Free radicals have been reported to participate in formation of gastric legions, and thus this scavenging action shows gastric lesion protective activity. It was known that Ginkgo biloba L. exhibits the effect of scavenging free radicals. In the present study, we attempted to isolate an active principle from Ginkgo biloba L.. Ginkgo biloba L. inhibited the formation of gastric lesions induced by ethanol, aspirin and indomethacin. An ethyl acetate and hexane layer of Ginkgo biloba L. gave sciadopitysin and 2-(12-heptadecenyl)-6-hydroxy-benzoic acid when separated by using the inhibitory activity on ethanol- induced gastric lesions in rats as an index. And these compounds had a positive effect on gastric lesion protection similarly to sucralfate.
Lymphangiogenesis plays important roles in physiological and pathological conditions. The induction of new lymphatic vessel formation is important for promoting wound repair and treatment in lymphatic diseases such as lymphedema. Polygonati Rhizoma (root of Polygonatum kingianum Coll. et Hemsl.), a traditional Chinese herbal medicine, has been shown to exhibit a variety of pharmacological activities in vivo and in vitro, such as anti-aging, hypoglycemic, neuroprotective and neuroremodeling effects. The network formation process of neurons is similar to the vascular system. The propose of this study was to investigate the effect of Polygonati Rhizoma methanol extract on lymphangiogenesis by using conditionally immortalized lymphatic endothelial (TR-LE) cells, a newly developed cell line originating from the thoracic duct of a transgenic rat expressing the temperature-sensitive SV40 large T-antigen. The results show that non-toxic doses of Polygonati Rhizoma at concentrations of 20 μg/ml and 50 μg/ml produced a slight and significant increase in capillary-like tube formation length of TR-LE cells (increased 15.8% and 40.7% from control, respectively) (p<0.01) after 4 h incubation on Matrigel. In addition, 50 μg/ml Polygonati Rhizoma significantly increased adhesion ability of TR-LE cells at 30 min (increased 44% from control) (p<0.05) and migration at 4 h of incubation (increased 37.5% from control) (p<0.01). However, the expansion of TR-LE cells treated with this extract (50 μg/ml) for 24 and 48 h did not show any statistically significant effect on cell proliferation. Here, we report, for the first time, that Polygonati Rhizoma induces lymphangiogenesis in vitro. This finding may provide an attractive reagent for pro-lymphangiogenic therapy.
The pharmacological effect of tokishakuyakusan was assessed by human transcriptome analysis. Tokishakuyakusan was administrated to 24 female participants, who had complained of feeling cold, edema and gynecological symptoms, for 4 weeks and the pharmacological effects were analyzed. Global transcription was assessed by cDNA microarray using RNA from nucleated cells in the subjects' peripheral blood. Overall, 953 genes were up-regulated and 1,067 were down-regulated with significant differences (p-value of Student's t-test <0.05, with FDR <0.05). A human Gene Ontology (GO) database and the software tool "KNApSAcK human gene classifier", which enables the comparison of the ratio of genes corresponding to functional-categories in an arbitrary gene set to that of the entire human gene set, were developed to understand significant transients in gene expression. The transients were functionally categorized into protein synthesis, transport facilitation, protein fate, transcription, cell cycle and DNA processing, cell fate, transcription, and cellular communication/signal transduction mechanism, with significance (p-value <0.01) determined by a z-test for comparing two proportions using KNApSAcK. Genes related to estrogen, GABAergic signaling, angiotensin and tumors were found to be significant categories.
When high-dose methotrexate (HDMTX) is administered in the treatment of primary central nervous system lymphoma (PCNSL), leucovorin rescue must often be extended due to a delay in the degradation of the blood concentra-tion of methotrexate (MTX). We determined whether or not a delay in the degradation of the MTX blood concentration and renal dysfunction could be prevented by a Japanese traditional medicine, saireito. Seventeen patients with PCNSL were treated with HDMTX. The first course of HDMTX was provided according to standard protocol, and a 3 g-dose of saireito was administered 3 times per day during the second course of HDMTX. Before the MTX blood concentration decreased to < 1 × 10-7 mol/l, the serum blood urea nitrogen (BUN) and creatinine (Cr) were measured and the creatinine clearance (CCr) was measured, with or without the administration of saireito. There were no cases that required prolonged administration of leucovorin rescue therapy during the second course of HDMTX with administration of saireito, whereas during the first course of HDMTX, 6 cases had a delay in the degradation of the MTX blood concentration, thus requiring prolongation of leucovorin rescue therapy. Moreover, after HDMTX therapy with the administration of saireito, BUN and Cr levels in the serum were significantly decreased and the CCr was significantly increased. It is suggested that saireito increases urine flow by inhibiting reabsorption of water in the distal tubule. Administration of saireito during HDMTX therapy is effective in preventing renal failure.
Donepezil, a drug used for the treatment of Alzheimer's disease, is metabolized mainly by CYP3A4 and CYP2D6 in humans, and its plasma concentration is elevated by coadministration of ketoconazole or cimetidine. Because yokukansan is reported to improve behavioral and psychological symptoms of dementia in Alzheimer's disease, it is likely that yokukansan is prescribed in combination with donepezil. We investigated whether ketoconazole, cimetidine and yokukansan affects the disposition of donepezil in rats. Ketoconazole (10 mg/kg) or cimetidine (200 mg/kg) was administered intraperitoneally to male Wistar rats. Donepezil hydrochloride (5 mg/kg) was then administered orally, and plasma donepezil concentration was measured by HPLC-UV. The plasma levels of donepezil were higher in the ketoconazole-coadministered group and the cimetidine-coadministered group than in the control group. The areas under the plasma concentration-time curve were also higher in these two groups than in the control group. In contrast, after repeated oral administration of yokukansan extract powder (1 g/kg) once a day for 7 days, plasma donepezil levels following oral administration of donepezil hydrochloride (5 mg/kg) did not differ from those in the control group. These results indicate that ketoconazole or cimetidine coadministered with donepezil elevates plasma donepezil levels in rats, but coadministered yokukansan has no effect on the disposition of donepezil. These results suggest that yokukansan is unlikely to cause pharmacokinetic interactions when coadministered with donepezil in clinical practice.
An excess of dihydrotestosterone (DHT) is considered to be an important factor causing acne, while testosterone 5α-reductase is responsible for converting testosterone into DHT. In the course of a search for plant resources used for treatment of acne from natural medicines, the 50% of ethanolic extract of "Eijitsu (dried fruits of Rosa multiflora)" showed the strongest inhibitory activity against testosterone 5α-reductase in the previous screening test. Examination of the constituents of the extract resulted in the isolation and/or identification of multiflorin A (1), multinoside A (2), multinoside A monoacetate (3), isoquercitrin (4), ursolic acid (5), 3-acetyl ursolic acid (6), betulinic acid (7), 3β, 6α, 19α-trihydroxyurs-12-en-28-oic acid (8), lauric acid (9), myristic acid (10), palmitic acid (11), oleic acid (12), linoleic acid (13) and γ-linolenic acid (14). Among them, three fatty acids (12-14) showed inhibitory activities with IC50 values of 52.2, 36.5 and 7.3 μg/ml, respectively. The chemical compositions of fatty acids in fractions were then examined by HPLC, as a result, the fraction with a stronger inhibitory activity showed higher contents of 12-14. These results suggest that unsaturated fatty acids (12-14) could be ascribed as active principles of the 50% ethanolic extract from R. multiflora. In addition, 5, 6, 8-10 and 12 were isolated from R. multiflora for the first time.