Oriental medicine (including Kampo medicine) treats patients on the basis of their overall symptoms and conditions, and plays an important role in tailor-made medicine. In Oriental medicine, the condition of "acquiring a disease" is known as mibyo. The concept of treating mibyo is similar to that of improving health-related quality of life (HRQOL) which has been defined and developed in Western medicine as a subjective assessment of health-based factors from on the patient's perspective. HRQOL has been broadly defined to include the physical, psychological, social aspects of health perception and functioning. Many HRQOL scales have been developed by clinicians to assess the effect of therapeutic or preventive intervention. HRQOL scales are questionnaires for the patients, and are thus patient-reported (self-administered).
Kampo medicine is a multi-component drug system comprising more than one crude drug; however, compared with Western medicine, there is insufficient evidence in literature regarding this as it is a unique treatment system. Oriental medicine researchers have been actively discussing measures to strengthen the levels of evidence of Kampo medicine; therefore, data from randomized clinical trials (RCTs) have increased. We investigated QOL data availability in domestic and international studies regarding crude drug products. Of 1995 international studies, 39 studies evaluated QOL from international researches. For domestic research, Evidence Report of Kampo Treatment 2010 and Appendix 2011 by special committee for Evidence-based medicine (EBM), The Japan Society for Oriental Medicine (JSOM), Evidence Report/ Clinical Practice Guidelines (ER/CPG-TF) summarized total 359 RCTs and one meta-analysis, 21 reports evaluated QOL, 17 reports were published after 2000. Our evaluation of these domestic and international studies suggests that QOL assessments have gradually gained widespread recognition. The levels of evidence for Kampo medicine have been increasing; however, QOL data are still very limited. The limited levels of evidence for QOL may be due to low QOL awareness, the difficulty to select QOL scale or the target patient population, and the difficulty to obtain a large number of participating patients.

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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a potent transcriptional activator and plays a central role in inducible expression of many cytoprotective genes, which produce proteins responsible for the detoxification of chemical carcinogens and the suppression of reactive oxygen species. Under basal conditions, Nrf2 is constantly degraded via the ubiquitin-proteasome pathway in a Kelch like ECH-associated protein 1 (Keap1)-dependent manner. Upon exposure to electrophilic and oxidative stresses, Nrf2 is able to escape Keap1-mediated repression, translocate into the nucleus, and activate the expression of its target genes. It is widely accepted that the induction of Nrf2-regulated enzymes results in protection against massive oxidative stress and chemical carcinogenesis. Nrf2 activators are developed as putative chemopreventive agents. In many human cancers, missense mutations in KEAP1 and NRF2 genes have been identified. These mutations are reported to result in permanent Nrf2 activation, leading to overexpression of cytoprotective enzymes. Constitutive induction of Nrf2-regulated enzymes can confer multiple advantages on cancer cells for their proliferation and resistance to chemotherapy. Suppression of abnormal Nrf2 activation is needed, therefore, for a new therapeutic approach against tumors resistant to cytotoxic action of anticancer drugs. However, there is little research to identify Nrf2 inducers and inhibitors from crude drugs. In this article, we investigated whether Nrf2 activity in mammalian cells was enhanced or suppressed by treatment with crude drugs and how modulation of Nrf2-reuglated enzymes by crude drugs affected cytotoxic action of chemical compounds.

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We have focused on the effects of Kampo medicines on cancer metastasis for some time, and 10 years ago we began to assess the medicines in terms of their ability to protect against cancer metastasis. Cancer cell motility is thought to be closely associated with metastatic processes; therefore, we tried to screen Kampo medicines for an inhibitor of cancer cell motility. The samples used for screening were sera from mice given a Kampo medicine such as juzentaihoto, hochuekkito, or maoto. The number of migrated cells was significantly reduced in serum obtained from mice given maoto, and the spontaneous metastasis of cancer cells in mice was significantly decreased by the oral administration of maoto. These results suggested that maoto suppresses cancer metastasis through the prevention of cancer cell motility. Furthermore, we investigated the effect of human sera after the intake of maoto on the motility of cancer cells. The sera collected from 10 volunteers after the intake of maoto showed inhibitory activity against cancer cell motility, indicating that maoto may be a novel inhibitor of cancer metastasis suitable for application in humans. To clarify the molecular mechanism by which maoto suppresses cancer cell motility, 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 it stimulates cell migration through tyrosine phosphorylation of the HGF receptor, c-Met. Maoto prevented HGF-induced cancer cell motility through the inhibition of the phosphorylation of c-Met, and this effect of maoto was derived from its major component, Ephedrae herba. Taken together, these results suggest that maoto may be a candidate drug for protecting patients from the recurrence and metastasis of cancer that expresses c-Met.

