• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.10
• /
• pp.4277-4283
• /
• 2015

Anthocyanin, a phenolic compound, has been reported to have an anti-inflammatory effect against lipopolysaccharide (LPS) induced changes in immune cells. However, little is known about the molecular mechanisms underlying its anti-inflammatory effects. Few research studies have concerned the anti-inflammation properties of colored rice extract as a functional material. Therefore, the purpose of this study was to examine anti-inflammatory effects of the polar fraction of black rice whole grain extracts (BR-WG-P) that features a high anthocyanin content. Our results showed that BR-WG-P significantly inhibited LPS-induced pro-inflammatory mediators, including production of NO and expression of iNOS and COX-2. In addition, secretion of pro-inflammatory cytokines including TNF-${\alpha}$ and IL-6 was also significantly inhibited. Moreover, BR-WG-P and anthocyanin inhibited NF-kB and AP-1 translocation into the nucleus. BR-WG-P also decreased the phosphorylation of ERK, p38 and JNK in a dose dependent manner. These results suggested that BR-WG-P might suppress LPS-induced inflammation via the inhibition of the MAPK signaling pathway leading to decrease of NF-kB and AP-1 translocation. All of these results indicate that BR-WG-P exhibits therapeutic potential associated with the anthocyanin content in the extract for treating inflammatory diseases associated with cancer.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.19 no.6
• /
• pp.1568-1572
• /
• 2005

Polycyclic aromatic hydrocarbon (PAH), such as benzo(a)pyrene (B(a)P), are toxic environmental contaminants known to enhance oxidative stress, production of pro-inflammatory and inflammatory cytokines. The present study was designed in order to determine whether wild ginseng (Panax ginseng C. A. Meyer) protect PAH-induced oxidative stress and inflammation. B(a)P (0.5 mg/kg, i.p.) treatment increased the distribution of immunoreactive cells for tumor necrosis factor $(TNF)-\alpha$ and cyclooxygenase (COX)-2 in peri-portal triad region and immunoreaction was shown in the cytoplasm of macrophage. Pre-treatment with wild ginseng significantly decreased immune responses in the rats treated with B(a)p. The rats given 50 mg/kg/day for 4 weeks before B(a)P treatment had 1.39-fold and 1.5-fold inhibition of $TNF-\alpha$ and COX-2 positive reaction, respectively. Wild ginseng extract alone had no effect on the distributional changes. The SOD activity as scavenger enzymes after wild ginseng administration dose-dependantly increased compared with butylated hydroxytoluene, a general radical scavenger. These data likely indicate that wild ginseng extract may act as inflammatory regulator in conjunction with inhibition of oxidant dependent metabolic activation in environmental contaminants-induced hepatic inflammation.

• Journal of Oriental Neuropsychiatry
• /
• v.25 no.4
• /
• pp.423-434
• /
• 2014

Objectives: Activated microglia cells play an important role in inflammatory responses in the central nervous system (CNS) which are involved in neurodegenerative diseases. We attempted to determine the anti-inflammatory effects of Cheongnoimyungshin-hwan (CNMSH) in microglia cells. Methods: We examined the effect of CNMSH on the inflammatory responses in BV2 microglia cells induced by lipopolysaccharide (LPS) and explored the mechanism underlying the action of CNMSH. Results: BV2 cells treated with LPS showed an up-regulation of nitric oxide (NO), prostaglandin $PGE_2(PGE_2)$ and interleukin $1{\beta}(IL-1{\beta})$ release, whereas CNMSH suppressed this up-regulation. CNMSH inhibited the induction of COX-2, iNOS and $IL-1{\beta}$ proteins in LPS-treated BV2 cells and blocked the LPS-induced phosphorylation and nuclear translocation of nuclear factor ${\kappa}B(NF-{\kappa}B$). Furthermore, CNMSH attenuated the LPS-induced phosphorylation of extracellular signal-regulated kinase and p38 mitogen activated protein kinase (MAPK), as well as the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, but did not inhibit the LPS-induced phosphorylation of c-Jun amino terminal kinase. Conclusions: These results suggest that the inhibitory effect of CNMSH on the LPS-induced production of inflammatory mediators and cytokines in BV2 cells is associated with the suppression of the $NF-{\kappa}B$ and PI3KAkt signaling pathways.

