著者

Naohiko ONO Yasundo YAMASAKI Noriyuki YAMAMOTO Akihiko SUNAMI Hidekazu MIYAKE

出版者

The Japanese Pharmacological Society

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.42, no.3, pp.431-439, 1986 (Released:2006-09-15)

参考文献数

23

被引用文献数

4 5

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The possible mechanism of the anti-inflammatory activity of proglumetacin maleate (PGM), a new indomethacin (IND) derivative interacting with arachidonic acid (AA) metabolism, was investigated to elucidate the contributions of PGM itself and its two major metabolites, desproglumideproglumetacin maleate (DPP) and IND. PGM caused much less inhibition of PGE2 formation by sheep seminal vesicle microsomes (IC50=310 μM) and TXB2 formation by a washed rabbit platelet suspension (IC50=6.3 μM) than IND. DPP also caused less inhibition of cyclooxygenase than IND. Moreover, PGM had less effect on sodium arachidonate (SAA)-induced rat platelet aggregation ex vivo and AA-induced sudden death in rabbits than IND. These results show that PGM has anti-inflammatory activity after its conversion to the active metabolite IND. However, the inhibitory effects of PGM and DPP were as strong as that of IND on SAA- or collageninduced rabbit platelet aggregation in vitro. These activities are considered to be associated with platelet membrane interaction. Moreover, unlike IND, PGM (IC50=1.5 μM) and DPP (IC50=16.3 μM) strongly inhibited 5-HETE formation by the cytosol of guinea pig polymorphonuclear leukocytes. This unique activity of PGM on 5-lipoxygenase may contribute to its anti-inflammatory activity.

著者

Kozo Yao Ken Nagashima Hiroyuki Miki

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.100, no.4, pp.243-261, 2006 (Released:2006-04-18)

参考文献数

135

被引用文献数

37 70

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Benidipine is a dihydropyridine-derived calcium channel blocker developed in Japan, with several unique mechanisms of action, that is, triple calcium channels (L, N, and T) blocking action with a membrane approach. Benidipine has relatively high vascular selectivity and is expected to show protective effects on vascular endothelial cells. Renal protective effects of benidipine also have been shown in several basic and clinical studies. Moreover, anti-oxidative action and enhancing nitric oxide production have been noted with this drug, following its cardio-protective effects in patients with ischemic heart diseases. In fact, benidipine exerted a better prognostic effect than other calcium channel blockers in the therapy for patients with vasospastic angina. In addition, benidipine showed reliable antihypertensive, renoprotective effects if used in combination with angiotensin II type 1 receptor blockers (ARBs) when adequate anti-hypertensive effects are not achieved by ARBs alone, indicating that benidipine is an useful calcium channel blocker in combination therapy for hypertension. Benidipine was launched on the Japanese market 14 years ago, but few severe side effects have been reported, suggesting that this is a drug with established safety and long-acting pharmacological effects.

著者

Satoshi Tanaka Atsushi Ichikawa

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.101, no.1, pp.19-23, 2006 (Released:2006-05-23)

参考文献数

47

被引用文献数

17 30

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Accumulating evidence has highlighted the importance of histamine in immune responses. The H1 receptor is involved not only in allergic inflammatory reactions but also in augmentation of helper T cell (Th)1 responses, whereas H2 receptor suppresses Th responses and participates in immune tolerance through interleukin-10 and transforming growth factor-β. Identification of the H4 receptor, which binds to histamine with high affinity and of which expression is limited to the hematopoietic system, has enhanced the importance of histamine in immune responses. However, since a majority of previous studies has evaluated the effects of exogenous histamine, it remains largely unknown how endogenously produced histamine is involved in regulation of such kinds of immune responses. Insight into precise roles of histamine in the immune system can not be obtained without correct understanding of both the predominance of a certain type of histamine receptor and the regulation of histamine synthesis. Here we review a part of the recent progress in histamine research in the field of immunology with attention to the source of involved histamine.

