• International Journal of Oral Biology
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• v.44 no.2
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• pp.55-61
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• 2019

The purpose of this study was to evaluate the effect of mangosteen extract complex (MEC; Garcinia mangostana L. and propolis extracts) on the inhibition of inflammation and prevention of alveolar bone loss using a ligature-induced periodontitis model. Rat molars were ligatured with silk, and $1{\mu}g/mL$ of lipopolysaccharide of Porphyromonas gingivalis was injected into the buccal and palatal gingivae of the teeth with or without treatment with the MEC. Changes in the expression levels of prostaglandin $E_2$ ($PGE_2$), interleukin-8 (IL-8), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-8 (MMP-8), cyclooxygenase (COX)-1, and COX-2 in gingival tissues were evaluated using enzyme-linked immunosorbent assays. Alveolar bone loss around the ligated molars was examined using micro-computed tomography. The expression levels of $PGE_2$, IL-8, iNOS, MMP-8, COX-1, and COX-2 in gingival tissues were significantly reduced in the group treated with a mixture of $16{\mu}g$ of mangosteen extract powder and $544{\mu}g$ of propolis extract powder (ligation [Lig] + lipopolysaccharide extracted from P. gingivalis KCOM 2804 [L] + MEC 1:34). Additionally, alveolar bone loss was significantly reduced in the Lig + L + MEC 1:34 group compared with that in other groups. These results indicate that the MEC could be useful in preventing and treating periodontitis.

• Korean Journal of Pharmacognosy
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• v.49 no.4
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• pp.305-311
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• 2018

Osteoarthritis (OA) is the most common form of joint disease, characterized by articular cartilage, osteonecrosis, and osteochondral bone erosion. It is an early, progressive disease that combines joint stiffness and joint pain and reduces cartilage function and condition. Interleukin-1 beta ($IL-1{\beta}$) is thought to be important to the pathogenesis of OA and significantly increases the expression of matrix metalloproteinases (MMPs), which play an important role in cartilage degradation in OA. Sparassis crispa (Wulf.) is an edible / medicinal mushroom that has been reported to variety of biological activities. In this study, investigated the Anti-inflammatory effect of Sparassis crispa (Wulf.) ethanol extract (SCE) on $IL-1{\beta}$ stimulated SW1353 chondrocytes. SCE decreased the expression and activity of MMPs by $IL-1{\beta}$ and decreased the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) associated with the inhibition of prostaglandin E2($PGE_2$) in $IL-1{\beta}$ stimulated SW-1353 chondrocytes. In addition, SCE inhibits the expression of MAPK (mitogen-activated protein kinase) and $NF-{\kappa}B$ (nuclear factor-kappa B) signaling in $IL-1{\beta}$ stimulated SW-1353 cells, and SCE inhibits the production of reactive oxygen species (ROS) through heme oxygenase-1 (HO-1) expression. Thus, it is suggested that SCE has a potential as an anti-inflammatory agent in osteoarthritis treatments.

• Journal of Korean Neurosurgical Society
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• v.62 no.2
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• pp.153-165
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• 2019

Objective : Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI. Methods : rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, $S100{\beta}$, brain derived neurotrophic factor (BDNF), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor $[TGF]-{\beta}$, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors. Results : rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), ${\beta}3$-tubulin and nestin as well as anti-inflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined. Conclusion : Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.25-33
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• 2019

Mesenchymal stem cells are classified as multipotent stem cells, due to their capability to transdifferentiate into various lineages that develop from mesoderm. Their popular appeal as cell-based therapy was initially based on the idea of their ability to restore tissue because of their differentiation potential in vitro; however, the lack of evidence of their differentiation to target cells in vivo led researchers to focus on their secreted trophic factors and their role as potential powerhouses on regulation of factors under different immunological environments and recover homeostasis. To date there are more than 800 clinical trials on humans related to MSCs as therapy, not to mention that in animals is actively being applied as therapeutic resource, though it has not been officially approved as one. But just as how results from clinical trials are important, so is to reveal the biological mechanisms involved on how these cells exert their healing properties to further enhance the application of MSCs on potential patients. In this review, we describe characteristics of MSCs, evaluate their benefits as tissue regenerative therapy and combination therapy, as well as their immunological properties, activation of MSCs that dictate their secreted factors, interactions with other immune cells, such as T cells and possible mechanisms and pathways involved in these interactions.

