• Korean Journal of Pharmacognosy
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• v.36 no.3 s.142
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• pp.209-219
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• 2005

In this study, we carried out the preparing standardization and regulation of processed Glycyrrhizae Radix (PGR) which have been widely used in oriental medicines. Glycyrrhizae Radix(GR) have been generally prepared by the stir-frying, or mix-frying with honey for the purpose of decreasing sweetness and augmenting vitality. Firstly, we tried to standardize PGR prepared by the stir-frying. We purchased 14 kinds of PGR and non-processed GR(NPGR) at oriental physician's offices and oriental pharmacies on a nation scale, respectively. The amounts of dry on loss, water extract, diluted ethanol extract, ether extract, total ash, acid insoluble ash, glycyrrhizin(GL), glycyrrhetic acid(GA) and liquiritin(LQ) of them were examined. The amounts of dry on loss, GL and LQ in commercial PGRs showed remarkable decrease, while GA showed increased as compared with NPGR. In order to standardize preparing method of PGR, the effect of heating time on physico-chemical parameters and biological activities were examined. Physico-chemical parameters such as dry on loss, extract amount, GL and LQ contents in PGRs showed decrease, however, GA was increased with heating time as compared with NPGR. Also, GA, obtained from heat-treated GR, was found as an artifact in PGRs. PGR was more effective than NPGA in vitro test of DPPH scavenging effect and TBA-Rs reducing effect. PGR and NPGR showed potent hepatoprotective effect on $CCl_4-intoxicated$ rats. Especially, PGR prepared by 80 min of heating was the most effective. Considering these results, the optimal condition for PGR preparation was $150^{\circ}C$ for 80 min.

• Molecules and Cells
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• v.38 no.1
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• pp.89-94
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• 2015

The shape and activity of mitochondria are tightly regulated by fusion and fission processes that are essential for maintaining normal cellular function. However, little is known about the involvement of mitochondrial dynamics in the development of the immune system. In this study, we demonstrate that mitochondrial dynamics play a role in the differentiation and migration of immature dendritic cells (imDCs). We show that mitochondrial elongation is induced during GM-CSF-stimulated differentiation of bone marrow progenitors to imDCs accompanied by upregulation of mitochondrial fusion proteins. These processes precede the changes in mitochondrial morphology and connectivity that occur during differentiation. Mfn2 and OPA1, but not Mfn1, are transcriptionally upregulated during differentiation; however, knockdown of Mfn2 and OPA1 does not induce any change in expression of CD11c, CDC80, or CD86. Notably, knockdown of Mfn2 or OPA1 by siRNA in imDCs significantly reduces CCR7 expression and CCL19-mediated migration. These results suggest that the mitochondrial fusion-related proteins Mfn2 and OPA1 are upregulated during bone marrow progenitor differentiation and promote the migration of imDCs by regulating the expression of CCR7.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.493-499
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• 2019

Macrophage-associated inflammation is crucial for the pathogenesis of diverse diseases including metabolic disorders. Rhodanthpyrone (Rho) is an active component of Gentiana rhodantha, which has been used in traditional Chinese medicine to treat inflammation. Although synthesis procedures of RhoA and RhoB were reported, the biological effects of the specific compounds have never been explored. In this study, the anti-inflammatory activity and mechanisms of action of RhoA and RhoB were studied in lipopolysaccharide (LPS)-stimulated macrophages. Pretreatment with RhoA and RhoB decreased inducible nitric oxide synthase and cyclooxygenase-2 expressions in RAW 264.7 cells and in thioglycollate-elicited mouse peritoneal macrophages. In addition, it downregulated transcript levels of several inflammatory genes in LPS-stimulated RAW 264.7 cells, including inflammatory cytokines/chemokines (Tnfa, Il6, and Ccl2) and inflammatory mediators (Nos2 and Ptgs2). Macrophage chemotaxis was also inhibited by treatment with the compounds. Mechanistic studies revealed that RhoA and RhoB suppressed the nuclear factor $(NF)-{\kappa}B$ pathway, but not the canonical mitogen activated protein kinase pathway, in LPS-stimulated condition. Moreover, the inhibitory effect of RhoA and RhoB on inflammatory gene expressions was attenuated by treatment with an $NF-{\kappa}B$ inhibitor. Our findings suggest that RhoA and RhoB play an anti-inflammatory role at least in part by suppressing the $NF-{\kappa}B$ pathway during macrophage-mediated inflammation.