著者

Yuji Ikegaya Norio Matsuki

出版者

The Japanese Pharmacological Society

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.89, no.3, pp.324-326, 2002 (Released:2002-07-22)

参考文献数

10

被引用文献数

8 12

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This paper reports that vasopressin is emetogenic in the house musk shrew Suncus murinus. Either intravenous or intracerebroventricular administration of vasopressin caused vomiting within a few minutes. The ED50 of intravenous vasopressin was as high as 4.67 μg/kg, whereas intracerebroventricularly injected vasopressin was effective at a low dose of 20 ng/brain. The emetogenic target of vasopressin may therefore be present in the central nervous system. We propose the Suncus as a useful animal for investigation of vasopressin-mediated emesis, including motion sickness.

著者

Suzuki Atsushi Sekiguchi Sahoko Asano Shogo ITOH Mitsuyasu

出版者

The Japanese Pharmacological Society

雑誌

Journal of pharmacological sciences (ISSN:13478613)

巻号頁・発行日

vol.106, no.4, pp.530-535, 2008-04-20

参考文献数

40

被引用文献数

3 21

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The prevention of osteoporotic fracture is an essential socioeconomical priority, especially in the developed countries including Japan. Estrogen, selective estrogen-receptor modulators (SERMs), and bisphosphonate are potent inhibitors of bone resorption; and they have clinical relevance to reduce osteoporotic fractures in postmenopausal women. However, we can prevent at most 50% of vertebral fractures with these agents. For the better compliance of aminobisphosphonate, the use of a daily bisphosphonate regimen is moving to a weekly or monthly bisphosphonate regimen. Both cathepsin K inhibitors and modulators of the RANK-RANKL system, which can reduce bone resorption, are the candidates for the future treatment of osteoporosis. As well as bone resorption, we need to increase bone formation to prevent osteoporotic fractures, particularly in elderly patients with low bone turnover. In the U.S., Europe, and Australia, they have already started intermittent parathyroid hormone injection and/or oral strontium ranelate to stimulate bone formation. We still need to discover new agents to reduce osteoporotic fractures for the better quality of life without fractures.<br>

著者

Tomio Okamura Masashi Tawa Ayman Geddawy Takashi Shimosato Hirotaka Iwasaki Haruo Shintaku Yuichi Yoshida Masahiro Masada Kazuya Shinozaki Takeshi Imamura

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.124, no.1, pp.76-85, 2014-01-20 (Released:2014-01-18)

参考文献数

41

被引用文献数

10 21

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Deficiency of tetrahydrobiopterin (BH4) in the vascular tissue contributes to endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O2−) generation in the insulin-resistant state. We investigated the effects of atorvastatin, a 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor; amlodipine, a calcium antagonist; and their combination on blood pressure, arterial relaxation and contraction, and vascular oxidative stress in aortas of high fructose–fed rats. Oral administration of atorvastatin for 8 weeks did not significantly lower blood pressure, but normalized angiotensin II–induced vasoconstriction and endothelial function in the fructose-fed rats. Atorvastatin treatment of fructose-fed rats increased vascular BH4 content, which was associated with an increase in endothelial NO synthase activity as well as a reduction in endothelial O2− production. On the other hand, administration of amlodipine did not affect the angiotensin II–induced vasoconstriction and endothelial function, but normalized the elevated blood pressure in the fructose-fed rats. The combined treatment did not show synergistic but additive beneficial effects. The present study suggests that combined therapy of HMG-CoA reductase inhibitors and calcium antagonists prevents functional vascular disorders in the insulin-resistant state, possibly resulting in the protection against or delay of development of hypertension, vascular dysfunction in diabetes, and thereafter atherosclerosis.

