• Animal cells and systems
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• v.14 no.4
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• pp.283-289
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• 2010

Ssanghwa-tang (SHT) is a traditional Korean herbal medicine widely prescribed to decrease fatigue following an illness. The purpose of this study was to investigate the effects of SHT on osteoclast differentiation in vitro, and on bone loss in ovariectomized (OVX) rats in vivo. SHT significantly reduced the receptor activator for the nuclear factor ${\kappa}B$ (NF-${\kappa}B$) ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP) activity, and multinucleated osteoclast formation in RAW264.7 cells without affecting cell viability. In addition, SHT significantly attenuated RANKL-induced mRNA expression levels of c-Src and cathepsin K. To examine the in vivo effect of SHT on OVX-induced bone loss in OVX rats, we administered SHT (0.6 g/kg BID) orally to OVX rats for 12 weeks. SHT administration significantly blocked OVX-induced decrease of femoral bone mineral density (BMD) and femoral trabeculae in OVX rats. In conclusion, these results suggest that SHT treatment effectively prevents OVX-induced bone loss, and this effect may result from its inhibitory effect on osteoclast differentiation.

• Korean Journal of Oriental Medicine
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• v.16 no.1
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• pp.149-155
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• 2010

Objective : Ssangwha-tang is a traditional medicine formula widely prescribed for a decrease of fatigue after an illness in Korea. The aim of this study is to investigate the effect of Ssangwha-tang fermented by Lactobacillus fermentum (SF) on osteoclast differentiation in vitro and on bone metabolism of an ovariectomized rat in vivo. Methods : Tartrate-resistant acid phosphatase activity and staining were applied to evaluate the formation of osteoclasts. Ovariectomized rats were orally administrated with SF (30 ml/kg/day) for 12 weeks. Serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglyceride, phosphate, calcium levels were determined. Effect of SF on bone loss were studied by histological analysis and the measurement of bone mineral density. Results : SF significantly inhibited tartrate-resistant acid phosphatase activity and formation of osteoclasts in RAW264.7 cells stimulated by receptor activator for nuclear factor ${\kappa}B$ (NF-${\kappa}B$) ligand (RANKL). In addition, SF significantly decreased the level of triglyceride and increased the level of low-density lipoprotein. Moreover, the decrease of trabeculae of the femur was partially prevented in ovariectomized rats administrated with SF. Conclusions : SF treatment could prevent ovariectomy induced bone loss and its effects could be medicated by the inhibition of osteoclastogenesis.

• Toxicological Research
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• v.33 no.4
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• pp.325-332
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• 2017

3-Bromo-4,5-dihydroxybenzaldehyde (BDB) is a natural bromophenol compound that is most commonly isolated from red algae. The present study was designed to investigate the anti-inflammatory properties of BDB on atopic dermatitis (AD) in mice induced by 2,4-dinitrochlorobenzene (DNCB) and on lipopolysaccharide (LPS)-stimulated murine macrophages. BDB treatment (100 mg/kg) resulted in suppression of the development of AD symptoms compared with the control treatment (induction-only), as demonstrated by reduced immunoglobulin E levels in serum, smaller lymph nodes with reduced thickness and length, a decrease in ear edema, and reduced levels of inflammatory cell infiltration in the ears. In RAW 264.7 murine macrophages, BDB (12.5, 25, 50, and $100{\mu}M$) suppressed the production of interleukin-6, a proinflammatory cytokine, in a dose-dependent manner. BDB also had an inhibitory effect on the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) and signal transducer and activator of transcription 1 (STAT1; Tyr 701), two major signaling molecules involved in cellular inflammation. Taken together, the results show that BDB treatment alleviates inflammatory responses in an atopic dermatitis mouse model and RAW 264.7 macrophages. These results suggest that BDB may be a useful therapeutic strategy for treating conditions involving allergic inflammation such as atopic dermatitis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.6
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• pp.396-402
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• 2018

Hataedock (HTD) treatment is a traditional preventive therapy for the fetal toxicosis- the acute allergic disease after childbirth, mainly manifested by a variety of skin allergies such as scab, phlegm. The aim of this study was to investigate the efficacy of HTD treatments for the alleviation of inflammation in Dermatophagoides farinae-induced obese NC/Nga mice. 20 mg/kg of Coptidis Rhizoma, Glycyrrhizae Radix (CRGR) extracts as a remedy of HTD treatments were orally administered to NC/Nga mice. We induced obesity in the mice by high-fat diet. To induce skin allergies, the extracts of Dermatophagoides farinae were topically applied on the NC/Nga mice at 4th-6th and 8th-10th weeks. Structural and molecular changes in the skin tissues were measured by immunohistochemical staining. HTD treatment decreased the atopic dermatitis (AD)-like symptoms including hemorrhage, erythema, erosion, edema, and dryness. HTD treatment suppressed the mast cell activation confirmed by reduction of $Fc{\varepsilon}RI$, substance P, and serotonin. The expression of several inflammatory mediators including nuclear factor-kappa B ($NF-{\kappa}B$) p65, inducible nitric oxide synthase (iNOS), vascular endothelial growth factors (VEGFs) was also decreased by HTD treatment. HTD treatment suppressed the allergic, inflammatory responses in the skin tissues of the NC/Nga mice by reducing mast cells and down-regulating several inflammatory mediators.

• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.85-92
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• 2020

One of the omega-3 essential fatty acids, docosahexaenoic acid (DHA), is a significant constituent of the cell membrane and the precursor of several potent lipid mediators. These mediators are considered to be important in preventing or treating several diseases. Resolvin D5, an oxidized lipid mediator derived from DHA, has been known to exert anti-inflammatory effects. However, the detailed mechanism underlying these effects has not yet been elucidated in human monocytic THP-1 cells. In the present study, we investigated the effects of resolvin D5 on inflammation-related signaling pathways, including the extracellular signal-regulated kinase (ERK)-nuclear factor (NF)-κB signaling pathway. Resolvin D5 downregulated the production of interleukin (IL)-6 and chemokine (C-C motif) ligand 5 (CCL5). Additionally, these inhibitory effects were found to be modulated by mitogen-activated protein kinase (MAPK) and NF-κB in lipopolysaccharide (LPS)-treated THP-1 cells. Resolvin D5 inhibited the LPS-stimulated phosphorylation of ERK and translocation of p65 and p50 into the nucleus, resulting in the inhibition of IL-6 and CCL5 production. These results revealed that resolvin D5 exerts anti-inflammatory effects in LPS-treated THP-1 cells by regulating the phosphorylation of ERK and nuclear translocation of NF-κB.

• The Journal of Internal Korean Medicine
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• v.44 no.6
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• pp.1243-1255
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• 2023

Objective: This study aims to explore the pharmacological effects and mechanisms of enzyme (Viscozyme)-treated garlic extract (EG) in an animal model of acute enteritis induced by lipopolysaccharide (LPS). Methods: The experiment included four subgroups: normal, control, EG200 (treated with 200 mg/kg EG), and EG400 (treated with 400 mg/kg EG). Drug administration lasted 3 days, followed by the induction of acute enteritis in all groups (except normal) through the intraperitoneal administration of 20 mg/kg of LPS 1 h after the last oral dose. Autopsy was conducted 24 h later to collect serum and colon tissue. Serum was analyzed for reactive oxygen species (ROS) and C-reactive protein (CRP), while Western blotting was performed on the colon tissue. Results: After analyzing the ROS and CRP levels in serum, the EG treatment group exhibited a significant decrease compared with the control group. The EG treatment group exhibited a significant decrease in the activation of the mitogen-activated protein kinases (MAPKs)/nuclear factor-kappa B p65 (NF-κB) pathway compared with the control group. EG administration significantly regulated apoptosis-related factors, including B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X, cysteine aspartyl-specific protease-3, and cytochrome C. Conclusions: EG treatment in mice with LPS-induced acute colitis reduced the ROS and CRP levels, suppressed the MAPKs/NF-κB pathway in the colon, and effectively alleviated acute enteritis by modulating apoptosis-related factors. Based on these findings, EG emerges as a promising candidate for the prevention and treatment of acute colitis, showing its potential therapeutic efficacy in this experimental model.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.3
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• pp.239-247
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• 2018

Chronic inflammation is known to have effects on various diseases such as gout, cancer, dementia, atopic disease, and obesity. In addition, since some signal cascades involved in the development of inflammation are known to affect the damage and aging of the skin tissue, studies are being conducted actively to control the inflammation mechanism. In order to mitigate or prevent inflammatory response, a number of researches have been made to develop anti-inflammatory materials from some plants. In particular, Stevia rebaudiana produces steviol glycosides (SG), a natural sweetener with a distinctive flavor. Studies on some of SG have been shown to have anti-inflammatory activity. Researchers of this study expected that more SG also possess anti-inflammatory activity, besides stevioside, rebaudioside A, and steviol. In order to confirm this possibility, the researchers screened inhibition activity of various steviol glucosides for NO production in RAW 264.7 cell lines. As a result, steviol ${\beta}-glucopyranosyl$ ester (SGE) showed the highest inhibitory activity among steviol derivatives treated at the same molar concentration. In addition, we found that mRNA expression level of $interleukin-1{\alpha}$ ($IL-1{\alpha}$), $interleukin-1{\beta}$ ($IL-1{\beta}$), cyclooxygenase-2 (COX-2), nuclear factor kappa-light chain-enhancer of activated B cells ($NF-{\kappa}B$) and inducible nitric oxide synthase (iNOS) was also decreased in a dose-dependent manner. These results show that SGE inhibits anti-inflammatory activity and NO production in mouse macrophage RAW 264.7 cells. It was confirmed that SGE has potential to be applied as an anti-inflammatory material.