• The Journal of Korean Medicine
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• v.39 no.4
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• pp.86-113
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• 2018

Objectives: We examined the effects of a mixed formula consisting of dried pomegranate concentrate powder (PCP) and the aqueous extracts of Eucommiae cortex (EC) and Achyranthis radix (AR) in rats with surgically induced osteoarthritis (OA). Methods: Two weeks after OA-inducing surgery, a PCP:EC:AR 5:4:1 (g/g) combination or single formula was orally administered. Changes in body weight, knee thickness, maximum knee extension angle, bone mineral density of the knee joints, femoral and tibial articular surfaces, and compressive strength of the femoral and tibial articular cartilage (AC) were assessed, along with the prostaglandin E2 level, 5-lipoxygenase, matrix metalloproteinase (MMP)-2 and MMP-9 activity, and chondrogenic gene mRNA expression in the femoral and tibial AC with the synovial membrane (SM). In addition, the number of cleaved poly(ADP-ribose) polymerase, cyclooxygenase and tumor necrosis factor-${\alpha}$-immunoreactive cells in the femoral and tibial AC with SM were monitored, and the rate of cell proliferation was determined with a 5-bromo-2'-deoxyuridine uptake assay. Results : The signs of surgically induced OA in rats were significantly inhibited by both PCP, EC and AR combined and single formulas. In particular, the combination formula-treated OA model rats showed dose-dependent, significantly increased inhibitory activity against all tested criteria compared with single formula-treated rats. Conclusions: Taken together, our results suggest that the combination formula synergistically increased the anti-OA effects of its components through anti-inflammatory and chondrogenic activity in rats with surgically induced OA. In addition, 200, 100 and 50 mg/kg combination formula treatments showed dose-dependent inhibitory activity against all of the tested criteria.

• Journal of Applied Biological Chemistry
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• v.62 no.3
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• pp.239-246
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• 2019

In this study, an evaluation of the anti-inflammatory effect of ferulic acid isolated from Tetragonia tetragonioides in lipopolysaccharide (LPS) simulated RAW 264.7 cells was made. The chemical structure of the active compound was elucidated by $^1H$-NMR, $^{13}C$-NMR, and FAB-MS, and was confirmed to be ferulic acid. Ferulic acid was purified via open column chromatography with Sephadex LH-20 and MCI gel CHP-20. To test the anti-inflammatory effect of ferulic acid, LPS-stimulated RAW 264.7 cells were treated in subsequent experiments with different concentrations of ferulic acid (5, 10, and $25{\mu}g/mL$) and the levels of inflammatory cytokines and enzymes were also measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Cell viability was above 95% at acid concentrations ranging from $5-25{\mu}g/mL$. The results showed that 30% of the production of nitric oxide and 66% of prostaglandin $E_2$ were inhibited by $25{\mu}g/mL$ of ferulic acid, it also inhibited the protein expression of both inducible nitric oxide synthase and cyclooxygenase-2 by 70%. Additionally, it inhibited the production of the pro-inflammatory cytokines, tumor necrosis factor-${\alpha}$, interleukin-6, and interleukin-$1{\beta}$ by 40, 75, and 77%, respectively. According to these results, the anti-inflammatory activity of ferulic acid was demonstrated via his implication in the inhibition of the expression and secretion of inflammatory substances in LPS-stimulated RAW 264.7 cells. Therefore, we concluded that ferulic acid can be used as a functional additive having anti-inflammatory activity.

• Natural Product Sciences
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• v.25 no.3
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• pp.238-243
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• 2019

In this study, the marker compounds of Curcumae Rhizoma (CR) were simultaneously quantified by high-performance liquid chromatography equipped with a photodiode array detector and the anti-inflammatory effects of CR extract and marker compounds in human benign prostatic hyperplasia epithelial-1 (BPH-1) cell lines were investigated. The marker components (4S,5S)-(+)-germacrone-4,5-epoxide, furanodienone, and germacrone, were separated on Gemini $C_{18}$ columns ($250mm{\times}4.6mm$, $5{\mu}m$) at $40^{\circ}C$ by using a gradient of two mobile phases eluting at 1.0 mL/min. Prostaglandin $E_2$ ($PGE_2$) levels in Human BPH-1 cells were determined with an ELISA kit. The coefficients of determination in a calibration curve of each analyte were all 0.9997. The limits of detection and quantification of the three compounds were $0.10-0.32{\mu}g/mL$ and $0.30-0.98{\mu}g/mL$, respectively. The content of three compounds, (4S,5S)-(+)-germacrone-4,5-epoxide, furanodienone, and germacrone, in the CR sample were found to be 5.79 - 5.92 mg/g, 4.72 - 4.86 mg/g, and 1.06 - 1.09 mg/g, respectively. Regarding pharmacological activity against benign prostatic hyperplasia, CR and its components significantly suppressed $PGE_2$ levels of BPH-1 cells. The established analysis method will help to improve quality assessment of CR samples and related products. In addition, CR and its components exhibit antiinflammatory activity in BPH-1 cells, suggesting the inhibitory efficacy of these compounds against the pathogenesis of BPH.