著者

Khaled Radad Gabriele Gille Linlin Liu Wolf-Dieter Rausch

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.100, no.3, pp.175-186, 2006 (Released:2006-03-18)

参考文献数

149

被引用文献数

89 179

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Ginseng, the root of Panax species, is a well-known herbal medicine. It has been used as a traditional medicine in China, Korea, and Japan for thousands of years and is now a popular and worldwide used natural medicine. The active ingredients of ginseng are ginsenosides which are also called ginseng saponins. Recently, there is increasing evidence in the literature on the pharmacological and physiological actions of ginseng. However, ginseng has been used primarily as a tonic to invigorate week bodies and help the restoration of homeostasis. Current in vivo and in vitro studies have shown its beneficial effects in a wide range of pathological conditions such as cardiovascular diseases, cancer, immune deficiency, and hepatotoxicity. Moreover, recent research has suggested that some of ginseng’s active ingredients also exert beneficial effects on aging, central nervous system (CNS) disorders, and neurodegenerative diseases. In general, antioxidant, anti-inflammatory, anti-apoptotic, and immune-stimulatory activities are mostly underlying the possible ginseng-mediated protective mechanisms. Next to animal studies, data from neural cell cultures contribute to the understanding of these mechanisms that involve decreasing nitric oxide (NO), scavenging of free radicals, and counteracting excitotoxicity. In this review, we focus on recently reported medicinal effects of ginseng and summarize the current knowledge of its effects on CNS disorders and neurodegenerative diseases.

著者

Makio Saeki Hiroshi Egusa

出版者

The Japanese Pharmacological Society

雑誌

Folia Pharmacologica Japonica (ISSN:00155691)

巻号頁・発行日

vol.144, no.6, pp.277-280, 2014 (Released:2014-12-10)

参考文献数

17

被引用文献数

1

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骨粗鬆症治療薬は骨吸収抑制薬と骨形成促進薬に分類される.従来の骨粗鬆症治療薬は骨吸収抑制薬が主流であったが,破骨細胞と骨芽細胞の活性が共役する機構が存在するために長期的には骨形成が低下して効果が減弱したり副作用が生じたりする問題点があった.骨形成促進薬anabolic agent としてはヒト副甲状腺ホルモン(parathyroid hormone:PTH)製剤であるテリパラチドが現在唯一の治療薬である.我々は破骨細胞におけるnuclear factor of activated T cells (NFAT)シグナルをターゲットとした骨吸収抑制薬の創薬を当初の目的として,RAW264.7 細胞を用いたセルベースアッセイ系を構築し,様々な化合物ライブラリーを用いた創薬スクリーニングを行ってきた.スクリーニング中に多くのNFAT 活性化小分子化合物を発見し,これらの破骨細胞を活性化させる化合物が,anabolic therapy に使用できる可能性があるのではないかと考えた.Anabolic agent として唯一臨床応用されているPTH 製剤が血中のカルシウム濃度を上昇させるしくみの一つに,骨吸収の促進がある.したがって,PTH の骨吸収促進という教科書的事実に固執していたら,テリパラチドが骨形成促進薬として開発されることもなかったであろう.PTH の持続的投与は骨吸収の促進をもたらすが,間歇的投与intermittent PTH(iPTH)treatment によるPTH の骨形成促進作用に注目したことが,テリパラチドという骨形成促進薬の開発につながった.我々はこのテリパラチドの例をヒントに,あえて破骨細胞の活性化薬をスクリーニングすることから,新しい骨形成促進薬を開発できないかと考えている.

著者

Liu Yan-Qiu You Song Tashiro Shin-ichi ONODERA Satoshi IKEJIMA Takashi

出版者

The Japanese Pharmacological Society

雑誌

Journal of pharmacological sciences (ISSN:13478613)

