 전립선암세포주인 DU-145의 세포자멸사를 유발함으로써 증식억제 효과가 있음을 나타낸 것으로, 전립선암의 예방과 치료에 대한 효과적인 치료제 개발에 도움이 될 것으로 기대된다.

• Journal of Microbiology and Biotechnology
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• v.27 no.2
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• pp.242-250
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• 2017

Anti-photoaging effects of standardized Siegesbeckia glabrescens extract (SGE) and its major active compound kirenol were investigated using Hs68 human dermal fibroblasts and hairless mice, respectively. UVB-irradiated hairless mice that received oral SGE (600 mg/kg/day) showed reduced wrinkle formation and skinfold thickness compared with the UVB-irradiated control. Furthermore, SGE treatment increased the mRNA levels of collagen synthesis genes (COL1A1, COL3A1, COL4A1, and COL7A1) and activated antioxidant enzyme (catalase), while suppressing matrix metalloproteinase (MMP-2, -3, -9, and -13) expression. In Hs68 fibroblasts, kirenol also significantly suppressed MMP expression while increasing the expression of COL1A1, COL3A1, and COL7A1. Collectively, our data demonstrate that both SGE and kirenol attenuated UVB-induced photoaging in hairless mice and fibroblasts through inhibition of the mitogen-activated protein kinases and nuclear factor kappa B pathways, suggesting that SGE has potential to serve as a natural anti-photoaging nutraceutical.

• Journal of Applied Biological Chemistry
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• v.62 no.1
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• pp.101-107
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• 2019

The objectives of this study were to evaluate the anti-aging effects and investigate the effect of simulated gastrointestinal (GI) digestion on the anti-aging properties and intestinal permeation of the potential fish collagen hydrolysates (FCH). Therefore, procollagen synthesis, matrix metalloproteinase-1 (MMP-1) production, and Caco-2 cell permeability were analyzed before and after in vitro digestion for FCHs, low-molecular weight fractions (<1 kDa), and high molecular weight fractions (>1 kDa). After being subjected to GI digestion, the level of MMP-1 inhibition was maintained, although the procollagen production was significantly (>20%) lower with all samples. Also, the digested FCHs and their <1 kDa fraction yielded 9.1 and 13.8% increased peptide transport, respectively, compared to undigested samples. Based on the effective intestinal permeation and high digestive enzyme stability, the <1 kDa fraction of FCHs is a potential bioactive material suitable for anti-aging applications in the food and cosmetics industries.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.2
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• pp.79-87
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• 2022

In this study, extracts of Boswellia serrata gum resin, Curcuma longa rhizome, and Terminalia chebula fruit were combined in different ratios, and their anti-osteoarthritis effects were compared to determine which combination had the best synergistic effect. B. serrata, C. longa, and T. chebula extracts in a 2:1:2 ratio exhibited higher antioxidative activity in scavenging DPPH radicals than did the individual extracts alone or the other extract combinations. Additionally, the 2:1:2 combination significantly improved the levels of enzymatic antioxidants and antioxidant-related proteins. Moreover, this same combination ratio decreased the protein levels of matrix metalloproteinase (MMP) 3 and MMP13 in interleukin-1β-stimulated human articular chondrocytes (HCHs) and increased those of aggrecan and collagen type II alpha 1 chain (COL2A1). Analysis of the underlying mechanisms revealed that the 2:1:2 combination significantly inhibited the phosphorylation of nuclear factor kappa B (NF-κB) p65, extracellular regulated protein kinase (ERK), and p38 mitogen-activated protein kinase (MAPK). Therefore, the 2:1:2 combination of these three plant extracts has the best potential for use as an effective dietary supplement for improving joint health compared with the individual extracts and their other combination ratios.

• Journal of Acupuncture Research
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• v.24 no.1
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• pp.151-163
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• 2007

Objectives : Juglandis Semen herbal acupuncture solution(JSS) has a broad array of clinical applications in oriental medicine, including treatment of chronic musculoskeletal diseases such as arthritis. This study was performed to investigate the global gene expression profiles using microarray assay in RAW 264.7 cell line treated with JSS and to advance our understanding of the pharmacologic effect of JSS. Methods : Change of the gene expression profile in RAW cell line following treatment with lipopolysaccharide(LPS) alone, or with LPS plus JSS was investigated with a cut-off level of 2 fold change in the expression. Especially, Change of the gene expression by treatment with LPS alone was compared with that by treatment with LPS plus JSS with a cut-off level of 1/2 fold change in the expression. Results: Of the 8170 genes profiled in this study, 51 were upragulated and 21 downregulated following LPS treatment, and 88 were upregulated and 69 downregulated following costimulation of JSS and LPS. Of the 51 genes upregulated following LPS treatment, 10 were downregulated following costimulation of JSS and LPS. Of the 21 genes downregulated following LPS treatment, 3 were upregulated following costimulation of JSS and LPS. Conclusion : JSS treatment induced upregulation of some genes including IL-10 and downregulation of that including MMP13 with its possible implication in an antiinflammatory action of JSS. However, further research on expression profile changes induced by JSS treatment is expected.