• Parasites, Hosts and Diseases
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• v.59 no.6
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• pp.547-556
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• 2021

Our objective was to investigate whether inflammatory microenvironment induced by Trichomonas vaginalis infection can stimulate proliferation of prostate cancer (PCa) cells in vitro and in vivo mouse experiments. The production of CXCL1 and CCL2 increased when cells of the mouse PCa cells (TRAMP-C2 cell line) were infected with live T. vaginalis. T. vaginalis-conditioned medium (TCM) prepared from co-culture of PCa cells and T. vaginalis increased PCa cells migration, proliferation and invasion. The cytokine receptors (CXCR2, CCR2, gp130) were expressed higher on the PCa cells treated with TCM. Pretreatment of PCa cells with antibodies to these cytokine receptors significantly reduced the proliferation, mobility and invasiveness of PCa cells, indicating that TCM has its effect through cytokine-cytokine receptor signaling. In C57BL/6 mice, the prostates injected with T. vaginalis mixed PCa cells were larger than those injected with PCa cells alone after 4 weeks. Expression of epithelial-mesenchymal transition markers and cyclin D1 in the prostate tissue injected with T. vaginalis mixed PCa cells increased than those of PCa cells alone. Collectively, it was suggested that inflammatory reactions by T. vaginalis-stimulated PCa cells increase the proliferation and invasion of PCa cells through cytokine-cytokine receptor signaling pathways.

• Genomics & Informatics
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• v.20 no.3
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• pp.32.1-32.15
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• 2022

Malaria is a life-threatening disease, and Africa is still one of the most affected endemic regions despite years of policy to limit infection and transmission rates. Further, studies into the variable efficacy of the vaccine are needed to provide a better understanding of protective immunity. Thus, the current study is designed to delineate the effect of each dose of vaccine on the transcriptional profiles of subjects to determine its efficacy and understand the molecular mechanisms underlying the protection this vaccine provides. Here, we used gene expression profiles of pre and post-vaccination patients after various doses of RTS,S based on samples collected from the Gene Expression Omnibus datasets. Subsequently, differential gene expression analysis using edgeR revealed the significantly (false discovery rate < 0.005) 158 downregulated and 61 upregulated genes between control vs. controlled human malaria infection samples. Further, enrichment analysis of significant genes delineated the involvement of CCL8, CXCL10, CXCL11, XCR1, CSF3, IFNB1, IFNE, IL12B, IL22, IL6, IL27, etc., genes which found to be upregulated after earlier doses but downregulated after the 3rd dose in cytokine-chemokine pathways. Notably, we identified 13 cytokine genes whose expression significantly varied during three doses. Eventually, these findings give insight into the dual role of cytokine responses in malaria pathogenesis. The variations in their expression patterns after various doses of vaccination are linked to the protection as it decreases the severe inflammatory effects in malaria patients. This study will be helpful in designing a better vaccine against malaria and understanding the functions of cytokine response as well.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.307-319
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• 2021

Dysregulation of the Wnt pathway causes various diseases including cancer, Parkinson's disease, Alzheimer's disease, schizophrenia, osteoporosis, obesity and chronic kidney diseases. The modulation of dysregulated Wnt pathway is absolutely necessary. In the present study, we evaluated the anti-inflammatory effect and the mechanism of action of Wnt-C59, a Wnt signaling inhibitor, in lipopolysaccharide (LPS)-stimulated epithelial cells and macrophage cells. Wnt-C59 showed a dose-dependent anti-inflammatory effect by suppressing the expression of proinflammatory cytokines including IL6, CCL2, IL1A, IL1B, and TNF in LPS-stimulated cells. The dysregulation of the Wnt/β-catenin pathway in LPS stimulated cells was suppressed by WntC59 treatment. The level of β-catenin, the executor protein of Wnt/β-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of β-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity. We found that the interaction between β-catenin and NF-κB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-κB activity for its target DNA binding and the reporter activity of NF-κB-responsive promoter showed identical patterns with the interaction between β-catenin and NF-κB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB, which results in the suppressions of the NF-κB activity and proinflammatory cytokine expression.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.36 no.1
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• pp.50-63
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• 2023

Objectives : This study used a network pharmacology approach to explore the active compounds and therapeutic mechanisms of Yijin-tang on Meniere's disease. Methods : The active compounds of Yijin-tang were screened via the TCMSP database and their target proteins were screened via the STITCH database. The GeneCard was used to establish the Meniere's disease-related genes. The intersection targets were obtained through Venny 2.1.0. The related protein interaction network was constructed with the STRING database, and topology analysis was performed through CytoNCA. GO biological function analysis and KEGG enrichment analysis for core targets were performed through the ClueGO. Results : Network analysis identified 126 compounds in five herbal medicines of Yijin-tang. Among them, 15 compounds(naringenin, beta-sitosterol, stigmasterol, baicalein, baicalin, calycosin, dihydrocapsaicin, formononetin, glabridin, isorhamnetin, kaempferol, mairin, quercetin, sitosterol, nobiletin) were the key chemicals. The target proteins were 119, and 7 proteins(TNF, CASP9, PARP1, CCL2, CFTR, NOS2, NOS1) were linked to Meniere's disease-related genes. Core genes in this network were TNF, CASP9, and NOS2. GO/KEGG pathway analysis results indicate that these targets are primarily involved in regulating biological processes, such as excitotoxicity, oxidative stress, and apoptosis. Conclusion : Pharmacological network analysis can help to explain the applicability of Yijin-tang on Meniere's disease.

