Kampo medications have been successfully used for patients with ulcerative colitis (UC) who have demonstrated difficulty in adjusting to conventional Western pharmacological therapy. These patients have developed serious adverse drug reactions and have shown little improvement or an actual decrease in Quality of Life (QOL) in spite of the pharmacological intervention. Kampo medications, on the other hand, can increase QOL in such patients. However, few reports are available that detail the effectiveness and/or mechanism(s) of action of Kampo medications for the treatment of UC. In this article, the characteristics of chemically-induced murine colitis are reviewed. Chemically-induced murine colitis is the most commonly employed experimental animal model of colitis and shares important characteristics with UC. Recent research regarding the administration and anti-inflammatory actions of Kampo medications for the management of experimental murine colitis, while limited, is also reviewed. In addition, the importance of herb combinations (as opposed to any single herb) that comprise Kampo formulations are described in the context of research from this laboratory. This work demonstrates that the herbs in Kampo medications may act synergistically to protect against dextran sulfate sodium (DSS)-induced murine colitis. Finally, the applicability of this work to the treatment of UC in human patients is discussed.
Suitability of carrot (Daucus carota L.) cultivars for "Yakuzen", which is a form of medicinal cooking based on theories of Oriental medicine, was evaluated by sensory test and amounts of functional constituents related to the taste and functionality. F1 cultivars and fourteen local cultivars which belonged to seven local varietal groups were used. As a result of sensory test, three local cultivars ('Hakata-Tokinashi-5-sun'; 'HT5', 'Kokubun-Senko-Onaga'; 'KSeO' and 'Sapporo-Futo'; 'SaF') were considered to have proper characteristics for "Yakuzen" because of their strong taste. And one of the F1 cultivars ('Chihama-5-sun'; 'C5') was also considered to be suitable, object cultivar 'Kouyou-2-gou' ('K2') and these four cultivars were evaluated in detail. Generally, selected four cultivars showed higher sourness, less sugar, higher ash and carotenoid content, and higher anti-oxidant activity than those of 'K2'. Amino acid contents of 'KSeO' and 'SaF' were ten and six times higher than those of 'K2', respectively. On one hand, 'K2' and 'C5' could characterize to be sweet but less functional. On the other hand, 'HT5', 'KSeO' and 'SaF' had complex taste and much functional constituents, although the factor loadings by principal component analysis were small. Besides, local cultivars had more volatile compounds than F1 cultivars. In conclusion, some local cultivars of carrot have stronger taste and more functional constituents than current F1 cultivars. 'Kokubun-Senko-Onaga' and 'Sapporo-Futo' were considered to be the most suitable material for "Yakuzen" dishes within the range of cultivars, because it showed strong flavor and taste with higher amount of functional constituents.
We evaluated the therapeutic efficacy of ethanol extracts of two Korean herbal medicines in an intranasal influenza virus infection model in mice. The ethanol extracts of Jahyang-dokgamaek (JD) 1 (2.26 g/kg) and 2 (1.64 or 4.92 g/kg) were orally administered to mice infected with influenza A/PR/8/34 virus twice or three times daily for 7 days after infection. Extracts JD1 (2.26 g/kg) and 2 (1.64 or 4.92 g/kg) significantly prevented body weight loss and/or prolonged survival times of infected mice. Extract JD2 moderately but significantly reduced virus titers in bronchoalveolar lavage fluid (BALF) on days 1 to 3 after infection. Both extracts exhibited significant anti-influenza virus activity in a plaque reduction assay, but their active concentrations were very high. Neither JD1 or 2 significantly affected the total numbers of infiltrated cells or the levels of interferon (IFN)-β in BALF on days 1 to 3. However, JD2 significantly elevated the levels of interleukin (IL)-12 and IFN-γ on day 1, promoted infiltration of neutrophils on day 2, and reduced the levels of tumor necrosis factor (TNF)-α on day 3. Similar trends were seen in infected mice with JD1 administration. Administration of the two extracts was suggested to promote infiltration of neutrophils into the lungs in the early phase of infection, resulting in activation of innate immunity and thereafter alleviation of inflammation as indicated by the reduction of the TNF-α level in the BALF. Thus, the efficacy of the two extracts against influenza virus infection was possibly based on the activation of early host immunity.