巻号頁・発行日

vol.98, no.4, pp.361-371, 2005-08-20

参考文献数

35

被引用文献数

3 26

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Our previous study showed that oridonin isolated from <i>Rabdosia rubescens</i> enhanced phagocytosis of apoptotic cells by macrophage-like U937 cells through tumor necrosis factor (TNF) α and interleukin (IL)-1β release. In this study, we further investigated signaling events involved in oridonin-augmented phagocytosis. Phagocytic stimulation was significantly suppressed by inhibitors, including a phosphoinositide 3-kinases (PI3K) inhibitor (wortmannin), a protein kinase C (PKC) inhibitor (stauroporine), and a phospholipase C (PLC) inhibitor (U73122). Exposure of U937 cells to oridonin caused an increase in PKC activity time- dependently, which was prevented by pretreatment with inhibitors of PI3K and PLC. Simultaneously, the activation of protein kinase B (PKB/Akt) and the increased expression of PLCγ2 were also blocked by wortmannin. In addition, an extracellular signal-regulated kinase (ERK) MAPK inhibitor, PD98059, suppressed oridonin-augmented phagocytosis, whereas the p38 MAPK inhibitor (SB203580) and c-Jun N-terminal kinase (JNK) MAPK inhibitor (SP98059) had no inhibitory effect. Furthermore, pretreatment of U937 cells with anti-TNFα and anti-IL-1β antibodies blocked oridonin-induced phagocytic stimulation as well as phosphorylation of ERK, but did not block the activation of PKC, indicating that these signaling events are triggered by oridonin, whereas secreted TNFα or IL-1β only activate the ERK-dependent pathway. Taken together, oridonin is suggested to enhance phagocytosis of apoptotic bodies by activating PI3K, PKC, and ERK-dependent pathways.<br>

著者

Zhong Qiu Liu Zhi Hong Jiang Kelvin Chan Hua Zhou Yuen Fan Wong Zhao Xiang Bian Hong Xi Xu Liang Liu

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.104, no.3, pp.283, 2007 (Released:2007-07-24)

被引用文献数

1 1

著者

野見山 シツヱ

出版者

The Japanese Pharmacological Society

雑誌

日本藥物學雜誌 (ISSN:03694461)

