• Molecules and Cells
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• v.46 no.10
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• pp.627-636
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• 2023

Periodontal disease is a chronic inflammatory disease that leads to the gradual destruction of the supporting structures of the teeth including gums, periodontal ligaments, alveolar bone, and root cementum. Recently, interests in alleviating symptoms of periodontitis (PD) using natural compounds is increasing. Avenanthramide-C (Avn-C) is a polyphenol found only in oats. It is known to exhibit various biological properties. To date, the effect of Avn-C on PD pathogenesis has not been confirmed. Therefore, this study aimed to verify the protective effects of Avn-C on periodontal inflammation and subsequent alveolar bone erosion in vitro and in vivo. Upregulated expression of catabolic factors, such as matrix metalloproteinase 1 (MMP1), MMP3, interleukin (IL)-6, IL-8, and COX2 induced by lipopolysaccharide and proinflammatory cytokines, IL-1β, and tumor necrosis factor α (TNF-α), was dramatically decreased by Avn-C treatment in human gingival fibroblasts and periodontal ligament cells. Moreover, alveolar bone erosion in the ligature-induced PD mouse model was ameliorated by intra-gingival injection of Avn-C. Molecular mechanism studies revealed that the inhibitory effects of Avn-C on the upregulation of catabolic factors were mediated via ERK (extracellular signal-regulated kinase) and NF-κB pathway that was activated by IL-1β or p38 MAPK and JNK signaling that was activated by TNF-α, respectively. Based on this study, we recommend that Avn-C may be a new natural compound that can be applied to PD treatment.

• Journal of Sasang Constitutional Medicine
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• v.16 no.1
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• pp.130-147
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• 2004

To investigate the antioxidant capacity of traditional Korean herb medicines, water extracts from 42 species which has been used for the Taeum constitution of Sasang Medicine, were tested on their antioxidant activity using radical scavenging effects against ABTS. Some Of them showed strong antioxidant capacities at $50{\mu}g$ concentration. And, antioxidant capacities of 2 prescriptions extract of Sasang Medicine, Cheongsimyeonja-tang and Yeoldahanso-tang, in the different concentration ($10{\mu}g$, $50{\mu}g$, and $100{\mu}g$) were determined. At the same time, the antiperoxidation effects of these 2 prescriptions extract were determined. Lipid peroxidation in brain homogenates induced by NADPH and $ADF-Fe^{2+}$ was strongly inhibited by Cheongsimyeonja-tang in vitro. The above-mentioned 2 prescriptions are a potent antioxidant capacity and antiperoxidation activity, further investigation into the in vivo antioxidant therapeutic potential for treatment of human disorders in brain tissue.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.200-206
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• 2014

N-(p-Coumaryol) tryptamine (CT), a phenolic amide, has been reported to exhibit anti-oxidant and anti-inflammatory activities. However, the underlying mechanism by which CT exerts its pharmacological properties has not been clearly demonstrated. The objective of this study is to elucidate the anti-inflammatory mechanism of CT in lipopolysaccharide (LPS)-challenged RAW264.7 macrophage cells. CT significantly inhibited LPS-induced extracellular secretion of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$, and protein expressions of iNOS and COX-2. In addition, CT significantly suppressed LPS-induced secretion of pro-inflammatory cytokines such as TNF-${\alpha}$ and IL-$1{\beta}$. To elucidate the underlying anti-inflammatory mechanism of CT, involvement of MAPK and Akt signaling pathways was examined. CT significantly attenuated LPS-induced activation of JNK/c-Jun, but not ERK and p38, in a concentration-dependent manner. Interestingly, CT appeared to suppress LPS-induced Akt phosphorylation. However, JNK inhibition, but not Akt inhibition, resulted in the suppression of LPS-induced responses, suggesting that JNK/c-Jun signaling pathway significantly contributes to LPS-induced inflammatory responses and that LPS-induced Akt phosphorylation might be a compensatory response to a stress condition. Taken together, the present study clearly demonstrates CT exerts anti-inflammatory activity through the suppression of JNK/c-Jun signaling pathway in LPS-challenged RAW264.7 macrophage cells.

