• Food Science and Preservation
• /
• v.23 no.3
• /
• pp.378-386
• /
• 2016

Anti-atherogenic effects in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated human umbilical vein endothelial cells (HUVEC) are involved in the suppression of oxidative stress, cell adhesion molecules, and pro-inflammatory factors. This study investigated the vascular inflammation inhibitory activity of traditional Doenjang plays a key role in the pathogenesis and progression of atherosclerosis. The protective effects of Korean Deonjang was investigated on the expression of cell adhesion molecules (CAMs) in tumor necrosis factor (TNF)-${\alpha}$-induced human umbilical vascular endothelial cells (HUVECs). Deonjang extracts (20, 50, $100{\mu}g/mL$) decreased the expression of 20 ng/mL TNF-${\alpha}$-induced vascular cell adhesion molecule (VCAM)-1 intracellular adhesion molecule (ICAM)-1 proteins, and their corresponding mRNA levels. Nitric oxides (NO) produced by endothlial nitric oxides synthase (eNOS) dilated blood vessels, which had protective effects against platelet and leukocyte adhesion. While TNF-${\alpha}$-induced suppressed the production of nitric oxide in HUVECs, Doenjang restored NO production in HUVECs. In addition, Deonjang reduced the TNF-${\alpha}$-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA levels. These results suggested that Doenjang can inhibited the production of cell adhesion molecules and inflammatory mediators, which could be a potential candidate for preventing atherosclerosis.

• IMMUNE NETWORK
• /
• v.1 no.2
• /
• pp.116-125
• /
• 2001

Background: Nitric oxide (NO) production has been described as a double-edged sword eliciting both pro- and anti-inflammatory effects in different immune reactions. This work was undertaken to investigate the immunoregulatory role of NO in experimental allergic encephalomyelitis (EAE) and experimental allergic uveitis (EAU). Method: We examined whether molsidomine (MSDM), a NO donor, administration to the myelin basic protein (MBP)- or interphotoreceptor retinoid binding protein (IRBP)-immunized rats could suppress EAE development by shifting toward the Th2 cytokine response. In the EAE experiments, the rats were treated orally with MSDM (10 mg/kg/day) at the early stage (-1~4 days) or throughout the experimental period (-1~15 days). Results: This resulted in significant amelioration of the disease and mild clinical symptoms, while MBP-immunization without MSDM administration showed severe EAE development. A marked reduction in inflammation was also observed in the spinal cord, indicating the crucial role of NO in the pathogenesis of EAE in in vivo. In the EAU experiments, a 24 h pre-treatment with MSDM prior to IRBP immunization resulted in significant inhibition of the disease. Furthermore, MSDM administration for 2 1 days completely reduced the incidence and severity of EAU. To investigate whether MSDM could modulate cytokine switching from Th 1 to Th2, culture supernatants of MBP- or IRBP-stimulated inguinal lymphocytes were analyzed. MSDM treatment enhanced IL-10 secretion but decreased IFN-${\gamma}$. IL-4 was undetectable in all groups. In contrast, the MBP-or IRBP-immunized rats without MSDM secreted high concentrations of IFN-${\gamma}$, but low concentrations of IL-10. Conclusion: In conclusion, NO administation suppresses EAE and EAU by modulating the Th1/Th2 balance during inflammatory immune responses. This work further suggests that NO may be useful in the therapeutic control of autoimmune disease.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.6
• /
• pp.661-670
• /
• 2018

Fimasartan, a new angiotensin II receptor antagonist, reduces myocyte damage and stabilizes atherosclerotic plaque through its anti-inflammatory effect in animal studies. We investigated the protective effects of pretreatment with fimasartan on ischemia-reperfusion injury (IRI) in a mouse model of ischemic renal damage. C57BL/6 mice were pretreated with or without 5 (IR-F5) or 10 (IR-F10) mg/kg/day fimasartan for 3 days. Renal ischemia was induced by clamping bilateral renal vascular pedicles for 30 min. Histology, pro-inflammatory cytokines, and apoptosis assays were evaluated 24 h after IRI. Compared to the untreated group, blood urea nitrogen and serum creatinine levels were significantly lower in the IR-F10 group. IR-F10 kidneys showed less tubular necrosis and interstitial fibrosis than untreated kidneys. The expression of F4/80, a macrophage infiltration marker, and tumor necrosis factor $(TNF)-{\alpha}$, decreased in the IR-F10 group. High-dose fimasartan treatment attenuated the upregulation of $TNF-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 in ischemic kidneys. Fewer TUNEL positive cells were observed in IR-F10 compared to control mice. Fimasartan caused a significant decrease in caspase-3 activity and the level of Bax, and increased the Bcl-2 level. Fimasartan preserved renal function and tubular architecture from IRI in a mouse ischemic renal injury model. Fimasartan also attenuated upregulation of inflammatory cytokines and decreased apoptosis of renal tubular cells. Our results suggest that fimasartan inhibited the process of tubular injury by preventing apoptosis induced by the inflammatory pathway.