巻号頁・発行日

vol.35, no.4, pp.458-496,en38, 1942

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Es wurde Hugugift, das von Assistent Tani aus den Ovarien von Sphaeroides rubripes extrahiert wurde, gebraucht. Ergebnisse : 1) Das Hugugift ruft eine motorische Lähmung hervor. Die Lähmung tritt jedoch am Meerschweinchen, sogar bei der Letaldose, nicht vollständig ein und direkt vor dem Tod Krampf. Beim Hunde erscheint eine hochgradige Lähmung. Krampf wird beim Tod nicht beobachtet. Bei der Katze kommen vollständige motorische Lähmung und Verlust des Muskeltonus zum Vorschein, aber Reflexe bleiben noch. 2) Durch die Reizung der Wundränder mit Reizhaaren, welche am Rücken vorher erzeugt wurden, werden durch Pantocain örtliche Anästhesie und durch Morphin schmerzstillende Fernwirkung ziemlich sicher bestätigt. Bei Hugugift wird die anästhesierende Fernwirkung nur bei schwerer Vergiftung nach der Letaldose bewiesen. In kleinen Dosen wird die Schmerzempfindung vielmehr empfindlicher. 3) Bemerkenswert ist es, dass kleine Dosen Hugugift bei der Katze wirken, als ob eine Parästhesie an der Fussohle vorhanden ist. Das wird auch bei Sinomenin beobachtet. Diese Erscheinung scheint mit der Abstumpfung der Tastsinne an Zungenspitze, Mundlippe und Fingerspitze, welche bei Tetrodotoxininjektion beim, Menschen eintritt, wesentlich gleich zu sein. 4) Bei Myalgie, Neuralgie oder Tendovaginitis wirkt Tetrodotoxin nur bei lokaler Anwendung schmerzstillend. Analgetische Fernwirkung ist nicht zu beweisen. Der Schmerzsinn wird immer vertärkt. 5) Hugugift in kleinen Dosen erweitert die Hautgefässe der Ohrmuschels und der Mundgegend des Meerschweinchens und der Katze. Beim Menschen lässt Tetrodotoxin das Kältegefühl an Unterschenkel und Lendenteile verschwinden. Dies beruht wohl auf der Erweiterung der Hautgefässe. 6) Intravenöse Injektion von kleinen Dosen Hugugift ruft beim Kaninchen eine leichtgradige Atmungsbeschleunigung, Zunahme der Herzschlagzahl und Blutdrucksteigerung hervor. Diese Wirkungen werden durch Urethannarkose abgeschwächt. In etwas grösseren Dosen bewirkt es erholbare Blutdrucksenkung und in noch grösseren Dosen Atemhemmung, Abnahme der Herzschlagzahl und Blutdrucksenkung. 7) Bei Amwendung in der Cysterna magna oder Seitenventrikel treten Atem-, Herz-und Blutdruckwirkung schon bei 1/50 Dose im Vergleich zu intravenöser Anwendung ein. Die Letaldose verkleinert sich zu ca. 1/100. Die Todesursache des Hugugifts soil die L7auml;hmung der lebenswichtigen Zentren sein. 8) Bei cysternaler Injektion ruft Hugugift sofort Atemhemmung und Blutdrucksenkung hervor, aber bei der Injektion in die Seitenventrikel zuerst eine vorübergehende Atmungsbeschleunigung, Schlagzahlzunahme des Herzens und Blutdrucksteigerung und dann Atemhemmung und Blutdrucksenkung. Diese Hemmung wird durch Veronal verstärkt, dagegen durch Coramin gehemmt. Hugugift wirkt auf die medullären Zentren von Anfang an lähmend, aber übt auf die Zentren im Zwischenhirn, wenigstens eine vorübergehende Erregung aus. Diese Erregung beruht vielleicht auf der Enthemmung. 9) Die Atem-und Blutdruckwirkung des Hugugiftes ist bei der Injektion in A. carotis communis dieselbe wie bei intravenOser. Dies zeigt, dass Hugugift auf die Chemorezeptoren des Carotissinus keine direkte Wirkung hat. 10) Hugugift wirkt bei Hunden und Katzen emetisch. Erbrechen ist bei ihnen die zuerst und immer auftretende Wirkung. Die Vermehrung der Speichelsekretion wird auch beobachtet. 11) Das Erbrechen verschwindet nicht durch Durchschneidung der Nervi vagi oder Atropinanwendung, sondern vollständig nach der Morphinanwendung. Durch Evipannatrium wird es abgeschwächt. Das Erbrechen ist zentraler und nicht peripherer Natur. 12) Auf die Darmbewegung wirkt Hugugift hemmend. Die Hemmung wird von der Lähmung der Darm.muske1atur selbst bedingt.

著者

Kim Ki Jung Cho Hyeong Seok Choi Se Joon Jeun Seung Hyun Kim Seong Yun Sung Ki-Wug

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.107, no.1, pp.57-65, 2008

被引用文献数

5

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The pharmacological action of riluzole, a drug that has been approved as a neuroprotective agent for the treatment of amyotrophic lateral sclerosis, has not yet been established. We examined the effects of riluzole on 5-hydroxytryptamine (5-HT)₃ receptors in NCB-20 neuroblastoma cells using the whole-cell voltage clamp technique combined with a fast drug application method. Co-application of riluzole (1 – 300 μM, 5 s) produced a dose-dependent reduction in peak amplitudes and in the rise slope of the currents induced by 2 μM 5-HT. In addition, 5-HT₃–mediated currents evoked by dopamine, a partial 5-HT₃–receptor agonist, were inhibited by riluzole co-application. These inhibitory effects were clearly shown at low concentrations of 5-HT. The decay time constants of the receptor desensitization and deactivation were also significantly attenuated by riluzole. G-protein inhibitors (pertussis toxin and guanosine 5'-[β-thio] diphosphate) did not completely block these inhibitory actions of riluzole. These results indicate that riluzole inhibits 5-HT₃–induced ion currents directly by slowing channel activation in NCB-20 neuroblastoma cells.<br>