• BMB Reports
• /
• v.47 no.11
• /
• pp.649-654
• /
• 2014

Neutrophils play an important role in the initiation of innate immunity against infection and injury. Although many different types of G-protein coupled receptors are functionally expressed in neutrophils, no reports have demonstrated functional expression of umami taste receptor in these cells. We observed that mouse neutrophils express the umami taste receptor T1R1/T1R3 through RNA sequencing and quantitative RT-PCR analysis. Stimulation of mouse neutrophils with L-alanine or L-serine, which are ligands for the umami taste receptor, elicited not only ERK or p38 MAPK phosphorylation but also chemotactic migration. Moreover, addition of L-alanine or L-serine markedly reduced the production of several cytokines including $TNF-{\alpha}$ induced by lipopoly-saccharide (LPS) through inhibition of $NF-{\kappa}B$ activity or STAT3 phosphorylation in neutrophils. Our findings demonstrate that neutrophils express the umami taste receptor, through which tastants stimulate neutrophils, resulting in chemotactic migration, and attenuation of LPS-induced inflammatory response.

• The Journal of Korean Medicine
• /
• v.28 no.4
• /
• pp.27-41
• /
• 2007

Aim : This study aimed at elucidating the effects of Inonotus obliquus on anti-tumor effects in vivo and immune-based characterization of the mushroom as a potential candidate for cancer remedy. Methods : To investigate the immunomodulatory effects of Inonotus obliquus, we investigated macrophage functions and NK cell activities through the measurement of NO production of macrophage, NK cell cytotoxicity and expressions of cytokines and genes regulating immune responses, in addition to pulmonary metastasis model in vivo. Results : Inonotus obliquus showed general cytotoxicity at high concentrations over the 100 ${\mu}g/m{\ell}$ on the both of normal and cancer cell lines. Inonotus obliquus showed both inhibitory and promotive effects on pulmonary colonization of CT-26 cell depending on period or route of administration in vivo. Conclusion : From these results, it cannot be concluded that Inonotus obliquus has cancer-specific activity. Furthermore, Inonotus obliquus has the provability to show adverse effects differently according to the concentration and the method of administration.

• Journal of Life Science
• /
• v.29 no.3
• /
• pp.325-331
• /
• 2019

Lettuce (Lactuca sativa L.) is one of the most popular green leafy vegetables, and it contains various beneficial components including polyphenolic compounds and has been known to possess various biological functions such as anti-microbial, anti-oxidative, and anti-inflammatory activities. In the present study, we prepared ethanol extract of dried lettuce (DLE) and investigated its anti-inflammatory activity. To evaluate the anti-inflammatory activity of DLE, nitric oxide (NO) production was measured in LPS-activated mouse macrophage RAW 264.7 cells. DLE significantly suppressed NO production in these cells without affecting cell viabilities while resveratrol was used as a positive control. DLE dramatically decreased the expression of pro-inflammatory genes such as iNOS and COX-2 at the mRNA and protein levels and reduced the expression of several cytokines including $IL-1{\alpha}$, $IL-1{\beta}$, IL-1F6, $TNF-{\alpha}$, CSF2 and CXCL10. In addition, DLE suppressed phosphorylation of MAPKs and the nuclear translocation of $NF-{\kappa}B$ p65 indicating DLE shows its anti-inflammatory activity via regulating MAPKs pathway and $NF-{\kappa}B$ pathways. And also, DLE reduced the production of reactive oxygen species in a dose-dependent manner. DLE increased HO-1 protein expression, and also increased the nuclear translocation of Nrf2. Overall, our results suggest that lettuce down-regulate various pro-inflammatory genes and have its anti-inflammatory activity via regulating MAPKs, $NF-{\kappa}B$, and Nrf2/HO-1 pathways.

• Archives of Pharmacal Research
• /
• v.27 no.9
• /
• pp.954-960
• /
• 2004

Expression of the NF-$textsc{k}$B-dependent genes responsible for inflammation, such as TNF-$\alpha$, IL-1$\beta$, and nitric oxide synthase (NOS), contributes to chronic inflammation which is a major cause of neurodegenerative diseases (i.e. Alzheimer＇s disease). Although NF-$textsc{k}$B plays a biphasic role in different cells like neurons and microglia, controlling the activation of NF-$textsc{k}$B is important for its negative feedback in either activation or inactivation. In this study, we found that ursodeoxycholic acid (UDCA) inhibited I$textsc{k}$B$\alpha$ degradation to block expression of the NF-$textsc{k}$B-dependent genes in microglia when activated by $\beta$-amyloid peptide (A$\beta$). We also showed that when microglia is activated by $A\beta$42, the expression of A20 is suppressed. These findings place A20 in the category of ' protective ' genes, protecting cells from pro-inflammatory reper-toires induced in response to inflammatory stimuli in activated microglia via NF-$textsc{k}$B activation. In light of the gene and proteins for NF-$textsc{k}$B-dependent gene and inactivator for NF-$textsc{k}$B (I$textsc{k}$B$\alpha$), the observations now reported suggest that UDCA plays a role in supporting the attenuation of the production of pro-inflammatory cytokines and NO via inactivation of NF-$textsc{k}$B. Moreover, an NF-$textsc{k}$B inhibitor such as A20 can collaborate and at least enhance the anti-inflammatory effect in microglia, thus giving a potent benefit for the treatment of neurodegenerative diseases such as AD.uch as AD.