• Archives of Plastic Surgery
• /
• v.42 no.1
• /
• pp.11-19
• /
• 2015

Background Wound healing is an interaction of a complex signaling cascade of cellular events, including inflammation, proliferation, and maturation. $K^+$ channels modulate the mitogen-activated protein kinase (MAPK) signaling pathway. Here, we investigated whether $K^+$ channel-activated MAPK signaling directs collagen synthesis and angiogenesis in wound healing. Methods The human skin fibroblast HS27 cell line was used to examine cell viability and collagen synthesis after potassium chloride (KCl) treatment by Cell Counting Kit-8 (CCK-8) and western blotting. To investigate whether $K^+$ ion channels function upstream of MAPK signaling, thus affecting collagen synthesis and angiogenesis, we examined alteration of MAPK expression after treatment with KCl (channel inhibitor), NS1619 (channel activator), or kinase inhibitors. To research the effect of KCl on angiogenesis, angiogenesis-related proteins such as thrombospondin 1 (TSP1), anti-angiogenic factor, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), pro-angiogenic factor were assayed by western blot. Results The viability of HS27 cells was not affected by 25 mM KCl. Collagen synthesis increased dependent on time and concentration of KCl exposure. The phosphorylations of MAPK proteins such as extracellular-signal-regulated kinase (ERK) and p38 increased about 2.5-3 fold in the KCl treatment cells and were inhibited by treatment of NS1619. TSP1 expression increased by 100%, bFGF expression decreased by 40%, and there is no significant differences in the VEGF level by KCl treatment, TSP1 was inhibited by NS1619 or kinase inhibitors. Conclusions Our results suggest that KCl may function as a therapeutic agent for wound healing in the skin through MAPK signaling mediated by the $K^+$ ion channel.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.46 no.2
• /
• pp.195-204
• /
• 2020

The purpose of this study was to investigate the effects of 14 Chung-bu medicinal materials described in the Dongui Bogam on inflammatory cytokine production in HaCaT human keratinocyte cells. In order to confirm this possibility, we screened inhibition activity of 17 cytokines using Bio-Plex Pro^TM Human Cytokine 17-plex assay in HaCaT cell lines. Of the 14 Chung-bu medicinal materials, Holotrichia (Ho) and Scorpio (Sc) exerted inhibitory effects on interleukin (IL)-5 production; Ho, Mantidis Ootheca (MO), and Hirudo (Hi) exerted inhibitory effects on IL-6 production; Ho, MO, Lumbricus (Lu), Hi, and Meretricis Concha (MC) showed significant inhibitory effects on IL-8 production; Gecko (Ge), Bombycis Faeces (BF), Cicadidae Periostracum (CP), and MC showed significant inhibitory effects on IL-13 production; and Testudinis Chinemis Plastrum et Carapax (TCPC), BF, and Lu exerted significant inhibitory effects on MIP-1β production. Results indicated that the Chung-bu medicinal materials might be a good candicate as potential anti-inflammatory agents for inhibition of skin inflammation. However, further investigations on these materials, including mechanistic studies, should be carried out to validated the effects in human skin equivalent models of dermatitis.

• Microbiology and Biotechnology Letters
• /
• v.39 no.3
• /
• pp.266-273
• /
• 2011

Although turmeric has numerous pharmacological effects, the poor water-solubility of curcuminoids, active components of turmeric, restricts their systemic availability in orally administered formulations and limits their therapeutic potential. In this study we attempted turmeric fermentation using several probiotic bacteria to improve its solubility, and also investigated the effects of turmeric and fermented turmeric on anti-inflammatory activity. Fermented turmeric, by L. johnsonii IDCC 9203, more strongly inhibited LPS-induced expression of the pro-inflammatory cytokines than non-fermented turmeric and fermented turmeric by other probiotic strains. We used an NC/Nga mouse model for mite antigen-induced atopic dermatitis to examine the efficacy of the fermented turmeric. Fermented turmeric-fed mice exhibited a significantly reduced serum IgE level and mitigated acute inflammation. When the fermented turmeric was pre-treated by oral administration, it had more preventive activity against acute anaphylactic reaction than the non-fermented group. In addition, we observed that fermentation of turmeric leads to increased water-solubility of curcumin and a change in the active components ratios for bisdemethoxycurcumin, demethoxycrucumin and curcumin. Taken together, these results strongly suggest that fermented turmeric by L. johnsonii IDCC 9203 could be used as a functional food ingredient for improving treatments for atopic dermatitis.

