• Journal of Korean Medicine Rehabilitation
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• v.21 no.2
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• pp.87-100
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• 2011

Objectives : This study was carried out to investigate the effects of Buja-tang treatment on the early change of the monosodium iodoacetate-induced osteoarthritis in rats. Methods : Arthritis was induced by injection of monosodium iodoacetate(MIA)(0.25 mg) into both knee joint cavities of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. The control group was taken distilled water and the treated group, extracts of Buja-tang by orally for 20 days. At the end of the experiment(20 days after MIA injection), gross and histopathological examinations on the articular structures of knee joints were performed. Proteoglycan(PG) content in articular cartilages was analyzed by safranine O staining method. And also, tumor necrosis factor-$\alpha$($TNF-{\alpha}$) and interleukin-$1{\beta}$($IL-1{\beta}$) contents in synovial fluid were measured by enzyme-linked immunosorbent assay(ELISA) method. Results : 1. Body weight(g) of the treated group was increased significantly compared with control group at 15 and 20 days after injection. 2. Grossly, the degree of osteoarthritis in the treated group was alleviated compared with the control group. 3. PG content in articular cartilage of the treated group was increased significantly compared with the control group. 4. Histopathologically, osteoarthritic score of the treated group was decreased significantly compared with the control group. 5. $TNF-{\alpha}$ content in synovial fluid of the treated group was decreased significantly compared with the control group. Conclusions : On the basis of these results, we suggest that Buja-tang have inhibiting effects on the progression of arthritis in MIA-induced osteoarthritis model. And it is related to inhibiting the activity of $TNF-{\alpha}$ in osteoarthritic chodrocytes and synovial membranes.

• Korean Journal of Food Science and Technology
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• v.33 no.1
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• pp.122-127
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• 2001

This study was conducted to investigate the characteristics and biological activities of the substance extracted from the fruit body of Formitopsis rosea. The substance was extracted by hot water and then it was separated high and low molecular weight fraction by ethanol precipitation, The high molecular weight fraction was found to be a proteoglycan composed of glucose, mannose, galactose, xylose, fructose, ribose and amino acids. The amino acids of proteoglycan were mainly threonine, isoleucine, glycine, aspartic acid. Anticomplementary activity of the high molecular weight fraction was higher than that of the low molecular weight fraction. And also, the high molecular weight fraction enhanced phagocytic activity and nitric oxide production of macrophage. In enzymatic lipid peroxidation reaction with $ADP-FeCl_3-NADPH$, the lipid peroxidation was inhibited 82.4% and 86.6% by high and low molecular weight fractions, in nonenzymatic lipid peroxidation reaction, it was 83.0% and 84.6%, respectively.

• BMB Reports
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• v.47 no.12
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• pp.679-684
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• 2014

GM-CSF plays a role in the nervous system, particularly in cases of injury. A therapeutic effect of GM-CSF has been reported in rat models of various central nervous system injuries. We previously showed that GM-CSF could enhance long-term recovery in a rat spinal cord injury model, inhibiting glial scar formation and increasing the integrity of axonal structure. Here, we investigated molecular the mechanism(s) by which GM-CSF suppressed glial scar formation in an in vitro system using primary astrocytes treated with TGF-${\beta}$. GM-CSF repressed the expression of chondroitin sulfate proteoglycan (CSPG) core proteins in astrocytes treated with TGF-${\beta}$. GM-CSF also inhibited the TGF-${\beta}$-induced Rho-ROCK pathway, which is important in CSPG expression. Finally, the inhibitory effect of GM-CSF was blocked by a JAK inhibitor. These results may provide the basis for GM-CSF's effects in glial scar inhibition and ultimately for its therapeutic effect on neural cell injuries.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.191-201
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• 2005

Background & Objective: Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Aralia cordata Thunb. in inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP activity in rabbit articular cartilage explants. Methods : The cartilage-protective effects of Aralia cordata Thunb. were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMP activity, measurement of lactate dehydrogenase activity and histological analysis in rabbit cartilage explants culture. Results : Interleukin-la (IL-1a) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Aralia cordata Thunb. significantly inhibited GAG and collagen release in a concentration-dependent manner. Aralia cordata Thunb. dose-dependently inhibited MMP-3 and MMP-13 expression and activities from IL-1a-treated cartilage explants cultures when tested at concentrations ranging from 0.02 to 0.2 mg/ml. Aralia cordata Thunb. had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Histological analysis indicated that Aralia cordata Thunb. reduced the degradation of the cartilage matrix compared with that of IL -1a-treated cartilage explants.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.3
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• pp.13-26
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• 2010

