Chemopreventive effects of standardized ethanol extract from the aerial parts of Artemisia princeps Pampanini cv. Sajabal via NF-κB inactivation on colitis-associated colon tumorigenesis in mice.

Chronic inflammation is an underlying risk factor of colon cancer, and NF-κB plays a critical role in the development of inflammation-associated colon cancer in an AOM/DSS mouse model. The aim of this study was to determine whether the standardized ethanol extract obtained from the aerial parts of Artemisia princeps Pampanini cv. Sajabal (EAPP) is effective at preventing inflammation-associated colon cancer, and if so, to identify the signaling pathways involved. In the present study, protective efficacy of EAPP on tumor formation and the infiltrations of monocytes and macrophages in colons of an AOM/DSS mouse model were evaluated. It was found that colitis and tumor burdens showed statistically meaningful improvements after EAPP administration. Furthermore, these improvements were accompanied by a reduction in NF-κB activity and in the levels of NF-κB-dependent pro-survival proteins, that is, survivin, cFLIP, XIAP, and Bcl-2. In vitro, EAPP significantly reduced NF-κB activation and the levels of IL-1ß and IL-8 mRNA and pro-survival proteins in HT-29 and HCT-116 colon cancer cells. Furthermore, EAPP caused caspase-dependent apoptosis. Based on these results, the authors suggest EAPP suppresses inflammatory responses and induces apoptosis partly via NF-κB inactivation, and that EAPP could be useful for the prevention of colitis-associated tumorigenesis.

Anti-inflammatory effect of a standardized triterpenoid-rich fraction isolated from Rubus coreanus on dextran sodium sulfate-induced acute colitis in mice and LPS-induced macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Rubus coreanus Miquel (Rosaceae), the Korean black raspberry, has traditionally been used to treat inflammatory diseases including diarrhea, asthma, stomach ailment, and cancer. Although previous studies showed that the 19α-hydroxyursane-type triterpenoids isolated from Rubus coreanus exerted anti-inflammatory activities, their effects on ulcerative colitis and mode of action have not been explored. This study was designed to assess the anti-inflammatory effects and the molecular mechanisms involving19α-hydroxyursane-type triterpenoid-rich fraction from Rubus coreanus (TFRC) on a mice model of colitis and lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. MATERIALS AND METHODS: Experimental colitis was induced by DSS for 7 days in ICR mice. Disease activity indices (DAI) took into account body weight, stool consistency, and gross bleeding. Histological changes and macrophage accumulation were observed by immunohistochemical analysis. Pro-inflammatory markers were determined using immunoassays, RT-PCR, and real time PCR. Signaling pathway involving nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) activation was determined by luciferase assay and Western blotting. RESULTS: In DSS-induced colitis mice, TFRC improved DAIs and pathological characteristics including colon shortening and colonic epithelium injury. TFRC suppressed tissue levels of pro-inflammatory cytokines and reduced macrophage infiltration into colonic tissues. In LPS-induced RAW 264.7 macrophages, TFRC inhibited the production of NO, PGE2, and pro-inflammatory cytokines by down-regulating the activation of NF-κB and p38 MAPK signaling. CONCLUSION: The study demonstrates that TFRC has potent anti-inflammatory effects on DSS-induced colonic injury and LPS-induced macrophage activation, and supports its possible therapeutic and preventive roles in colitis.

Arvelexin inhibits colonic inflammation by suppression of NF-κB activation in dextran sulfate sodium-induced mice and TNF-α-induced colonic epithelial cells.

Recently, we reported the anti-inflammatory effects of arvelexin isolated from Brassica rapa in macrophages. In the present study, the effects of arvelexin were investigated in a dextran sulfate sodium (DSS)-induced colitis mouse model and in a cellular model. In the DSS-induced colitis model, arvelexin significantly reduced the severity of colitis, as assessed by disease activity, colonic damage, neutrophil infiltration, and levels of colonic iNOS. Moreover, arvelexin inhibited the expressions of IL-8, IP-10, ICAM-1, and VCAM-1 in HT-29 colonic epithelial cells. Arvelexin also inhibited the TNF-α-induced adhesion of U937 monocytic cells to HT-29 cells. Furthermore, arvelexin reduced p65 NF-κB subunit translocation to the nucleus and IκBα degradation in the colonic tissues and in TNF-α-induced HT-29 cells. These results demonstrate that the ameliorative effects of arvelexin on colonic injury are mainly related to its ability to inhibit the inflammatory responses via NF-κB inactivation, and support its possible therapeutic role in colitis.