• Journal of Acupuncture Research
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• v.39 no.1
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• pp.40-48
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• 2022

Background: This study was performed to determine the effects of liposome-encapsulated bee venom (BV) treatment of inflammatory factors in atopic dermatitis (AD) compared with BV treatment. Methods: AD was induced by phthalic anhydride in mice and the effects of BV liposomes were measured. Using Leica Application Suite, thickened epidermis and dermis were measured after BV liposome treatment (0.05 and 0.1 ㎍/mL). The number of stained mast cells and the concentration of immunoglobulin (Ig)E were measured. Serum IgE concentration was analyzed using an enzyme-linked immunosorbent assay. The serum concentrations of interleukin (IL)-1, IL-4, and IL-6 inflammatory cytokines were measured. The levels of messenger ribonucleic acid expression of proinflammatory cytokines and chemokines were measured using reverse transcription polymerase chain reaction. Inhibition of mitogen-activated protein kinase activation, was analyzed on western blot. To measure the transcriptional activity (NF-κB inhibition by BV liposomes), western blots (p65, p-IκB, p50, and IκB) were also performed. Results: The weight of lymph nodes, serum IgE concentrations, morphological changes in the skins from the backs of the mice, and mast cell numbers in inflamed tissues were noticeably lower in the BV liposome treatment group compared with the BV treatment group. The concentrations of pro-inflammatory cytokines (IL-1, IL-4, IL-6) and chemokines (TSLP, CCL22) were also reduced. Activation of mitogen-activated protein kinase (p-ERK and p-p38), and transcriptional activity (p65, p-IκB, p50, and IκB) was strongly suppressed in the BV liposome group. Conclusion: BV liposomes may have a better therapeutic effect than BV for the treatment of AD.

• Food Science of Animal Resources
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• v.42 no.5
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• pp.800-815
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• 2022

This study aimed to obtain high Fischer's ratio oligopeptides from goat whey (HFO) and investigate antioxidant property of it. Hydrolysis of goat whey was done with the approach of sequential digestion of pepsin and flavourzyme. With the adsorption of aromatic amino acids by activated carbon, HFO with a Fischer's ratio of 27.070 and a molecular weight of 200-1,000 Da were obtained, and the branched-chain amino acids accounted for 22.87%. Then the antioxidant activity of HFO was evaluated. At the concentrations of 2.0 mg/mL and 0.50 mg/mL, HFO scavenged 77.27% and 99.63% of 1,1-diphenyl-2-picrylhydrazyl and 3-ethylbenzthiazoline-6-sulphonate free radicals respectively. The scavenging rate of HFO against hydroxyl radicals reached 92.31% at the concentration of 0.25 mg/mL. Animal experiments demonstrated that HFO could moderate the changes of malondialdehyde, superoxide dismutase and glutathione peroxidase caused by CCl₄-induced oxidative stress in vivo. This study indicated that HFO from goat whey was capable of oxidation resistance both in vivo and in vitro, which provided a scientific basis for the high-value processing and application of goat milk whey.

• BMB Reports
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• v.55 no.10
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• pp.512-517
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• 2022

Traumatic brain injury (TBI) is brain damage which is caused by the impact of external mechanical forces. TBI can lead to the temporary or permanent impairment of physical and cognitive abilities, resulting in abnormal behavior. We recently observed that a single session of early exercise in animals with TBI improved their behavioral performance in the absence of other cognitive abnormalities. In the present study, we investigated the therapeutic effects of continuous exercise during the early stages of TBI in rats. We found that continuous low-intensity exercise in early-stage improves the locomotion recovery in the TBI of animal models; however, it does not significantly enhance short-term memory capabilities. Moreover, continuous early exercise not only reduces the protein expression of cerebral damage-related markers, such as Glial Fibrillary Acid Protein (GFAP), Neuron-Specific Enolase (NSE), S100β, Protein Gene Products 9.5 (PGP9.5), and Heat Shock Protein 70 (HSP70), but it also decreases the expression of apoptosis-related protein BAX and cleaved caspase 3. Furthermore, exercise training in animals with TBI decreases the microglia activation and the expression of inflammatory cytokines in the serum, such as CCL20, IL-13, IL-1α, and IL-1β. These findings thus demonstrate that early exercise therapy for TBI may be an effective strategy in improving physiological function, and that serum protein levels are useful biomarkers for the predicition of the effectiveness of early exercise therapy.