Objectives : This study was to investigate the effects of Imyo-san treatment on the monosodium iodoacetate-induced osteoarthritis in rats. Methods : Arthritis was induced by injection of monosodium iodoacetate(MIA)(0.5 mg) into both knee joint cavities of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. Control group was taken distilled water and treated group was taken extracts of Imyo-san by orally for 20 days. At the end of experiment(20day after MIA injection), gross and histopathological examination on the articular structures of knee joints were performed. Blood cell counts and proteoglycan(PG) contents in articular cartilages were analysed. And also, tumor necrosis factor-$\alpha$($TNF-{\alpha}$) and interleukin-$1{\beta}$($IL-1{\beta}$) contents synovial fluids were measured by enzyme-liked immunosorbent assay(ELISA) method. Results : 1. Body weight(g) of the treated group were increased significantly compared with control group at 15 and 20 days after injection. 2. Grossly, degree of osteoarthritis in the treated group was alleviated compared with the control group. 3. PG content in articular cartilage of the treated group was increased significantly compared with the control group. 4. Histopathologically, osteoarthritic scores of the treated group was decreased significantly compared with the control group. 5. $TNF-{\alpha}$ content in synovial fluid of the treated group was decreased significantly compared with the control group. Conclusions : On the basis of these results, we suggested that Imyo-san has inhibiting effects on the progression of arthritis in MIA-induced osteoarthritis model.

• BMB Reports
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• v.56 no.8
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• pp.445-450
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• 2023

The development of atherosclerotic cardiovascular disease is associated with the phenotypic switching of vascular smooth muscle cells (SMCs) from a contractile to a synthetic state, leading to cell migration and proliferation. Platelet-derived growth factor-BB (PDGF-BB) modulates this de-differentiation by initiating a number of biological processes. In this study, we show that gene expression of hyaluronic acid (HA) and proteoglycan link protein 1 (HAPLN1) was upregulated during differentiation of human aortic SMCs (HASMCs) into a contractile state, but downregulated upon during PDGF-BB-induced dedifferentiation. This is the first study showing that the treatment of HASMCs with full-length recombinant human HAPLN1 (rhHAPLN1) significantly reversed PDGF-BB-induced decrease in the protein levels of contractile markers (SM22α, α-SMA, calponin, and SM-MHC), and inhibited the proliferation and migration of HASMCs induced by PDGF-BB. Furthermore, our results show that rhHAPLN1 significantly inhibited the phosphorylation of FAK, AKT, STAT3, p38 MAPK and Raf mediated by the binding of PDGF-BB to PDGFRβ. Together, these results indicated that rhHAPLN1 can suppress the PDGF-BB-stimulated phenotypic switching and subsequent de-differentiation of HASMCs, highlighting its potential as a novel therapeutic target for atherosclerosis and other vascular diseases.

• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.550-558
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• 2023

Hair loss is a common condition that can have a negative impact on an individual's quality of life. The severe side effects and the low efficacy of current hair loss medications create unmet needs in the field of hair loss treatment. Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1), one of the components of the extracellular matrix, has been shown to play a role in maintaining its integrity. HAPLN1 was examined for its ability to impact hair growth with less side effects than existing hair loss treatments. HAPLN1 was predominantly expressed in the anagen phase in three stages of the hair growth cycle in mice and promotes the proliferation of human hair matrix cells. Also, recombinant human HAPLN1 (rhHAPLN1) was shown to selectively increase the levels of transforming growth factor-β receptor II in human hair matrix cells. Furthermore, we observed concomitant activation of the ERK1/2 signaling pathway following treatment with rhHAPLN1. Our results indicate that rhHAPLN1 elicits its cell proliferation effect via the TGF-β2-induced ERK1/2 pathway. The prompt entering of the hair follicles into the anagen phase was observed in the rhHAPLN1-treated group, compared to the vehicle-treated group. Insights into the mechanism underlying such hair growth effects of HAPLN1 will provide a novel potential strategy for treating hair loss with much lower side effects than the current treatments.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.629-639
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• 2023