• Journal of Microbiology and Biotechnology
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• v.29 no.1
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• pp.151-159
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• 2019

Lipoteichoic acid isolated from Lactobacillus plantarum K8 (pLTA) alleviates lipopolysaccharide (LPS)-induced excessive inflammation through inhibition of $TNF-{\alpha}$ and interleukin (IL)-6. In addition, pLTA increases the survival rate of mice in a septic shock model. In the current study, we have found that pLTA contributes to homeostasis through regulation of pro- and anti-inflammatory cytokine production. In detail, pLTA decreased the production of IL-10 by phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells stimulated with prostaglandin E2 (PGE-2) and LPS. However, $TNF-{\alpha}$ production which was inhibited by PGE-2+LPS increased by pLTA treatment. The regulatory effects of IL-10 and $TNF-{\alpha}$ induced by PGE-2 and LPS in PMA-differentiated THP-1 cells were mediated by pLTA, but not by other LTAs isolated from either Staphylococcus aureus (aLTA) or L. sakei (sLTA). Further studies revealed that pLTA-mediated IL-10 inhibition and $TNF-{\alpha}$ induction in PGE-2+LPS-stimulated PMA-differentiated THP-1 cells were mediated by dephosphorylation of p38 and phosphorylation of c-Jun N-terminal kinase (JNK), respectively. Reduction of pLTA-mediated IL-10 inhibited the metastasis of breast cancer cells (MDA-MB-231), which was induced by IL-10 or conditioned media prepared from PGE-2+LPS-stimulated PMA-differentiated THP-1 cells. Taken together, our data suggest that pLTA contributes to inflammatory homeostasis through induction of repressed pro-inflammatory cytokines as well as inhibition of excessive anti-inflammatory cytokines.

• Nutrition Research and Practice
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• v.13 no.3
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• pp.189-195
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• 2019

BACKGROUND/OBJECTIVES: Although aged black garlic has various biological activities such as anti-allergy, anti-inflammation and neuroprotection, effect of aged black garlic on chemically contact dermatitis is unclarified. MATERIALS/METHODS: To evaluate anti-dermatitic activity of aged black garlic extract, we investigated effects of a fraction of aged black garlic extract (BG10) on both in vivo and in vitro. RESULTS: BG10 almost inhibited formation of nitric monoxide and interleukin-6 (IL-6; $IC_{50}$, $7.07{\mu}g/mL$) at $25{\mu}g/mL$, and dose-dependently reduced production of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$; $IC_{50}$, $52.07{\mu}g/mL$) and prostaglandin $E_2$ ($IC_{50}$, $38.46{\mu}g/mL$) in lipopolysaccharide-stimulated RAW264.7 cells. In addition, BG10 significantly inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear $NF-{\kappa}B$, and improved that of cytosolic levels of $NF-{\kappa}B$ and $I{\kappa}B{\alpha}$ in the cells. Consistent with in vitro studies, BG10 (0.5 mg/mL) not only reduced ear edema but also suppressed the formation of IL-6 and $TNF-{\alpha}$ induced by 12-O-tetradecanoylphorbol-13-acetate in ear tissues of mice. CONCLUSIONS: These findings suggest BG10 has anti-dermatitic activity through inhibiting activation of macrophages. Therefore, such effects of BG10 may provide information for the application of aged black garlic for prevention and therapy of contact dermatitis.

• Korean Journal of Pharmacognosy
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• v.52 no.3
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• pp.192-201
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• 2021

Dangguisu-san (DGSS) is widely known traditional herbal medicinal formula in Korea for treatment of traumatic injury by traffic accident, ecchymosis, abdominal distension and anti-thrombosis of blood. This study was conducted to develop the simultaneous analyze method using high performance liquid chromatography (HPLC) and examine the effect of anti-inflammatory activity of DGSS-dry extract (DGSS-DE) and DGSS-mix extract powder (DGSS-MEP). Physicochemical characteristics of DGSS-DE and DGSS-MEP showed that there is no significant difference in pH, titratable acidity, total soluble solid content and browning degree except for color value (L, a, b). 15 functional constituents of DGSS were identified and the correlation coefficient values of DGSS-DE and DGSS-MEP were conformed 0.950. Also, DGSS-DE and DGSS-MEP significantly decreased the secretion of nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) through inhibited expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, IL-6, and TNF-α. From these result, DGSS-MEP showed similar chemical composition and anti-inflammatory effect to DGSS-DE. Therefore, DGSS-DE and DGSS-MEP may be useful as potential source of drug to prevent inflammation.