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[PURPOSE] To estimate clinical application of shiunko for reducing complications related to cancer treatment, such as radiation-induced dermatitis and hand-foot syndrome induced by molecular target drugs.
[METHODS] Patients involved in this study were as follows: 1. Thirty-one patients with simple scalp dermatitis induced by radiotherapy for brain tumors; 2. Nine patients with severe dermatitis from concurrent treatment with chemotherapy and radiotherapy for cancers including nasopharyngeal cancer; 3. Prophylactic usage of shiunko in four patients with radiation-induced scalp dermatitis; and 4. Six patients with dermal complications caused by molecular target drugs including hand-foot syndrome. Shiunko was applied in the same manner as in the treatment with standard ointment. The efficacy was evaluated with the improvement rate of the symptoms: excellent (more than 80%), good (more than 50%), fair (less than 50%), and no effect (less than 30%).
[RESULTS] Favorable therapeutic effects were observed in all patients. Shiunko not only showed prominent analgesic effects in all cases, which were not achieved in corticosteroid treatment, but also promoted healing in areas eroded by radiation. The patients with hand-foot syndrome gave the highest evaluations for moisturizing and analgesic effects.
[CONCLUSION] Shiunko is expected to be an effective ointment for treating scalp dermatitis caused by radiation and dermal complications induced by molecular target drugs.

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Kasseki' in Japanese or 'Huashi' in Chinese are highly similar crude mineral drugs. Though almost the same Chinese characters are used for both, the definition of the former in The Japanese Pharmacopoeia (JP) is different from that of the latter in Pharmacopoeia of The People's Republic of China (CP). Namely, Kasseki is defined as "a mineral substance, mainly composed of aluminum silicate hydrate and silicon dioxide" in JP, while Huashi is defined as "mainly hydrated magnesium silicate" in CP. Since the Kasseki used in Japan is imported from China, discrimination of these two is important from the viewpoint of regulatory science. In this report we applied a taste-sensing system having artificial lipid membrane sensors to discriminate between Kasseki and Huashi.
First, seven types of sensors were tested on serial concentrations of water extracts of Kasseki and Huashi. The results suggested that the AC0 and AAE sensors were appropriate for our purpose when 1% (w/w) water extracts of samples were used. Next, we tested ten each of Kasseki and Huashi samples in this condition. For the Kasseki samples, both sensors showed specifically localized output values ranging from 0 to -5 mV. By contrast, for the Huashi samples, AC0 characteristically showed output values deviating from the range within ± 5 mV and AAE showed a wide range of output values, from -22 to 1 mV. These data suggest that the taste-sensing system can discriminate Kasseki from Huashi when their 1% (w/w) water extracts are measured by AC0 and AAE sensors.

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This study was designed to investigate the effects and associated mechanisms of the aqueous extract of Astragalus membranaceus Bunge (A. membranaceus) leaves on vascular contractions in rat thoracic aorta. In intact endothelium rings that had been pre-contracted with noradrenaline, the aqueous extract induced relaxation of the rings in a dose-dependent manner. Although this induction process was also effective following pre-incubation of the rings with indomethacin, pre-incubation with N ω-nitro-L-arginine methyl ester inhibited the induction. In an in vivo study, the intravenous injection of the aqueous extract led to an increase in serum nitric oxide levels in rat. To elucidate the effective component with the aqueous extract, the mixture was partitioned between water and n-butanol. The water-soluble fraction induced endothelium-dependent vasodilation, whereas the n-butanol-soluble fraction relaxed rat aortas pre-contracted with noradrenaline, both in the presence and absence of endothelium. These results suggest that endothelium-dependent nitric oxide could play a major role in vasodilation induced by the aqueous extract of the A. membranaceus leaves. Moreover, the active ingredients of the water extract could be included in the water-soluble fraction.

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