Cardiovascular diseases (CVDs) are the most common cardiovascular system disorders. Cellular senescence is a key mechanism associated with dysfunction of aged vascular endothelium. Hyaluronic acid and proteoglycan link protein 1 (HAPLN1) has been known to non-covalently link hyaluronic acid (HA) and proteoglycans (PGs), and forms and stabilizes HAPLN1-containing aggregates as a major component of extracellular matrix. Our previous study showed that serum levels of HAPLN1 decrease with aging. Here, we found that the HAPLN1 gene expression was reduced in senescent human umbilical vein endothelial cells (HUVECs). Moreover, a recombinant human HAPLN1 (rhHAPLN1) decreased the activity of senescence-associated β-gal and inhibited the production of senescence-associated secretory phenotypes, including IL-1β, CCL2, and IL-6. rhHAPLN1 also downregulated IL-17A levels, which is known to play a key role in vascular endothelial senescence. In addition, rhHAPLN1 protected senescent HUVECs from oxidative stress by reducing cellular reactive oxygen species levels, thus promoting the function and survival of HUVECs and leading to cellular proliferation, migration, and angiogenesis. We also found that rhHAPLN1 not only increases the sirtuin 1 (SIRT1) levels, but also reduces the cellular senescence markers levels, such as p53, p21, and p16. Taken together, our data indicate that rhHAPLN1 delays or inhibits the endothelial senescence induced by various aging factors, such as replicative, IL-17A, and oxidative stress-induced senescence, thus suggesting that rhHAPLN1 may be a promising therapeutic for CVD and atherosclerosis.

• Molecules and Cells
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• v.46 no.9
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• pp.558-572
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• 2023

Chronic obstructive pulmonary disease (COPD) will be the third leading cause of death worldwide by 2030. One of its components, emphysema, has been defined as a lung disease that irreversibly damages the lungs' alveoli. Treatment is currently unavailable for emphysema symptoms and complete cure of the disease. Hyaluronan (HA) and proteoglycan link protein 1 (HAPLN1), an HA-binding protein linking HA in the extracellular matrix to stabilize the proteoglycan structure, forms a bulky hydrogel-like aggregate. Studies on the biological role of the full-length HAPLN1, a simple structure-stabilizing protein, are limited. Here, we demonstrated for the first time that treating human alveolar epithelial type 2 cells with recombinant human HAPLN1 (rhHAPLN1) increased TGF-β receptor 1 (TGF-β RI) protein levels, but not TGF-β RII, in a CD44-dependent manner with concurrent enhancement of the phosphorylated Smad3 (p-Smad3), but not p-Smad2, upon TGF-β1 stimulation. Furthermore, rhHAPLN1 significantly increased sirtuins levels (i.e., SIRT1/2/6) without TGF-β1 and inhibited acetylated p300 levels that were increased by TGF-β1. rhHAPLN1 is crucial in regulating cellular senescence, including p53, p21, and p16, and inflammation markers such as p-NF-κB and Nrf2. Both senile emphysema mouse model induced via intraperitoneal rhHAPLN1 injections and porcine pancreatic elastase (PPE)-induced COPD mouse model generated via rhHAPLN1-containing aerosols inhalations showed a significantly potent efficacy in reducing alveolar spaces enlargement. Preclinical trials are underway to investigate the effects of inhaled rhHAPLN1-containing aerosols on several COPD animal models.

• The Korean Journal of Mycology
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• v.29 no.1
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• pp.15-21
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• 2001

This study was conducted to investigate the immunomodulatory activities of proteoglycan extracted from cultured mycelia of Ganoderma lucidum IY009. The proteoglycan contained two polymer peaks, one was the higher MW peak of 2,000 kD and the other was low peaks of 12kD. To understand the part of strong pharmaceutical activity between two peak, the proteoglycan was separated by ultrafiltration and column chromatography and then examined the various pharmaceutical effects. High molecular weight fraction possesing high content of ${\beta}-linked$ glucan was exhibited high antitumor activity, against sarcoma 180 bearing ICR mouse. And also, anticomplementary activity was highly observed in high molecule fraction than low it fraction. When the raw 264.7 and murine peritoneal macrophage treated with low fraction, high fraction and other stimuli. The activities inducing tumor necrosis factor of the high factions were $2.2{\sim}2.5$ times stronger than that of low fraction.