• The Journal of Korean Medicine
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• v.42 no.4
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• pp.150-163
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• 2021

Objectives: The purpose of this study was to confirm the effects of Liriope platyphylla extract on relieving Gastroesophageal reflux disease (GERD) through regulation of acid secretion. Methods: 8-week-old ICR mice were divided into untreated control group (Ctrl), GERD elecitation group (GERDE), Omeprazole administrate group before GERD elicitation (OMA), and Liriope platyphylla extract administrate group before GERD elicitation (LPA). After inducing GERD, gross observation and histological examination were performed and ATP6V1B1 (ATPase H+ Transporting V1 Subunit B1), GRPR (Gastrin-releasing peptide receptor), COX-1 (Cyclooxygenase 1), 8-OHdG (8-hydroxy-2'-deoxyguanosine), Cathelicidin, p-JNK (phospho c-Jun N-terminal kinase) were observed to confirm the damage defense effect of the esophageal mucosa, acid secretion regulation, antioxidant, anti-inflammatory, mucosal protection, and apoptosis regulation Results: OMA and LPA showed lower levels of damage compared to GERDE in gross observation and histological examination. ATP6V1B1, GRPR, and 8-OHdG showed lower positive reactions in OMA and LPA than in GERDE. COX-1 were less positive in GERDE and OMA than in Ctrl, but showed higher secretion in LPA than in Ctrl. Cathelicidin showed a decreased positive reaction in GERDE, OMA and LPA compared to Ctrl, but the decrease in positive reaction was smaller in OMA and LPA compared to GERDE. p-JNK showed increased positive reaction in GERDE, OMA and LPA than in Ctrl, but the increase in the positive reaction was smaller in the OMA and LPA compared to GERDE. Conclusions: The effects of Liriope platyphylla extract on esophageal mucosal damage protection, acid secretion regulation, antioxidant, anti-inflammatory, mucosal protection and apoptosis regulation were confirmed.

• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.306-313
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• 2024

Given the diversity of vegetables utilized in food fermentation and various lactic acid bacteria (LAB) populations in these materials, comprehensive studies on LAB from vegetable foods, including kimchi, are imperative. Therefore, this study aimed to investigate the obesity-related inflammation response of three metabolites-phenyllactic acid (PLA), indole-3-lactic acid (ILA), and leucic acid (LA)-produced by LAB (Companilactobacillus allii WiKim39 and Lactococcus lactis WiKim0124) isolated from kimchi. Their effects on tumor necrosis factor-α-induced changes in adipokines and inflammatory response in adipose-derived human mesenchymal stem cells were examined. The study results showed that PLA, ILA, and LA, particularly PLA, effectively reduced lipid accumulation and triglyceride, glycerol, free fatty acid, and adiponectin levels. Furthermore, the identified metabolites were found to modulate the expression of signaling proteins involved in adipogenesis and inflammation. Specifically, these metabolites were associated with enriched expression in the chemokine signaling pathway and cytokine-cytokine receptor interaction, which are critical pathways involved in regulating immune responses and inflammation. PLA, ILA, and LA also suppressed the secretion of pro-inflammatory cytokines and several inflammatory markers, with the PLA-treated group exhibiting the lowest levels. These results suggest that PLA, ILA, and LA are potential therapeutic agents for treating obesity and inflammation by regulating adipokine secretion and suppressing pro-inflammatory cytokine production.

• Natural Product Sciences
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• v.25 no.2
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• pp.165-171
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• 2019

Although the functions of a standardized extract of Gingko biloba leaves (EGb $761^{(R)}$) has been reported with regard to neurobiological properties, no attention has been paid to the impact of EGb $761^{(R)}$ on the neuronal regulation of energy homeostasis. To evaluate the hypothesis that EGb $761^{(R)}$ affect the secretion of peptide tyrosine tyrosine (PYY) and the activation of free fatty acid receptor 4 (FFA4), which are involved in the neuronal circuitries that control energy homeostasis by inducing the transfer of information about the influx of energy to the brain, we examined whether EGb $761^{(R)}$ can stimulate PYY secretion in the enteroendocrine NCI-H716 cells and if EGb $761^{(R)}$ can activate FFA4 in FFA4-expressing cells. In NCI-H716 cells, EGb $761^{(R)}$ stimulated PYY secretion and the EGb $761^{(R)}$-induced PYY secretion was involved in the increase in intracellular $Ca^{2+}$ concentration and the activation of FFA4. Furthermore, in FFA4-expressing cells, EGb $761^{(R)}$ activated FFA4. These results suggest that EGb $761^{(R)}$ may affect the control of energy homeostasis via the regulation of PYY secretion and FFA4 activation.

