사상자

Osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, has been shown to induce various beneficial biochemical effects such as anti-inflammatory and antitumor. In the present study, we examined whether osthole could sensitize TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human renal carcinoma Caki cells. We found that osthole and TRAIL alone, had no effect on apoptosis, but combined treatment with osthole and TRAIL markedly induced apoptosis in Caki (renal carcinoma), U251MG (glioma) and MDA-MB-231 (breast carcinoma) cells. In contrast, combined treatment with osthole and TRAIL did not induce apoptosis in normal human skin fibroblast cells. Osthole induced downregulation of cellular FLICE-like inhibitory protein (c-FLIP) expression, and overexpression of c-FLIP markedly blocked apoptosis induced by the combined treatment with osthole and TRAIL. In addition, osthole markedly reduced mitochondrial membrane potential levels, and increased cytosolic cytochrome c release in combined treatment with osthole and TRAIL. Therefore, these data suggest that osthole may be an efficient TRAIL sensitizer.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Yizhi prescription (BSYZ) is a traditional Chinese compound prescription, which is commonly used in China for treating ShenXu and hypophrenia based on traditional Chinese medicine and Alzheimer's Disease according to modern Chinese medicine. Cnidium monnieri (L.) Cusson fruits (CM) is treated as the main herb of BSYZ, and its main active ingredient Osthole (OST) is considered as one of the major active ingredients of BSYZ. Even though OST plays an important role in the BSYZ its bioavailability is poor. In order to investigate whether the bioavailability of OST was influenced by BSYZ and CM extract, the comparative evaluations on pharmacokinetics of OST after oral administration of pure OST at different doses, CM and BSYZ extract were studied. MATERIALS AND METHODS: 30 rats were randomly assigned to five groups and orally administered with pure OST at different doses (15, 75 and 150 mg/kg), CM (15 mg/kg OST) and BSYZ (15 mg/kg OST) extract. At different predetermined time points after administration, the concentrations of OST in rat plasma were determined by using the HPLC-UV method, and main pharmacokinetic parameters were investigated. RESULTS: The results showed that the pharmacokinetic parameters of OST were significantly different (p<0.05) among the groups. The AUC(0→t), AUC(0→∞) and Cmax of OST were significantly increased after oral administration of BSYZ extract, followed by CM extract, in comparison to pure osthole at different doses. CONCLUSIONS: This present study indicated that the bioavailability of pure OST after oral administration was extremely low and it was dramatically enhanced because of the synergistic effect of the traditional Chinese Bushen Yizhi prescription. © 2013 Published by Elsevier Ireland Ltd.

