• Toxicological Research
• /
• v.28 no.1
• /
• pp.5-9
• /
• 2012

It has been shown that the accumulation of prion in the cytoplasm can result in neurodegenerative disorders. Synthetic prion peptide 106-126 (PrP) is a glycoprotein that is expressed predominantly by neurons and other cells, including glial cells. Prion-induced chronic neurodegeneration has a substantial inflammatory component, and an increase in the levels of matrix metalloproteinases (MMPs) may play an important role in neurodegenerative development and progression. However, the expression of MMPs in PrP induced rat astrocytes and microglia has not yet been compared. Thus, in this study, we examined the fluorescence intensity of CD11b positive microglia and Glial Fibrillary Acidic Protein (GFAP) positive astrocytes and found that the fluorescent intensity was increased following incubation with PrP at 24 hours in a dose-dependent manner. We also observed an increase in interleukin-1 beta (IL-$1{\beta}$) and tumor necrosis factor alpha (TNF-${\alpha}$) protein expression, which are initial inflammatory cytokines, in both PrP induced astrocytes and microglia. Furthermore, an increase MMP-1, 3 and 11 expressions in PrP induced astrocytes and microglia was observed by real time PCR. Our results demonstrated PrP induced activation of astrocytes and microglia respectively, which resulted in an increase in inflammatory cytokines and MMPs expression. These results provide the insight into the different sensitivities of glial cells to PrP.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.10
• /
• pp.5291-5298
• /
• 2012

Beta-asarone is one of the main bioactive constituents in traditional Chinese medicine Acorus calamu. Previous studies have shown that it has antifungal and anthelmintic activities. However, little is known about its anticancer effects. This study aimed to determine inhibitory effects on LoVo colon cancer cell proliferation and to clarify the underlying mechanisms in vitro and in vivo. Dose-response and time-course anti-proliferation effects were examined by MTT assay. Our results demonstrated that LoVo cell viability showed dose- and time-dependence on ${\beta}$-asarone. We further assessed anti-proliferation effects as ${\beta}$-asarone-induced apoptosis by annexin V-fluorescein isothiocyanate/propidium iodide assay usinga flow cytometer and observed characteristic nuclear fragmentation and chromatin condensation of apoptosis by microscopy. Moreover, we found the apoptosis to be induced through the mitochondrial/caspase pathway by decreasing mitochondrial membrane potential (MMP) and reducing the Bcl-2-to-Bax ratio, in addition to activating the caspase-9 and caspase-3 cascades. Additionally, the apoptosis could be inhibited by a pan-caspase inhibitor, carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). When nude mice bearing LoVo tumor xenografts were treated with ${\beta}$-asarone, tumor volumes were reduced and terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assays of excised tissue also demonstrated apoptotic changes. Taken together, these findings for the first time provide evidence that ${\beta}$-asarone can suppress the growth of colon cancer and the induced apoptosis is possibly mediated through mitochondria/caspase pathways.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.30 no.2
• /
• pp.109-115
• /
• 2016

Hataedock is a Korean medical treatment that administers herbal extracts orally to newborn infants. This method is used for alleviating harmful heat and excreting fetal wastes by meconium. The purpose of this study was to evaluate anti-inflammatory effect of Hataedock method with Douchi on 2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD). The 3-week-old NC/Nga mice were divided into 3 groups: the control group (Ctrl), the AD-induced group (AE), and the Hataedock-treated group (GT). Only the GT group was treated with Hataedock at the 3rd week. After 28 days from Hataedock treatment, we induced AD-like dermatitis to the AE and GT group by DNFB. The effects of Hataedock were evaluated by immunohistochemical method. In the epithelium, PKC-positive reaction of the GT group was decreased by 57%. In the dermal papillae, IL-4-positive reaction was decreased by 34%. In the dermis, the distribution of degranulated mast cells was decreased and substance P-positive reaction was decreased by 49%. In the skin tissue, edema was decreased and MMP-9-positive reaction was decreased by 71%. Tissue damage such as epithelial cell hyperplasia, infiltration of granulocyte and lymphocyte, and capillary distribution were also decreased. The Hataedock method with Douchi maintained skin barrier and inhibited skin-damaging factors via regulating Th2 differentiation. In conclusion, Hataedock has a potential for preventative treatment of AD. Further studies are necessary to investigate the immune-regulating mechanism and verify the safety and efficacy of the Hataedock method.

