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      • Eryngium foetidum Suppresses Inflammatory Mediators Produced by Macrophages

        Mekhora, Chusana,Muangnoi, Channarong,Chingsuwanrote, Pimjai,Dawilai, Suwitcha,Svasti, Saovaros,Chasri, Kaimuk,Tuntipopipat, Siriporn Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.2

        Objective: This study assessed anti-inflammatory and antioxidant activities of $E.$ $foetidum$ leaf extract on LPS-activated murine macrophages. Methods: RAW264.7 cells were pretreated with or without $E.$ $foetidum$ extract for 1 h prior to incubation with LPS for 24 h. Anti-inflammatory activity was evaluated with reference to iNOS, COX-2, TNF-${\alpha}$ and IL-6 gene expression. In addition, NO and intracellular ROS generation were determined by Griess method and fluorescence intensity and activation of MAPKs and $I{\kappa}B$ by Western blotting. Results: Prior treatment with $E.$ $foetidum$ leaf extract inhibited elevation of IL-6, TNF-${\alpha}$, iNOS and COX-2, together with their cognate mRNAs in a dose-dependent manner. NO and intracellular ROS contents were similarly reduced. These effects were due to inhibition of LPS-induced phosphorylation of JNK and p38 as well as $I{\kappa}B$. $E.$ $foetidum$ ethanol extract were shown to contain lutein, ${\beta}$-carotene, chlorogenic acid, kaempferol and caffeic acid, compounds known to exert these bioactive properties. Conclusions: $E.$ $foetidum$ leaf extract possesses suppressive effects against pro-inflammatory mediators. Thus, $E.$ $foetidum$ has a high potential to be used as a food supplement to reduce risk of cancer associated with inflammation.

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        Anti-Inflammatory Activities of Extracts of Thai Spices and Herbs with Lipopolysaccharide-Activated RAW 264.7 Murine Macrophages

        Siriporn Tuntipopipat,Channarong Muangnoi,Mark L. Failla 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.6

        Nitric oxide (NO) and tumor necrosis factor-α (TNF-α) play important roles in inflammatory processes. This study examined whether 13 spices/herbs commonly used in Thai dishes modulate the production of NO and TNF-α by the RAW 264.7 mouse macrophage cell line pretreated with plant extracts (1–100μg/mL) prior to activation by bacterial lipopolysaccharide (LPS). Tested plant tissues were extracted with ethanol with the exception of roselle, which was extracted with 70% acetone. Eight of the 13 plant extracts inhibited NO and TNF-α production in a dose-dependent manner without exerting cytotoxicity. Extract from Limnophila aromatica (Kyeng) was the most robust suppressor of NO production, followed by dill, kaffer lime, chili, Teaw, mint, sweet basil, and pea eggplant, respectively (range of 50% inhibitory concentration [IC50]=11.4–74.6μg/mL). Kyeng also exhibited the greatest inhibition of TNF-α production (IC50=10.5μg/mL). IC50 values for NO and TNF-α production in LPS-activated RAW 264.7 cells for these extracts were highly correlated (r=0.772, P=.025). These results suggest that extracts from some spices/herbs in the habitual Thai diet possess anti-inflammatory activity. Moreover, the results support the use of NO production in LPS-activated RAW 264.7 cells as a rapid and cost-effective tool for screening the anti-inflammatory activity of extracts of spices/herbs.

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        Synthesis, physicochemical properties, and protective effects of a novel water-soluble tetrahydrocurcumin-diglutaric acid prodrug on ethanol-induced toxicity in HepG2 cells

        Jongjitphisut Nattapong,Phumsuay Rianthong,Thitikornpong Worathat,Rashatasakhon Paitoon,Muangnoi Chawanphat,Vajragupta Opa,Rojsitthisak Pornchai 한국약제학회 2022 Journal of Pharmaceutical Investigation Vol.52 No.4

        Purpose Tetrahydrocurcumin (THC) is a major reductive metabolite of curcumin that exhibits potent antioxidant effects; however, its pharmacological activities are limited by its poor water solubility. To overcome this, tetrahydrocurcumindiglutaric acid (TDG), a novel water-soluble ester prodrug of THC, was synthesized and evaluated for its protective effects against ethanol-induced toxicity in liver cells. Methods A simple esterification reaction was used to synthesize TDG. Physicochemical properties including water solubility, partition coefficient, chemical stability, and drug release were evaluated. The in vitro protective effects of TDG against ethanol-induced toxicity in HepG2 cells were evaluated on cell viability, reactive oxygen species (ROS) accumulation, oxidative stress, and apoptosis using MTT, DCFH-DA, antioxidant enzyme activity, and caspase activity assays, respectively. Results TDG was successfully synthesized in good yield, and its chemical structure was confirmed via FT-IR, NMR, and high-resolution mass spectra. The solubility of TDG was greater than that of THC in phosphate buffer (pH 6.8) and able to release THC into the plasma. TDG exhibited protective effects by increasing cell viability compared with THC. Further studies on the hepatoprotective mechanisms revealed that TDG significantly reduced intracellular ROS compared with THC by restoring the antioxidant system (catalase, glutathione peroxidase, and glutathione levels). Moreover, TDG and THC inhibited apoptosis by modulating the activation of caspase-3 and -9. Conclusion The results indicate that TDG represents a potential preclinical and clinical candidate for further hepatoprotective evaluation. Additionally, glutaric acid serves as a promoiety for conjugating bioactive molecules to enhance their water solubility and pharmacological effects.

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