• Journal of Ginseng Research
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• v.46 no.5
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• pp.628-635
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• 2022

Background: Ulcerative colitis (UC) is the large intestine disease that results in chronic inflammation and ulcers in the colon. Rg3-enriched Korean Red Ginseng extract (Rg3-RGE) is known for its pharmacological activities. Persicaria tinctoria (PT) is also used in the treatment of various inflammatory diseases. The aim of this study is to investigate the attenuating effects of Rg3-RGE with PT on oxazolone (OXA)-induced UC in mice. Methods: A total of six groups of mice including control group, OXA (as model group, 1.5%) group, sulfasalazine (75 mg/kg) group, Rg3-RGE (20 mg/kg) group, PT (300 mg/kg) group, and Rg3-RGE (10 mg/kg) with PT (150 mg/kg) group. Data on the colon length, body weight, disease activity index (DAI), histological changes, nitric oxide (NO) assay, Real-time PCR of inflammatory factors, ELISA of inflammatory factors, Western blot, and flow cytometry analysis were obtained. Results: Overall, the combination treatment of Rg3-RGE and PT significantly improved the colon length and body weight and decreased the DAI in mice compared with the treatment with OXA. Additionally, the histological injury was also reduced by the combination treatment. Moreover, the NO production level and inflammatory mediators and cytokines were significantly downregulated in the Rg3-RGE with the PT group compared with the model group. Also, NLR family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-𝛋B) were suppressed in the combination treatment group compared with the OXA group. Furthermore, the number of immune cell subtypes of CD4⁺ T-helper cells, CD19⁺ B-cells, and CD4⁺ and CD25⁺ regulatory T-cells (Tregs) was improved in the Rg3-RGE with the PT group compared with the OXA group. Conclusion: Overall, the mixture of Rg3-RGE and PT is an effective therapeutic treatment for UC.

• Journal of Nutrition and Health
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• v.53 no.5
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• pp.452-463
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• 2020

Purpose: Aster tataricus (AT) is one of the Asteraceae perennial herbs used in traditional Chinese medicine. The herb contains various bioactive substances, such as flavonoids, isoflavonoids, and phenolic compounds in the roots, and exhibits a range of effects including anti-bacterial, anti-oxidant, and anti-inflammatory activities. This study compared the immunomodulatory effects of ethanol and water extracts of whole AT, except the roots, and analyzed the molecular mechanisms for the regulatory effects on cytokine secretion from THP-1 cells. Methods: The effects of AT extract on the cell viability and proliferation of THP-1 cells were analyzed using the Cell Counting Kit-8 method. The concentrations of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the cell culture supernatant of the AT-treated THP-1 cells were measured using an enzyme-linked immunosorbent assay. The protein levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), inhibitor of nuclear factor kappa B (IκBα), and mitogen-activated protein kinase (MAPK) phosphorylation in the cell lysates were determined by western blotting. Results: The water extract and the ethanol extract of AT did not affect the cell viability, and increased the proliferation of THP-1 cells significantly compared to the vehicle. The water extract increased the secretion of IL-1β from THP-1 cells in a dose-dependent manner, but the ethanol extract had no effect. The expression of COX-2 and iNOS protein and the phosphorylation of MAPK and Akt were induced in AT-treated cells. In addition, IκBα was degraded by AT in a concentration-dependent manner. IL-1β secretion by AT was reduced by extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors, while TNF-α secretion was decreased by inhibitors of ERK, p38 MAPK, and JNK. Interestingly, the p38 MAPK inhibitor increased the production of IL-1β by AT further. Conclusion: The water extract of the above-ground parts of AT contains immunomodulatory bioactive substances that stimulate immune cells through the MAPK signaling pathway.

• Korean Journal of Microbiology
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• v.41 no.2
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• pp.99-104
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• 2005

Corynebacterial clones which exert regulatory effects on the expression of the glyoxylate bypass genes were isolated using a reporter plasmid carrying the enteric lacZ fused to the aceB promoter of Corynebacterium glutamicum. Some clones carried common fragments as turned out by DNA mapping technique. Subcloning analysis followed by the measurement of $\beta-galactosidase$ activity in Escherichia coli identified the region responsible for the aceB-repressing activity. Sequence analysis of the DNA fragment identified two independent ORFs of ORF1 and ORF2. Among them, ORF2 was turned out to be responsible for the aceB-repressing activity. ORF1 encoded a 23,216 Da protein composed of 206 amino acids. Sequence similarity search indicated that the ORF may encode a ECF-type $\sigma$ factor and designated sigH. To identify the function of sigH, C. glutamicum sigH mutant was constructed by gene disruption technique and the sigH mutant showed growth retardation as compared to the wild type strain. In addition, the mutant strain showed sensitivity to oxidative-stress generating agent plumbagin. This result imply that sigH is probably involved in the stress response occurring during normal cell growth.