• Journal of Food Hygiene and Safety
• /
• v.31 no.1
• /
• pp.59-66
• /
• 2016

It has been generally accepted that obesity and overweight are associated with metabolic diseases and cancer incidence. In fact, obesity increased risks of cancers i.e. breast, liver, pancreatic and prostate. Celastrol is a pentacyclic triterpenoid isolated from Thunder god vine, was used as a Chinese traditional medicine for treatment of inflammatory disorders such as arthritis, lupus erythematosus and Alzheimer's disease. Also, celastrol has various biological properties of chemo-preventive, neuro-protective, and anti-oxidant effects. Recent studies demonstrated that celastrol has anti-proliferation effects in different type of obesity-related cancers and suppresses tumor progression and metastasis. Anticancer effects of celastrol include regulation of $NF-{\kappa}B$, heat shock protein, JNK, VEGF, CXCR4, Akt/mTOR, MMP-9 and so on. For these reasons, celastrol has shown to be a promising anti-tumor agent. In this review, we will address the anticancer activities and multiple mechanisms of celastrol in obesity-related cancers.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.35 no.1
• /
• pp.28-34
• /
• 2006

The ethanol extracts of Puerariae Radix inhibited cyclooxygenase-2 (COX-2) activity in bone marrow derived mast cells (BMMC). COX-2 is responsible for the production of large amounts of proinflammatory prostaglandins (PGs) at the inflammatory site. We have investigated the anti-inflammatory effect of ethyl acetate fraction from $70\%$ ethanol extract of Puerariae Radix (EPR), and attempted acetic acid induced writhing to verify the analgesic effect. Inflammation was induced by interleukin-1 (IL-1), tumor necrosis factor-a (TNF-a), $inteferon-\gamma$ $(IFN-\gamma)$ and lipopolysaccharide (LPS). EPR showed strong inhibitory efficacy against cytokine-induced proteoglycan degradation, prostaglandin $E_2\;(PGE_2)$ production, nitric oxide (NO) production, and matrix-metalloproteinases (MMPs) expression in mouse macrophage and rabbit articular chondrocyte. In the writhing test, EPR $(200\~400\;mg/kg)$ exhibited a dose-dependent inhibition of writhing. The results indicate that EPR have anti-inflammatory and analgesic activities, and could be a good herbal medicine candidate for treating of osteoarthritis (OA).

• Biomolecules & Therapeutics
• /
• v.25 no.2
• /
• pp.213-221
• /
• 2017

Baicalein, a natural flavonoid obtained from the rhizome of Scutellaria baicalensis Georgi, has been reported to have anticancer activities in several human cancer cell lines. However, its antimetastatic effects and associated mechanisms in melanoma cells have not been extensively studied. The current study examined the effects of baicalein on cell motility and anti-invasive activity using mouse melanoma B16F10 cells. Within the noncytotoxic concentration range, baicalein significantly inhibited the cell motility and invasiveness of B16F10 cells in a concentration-dependent manner. Baicalein also reduced the activity and expression of matrix metalloproteinase (MMP)-2 and -9; however, the levels of tissue inhibitor of metalloproteinase-1 and -2 were concomitantly increased. The inhibitory effects of baicalein on cell motility and invasiveness were found to be associated with its tightening of tight junction (TJ), which was demonstrated by an increase in transepithelial electrical resistance and downregulation of the claudin family of proteins. Additionally, treatment with baicalein markedly reduced the expression levels of lipopolysaccharide-induced phosphorylated Akt and the invasive activity in B16F10 cells. Taken together, these results suggest that baicalein inhibits B16F10 melanoma cell migration and invasion by reducing the expression of MMPs and tightening TJ through the suppression of claudin expression, possibly in association with a suppression of the phosphoinositide 3-kinase/Akt signaling pathway.

• Journal of Microbiology and Biotechnology
• /
• v.32 no.9
• /
• pp.1154-1167
• /
• 2022

In this study, we investigated the anti-amnesic effect of Korean red pine (Pinus densiflora) bark extract (KRPBE) against amyloid beta_1-42 (Aβ_1-42)-induced neurotoxicity. We found that treatment with KRPBE improved the behavioral function in Aβ-induced mice, and also boosted the antioxidant system in mice by decreasing malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activities, and reducing glutathione (GSH) levels. In addition, KRPBE improved the cholinergic system by suppressing reduced acetylcholine (ACh) content while also activating acetylcholinesterase (AChE), regulating the expression of choline acetyltransferase (ChAT), postsynaptic density protein-95 (PSD-95), and synaptophysin. KRPBE also showed an ameliorating effect on cerebral mitochondrial deficit by regulating reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and ATP levels. Moreover, KRPBE modulated the expression levels of neurotoxicity indicators Aβ and phosphorylated tau (p-tau) and inflammatory cytokines TNF-α, p-IκB-α, and IL-1β. Furthermore, we found that KRPBE improved the expression levels of neuronal apoptosis-related markers BAX and BCl-2 and increased the expression levels of BDNF and p-CREB. Therefore, this study suggests that KRPBE treatment has an anti-amnestic effect by modulating cholinergic system dysfunction and neuroinflammation in Aβ_1-42-induced cognitive impairment in mice.