• Journal of Life Science
• /
• v.28 no.3
• /
• pp.339-344
• /
• 2018

Schizandra chinensis has been used as a traditional Chinese medicine and is known to have various bioactive components, including schizandrin and gomisin A. In the current study, we investigated the anti-inflammatory activities and their working mechanisms of ethanol extracts of pomace of Schizandra chinensis (PSC), schizandrin (SZ), and gomisin A (GA). First, we analyzed the effects of PSC on nitric oxide (NO) production and cell viabilities in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results indicated that PSC dramatically reduced NO production in LPS-activated RAW264.7 cells in a dose-dependent manner without affecting cell viabilities. PSC also decreased the expression of pro-inflammatory genes iNOS and COX-2, whereas the expression of TNF-${\alpha}$ was not affected by PSC. In addition, PSC inhibited phosphorylation of p38, ERK1/2, and JNK but did not change the expression of their total protein. The results indicate that PSC can regulate LPS-induced inflammatory responses by suppressing MAPK (mitogen-activated protein kinase) signaling. We also analyzed the effects of SZ and GA on NO production and cell viabilities in RAW264.7 cells. The results showed that SZ and GA also decreased NO production in a dose-dependent manner in LPS-activated RAW 264.7 cells without affecting cell viabilities. SZ reduced the expression of iNOS, whereas GA downregulated iNOS and COX-2. Overall, these findings clarify the molecular mechanisms of the anti-inflammatory effects mediated by PSC, SZ, and GA.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.40 no.9
• /
• pp.1333-1339
• /
• 2011

After mulberry (Morus alba) leaves were fermented with Hericium erinaceum mycelium by solid-state culture to enhance physiological activity, fermented mulberry leaves (MA-HE) was extracted by hot-water (MA-HEHW) and ethanol (MA-HE-E). MA-HE-HW showed enhanced mitogenic and intestinal immune system modulating activities (1.41 and 1.52 fold of saline control, respectively) compared to hot-water extracts of non-fermented mulberry leaves (MA-HW) and H. erinaceum mycelium (HE-HW) at $100\;{\mu}g$/mL. Meanwhile, when we tested the inhibitory effects of extracts on nitric oxide (NO), tumor necrosis factor (TNF)-${\alpha}$, and interleukin (IL)-$1{\beta}$ and IL-6 production, MA-HE-E significantly inhibited these pro-inflammatory mediators in LPS-stimulated RAW 264.7 cells (45.1, 41.3, 70.2, and 55.7% inhibition of LPS control at $1,000\;{\mu}g$/mL). In addition, MA-HE-HW and MA-HE-E did not show any cytotoxicity on RAW 264.7 cells at $1,000\;{\mu}g$/mL whereas HE-E and MA-E indicated cytotoxicity (80.1 and 30.7% cell viability of saline control). These results suggest that mulberry leaves fermented with H. erinaceum by solid-state culture might have enhanced immunomodulatory and anti-inflammatory effects compared to non-fermented mulberry leaves, resulting in ingredients biotransformed for fermentation with H. erinaceum mycelium.

• Food Science and Preservation
• /
• v.24 no.8
• /
• pp.1149-1157
• /
• 2017

Inflammation is the first response of the immune system to infection or irritation in our body. The use of medicinal plants has been widely applied as an alternative source for drug development. One of marine natural resources, the anti-inflammatory effect of Ishige sinicola ethanol extract (ISEE), was evaluated by using LPS-induced RAW 264.7 cell and mice model. As a result, the production of nitric oxide (NO) and pro-inflammatory cytokines (IL-6, IL-$1{\beta}$, TNF-${\alpha}$) were inhibited with increasing concentration of ISEE without any cytotoxicity. Furthermore, ISEE suppressed the expression of not only inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-${\kappa}B$) p65, and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. In mice ear edema test, the formation of edema was reduced at the highest dosage of ISEE and the reduction of the number of infiltrated mast cells was observed in histological analysis. These results indicate that ISEE has a potent anti-inflammatory activity and can be used as a pharmaceutical material for many kinds of inflammatory disease.

• Journal of Life Science
• /
• v.30 no.2
• /
• pp.113-121
• /
• 2020

Macrophages are initiators for regulating a host's defenses to eliminate pathogens and trigger tissue repair. Macrophages are classified into two types: classically (M1) activated macrophages and alternatively (M2) activated macrophages. M1-phenotype macrophages directly or indirectly kill infectious organisms and tumor cells via pro-inflammatory responses, whereas M2-phenotype macrophages remodel wounded tissue through anti-inflammatory responses. In this paper, we investigated how Phellinus linteus hot water extract passed from Diaion HP-20 resin (PLEP) regulates polarization of M1-like or M2-like macrophages in human THP-1 cells. PLEP did not have cytotoxicity at a high concentration of 300 ㎍/ml. We observed morphological alteration of the THP-1 cells, which are stimulated by PLEP, LPS/INF-γ (M1 stimulators) or IL-4/IL13 (M2 stimulators). PLEP exposure induced morphology contiguous with LPS/INF-γ. qPCR was also performed to determine whether PLEP influences M1 or M2 polarization-related genes. M1-phenotype macrophage-specific genes, such as TNF-α, IL-1β, IL-6, IL-8, CXCL10 and CCR7, were enhanced by PLEP in a dose-dependent manner similar to LPS/INF-γ. Conversely, M2-phenotype-specific genes, such as MRC-1, DC-SIGN, CCL17 and CCL22, were suppressed by PLEP. PLEP also significantly up-regulated secretory inflammation cytokines related to M1 polarization of macrophages, including TNFα, IL-1β and IL-6, which was similar to the gene expression. Further, MAPK and NF-κB signaling were increased by treatment with PLEP, resulting in enhancement of cytokine secretion. PLEP might therefore be used as a promising booster of pro-inflammatory responses through M1 polarization of human THP-1 cells.