Capsicum ethanol extracts and capsaicin enhance interleukin-2 and interferon-gamma production in cultured murine Peyer\u27s patch cells ex vivo

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学部We investigated the effects of red pepper (Capsicum annuum Lin.) extracts (capsicum extract) and its main pungent capsaicin on T helper 1 (Th1) and 2 (Th2) cytokine production in cultured murine Peyer\u27s patch (PP) cells in vitro and ex vivo. Direct administration of capsicum extract (1 and 10 μg/ml) and capsaicin (3 and 30 μM) resulted in suppression of interleukin (IL)-2, interferon (IFN)-γ, IL-4 and IL-5 production. In an ex vivo experiment using PP cells removed from the mice after oral administration of capsicum extract (10 mg/kg/day for 4 consecutive days), IL-2, IFN-γ and IL-5 increased in response to concanavalin A (Con A). Oral administration of 3 mg/kg/day capsaicin, one active constituent of the extract, also enhanced IL-2, INF-γ and IL-4 production in response to Con A stimulation but did not influence the production of IL-5. Orally administered capsazepine (3 mg/kg/day), a selective transient receptor potential vanilloid 1 (TRPV1) antagonist, slightly enhanced IL-2 production also irrespective of Con A stimulation. The capsaicin-induced enhancement of both IL-2 and IFN-γ production was not reduced by oral administration of capsazepine (3 mg/kg/day), suggesting a TRPV1 receptor-independent mechanism. Flow cytometric analysis revealed that the population of CD3+ cells in the PP cells was significantly reduced while CD19+ cells increased after oral administration of capsicum extract (1 and 10 mg/kg/day) and capsaicin (0.3 and 3 mg/kg/day). Capsazepine (3 mg/kg/day) weakly but significantly reversed these effects. Orally administered capsicum extract and capsaicin did not change the T cell subset (CD4+ and CD8+), Th1 (IFN-γ+) and T2 (IL-4+) ratio. These findings indicate that capsicum extract and capsaicin modulate T cell-immune responses, and their immunomodulatory effects on murine PP cells are partly due to both TRPV1-dependent and -independent pathway. © 2007 Elsevier Inc. All rights reserved

Oral administration of Ren-shen-yang-rong-tang \u27ninjin\u27yoeito\u27 protects against hematotoxicity and induces immature erythroid progenitor cells in 5-Fluorouracil-induced anemia

金沢大学医薬保健研究域薬学系The purpose of this study was to investigate the efficacy of four different Japanese and Chinese herbal prescriptions, Ren-Shen-Yang-Rong-Tang (Ninjin\u27yoeito, NYT), Chai-Hu-Gui-Zhi-Gan-Jiang-Tang (Saikokeishikankyoto, SKKT), Si-Jun-Zi-Tang (Shikunshito, SKT) and Si-Wu-Tang (Shimotsuto, SMT), which are traditionally used for anemia and fatigue, against hematotoxicity in mice treated with 5-fluorouracil (5-FU). NYT 1100 mg kg-1 day-1 injected orally for 7 consecutive days before and after 5-FU injection significantly suppressed reductions in red blood cell, white blood cell and platelet counts in peripheral blood, and accelerated their recovery. Administration of SKKT also produced a slight but significant improvement in 5-FU-induced erythrocytopenia, whereas SMT and SKT could not prevent anemia. Oral injection of NYT also inhibited 5-FU-induced decreases in peripheral reticulocyte and bone marrow cell counts on day 10, and markedly hastened their recovery on day 20, in a dose-dependent manner. Erythroid progenitor colonies, such as colony forming units-erythroid and burst forming units-erythroid, formed by marrow cells from mice treated with 5-FU were significantly increased by oral administration of NYT. These findings suggest that NYT has the potential to protect against hematotoxicity, and also has hematopoietic activity, through stimulation of immature erythroid progenitor cell differentiation.出版者許諾要件により全文公開は2010年7月より

Bioactive Phenylpropanoid Glycosides from Tabebuia avellanedae

Three novel phenylpropanoid glycosides 2, 5, 6 were isolated from water extract of Tabebuia avellanedae, together with three known phenylpropanoid glycosides 1, 3, 4. All compounds were identified on the basis of spectroscopic analysis and chemical methods and, for known compounds, by comparison with published data. All isolated compounds showed strong antioxidant activity in the DPPH assay, and compound 5 give the highest antioxidant activity among all compounds, with an IC50 of 0.12 µM. All compounds exhibited moderate inhibitory effect on cytochrome CYP3A4 enzyme

Studies for developing Japanese Taila, an Ayurvedic medicated oil

金沢大学医薬保健研究域薬学系Jatyadi Taila(J)はアーユルヴェーダ（インド伝統医学）で用いられる薬用オイルであり，特に薬線Kshara Sutraを用いた痔瘻手術の際に用いられている。この手術方法は日本へも導入されているが，Jについては薬理作用，毒性および術後処置について未だ明らかにされていない。そこで本研究では，培養ヒト表皮角化細胞におけるケモカイン・インターロイキン（IL）-8の産出および細胞増殖作用に対するJの効果を調査した。さらにJの代替品として紫雲膏および中黄膏を構成する生薬に基づいたオイルを調製することを試みた。JはTPAで共刺激された角化細胞中のIL-8 産出に影響を及ぼさなかったが，強い細胞毒性を示した。鬱金で作ったオイルは角化細胞中のIL-8産出および細胞毒性を示した。鬱金および黄柏で作ったオイルはIL-8産出を抑える傾向を示した。Jのメタノール画分は細胞毒性を示さずIL-8産出を抑制した。ゴマ油や紫根で作ったオイルのメタノール画分は有意に角化細胞を増殖させたが，IL-8産出に影響を及ぼさなかった。以上よりJは角化細胞の炎症反応の調節を通じて皮膚炎を抑制する可能性があることが示された。紫雲膏や中黄膏に基づいたオイルがKshara Sutraによる手術を受けた患者に役立つ可能性がある。An Ayurvedic medicated oil, Jatyadi Taila (J), is known to be used in Ayurveda (Indian traditional medicine), especially for anal fistula surgery involving the medicated thread Kshara Sutra. Although this surgical method has been introduced into Japan, the pharmacological efficacy, toxicity and postoperative care for J remain unclear. In this study, we investigated the effects of this oil on production of the chemokine interleukin (IL)-8 as well as cell proliferation in cultured human epidermal keratinocytes. We also attempted to create an oil for Kshara Sutra based on Kampo ointments such as shiunko and chuoko, instead of J. J itself did not affect IL-8 production in keratinocytes co-stimulated with TPA, but showed a strong cytotoxicity toward this cell line. Among the tested oils, oil of turmeric resulted in suppression of not only IL-8 production but also cell growth in cultured keratinocytes. Oil of turmeric and Phellodendri Cortex showed a tendency to suppress IL-8 production under the same condition. The methanol-eluted fractions of J suppressed IL-8 production without any significant cytotoxicity. The methanol fraction of the oil from sesame or Lithospermi Radix significantly enhanced the proliferation of keratinocytes without IL-8 production. These findings indicate that the Ayurvedic oil J may have potential for suppression of skin inflammation through regulation of the keratinocyte inflammatory response. It is further proposed that Japanese Taila based on shiunko and chuoko might be useful for Kshara Sutra surgery in patients. © 2012, Medical and Pharmaceutical Society for WAKAN-YAKU. All rights reserved