• Journal of Microbiology
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• v.41 no.3
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• pp.175-182
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• 2003

Production of ribosomally synthesized antimicrobial peptides usually referred to as bacteriocins is an inducible trait in several gram positive bacteria, particularly in those belonging to the group of lactic acid bacteria. In many of these organisms, production of bacteriocins is inducible and induction requires secretion and extracellular accumulation of peptides that act as chemical messengers and trigger bacteriocin production. These inducer peptides are often referred to as autoinducers and are believed to permit a quorum sensing-based regulation of bacteriocin production. Notably, the peptides acting as autoinducers are dedicated peptides with or without antimicrobial activity or the bacteriocins themselves. The autoinducer-dependent induction of bacteriocin production requires histidine protein kinases and response regulator proteins of two-component signal transduction systems. The current working model for the regulation of class II bacteriocin production in lactic acid bacteria and the most relevant direct and indirect pieces of evidence supporting the model are discussed in this minireview.

• BMB Reports
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• v.54 no.5
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• pp.278-283
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• 2021

Our understanding of the differential effects between specific omega-3 fatty acids is incomplete. Here, we aimed to evaluate the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on T-helper type 1 (Th1) cell responses and identify the pathways associated with these responses. Naïve CD4⁺ T cells were co-cultured with bone marrow-derived dendritic cells (DCs) in the presence or absence of palmitate (PA), DHA, or EPA. DHA or EPA treatment lowered the number of differentiated IFN-γ-positive cells and inhibited the secretion of IFN-γ, whereas only DHA increased IL-2 and reduced TNF-α secretion. There was reduced expression of MHC II on DCs after DHA or EPA treatment. In the DC-independent model, DHA and EPA reduced Th1 cell differentiation and lowered the cell number. DHA and EPA markedly inhibited IFN-γ secretion, while only EPA reduced TNF-α secretion. Microarray analysis identified pathways involved in inflammation, immunity, metabolism, and cell proliferation. Moreover, DHA and EPA inhibited Th1 cells through the regulation of diverse pathways and genes, including Igf1 and Cpt1a. Our results showed that DHA and EPA had largely comparable inhibitory effects on Th1 cell differentiation. However, each of the fatty acids also had distinct effects on specific cytokine secretion, particularly according to the presence of DCs.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.496-504
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• 2022

Background: Cigarette smoke (CS) is considered a principal cause of chronic obstructive pulmonary disease (COPD) and is associated with mucus hypersecretion and airway inflammation. Ginsenoside compound K (CK), a product of ginsenoside metabolism, has various biological activities. Studies on the effects of CK for the treatment of COPD and mucus hypersecretion, including the underlying signaling mechanism, have not yet been conducted. Methods: To study the protective effects and molecular mechanism of CK, phorbol 12-myristate 13-acetate (PMA)-induced human airway epithelial (NCI-H292) cells were used as a cellular model of airway inflammation. An experimental mouse COPD model was also established via CS inhalation and intranasal administration of lipopolysaccharide. Mucin 5AC (MUC5AC), monocyte chemoattractant protein-1, tumor necrosis factor-α (TNF-α), and interleukin-6 secretion, as well as elastase activity and reactive oxygen species production, were determined through enzyme-linked immunosorbent assay. Inflammatory cell influx and mucus secretion in mouse lung tissues were estimated using hematoxylin and eosin and periodic acid-schiff staining, respectively. PKCδ and its downstream signaling molecules were analyzed via western blotting. Results: CK prevented the secretion of MUC5AC and TNF-α in PMA-stimulated NCI-H292 cells and exhibited a protective effect in COPD mice via the suppression of inflammatory mediators and mucus secretion. These effects were accompanied by an inactivation of PKCδ and related signaling in vitro and in vivo. Conclusion: CK suppressed pulmonary inflammation and mucus secretion in COPD mouse model through PKC regulation, highlighting the compound's potential as a useful adjuvant in the prevention and treatment of COPD.