• Journal of Environmental Health Sciences
• /
• v.48 no.6
• /
• pp.315-323
• /
• 2022

Background: Socioeconomical disadvantaged communities are more vulnerable to environmental chemical exposure and associated health effects. However, there is limited information on chemical exposure among vulnerable populations in Korea. Objectives: This study investigated chemical exposure among underprivileged populations. We measured urinary metabolites of phthalates in urban disadvantaged communities and investigated their correlations with residential environment factors and relative socioeconomic vulnerability. Methods: Urine samples were collected from 64 residents in a disadvantaged community in Seoul. A total of eight phthalate metabolites were analyzed by liquid chromatography-mass spectroscopy. Analytical method used by the Korean National Environmental Health Survey (KoNEHS) was employed. Covariate variance analysis and general linear regression adjusted with age, sex and smoking were performed. Results: Several phthalate metabolites, namely monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-n-butyl phthalate (MnBP) had higher levels than those reported in the adults of 4th KoNEHS. Notably, the MnBP level was higher in the lower socioeconomic group (geometric mean [GM]=47.3 ㎍/g creatinine) compared to non-recipients (GM=31.9 ㎍/g creatinine) and the national reference level (GM=22.0, 28.2 and 32.2 ㎍/g creatinine for adults, 60's and 70's, respectively.). When age, sex and smoking were adjusted, MEP and MnBP were significantly increased the lower socioeconomic group than non-recipients (p=0.014, p=0.023). The lower socioeconomic group's age of flooring were higher than non-recipients, not statistically significant. Conclusions: These results suggest that a relatively low income and aged flooring could be considered as risk factors for increased levels of phthalate metabolites in socioeconomic vulnerable populations.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2023.04a
• /
• pp.50-50
• /
• 2023

Prostaglandin E2(PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because PGE2 functions by signaling through PGE2 receptors (Eps), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting Eps. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibititing the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinases (MMP)-9 as well as the down-regulation of COX-2 expression and PGE2 production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells. Through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

• International Journal of Stem Cells
• /
• v.16 no.1
• /
• pp.52-65
• /
• 2023

Background and Objectives: Epithelial-Mesenchymal transition (EMT) is one of the origins of myofibroblasts in renal interstitial fibrosis. Mesenchymal stem cells (MSCs) alleviating EMT has been proved, but the concrete mechanism is unclear. To explore the mechanism, serum-free MSCs conditioned medium (SF-MSCs-CM) was used to treat rat renal tubular epithelial cells (NRK-52E) fibrosis induced by transforming growth factor-β1 (TGF-β1) which ameliorated EMT. Methods and Results: Galectin-3 knockdown (Gal-3 KD) and overexpression (Gal-3 OE) lentiviral vectors were established and transfected into NRK-52E. NRK-52E fibrosis model was induced by TGF-β1 and treated with the SF-MSCs-CM for 24 h after modelling. Fibrosis and autophagy related indexes were detected by western blot and immunocytochemistry. In model group, the expressions of α-smooth muscle actin (α-SMA), fibronectin (FN), Galectin-3, Snail, Kim-1, and the ratios of P-Akt/Akt, P-GSK3β/GSK3β, P-PI3K/PI3K, P-mTOR/mTOR, TIMP1/MMP9, and LC3B-II/I were obviously increased, and E-Cadherin (E-cad) and P62 decreased significantly compared with control group. SF-MSCs-CM showed an opposite trend after treatment compared with model group. Whether in Gal-3 KD or Gal-3 OE NRK-52E cells, SF-MSCs-CM also showed similar trends. However, the effects of anti-fibrosis and enhanced autophagy in Gal-3 KD cells were more obvious than those in Gal-3 OE cells. Conclusions: SF-MSCs-CM probably alleviated the EMT via inhibiting Galectin-3/Akt/GSK3β/Snail pathway. Meanwhile, Gal-3 KD possibly enhanced autophagy via inhibiting Galectin-3/Akt/mTOR pathway, which synergistically ameliorated renal fibrosis. Targeting galectin-3 may be a potential target for the treatment of renal fibrosis.