• Toxicological Research
• /
• v.28 no.4
• /
• pp.255-262
• /
• 2012

Inflammation is the immune system's response to infection and injury-related disorders, and is related to pro-inflammatory factors (NO, $PGE_2$, cytokines, etc.) produced by inflammatory cells. Atopic dermatitis (AD) is a representative inflammatory skin disease that is characterized by increasing serum levels of inflammatory chemokines, including macrophage-derived chemokine (MDC). Carpinus tschonoskii is a member of the genus Carpinus. We investigated the anti-inflammatory activity of C. tschonoskii by studying the effects of various solvent fractions prepared from its leaves on inflammatory mediators in HaCaT and RAW264.7 cells. We found that the chloroform fraction of C. tschonoskii inhibited MDC at both the protein and mRNA levels in HaCaT cells, acting via the inhibition of STAT1 in the IFN-${\gamma}$ signaling pathway. In addition, the chloroform fraction significantly suppressed the expression of inflammatory factors induced by lipopolysaccharide stimulation, except COX-2 and TNF-${\alpha}$. These results suggest that the chloroform fraction of C. tschonoskii leaves may include a component with potential anti-inflammatory activity.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.41 no.10
• /
• pp.1371-1377
• /
• 2012

Biological activities of Korean Panax ginseng 55% ethanol extract (KPGE) were investigated. The measured total polyphenol content of KPGE was 357.45 mg/100 g. KPGE showed the highest ${\alpha},{\alpha}$-diphenyl-${\beta}$-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS) radical scavenging activities of 80% and 86% at 1,000 ${\mu}g/mL$, respectively. DPPH and ABTS radical scavenging activities significantly increased in a KPGE concentration-dependent manner. SOD-like activity of KPGE (1, 10, and 100 ${\mu}g/mL$) increased from 22% up to 33% at KPGE concentrations of 500 and 1,000 ${\mu}g/mL$. KPGE treatment significantly suppressed the generation of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and cytokines (tumor necrosis factor-alpha: TNF-${\alpha}$, interleukin-6: IL-6, interleukin-$1{\beta}$: IL-$1{\beta}$), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. KPGE demonstrated strong anti-inflammatory activity that reduced NO and $PGE_2$ production in LPS-stimulated RAW 264.7 cells. Even low concentrations of KPGE (1 and 10 ${\mu}g/mL$) reduced $PGE_2$ and NO production in RAW 264.7 macrophages without LPS-stimulation, respectively. At concentrations of 100, 500, and 1,000 ${\mu}g/mL$, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 production were significantly suppressed. The results of our study suggest the potential of Korean Panax ginseng as an excellent antioxidant substance for inhibiting inflammatory mediators. Therefore, Korean Panax ginseng (KPGE) may be used as a therapeutic approach to various inflammatory diseases.

• Biomolecules & Therapeutics
• /
• v.22 no.1
• /
• pp.10-16
• /
• 2014

Derivatives of caffeic acid have been reported to possess diverse pharmacological properties such as anti-inflammatory, anti-tumor, and neuroprotective effects. However, the biological activity of methyl p-hydroxycinnamate, an ester derivative of caffeic acid, has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of methyl p-hydroxycinnamate in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Methyl p-hydroxycinnamate significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$ and the protein expression of iNOS and COX-2. Methyl p-hydroxycinnamate also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-$1{\beta}$ and TNF-${\alpha}$. In addition, methyl p-hydroxycinnamate significantly suppressed LPS-induced degradation of $I{\kappa}B$, which retains NF-${\kappa}B$ in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-${\kappa}B$ in the nucleus. Methyl p-hydroxycinnamate exhibited significantly increased Akt phosphorylation in a concentration-dependent manner. Furthermore, inhibition of Akt signaling pathway with wortmaninn abolished methyl p-hydroxycinnamate-induced Akt phosphorylation. Taken together, the present study clearly demonstrates that methyl p-hydroxycinnamate exhibits anti-inflammatory activity through the activation of Akt signaling pathway in LPS-stimulated RAW264.7 macrophage cells.