• Herbal Formula Science
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• v.32 no.3
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• pp.297-310
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• 2024

Objective : This study was conducted to investigate the anti-inflammatory and laxative effects of Polycan in TNF-α-treated HT-29 intestinal epithelial cells and loperamide-induced constipation in vivo models, respectively. Methods : To evaluate the anti-inflammatory effects of Polycan, HT-29 cells were treated with TNF-α in the presence or absence of Polycan. IL-8 production was measured by enzyme-linked immunosorbent assay (ELISA). MAPK phosphorylation, nuclear translocation of NF-κB, and phosphorylation of IκB were assessed by Western blot analysis. To investigate the laxative effects of Polycan, 6-week-old SD rats (8 female rats per group) were orally administered Polycan or Chicory Fiber as a positive control for 4 weeks, and constipation was induced with loperamide treatment for 10 days before sacrifice. One day before sacrifice, a charcoal meal was administered to evaluate intestinal transit times. The periodically collected feces were used to assess the number of fecal pellets and fecal water content. Results : Polycan inhibited TNF-α-induced IL-8 expression in dose-dependent manner. Furthermore, Polycan suppressed TNF-α-induced phosphorylation of MAPKs (ERK1/2, p38 and JNK), degradation of Iκ-Bα and nuclear translocation of NF-κB. In an in vivo constipation model, the number of fecal pellets per food intake was significantly increased in rats administered with Polycan, both 1 day and 7 days after loperamide treatment. The water content of fecal pellets was restored in the Polycan groups starting 7 days after loperamide treatment. In addition, Polycan intake significantly enhanced the gastrointestinal transit ratio of a charcoal meal but reduced the number of intestinal fecal pellets. Conclusions : These results suggest that Polycan suppressed TNF-α-induced inflammation by blocking both the MAPK and NF-κB pathways in HT-29 cells. Additionally, in a loperamide-induced constipation model, Polycan showed clear laxative effects by increasing the number of fecal pellets, fecal water content, and intestinal transit ratio of a charcoal meal.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.99-107
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• 2016

Triclosan is an antimicrobial or sanitizing agent used in personal care and household products such as toothpaste, soaps, mouthwashes and kitchen utensils. There are increasing evidence of the potentially harmful effects of triclosan in many systemic and cellular processes of the body. In this study, we investigated the effects of triclosan in the survivability of cultured rat neural stem cells (NSCs). Cortical cells from embryonic day 14 rat embryos were isolated and cultured in vitro. After stabilizing the culture, triclosan was introduced to the cells with concentrations ranging from $1{\mu}M$ to $50{\mu}M$ and in varied time periods. Thereafter, cell viability parameters were measured using MTT assay and PI staining. TCS decreased the cell viability of treated NSC in a concentration-dependent manner along with increased expressions of apoptotic markers, cleaved caspase-3 and Bax, while reduced expression of Bcl2. To explore the mechanisms underlying the effects of TCS in NSC, we measured the activation of MAPKs and intracellular ROS. TCS at $50{\mu}M$ induced the activations of both p38 and JNK, which may adversely affect cell survival. In contrast, the activities of ERK, Akt and PI3K, which are positively correlated with cell survival, were inhibited. Moreover, TCS at this concentration augmented the ROS generation in treated NSC and depleted the glutathione activity. Taken together, these results suggest that TCS can induce neurodegenerative effects in developing rat brains through mechanisms involving ROS activation and apoptosis initiation.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.4
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• pp.36-48
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• 2008