We have previously reported that maoto inhibits a serum-induced motility of human breast cancer MDA-MB-231 cells. However, the molecular mechanism by which maoto realizes this inhibition was not elucidated. In this study, we focused on the effects of maoto on hepatocyte growth factor (HGF)-c-Met signaling, because HGF is one of the growth factors in serum and stimulates cell migration through tyrosine phosphorylation of c-Met. A Transwell migration assay demonstrated that maoto extract prevented the HGF-induced motility, and a major component of maoto, Ephedrae herba extract, had the same effect. However, both extracts of maoto that did not contain Ephedrae herba (maotokyomao) and a reference prescription, shikunshito, had no such effect. To confirm the effects of maoto and Ephedrae herba on HGF-c-Met signaling,we examined the effects of these medicines on HGF-induced phosphorylation of c-Met. Both extracts of maoto and Ephedrae herba inhibited c-Met phosphorylation, but neither maotokyomao extract nor shikunshito extract had such effects. Moreover, Ephedrae herba extract directly inhibited the tyrosine-kinase activity of c-Met and suppressed the HGF-induced phosphorylations of Akt, which is a signal molecule downstream of c-Met. We further investigated whether maoto and Ephedrae herba inhibit the expression of c-Met. The c-Met protein and gene expression were reduced after 24 h of the treatment with maoto extract or Ephedrae herba extract. These inhibitory effects of maoto were lost by removal of Ephedrae herba from the prescription, suggesting that the effects were attributable to Ephedrae herba. Taken together, these results suggested that Ephedrae herba, a major component of maoto, inhibits the HGF-induced motility of MDA-MB-231 cells by the suppression of HGF-c-Met-Akt signaling through the inhibition of both c-Met tyrosine phosphorylation and c-Met expression.
Glycyrrhizin (a major component of licorice root) affects the entry of a virus into cells mostly by suppressing the fluidity of the plasma membrane and viral envelope. This activity has been recognized in cells infected by human immunodeficiency virus (HIV) and other viruses. In these infections, apoptosis is initiated via virus-cell membrane interactions. Therefore, the anti-apoptotic activity of glycyrrhizin and its possible mechanism was investigated in the current study. Anti-apoptotic activity of glycyrrhizin was recognized at 0.15mM by DNA and nuclear fragmentation assays. Glycyrrhizin decreased the number of apoptotic cells with no effect on HIV production at this concentration (0.15mM) in cultures of MT4 cells infected with HIV, although 3'-azido-2',3'-dideoxythymidine (AZT) suppressed both the proportion of apoptotic cells and HIV production to the similar levels in a dose-dependent manner. Glycyrrhizin inhibited apoptosis induced by feline immunodeficiency virus (FIV) at 0.6mM with no effect on FIV production as assessed by FIV-reverse transcriptase activity in cultures of Mya-1 cells infected with FIV. Apoptosis was prevented by pre-treatment with glycyrrhizin (P<0.05), but not AZT. Glycyrrhizin diminished the expression of CD4 in untreated cells to 54% dose-dependently without affecting the expression of Fas, CXCR4, and MHC class I. In conclusion, glycyrrhizin diminished the expression of cell surface CD4, which might affect the cross-linking of CD4 with HIV, thereby inhibiting the cascade leading to apoptosis. Because the binding of FIV-spike with CD4 was not recognized, the inhibitory activity of glycyrrhizin against FIV-induced apoptosis may be caused through the cascade involving other cell-surface molecule (s).
Hypoxia of renal tissue has recently been considered the common final pathway leading to end-stage renal failure in chronic renal failure. Our last study demonstrated that the Kampo formula hachimijiogan might have a renal protective effect by the influence of hypoxia inducible factor (HIF). In this study, the active components of hachimijiogan and their mechanisms were studied using a rat proximal tubular epithelial cell line cultured in hypoxic state. The eight crude drugs composing hachimijiogan were added to proximal tubular epithelial cells, and HIF-1α mRNA, its protein, and its downstream target genes, vascular endothelial growth factor (VEGF) and glucose transporter 1 (Glut-1) mRNA were measured. The results were that Cinnamomi Cortex and Moutan Cortex increased HIF-1α protein, VEGF and Glut-1 mRNA when cultured for 6 hours, without increasing HIF-1α mRNA. Furthermore, cinnamaldehyde and paeonol, the main integrants of Cinnamomi Cortex and Moutan Cortex, respectively, also increased HIF-1α protein, VEGF and Glut-1 mRNA. Because the expression of HIF-1α mRNA did not increase but the level of HIF-1α protein increased when treated by cinnamaldehyde and paeonol, their mechanisms were thought to inhibit the decomposition of HIF-1α protein.