著者

Yasushi Fujio Makiko Maeda Tomomi Mohri Masanori Obana Tomohiko Iwakura Akiko Hayama Tomomi Yamashita Hiroyuki Nakayama Junichi Azuma

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.117, no.4, pp.213-222, 2011 (Released:2011-12-15)

参考文献数

74

被引用文献数

24 36

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Postnatal cardiomyocytes have only limited capacity of proliferation. Therefore, the myocardium is intrinsically equipped with cardioprotective machineries and protects itself from pathological stresses. One of the most important cardioprotective systems is the signal network of autocrine/paracrine factors, including neurohumoral factors, growth factors, and cytokines. In this review, we focus on the roles of interleukin-6 (IL-6) family cytokines, also known as glycoprotein 130 (gp130) cytokines, in cardioprotection. These cytokines make a complex with their specific cytokine receptor α-subunits. The cytokine-receptor α-subunit complex binds to gp130, a common receptor of the IL-6 family, followed by the activation of JAK/STAT, ERK, and PI3 kinase/Akt pathways. In cardiomyocytes, signals through gp130 promote cell survival and angiogenesis through the JAK/STAT pathway. Activation of gp130 in cardiac stem cells induces their endothelial transdifferentiation, leading to neovascularization. Recently, accumulating evidence has revealed that altered JAK/STAT activity is associated with heart failure, suggesting that the JAK/STAT pathway is a therapeutic target against cardiovascular diseases. Interestingly, activation of the JAK/STAT pathway with interleukin-11 (IL-11) exhibits preconditioning effects in ischemia/reperfusion model. Moreover, IL-11 treatment after coronary ligation prevents cardiac remodeling through the JAK/STAT pathway. Since IL-11 is used for patients with thrombocytopenia, we propose that IL-11 is a candidate cytokine clinically available for cardioprotection therapy.

著者

Kuribara Hisashi

出版者

The Japanese Pharmacological Society

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.64, no.4, pp.273-280, 1994

被引用文献数

3 12

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Behavioral effects of p.o. administration of SUN 8399, a selective 5-HT<SUB>1A</SUB> agonist, on the operant behavior under a MULT VI 1.5 min/FR 5-punishment schedule of food reinforcement and on the ambulatory activity were evaluated in mice, and the characteristics were compared with those of other 5-HT<SUB>1A</SUB> agonists, buspirone and tandospirone, and the benzodiazepine diazepam. Diazepam (3 and 10 mg/kg) significantly increased the punished response without eliciting any significant change in the non-punished response; i.e., showing anticonflict action. SUN 8399 (3-30 mg/kg) and buspirone (1-10 mg/kg) did not significantly change either the punished or non-punished responses. Tandospirone significantly increased the non-punished response at 10 mg/kg, but significantly decreased both the punished and non- punished responses at 30 mg/kg. The single administration of SUN 8399 (10 mg/kg), buspirone (3 and 30 mg/kg) and tandospirone (10 and 30 mg/kg) significantly increased the ambulatory activity, while diazepam tended to decrease it. The ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) was reduced by buspirone (10 and 30 mg/kg) and tandospirone (10 and 30 mg/kg), but enhanced by diazepam (3 and 10 mg/kg). Buspirone (30 mg/kg), tandospirone (10 and 30 mg/kg) and diazepam (3 and 10 mg/kg) significantly reduced the ambulation-increasing effect of scopolamine (0.5 mg/kg, s.c.). SUN 8399 (3-100 mg/kg) did not modify the effects of either methamphetamine or scopolamine. The present results suggest that 5-HT<SUB>1A</SUB> agonists scarcely show anticonflict action on the Geller-type conflict behavior in mice. However, SUN 8399 possesses different behavioral characteristics from those of the other two 5-HT<SUB>1A</SUB> agonists in terms of interactions with methamphetamine and scopolamine.