• The Korean Journal of Zoology
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• v.39 no.3
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• pp.317-324
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• 1996

Osteoclast has been known as a primary responsible cell for the bone resorption. The activation of osteoclast, therefore, may be the key event in the regulation of bone growth and remodeling. Various factors were reported to have influence on the resorbing activity of osteoclast in organ culture. Among those factors, transforming growth factor-$\beta$ (TGF-$\beta$) has been known to have a profound effect on bone metabolism. Since a large amount of TGF-$\beta$ presents in bone tissue, it may be important for the understanding the regulatory mechanism of bone resorption to elucidate the effect of TGF-$\beta$ on the osteoclast. We have reported the dlsaggregated chick embryonic osteoclast culture as an useful assay method for determining the resorption activity of osteoclast. In this culture, we found that TGF-$\beta$ significantly enhaced the osteoclastic bone resorption activity. We also found that the timulatory effect seemed to be an indirect one that is mediated by other cells. As nordihydroguaiaretic acid significantly inhibited the TGF-$\beta$1-induced osteoclastic bone resorption, we suggest that the lipoxygenase derivative of arachidonic acid may participate in the action of TGF-$\beta$ as a paracrine or an autocrine mediator.

• The Korean Journal of Malacology
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• v.28 no.4
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• pp.377-384
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• 2012

The importance of biological resources has been gradually increasing, and mollusks have been utilized as main fishery resources in terrestrial ecosystems. But little is known about genomic and transcriptional analysis in mollusks. This is the first report on the transcriptomic profile of Meretrix lusoria. In this study, we constructed cDNA library and determined 542 of distinct EST sequences composed of 284 singletons and 95 contigs. At first, we identified 180 of EST sequences that have significant hits on protein sequences of the exclusive Mollusks database through BLASTX program and 343 of EST sequences that have significant hits on NCBI NR database. We also found that 211 of putative sequences through local BLAST (blastx, E < e-10) search against KOG database were classified into 16 functional categories. Some kinds of immune response related genes encoding allograft inflammatory factor 1 (AIF-1), B-cell translocation gene 1 (BTG1), C-type lectin A, thioester-containing protein and 26S proteasome regulatory complex were identified. To determine phylogenetic relationship, we identified partial sequences of four genes (COX1, COX2, 12S rRNA and NADH dehydrogenase) that significantly matched with the mitochondrial genomes of 3 species-Ml (Meretrix lusoria), Mp (Meretrix petechialis) and Mm (Meretrix meretrix). As a result, we found that there was a little bit of a difference between sequences of Korean isolates and other known isolates. This study will be useful to develop breeding technology and might also be helpful to establish a classification system.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.437-444
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• 2016

Background: Although Korean Red Ginseng (KRG) has been traditionally used for a long time, its anti-inflammatory role and underlying molecular and cellular mechanisms have been poorly understood. In this study, the anti-inflammatory roles of KRG-derived components, namely, water extract (KRG-WE), saponin fraction (KRG-SF), and nonsaponin fraction (KRG-NSF), were investigated. Methods: To check saponin levels in the test fractions, KRG-WE, KRG-NSF, and KRG-SF were analyzed using high-performance liquid chromatography. The anti-inflammatory roles and underlying cellular and molecular mechanisms of these components were investigated using a macrophage-like cell line (RAW264.7 cells) and an acute gastritis model in mice. Results: Of the tested fractions, KGR-SF (but not KRG-NSF and KRG-WE) markedly inhibited the viability of RAW264.7 cells, and splenocytes at more than 500 mg/mL significantly suppressed NO production at $100{\mu}g/mL$, diminished mRNA expression of inflammatory genes such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interferon-${\beta}$ at $200{\mu}g/mL$, and completely blocked phagocytic uptake by RAW264.7 cells. All three fractions suppressed luciferase activity triggered by interferon regulatory factor 3 (IRF3), but not that triggered by activator protein-1 and nuclear factor-kappa B. Phospho-IRF3 and phospho-TBK1 were simultaneously decreased in KRG-SF. Interestingly, all these fractions, when orally administered, clearly ameliorated the symptoms of gastric ulcer in HCl/ethanol-induced gastritis mice. Conclusion: These results suggest that KRG-WE, KRG-NSF, and KRG-SF might have anti-inflammatory properties, mostly because of the suppression of the IRF3 pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.365-372
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• 2015

Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor $(NF)-{\kappa}B$, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.