• Journal of Life Science
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• v.29 no.8
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• pp.854-860
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• 2019

This study investigated the optimum pH conditions for efficient extraction of protein from defatted Tenebrio molitor (TM) larvae. We examined the anti-inflammatory effect of protein derived from defatted TM larvae obtained by an alkaline extraction method. Six extraction pH values (7, 8, 9, 10, 11, and 12) and three precipitation pH values (2, 4, and 6) were used. The protein content, browning degree, and recovery yield of the protein obtained under each pH condition were determined. For efficient extraction of protein from defatted TM larvae, a combination of an extraction pH of 9 and precipitation pH of 4 resulted in a 32.4% recovery yield based on the extraction value and degree of browning. To determine whether the protein ameliorated inflammation by inhibition of macrophage activation by lipopolysaccharides (LPS), we measured nitric oxide (NO), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated raw 264.7 macrophage cells. The protein markedly inhibited the production of NO without cytotoxicity and reduced the expression level of COX-2 and iNOS protein through the regulation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B ($NF-{\kappa}B$) signaling. These results suggested that protein derived from TM larvae could have potential applications in anti-inflammatory therapeutic agents and protein supplements.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.9
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• pp.1507-1519
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• 2020

Objective: The current research was aimed to profile the transcriptomic picture of the peripheral blood lymphocytes (PBLs) associated with immunity in Chinese Holsteins supplemented orally with coated folic acid during the periparturient period. Methods: The total of 123 perinatal cows were selected for this study and divided into three groups; group A (n = 41, 240 mg/500 kg cow/d), group B (n = 40, 120 mg/500 kg cow/d) and group C (n = 42, 0 mg/cow/d) based on the quantity of folic acid fed. Three samples of PBLs were selected from each folic acid treated group (high, low, and control) and RNA sequencing method was carried out for transcriptomic analysis. Results: The analysis revealed that a higher number of genes and pathways were regulated in response to high and low folic acid supplementation compared to the controls. We reported the novel pathways tumor necrosis factor (TNF) signaling, antigen processing and presentation, Staphylococcus aureus infection and nuclear factor (NF)-kappa B signaling pathways) and the key genes (e.g. C-X-C motif chemokine ligand 10, TNF receptor superfamily member 1A, cluster difference 4, major histocompatibility complex, class II, DQ beta, NF-kappa-B inhibitor alpha, and TNF superfamily 13) having great importance in immunity and anti-inflammation in the periparturient cows in response to coated folic acid treatment. Conclusion: Collectively, our study profiled first-time transcriptomic analysis of bovine lymphocytes and compared the involved cytokines, genes, and pathways between high vs control and low vs control. Our data suggest that the low folic acid supplementation (120 mg/500 kg) could be a good choice to boost appropriate immunity and anti-inflammation as well as might being applied to the health improvement of perinatal dairy cows.

• Nutrition Research and Practice
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• v.16 no.6
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• pp.729-744
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• 2022

BACKGROUND/OBJECTIVES: 4-Hydroxy-2-nonenal (HNE) is a biomarker for oxidative stress to induce inflammation. Methionine is an essential sulfur-containing amino acid with antioxidative activity. On the other hand, the evidence on whether and how methionine can depress HNE-derived inflammation is lacking. In particular, the link between the regulation of the nuclear factor-κB (NF-κB) signaling pathway and methionine intake is unclear. This study examined the link between depression from HNE accumulation and the anti-inflammatory function of ⳑ-methionine in rats. MATERIALS/METHODS: Male Wistar rats (3-week-old, weighing 70-80 g) were administered different levels of ⳑ-methionine orally at 215.0, 268.8, 322.5, and 430.0 mg/kg body weight for two weeks. The control group was fed commercial pellets. The hepatic HNE contents and the protein expression and mRNA levels of the inflammatory mediators were measured. The interleukin-10 (IL-10) and glutathione S-transferase (GST) levels were also estimated. RESULTS: Compared to the control group, hepatic HNE levels were reduced significantly in all groups fed ⳑ-methionine, which were attributed to the stimulation of GST by ⳑ-methionine. With decreasing HNE levels, ⳑ-methionine inhibited the activation of NF-κB by up-regulating inhibitory κBα and depressing phosphoinositide 3 kinase/protein kinase B. The mRNA levels of the inflammatory mediators (cyclooxygenase-2, interleukin-1β, interleukin-6, inducible nitric oxide synthase, tumor necrotic factor alpha) were decreased significantly by ⳑ-methionine. In contrast, the protein expression of these inflammatory mediators was effectively down regulated by ⳑ-methionine. The anti-inflammatory action of ⳑ-methionine was also reflected by the up-regulation of IL-10. CONCLUSIONS: This study revealed a link between the inhibition of HNE accumulation and the depression of inflammation in growing rats, which was attributed to ⳑ-methionine availability. The anti-inflammatory mechanism exerted by ⳑ-methionine was to inhibit NF-κB activation and to up-regulate GST.