• Journal of Nutrition and Health
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• v.36 no.3
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• pp.270-279
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• 2003

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid (LA) and exhibits anticarcinogenic activity in a variety of animal models. We have previously observed that CLA inhibited the growth of Caco-2 cells, a human colon adenocarcinoma cell line. The present study was performed to determine whether the growth inhibitory effect of CLA is related to change in secretion of IGF- II and/or IGF-binding proteins (IGFBPs) that have been shown to regulate Caco-2 cell proliferation by an autocrine mechanism. Cells were incubated in serum-free medium with various concentrations of CLA or linoleic acid (LA). Immunoblot analysis of 24-hours, serum-free, conditioned medium using a monoclonal anti-IGF-IIantibody revealed that Caco-2 cells secreted both mature 6,500 Mr and higher Mr forms of pro IGF-II. The levels of pro IGF-II and mature IGF-IIwere decreased by 43 $\pm$ 2% and 53 $\pm$ 6%, respectively by treatment with 50 $\mu$ M CLA. LA slightly increased pro IGF- II levels. Results from Northern blot analysis showed that CLA decreased IGF-II mRNA levels at 50 $\mu$ M concentration suggesting that CLA regulation of IGF-II protein expression occurs partly at the transcriptional level. Ligand blot analysis of conditioned media using 1251-IGF-II revealed that CLA slightly decreased IGFBP-2 levels and increased IGFBP-4 levels. We confirmed our previous results that CLA inhibited cell growth in a dose-dependent manner but LA slightly increased cell growth. Exogenous IGF-II mitigated the growth inhibitory effect of CLA. These results indicate that the growth inhibitory effect of CLA may be at least in part mediated by decreasing IGF-II and IGFBP-2 secretion and increasing IGFBP-4 secretion in Caco-2 cells.

• Korean Journal of Veterinary Research
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• v.46 no.2
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• pp.97-105
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• 2006

All-trans retinoic acid (AtRA) induces growth inhibition and apoptosis in a variety of tumer cells, including MCF-7 cells. Insulin-like growth factors (IGFs) system has been reported to be associated with the development of cancer. Although MCF-7 cell with AtRA is to be the major stimulus for the cell growth and apoptosis, the mechanism of insulin-like growth factor-I (IGF-I)/insulin-like growth factor binding protein-3 (IGFBP-3) system remains to be elucidated. Thus, this study was conducted to the effect of AtRA on the gene expression and level of IGF-I and IGFBP-3. In addition, we investigated the involvement of PKC-${\delta}$ on the IGF-I and IGFBP-3 secretion in MCF-7 cell. AtRA(${\geq}10^{-7}M$) decreased the IGF-1 secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cells. Especially, the treatment of AtRA at 72 hours caused a significant reduction in the IGF-I secretion and mRNA expressions but increment in IGFBP-3 secretion and mRNA expressions (p < 0.05). $10^{-7}M$ AtRA activated PKC-${\delta}$ that is one among PKC-$\iota$, ${\alpha}$, ${\lambda}$ and ${\delta}$ in MCF-7 cell. Rotllerin, a PKC-${\delta}$ inhibitor, blocked AtRA-induced inhibition of the IGF-I and mRNA expressions, and increase of lGFBP-3 and mRNA expressions in MCF-7 cell. Together, AtRA inhibited the IGF-I secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cell. Furthermore, AtRA-induced alteration of IGF-I, IGFBP-3 secretion, and the gene expressions were mediated via PKC-${\delta}$ activity.

• Journal of Microbiology and Biotechnology
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• v.26 no.7
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• pp.1198-1205
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• 2016

Lactic acid bacteria (LAB) have beneficial effects on intestinal health and skin diseases. Lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria, is known to induce the production of several cytokines such as TNF-α, IL-1β, and IL-8 and affect the intestinal microflora, anti-aging, sepsis, and cholesterol level. In this study, Weissella cibaria was isolated from Indian dairy products, and we examined its immune-enhancing effects. Live and heat-killed W. cibaria did not induce the secretion of immune-related cytokines, whereas LTA isolated from W. cibaria (cLTA) significantly increased the secretion of TNF-α, IL-1β, and IL-6 in a dose-dependent manner. cLTA increased the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells, p38 mitogen-activated protein kinases, and c-Jun N-terminal kinases in THP-1 cells. The secretion of TNF-α and IL-6 was also increased in the cLTA-treated mouse splenocytes. These results suggest that cLTA, but not W. cibaria whole cells, has immune-boosting potential and can be used to treat immunosuppression diseases.

• Journal of Ginseng Research
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• v.46 no.6
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• pp.780-789
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• 2022

Background: Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods: CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results: CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions: The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.