Roxatidine suppresses inflammatory responses via inhibition of NF-κB and p38 MAPK activation in LPS-induced RAW 264.7 macrophages.

Roxatidine is a novel, specific, competitive H(2) -receptor antagonist that is used to treat gastric and duodenal ulcers, and which is known to suppress the growth of several tumors by reducing vascular endothelial growth factor (VEGF) expression. Nevertheless, it remains unclear whether roxatidine has anti-inflammatory effects. In this study, we the authors investigated the anti-inflammatory effect of roxatidine in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. It was found that roxatidine dose-dependently inhibited the productions of prostaglandin E(2) (PGE(2)), nitric oxide (NO), and histamine, and the protein and mRNA expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and histidine decarboxylase (HDC). In addition, roxatidine reduced the productions and expressions of VEGF-1 and pro-inflammatory cytokines, including those of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). Electrophoretic mobility shift assays (EMSA) and reporter gene assays revealed that treatment with roxatidine attenuated the LPS-induced DNA-binding and transcriptional activity of nuclear factor kappa B (NF-κB). In addition, it was found that pretreatment with roxatidine significantly inhibited the nuclear translocations of the p65 and p50 subunits of NF-κB, and these inhibitions were not found to be associated with decreases in the phosphorylation or degradation of inhibitory kappa B-α (IκBα). Furthermore, roxatidine suppressed the phosphorylation of p38 MAP kinase, but not of IκB kinase-α/ß (IKKα/ß), c-Jun NH(2) -terminal kinase (JNK), or extracellular signal-regulated kinase (ERK). Taken together, these results indicate that the anti-inflammatory properties of roxatidine in LPS-treated RAW 264.7 macrophages are mediated by the inhibition of NF-κB transcriptional activity and the p38 MAP kinase pathway.

Punch excision combined with erbium:YAG fractional laser: its application on different types of scars in Asian patients (a pilot study).

Scars cause significant impact on the quality of life of the affected patients and compel the search for more effective treatments. Ablative laser skin resurfacing, either alone or in combination with other modalities, is the gold standard for treating various scars but is associated with prolonged recovery and many side effects. To address these limitations, newer modalities employing the principle of fractional photothermolysis have emerged. Herein, we investigated the combined effect of punch excision and the erbium:YAG (Er:YAG) fractional laser on different types of scars in Asian individuals.

Anti-inflammatory effects of methanol extract of Patrinia scabiosaefolia in mice with ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Patrinia scabiosaefolia Fisch is used in folk medicines to treat intestinal abscesses, acute appendicitis, and dysentery in Asia. Although recent reports indicate that Patrinia scabiosaefolia has sedative and anti-tumor effects, its effects on ulcerative colitis have not been previously explored. AIM OF THE STUDY: To determine the effects and the mode of action of the methanol extract of the roots of Patrinia scabiosaefolia (PME) on a model of colitis in mice induced by dextran sulfate sodium (DSS). MATERIALS AND METHODS: We induced colitis using DSS in 5-week-ICR mice over 7 days and estimated disease activity index (DAI), which took into account body weight, stool consistency, gross bleeding, and tissue myeloperoxidase (MPO) accumulation. Colon lengths and spleen weights were measured. Histological changes were observed by H&E staining. Pro-inflammatory mediators, namely, nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), were determined using Griess assays, immunoassays, and by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR), respectively. RESULTS: PME significantly attenuated DSS-induced DAI scores and tissue MPO accumulation, which implied that it suppressed weight loss, diarrhea, gross bleeding, and the infiltrations of immune cells. PME administration also effectively and dose-dependently prevented shortening of colon length and enlargement of spleen size. Histological examinations indicated that PME suppressed edema, mucosal damage, and the loss of crypts induced by DSS. Furthermore, PME inhibited the abnormal secretions and mRNA expressions of pro-inflammatory cytokines, such as, TNF-α, IL-1ß, and IL-6. CONCLUSION: These results suggest that PME has an anti-inflammatory effect at colorectal sites that is due to the down-regulations of the productions and expressions of inflammatory mediators, and that it may have therapeutic value in the setting of inflammatory bowel disease (IBD).