Osthole, a bioactive simple coumarin derivative extracted from many medicinal plants such as Cnidium monnieri (L.) Cusson, exerts a broad spectrum of pharmacological activities and is considered to have potential therapeutic applications. The aim of this study was to investigate the potential neuroprotective role of osthole against ischemic injury in vitro, as well as the potential mechanism. Cultured cortical neurons were exposed to oxygen and glucose deprivation (OGD) for 4 h followed by a 24 h reperfusion. Osthole exhibited remarkable neuroprotection in a dose-dependent manner and the effect required presence of osthole during both OGD and reperfusion phases. Western blot was used to examine the activation of three members of mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 kinase (p38). We found that osthole prolonged activation of ERK1/2 and prevented activation of JNK. Furthermore, we investigated the effects of MAPKs inhibitors on osthole-induced protection. The results demonstrated that the protection of osthole was partly reversed by PD98059, a selective inhibitor of ERK1/2, but further enhanced by the JNK inhibitor SP600125. In addition, osthole-induced reduction of neuronal apoptosis was abrogated by the ERK1/2 inhibitor PD98059, whereas the total neuronal death was further decreased by the JNK inhibitor SP600125. In summary, these data suggested that osthole had neuroprotective effect against ischemic injury in vitro, and the protection possibly was associated with prolonged activation of ERK1/2 and suppression of JNK activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Topical Chinese herbal medicine (CHM) is commonly used to relieve atopic dermatitis (AD); however, the up-to-date evidence concerning the effectiveness of topical CHM on treating AD is lacking. Moreover, the CHM prescriptions are often too complicated to realize the overall mechanisms of CHM, especially when compared to western medicines (WM). AIM OF THE STUDY: To evaluate the effectiveness of topical CHM for treating AD by conducting a meta-analysis on randomized clinical trials (RCTs). METHODS: Twenty RCTs comparing topical CHM to active control/placebo were included in the final analysis. The primary outcome was the symptom scores changed from baseline and the effectiveness rate was the secondary outcome. Subgroup analysis on different initial symptom severity and the different interventions in control groups was performed. System pharmacology analysis was performed to explore core CHM and possible pharmacological mechanisms of CHM for AD. RESULTS: Compared with active/blank placebo, topical CHM seemed more effective (SMD: -0.35, 95 %CI: -0.59 to -0.10, p-value = 0.005, I2 = 60%). The effectiveness rate was higher (RR: 1.29, 95 %CI 1.15-1.44, p-value <0.00001, I2 = 71%). In subgroup analysis, mild and moderate AD patients with topical CHM were more effective than placebo (SMD: -0.28, 95 %CI -0.56 to -0.01, p-value = 0.04, I2 = 5%; -0.34, 95%CI -0.64 to -0.03, p-value = 0.03, I2 = 0%, separately). Topical CHM has 1.25 times more effective than the topical glucocorticoid (95 %CI 1.09-1.43, p-value = 0.001, I2 = 64%). Core CHMs, such as Phellodendron chinense C.K. Schneid., Sophora flavescens Ait., Cnidium monnieri (L.) Cusson, and Dictamnus dasycarpus Turcz., had effects on the pathways on immune and metabolism systems different from WM. CONCLUSION: Our results exploit the potential role of CHM on treating AD, especially for mild and moderate AD.

This systematic review examines the current state of the evidence for the efficacy and safety of herbal medicines (HMs) used topically in conjunction with anti-psoriatic pharmacotherapy (APP) in the treatment of psoriasis. Searches were conducted in September 2012 of PubMed, EMBASE, Cochrane Library, two Chinese databases (China National Knowledge Infrastructure and Chinese Scientific Journals Full Text Database) and of article reference lists. We included randomized controlled trials published in English, Chinese or Japanese that investigated topical HM combined with APP used systemically and/or topically compared to pharmacotherapy alone. Studies employing phototherapy were excluded. Two authors conducted searches, extracted data on study characteristics and outcomes, and assessed Risk of Bias. Disagreements were resolved by discussion with a third author. Eight studies met the inclusion criteria. All used multi-herb formulae, four in herbal baths, three in herbal ointments or creams, and one as herbal steam. The pooled data indicated a benefit for the add-on effect of herbal therapy to APP. Adding these topical HMs to conventional pharmacotherapy appeared to produce short-term additional clinical benefits. No serious adverse events were reported. Experimental studies suggest that some of the herbs possess anti-inflammatory, anti-pruritic, and/or anti-proliferative activities. However, these results need to be interpreted with caution due to methodological weaknesses and the lack of replicated studies. Studies that address the identified methodological deficiencies are required to further investigate the efficacy and safety of these HMs as adjunct therapies for psoriasis.

This study was to evaluate the clinical efficacy of Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in), a Japanese traditional herbal medicine, in stabilizing postpartum psychological state. We enrolled 268 women who had a normal delivery in Osaka Medical College Hospital or its affiliated clinics and randomly assigned them to the following two groups: a group of 134 women who received Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) at a dose of 6.0 g/day and another group of 134 women without Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) (control group). We observed 2.06-fold and 1.67-fold higher incidences of depressive mood and nervousness, respectively, after delivery in the control group than in the Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) group. Within 3 weeks of postpartum, there was a significant difference in the incidences of maternity blues between the Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) group (15.7%; 21/134) and the control group (32.1%; 43/134) (p = 0.0195). No adverse effects were observed in this study. The results of this study demonstrate the beneficial clinical effects of Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) in stabilizing psychological state in the postpartum period. Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) can be expected to improve the mental health of women in the postpartum period and prevent maternity blues.