Purpose: The purpose of this study is to investigate anti-inflammatory effect and immune responses of aqueous extract from Fructus Chaenomelis (FC). Methods: We studied anti-inflammatory effect by means of examining the production of NO(nitric oxide) and expressions of pro-inflammatory cytokine (TNF-$\alpha$(tumor necrosis factor-alpha), IL(Interleukin)-6, IL-12) in the LPS-induced peritoneal macrophages of mice. Also, The western blot analysis has been done to look into the mechanism of anti-inflammatory effect. Results: 1. The FC extract did not have any cytotoxicity in the peritoneal macrophages. 2. The FC extract inhibits the productions of NO, IL-6. IL-12 in the LPS-stimulated peritoneal macrophages of mice, but not of TNF-$\alpha$. 3. The FC extract inhibits the activation of NF-${\kappa}B$(nuclear factor-kappa B) by keeping $I{\kappa}B-\alpha$(inhibitory kappa B-alpha) from degradating, but not of MAPKs(mitogen-activated protein kinases) such as ERK(extracelluar signa 1-regulated kinase), JNK(c-Jun N-terminal kinase), p38. Conclusion: These results show that FC extract inhibits the production of pro-inflammatory cytokines such as IL-6. IL-12. NO by inhibiting NF-${\kappa}B$ activation in the peritoneal macrophages of mice. In conclusion, this experiment suggests that FC extract may be effective for the treatment of acute and chronic inflammation including genitourinary infection.

• Journal of Web Engineering
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• v.14 no.19
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• pp.4103-4118
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• 2022

The physiological or dietary advantages of germinated grains have been the subject of numerous discussions over the past decade. Around 23 million tons of oats are consumed globally, making up a sizeable portion of the global grain market. Oat seedlings contain more protein, beta-glucan, free amino acids, and phenolic compounds than seeds. The progressive neurodegenerative disorder of Alzheimer's is accompanied by worsening memory and cognitive function. A key indicator of this disorder is the unusual buildup of amyloid-beta protein (or Aβ) in human brains. In this context, oat seedling extract (OSE) has been identified as a new therapeutic candidate for AD, due to its antioxidant activity and AD-specific mechanism of action. This study directly investigated how OSE affected AD and its impacts by examining the cognitive function and exploring the inflammatory response mechanism. The dried oat seedlings were grounded finely with a grinder, inserted with 50% fermented ethanol 10 times (w/v), and extracted by stirring for 10 h at 45 ℃. After filtering the extract by 0.22 um filter, some of it was used for UHPLC analysis. The results indicated that the treatment with OSE protects against Aβ25-35-induced cytotoxicity in BV2 cells. Tg-5Xfad AD mice had strong deposition of Aβ throughout their brains, while WT mice did not exhibit any such deposition within their brains. A drastic reduction was observed in terms of numbers, as well as the size, of Aβ plaques within Tg-5Xfad AD mice exposed to OSE. This study indicated OSE's neuroprotective impacts against neurodegeneration, synaptic dysfunction, and neuroinflammation induced by amyloid-beta. Our results suggest that OSE acts as a neuroprotective agent to combat AD-specific apoptotic cell death, neuroinflammation, amyloid-beta accumulation, as well as synaptic dysfunction in AD mice's brains. Furthermore, the study indicated that OSE treatment affects JNK/ERK/p38 MAPK signaling, with considerable inhibition in p-JNK, p-p38, and p-ERK levels seen in the brain of OSE-treated Tg-5Xfad AD mice.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.3
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• pp.14-25
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• 2010

Purpose: The purpose of this study is to investigate inhibitory effect on the maturation of dendritic cells from aqueous extract from Nardostachys Jatamansi(NJ). Methods: I examined the phenotypic maturation(class II MHC, CD40, CD86), expression of pro-inflammatory cytokine(TNF-$\alpha$, IL-6, IL-12) and endocytosis of FITC-Dextran in the LPS-induced bone marrow-derived dendritic cells(BMDCs) of mice. Furthermore, the Western-blot analysis reveals the mechanism of inhibitory effect. Results: 1. The NJ extract inhibited the phenotypic maturation of BMDCs in a dose-dependent manner. 2. The NJ extract inhibited the LPS induced cytokine production of BMDCs in a dose-dependent manner. 3. The NJ extract enhanced the endocytosis of Dex-FITC in LPS treated DC. 4. The NJ extract inhibited the activation of JNK and p38 phosphorylation, but not ERK phosphorylation of MAPK family and doesn't inhibit Ik-Ba degradation in LPS-stimulated BMDCs. Conclusion: These results suggest that NJ extract is able to attenuate the inflammation and maturation in BMDCs and may inhibit proliferation of T cells. In conclusion, this experiment suggests that NJ extract may be useful in hypersensitivity disease including autoimmune disease.