著者

Tsugunobu Andoh Qun Zhang Takumi Yamamoto Manabu Tayama Masao Hattori Ken Tanaka Yasushi Kuraishi

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.114, no.3, pp.292-297, 2010 (Released:2010-11-16)

参考文献数

30

被引用文献数

7 17

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Recently, we showed that a methanol extract of Ganoderma lucidum inhibits scratching, an itch-related response, induced by intradermal injections of some pruritogens in mice. The present study investigated whether G. lucidum extract would inhibit allergic itch. In mice sensitized with an extract of salivary gland of mosquito (ESGM), an intradermal injection of ESGM elicited scratching, which was suppressed by oral administration of G. lucidum extract (100 and 300 mg/kg). The scratching was inhibited by the H1 histamine–receptor antagonist azelastine, but not by the peripherally acting H1-antagonist terfenadine, at the oral dose of 30 mg/kg. In sensitized mice, ESGM increased the activity of cutaneous nerve, which was suppressed by G. lucidum extract (300 mg/kg). Although terfenadine (30 mg/kg) inhibited plasma extravasation induced by ESGM in the sensitized mice, G. lucidum extract (300 mg/kg) was without effect. These results suggest that G. lucidum extract relieves allergic itch through a peripheral action. The results support the idea that mast cells and H1 histamine receptors are not the primary sites of the antipruritic action of G. lucidum extract.

著者

Shin Tokunaga Yasuhiro Takeda Kazuaki Shinomiya Masahiro Hirase Chiaki Kamei

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.103, no.2, pp.201-206, 2007 (Released:2007-02-20)

参考文献数

29

被引用文献数

29 36

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The present study was undertaken to investigate the effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats in comparison with those of nitrazepam. Electrodes were chronically implanted into the frontal cortex and the dorsal neck muscle of rats for the electroencephalogram (EEG) and electromyogram (EMG), respectively. EEG and EMG were recorded with an electroencephalograph. SleepSign ver. 2.0 was used for EEG and EMG analysis. The total times of waking, non-rapid eye movement (non-REM), and rapid eye movement (REM) sleep were measured from 10:00 to 16:00. Nitrazepam showed a significant decrease in sleep latency, total waking time, and delta activity and an increase in the total non-REM sleep time. A significant decrease in the sleep latency was observed with diphenhydramine, chlorpheniramine, and cyproheptadine. Cyproheptadine also caused a significant decrease in the total waking time and increases in total non-REM sleep time, REM sleep time, slow wave sleep, and delta activity, although no remarkable effects were observed with diphenhydramine and chlorpheniramine. In conclusion, cyproheptadine can be useful as a hypnotic, having not only sleep inducing-effects, but also sleep quantity- and quality-increasing effects.

著者

Yoshiomi Oka Shinichi Iwai Hitoshi Amano Yuko Irie Kentaro Yatomi Kakei Ryu Shoji Yamada Katsunori Inagaki Katsuji Oguchi

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

pp.1112190632, (Released:2011-12-21)

参考文献数

60

被引用文献数

82 120

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Matrix metalloproteinases (MMPs) play an important role in degeneration of the matrix associated with bone and cartilage. Regulation of osteoclast activity is essential in the treatment of bone disease, including osteoporosis and rheumatoid arthritis. Polyphenols in green tea, particularly epigallocatechin-3-gallate (EGCG), inhibit MMPs expression and activity. However, the effects of the black tea polyphenol, theaflavin-3,3′-digallate (TFDG), on osteoclast and MMP activity are unknown. Therefore, we examined whether TFDG and EGCG affect MMP activity and osteoclast formation and differentiation in vitro. TFDG or EGCG (10 and 100 μM) was added to cultures of rat osteoclast precursors cells and mature osteoclasts. Numbers of multinucleated osteoclasts and actin rings decreased in polyphenol-treated cultures relative to control cultures. MMP-2 and MMP-9 activities were lower in TFDG- and EGCG-treated rat osteoclast precursor cells than in control cultures. MMP-9 mRNA levels declined significantly in TFDG-treated osteoclasts in comparison to control osteoclasts. TFDG and EGCG inhibited the formation and differentiation of osteoclasts via inhibition of MMPs. TFDG may suppress actin ring formation more effectively than EGCG. Thus, TFDG and EGCG may be suitable agents or lead compounds for the treatment of bone resorption diseases.