• Animal Bioscience
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• v.34 no.6
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• pp.975-984
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• 2021

Objective: Inbreeding depression of reproduction is a major concern in the conservation of native chicken genetic resources. Here, based on the successful development of strongly inbred (Sinb) and weakly inbred (Winb) Langshan chickens, we aimed to evaluate inbreeding effects on reproductive traits and identify candidate genes involved in inbreeding depression of reproduction in Langshan chickens. Methods: A two-sample t-test was performed to estimate the differences in phenotypic values of reproductive traits between Sinb and Winb chicken groups. Three healthy chickens with reproductive trait values around the group mean values were selected from each of the groups. Differences in ovarian and hypothalamus transcriptomes between the two groups of chickens were analyzed by RNA sequencing (RNA-Seq). Results: The Sinb chicken group showed an obvious inbreeding depression in reproduction, especially for traits of age at the first egg and egg number at 300 days (p<0.01). Furthermore, 68 and 618 differentially expressed genes (DEGs) were obtained in the hypothalamus and ovary between the two chicken groups, respectively. In the hypothalamus, DEGs were mainly enriched in the pathways related to vitamin metabolism, signal transduction and development of the reproductive system, such as the riboflavin metabolism, Wnt signaling pathway, extracellular matrix-receptor interaction and focal adhesion pathways, including stimulated by retinoic acid 6, serpin family F member 1, secreted frizzled related protein 2, Wnt family member 6, and frizzled class receptor 4 genes. In the ovary, DEGs were significantly enriched in pathways associated with basic metabolism, including amino acid metabolism, oxidative phosphorylation, and glycosaminoglycan degradation. A series of key DEGs involved in folate biosynthesis (gamma-glutamyl hydrolase, guanosine triphosphate cyclohydrolase 1), oocyte meiosis and ovarian function (cytoplasmic polyadenylation element binding protein 1, structural maintenance of chromosomes 1B, and speedy/RINGO cell cycle regulator family member A), spermatogenesis and male fertility (prostaglandin D2 synthase 21 kDa), Mov10 RISC complex RNA helicase like 1, and deuterosome assembly protein 1) were identified, and these may play important roles in inbreeding depression in reproduction. Conclusion: The results improve our understanding of the regulatory mechanisms underlying inbreeding depression in chicken reproduction and provide a theoretical basis for the conservation of species resources.

• Journal of Veterinary Science
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• v.22 no.3
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• pp.39.18-39.18
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• 2021

Background: Interferon lambda receptor 1 (IFNLR1) is a type II cytokine receptor that clings to interleukins IL-28A, IL29B, and IL-29 referred to as type III IFNs (IFN-λs). IFN-λs act through the JAK-STAT signaling pathway to exert antiviral effects related to preventing and curing an infection. Although the immune function of IFN-λs in virus invasion has been described, the molecular mechanism of IFNLR1 in that process is unclear. Objectives: The purpose of this study was to elucidate the role of IFNLR1 in the pathogenesis and treatment of porcine reproductive and respiratory syndrome virus (PRRSV). Methods: The effects of IFNLR1 on the proliferation of porcine alveolar macrophages (PAMs) during PRRSV infection were investigated using interference and overexpression methods. Results: In this study, the expressions of the IFNLR1 gene in the liver, large intestine, small intestine, kidney, and lung tissues of Dapulian pigs were significantly higher than those in Landrace pigs. It was determined that porcine IFNLR1 overexpression suppresses PRRSV replication. The qRT-PCR results revealed that overexpression of IFNLR1 upregulated antiviral and IFN-stimulated genes. IFNLR1 overexpression inhibits the proliferation of PAMs and upregulation of p-STAT1. By contrast, knockdown of IFNLR1 expression promotes PAMs proliferation. The G0/G1 phase proportion in IFNLR1-overexpressing cells increased, and the opposite change was observed in IFNLR1-underexpressing cells. After inhibition of the JAK/STAT signaling pathway, the G2/M phase proportion in the IFNLR1-overexpressing cells showed a significant increasing trend. In conclusion, overexpression of IFNLR1 induces activation of the JAK/STAT pathway, thereby inhibiting the proliferation of PAMs infected with PRRSV. Conclusion: Expression of the IFNLR1 gene has an important regulatory role in PRRSV-infected PAMs, indicating it has potential as a molecular target in developing a new strategy for the treatment of PRRSV.

• Journal of Life Science
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• v.31 no.7
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• pp.686-697
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• 2021

Propolis is a resinous substance produced by honeybees, which they use to protect their hives. Honeybees produce propolis by mixing exudates from the various trees and plants with saliva and beeswax. It has been used since around 300 B.C. as a folk medicine to cure wounds. Propolis contains many physiologically active components, such as flavonoids, phenolic compounds, and beeswax. Because of its functional components, propolis has a wide spectrum of biological applications. The compounds in propolis and its biological activity can vary according to the location of nectar source and extraction method. Propolis is most commonly known for its anti-microorganism activity against bacteria, viruses, and fungi. Artepillin C and caffeic acid phenethyl ester (CAPE) have been identified as regulatory compounds that reduce inflammation and exert immunosuppressive reactions on T lymphocytes. Through its anti-inflammatory activity, propolis exhibits anti-tumor activity, including the inhibition of cancer cell proliferation, the blocking of tumor signaling cascades, and antiangiogenesis. However, for the more apply of propolis its analysis of nectar source, identifying of propolis compound, the molecular mechanism of propolis and the investigation of compounds synergistic effects are essential. In this study, we described the physiological activity of propolis isolated from honeybees.