• IMMUNE NETWORK
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• v.16 no.4
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• pp.242-248
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• 2016

Thymic atrophy is a complication that results from exposure to many environmental stressors, disease treatments, and microbial challenges. Such acute stress-associated thymic loss can have a dramatic impact on the host's ability to replenish the necessary naïve T cell output to reconstitute the peripheral T cell numbers and repertoire to respond to new antigenic challenges. We have previously reported that treatment with the orexigenic hormone ghrelin results in an increase in the number and proliferation of thymocytes after dexamethasone challenge, suggesting a role for ghrelin in restraint stress-induced thymic involution and cell apoptosis and its potential use as a thymostimulatory agent. In an effort to understand how ghrelin suppresses thymic T cell apoptosis, we have examined the various signaling pathways induced by receptor-specific ghrelin stimulation using a restraint stress mouse model. In this model, stress-induced apoptosis in thymocytes was effectively blocked by ghrelin. Western blot analysis demonstrated that ghrelin prevents the cleavage of pro-apoptotic proteins such as Bim, Caspase-3, and PARP. In addition, ghrelin stimulation activates the Akt and Mitogen-activated protein kinases (MAPK) signaling pathways in a time/dose-dependent manner. Moreover, we also revealed the involvement of the FoxO3a pathway in the phosphorylation of Akt and ERK1/2. Together, these findings suggest that ghrelin inhibits apoptosis by modulating the stress-induced apoptotic signal pathway in the restraint-induced thymic apoptosis.

• Molecules and Cells
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• v.21 no.1
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• pp.42-51
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• 2006

We investigated the mechanism of contraction induced by S1P in esophageal smooth muscle cells. Western blot analysis demonstrated that $S1P_1$, $S1P_2$, $S1P_3$, and $S1P_5$ receptors existed in the cat esophagus. Only penetration of EDG-5 ($S1P_2$) antibody into permeabilized cells inhibited S1P-induced contraction. Pertussis toxin (PTX) also inhibited contraction, suggesting that it was mediated by $S1P_2$ receptors coupled to a PTXsensitive $G_i$ protein. Specific antibodies to $G_{i2}$, $G_q$ and $G_{\beta}$ inhibited contraction, implying that the S1P-induced contraction depends on PTX-insensitive $G_q$ and $G_{\beta}$ dimers as well as the PTX-sensitive $G_{i2}$. Contraction was not affected by the phospholipase $A_2$ inhibitor DEDA, or the PLD inhibitor ${\rho}$-chloromercuribenzoate, but it was abolished by the PLC inhibitor U73122. Incubation of permeabilized cells with $PLC{\beta}3$ antibody also inhibited contraction. Contraction involved the activation of a PKC pathway since it was affected by GF109203X and chelerythrine. Since $PKC{\varepsilon}$ antibody inhibited contraction, $PKC{\varepsilon}$ may be required. Preincubation of the muscle cells with the MEK inhibitor PD98059 blocked S1P-induced contraction, but the p38 MAP kinase inhibitor SB202190 did not. In addition, co-treatment of cells with GF 109203X and PD98059 did not have a synergistic effect, suggesting that these two kinases are involved in the same signaling pathway. Our data suggest that S1P-induced contraction in esophageal smooth muscle cells is mediated by $S1P_2$ receptors coupled to PTX-sensitive $G_{i2}$ proteins, and PTX-insensitive $G_q$ and $G_{\beta}$ proteins, and that the resulting activation of the $PLC{\beta}3$ and $PKC{\varepsilon}$ pathway leads to activation of a p44/p42 MAPK pathway.