著者

Motohisa Suzuki Mayumi Suzuki Kazunori Sato Sekiko Dohi Takashi Sato Akihiro Matsuura Atsushi Hiraide

出版者

The Japanese Pharmacological Society

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.87, no.2, pp.143-150, 2001 (Released:2001-11-05)

参考文献数

31

被引用文献数

76 121

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Although improving energy metabolism in ischemic brain has been accepted for the treatment of cerebrovascular diseases, administration of glucose, as an energy substrate, would aggravate ischemic brain damage via activating anaerobic glycolysis, which leads to lactate accumulation. β-hydroxybutyrate (BHB) is one of the ketone bodies that can be utilized as an energy source during starvation. The purpose of our study was to define the protective effects of BHB on brain damage induced by hypoxia, anoxia and ischemia. The isotonic solution of BHB administered 30 min before the induction of ischemia at doses over 50 mg · k g −1 · h −1 showed remarkable protective effects against hypoxia and anoxia. BHB administered immediately after a bilateral carotid artery ligation at a dose of 30 mg · kg−1 · h −1 significantly suppressed the elevation of cerebral water and sodium contents as well as maintaining high ATP and low lactate levels. In contrast, glycerin, a hypertonic agent, substantially reduced the water content but did not show any significant effect on other parameters. We demonstrated that BHB, unlike glycerin, when used as an energy substrate in ischemic brain, has protective effects on cerebral hypoxia, anoxia and ischemia-induced metabolic change.

著者

Yuko Taki Yuko Yamazaki Fumio Shimura Shizuo Yamada Keizo Umegaki

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.109, no.3, pp.459-462, 2009 (Released:2009-03-20)

参考文献数

14

被引用文献数

13 20

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A single dose by gavage of bilobalide (30 mg/kg) was found to produce a time-dependent induction of hepatic cytochrome P450 (CYP) enzyme activity and protein expression in rats. An RT-PCR study further showed that mRNA expression of CYP2B was maximal at 6 h. Plasma and liver bilobalide concentration in rats following administration of Ginkgo biloba extract equivalent to bilobalide of approximately 40 mg/kg showed a similar response to that exhibited by mRNA expression. These findings suggest that bilobalide markedly induced hepatic CYPs, but the induction could be mitigated due to rapid elimination from the liver.

著者

Yoshinobu Kiso

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.115, no.4, pp.471-475, 2011 (Released:2011-04-15)

参考文献数

28

被引用文献数

19 23

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Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are major constituents of cell membranes and play important roles in preserving physiological and psychological function. Recently, data from several studies have indicated that impairments in long-term potentiation (LTP), the process underlying plasticity in synaptic connections, are associated with a decrease in membrane ARA and DHA in aged rats; and treatment of aged rats with either of these polyunsaturated fatty acids (PUFAs) reverses age-related decrease in LTP and the decrease in membrane fatty acid concentration. This review focuses on our recent findings concerning the effects of ARA and DHA on the age-related decline in the function of the brain and cardiovascular system. ARA supplementation decreased P300 latency and increased P300 amplitude of event-related potentials in healthy elderly men. Cognitive impairments in patients with mild cognitive impairment (MCI) and patients with organic brain lesions were significantly improved with ARA and DHA supplementation. ARA and DHA supplementation also increased coronary flow velocity reserve in elderly individuals; this suggests beneficial effects of PUFAs on coronary microcirculation. In conclusion, ARA and DHA may be beneficial in preventing and/or improving age-related declines in brain and cardiovascular system function.