著者

Lucia S. Yoshida Tomie Kawada Kaoru Irie Yasukatsu Yuda Toshiyuki Himi Fumihiko Ikemoto Hiromi Takano-Ohmuro

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.112, no.3, pp.343-351, 2010 (Released:2010-03-19)

参考文献数

32

被引用文献数

16 23

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Recently, an isomeric mixture of herbal anti-inflammatory naphthoquinones shikonin and alkannin, and their derivatives, have been found to impair cellular responses involving nitric oxide (NO) and NO synthesis, like the acetylcholine-induced relaxation response of rat thoracic aorta and NO release from murine RAW 264.7 macrophages. However, the mechanisms of such effects, including whether NO synthase (NOS) activity is affected, remained unclear. We herein investigate possible targets of shikonin in these NOS-related events. Shikonin by itself dose-dependently inhibited the rat thoracic aorta relaxation in response to acetylcholine (pD′2 value: 6.29). Its optical enantiomer, alkannin, was equally inhibitory in the aorta relaxation–response assay. In RAW 264.7 cells, shikonin inhibited the lipopolysaccharide-induced NO production by 82% at 1 μM. A cell-free assay to verify direct effects on NOS activity showed that shikonin inhibits all isoforms of NOS (IC50s, 4 – 7 μM), suggesting NOS as an inhibition target in both the events. Further possible targets of shikonin that might be involved in the inhibitions of the acetylcholine-induced aorta relaxation response and the NO generation by RAW 264.7 cells are also discussed. It is shown for the first time that shikonin inhibits NOS activity.

著者

Geng-Ruei Chang Yi-Shin Chiu Ying-Ying Wu Wen-Ying Chen Jiunn-Wang Liao Te-Hsin Chao Frank Chiahung Mao

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.109, no.4, pp.496-503, 2009 (Released:2009-04-17)

参考文献数

51

被引用文献数

105 122

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Rapamycin (RAPA), an immunosuprpressive drug used extensively to prevent graft rejection in transplant patients, has been reported to inhibit adipogenesis in vitro. In this study, we investigated the anti-obesity effects of RAPA in C57BL/6J mice on a high-fat diet (HFD). Mice treated with RAPA (2 mg/kg per week for 16 weeks) had reduced body weight and epididymal fat pads/body weight, reduced daily food efficiency, and lower serum leptin and insulin levels compared with the HFD control mice. However, RAPA-treated mice were hyperphagic, demonstrating an increase in food intake. Dissection of RAPA-treated mice revealed a marked reduction in fatty liver scores, average fat cell size, and percentage of large adipocytes of retroperitoneal and epididymal white adipose tissue (RWAT and EWAT), compared to the HFD control mice. These results suggest that RAPA prevented the effect of the high-fat diet on the rate of accretion in body weight via reducing lipid accumulation, despite greater food intake. It is likely that RAPA may serve as a potential strategy for body weight control and/or anti-obesity therapy.

著者

Jesús Hermida J. Carlos Tutor

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.97, no.4, pp.489-493, 2005 (Released:2005-04-20)

参考文献数

18

被引用文献数

24 32

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In patients with hypoalbuminemia, the total serum concentration of valproic acid may offer poor clinical information; however, very few clinical laboratories routinely analyze the free concentration of the drug. The aim of this study was to design a procedure to normalize the total concentration of valproic acid according to the level of serum albumin and using previously published free fraction values. In 121 adult patients, with albumin levels of 18 – 41 g/L, the total concentration of valproic acid was normalized using the derived equation: CN = αHCH/6.5, where αH is the free fraction of the drug corresponding to the patient’s particular albuminemia and CH is the total concentration of valproic acid. The value of 6.5 corresponds to the free fraction of the drug for a serum albumin of 42 g/L (percentile 50 of the reference range). For total concentrations lower than 75 mg/L, the predicted normalized valproic acid concentrations were reasonably concordant with the observed normalized concentrations calculated using the data from a protein-binding study. In a significant number of cases, subtherapeutic concentrations of the drug became therapeutic and even supratherapeutic when corrected according to the albumin levels. Furthermore, cases with therapeutic drug concentrations frequently became supratherapeutic when normalized. The limitations and clinical aplications of the proposed formula for normalizing the total concentration of valproic acid are presented. It is concluded that it may be useful for the posological management of hypoalbuminemic patients when the free concentration of the drug is not available, and decisions have to be made based on the total serum concentration.

著者

Satoru Ebihara Masahiro Kohzuki Yasunori Sumi Takae Ebihara

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.115, no.2, pp.99-104, 2011 (Released:2011-02-18)

参考文献数

37

被引用文献数

33 44

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Morbidity and mortality from aspiration pneumonia continues to be a major health problem in the elderly. A swallowing disorder, such as a delayed triggering of the swallowing reflex, exists in patients with aspiration pneumonia. We found that the swallowing reflex in elderly people was temperature-sensitive. The swallowing reflex was delayed when the temperature of the food was close to body temperature. The actual swallowing time shortened when the temperature difference increases. The improvement of swallowing reflex by temperature stimuli could be mediated by the temperature-sensitive transient receptor potential (TRP) channel. The administration of a pastille with capsaicin as an agonist stimulus of TRPV1, a warm-temperature receptor, decreased the delay in swallowing reflex. Food with menthol, an agonist of TRPM8, a cold-temperature receptor, also decreased the delay in swallowing reflex. Olfactory stimulation such as black pepper was useful to improve the swallowing reflex for people with low activity of daily living (ADL) levels or with decreased consciousness. Oral care also shortened the latent time of swallowing reflex presumably due to stimulating the nociception of the oral cavity. A combination of these sensory stimuli may improve the swallowing disorders and prevent aspiration pneumonia.

著者

Akihiro Tanaka Katsuya Suemaru Hiroaki Araki

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

pp.0709070001, (Released:2007-09-08)

参考文献数

27

被引用文献数

34 35

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In clinical practice, the measurement of endogenous serum substances in order to estimate glomerular filtration rate (GFR) is commonly performed, and the serum creatinine level has become the most commonly used serum marker of renal function. However, the measurement of the serum creatinine concentration can sometimes lead to an overestimation of GFR, especially in the elderly. In recent years, it has been suggested that GFR can be predicted based on the serum cystatin C concentrations and that the serum cystatin C concentration is not influenced by gender or age. A recent meta-analysis demonstrated that serum cystatin C is a better marker for GFR than serum creatinine. In clinical practice, it has been suggested that serum cystatin C can optimize early detection for diabetic or hypertensive nephropathy. In addition, the use of serum cystatin C is possibly more appropriate for establishing an appropriate dose adjustment of drugs that are mainly eliminated by the kidney.

著者

Donald M. Bers Sanda Despa

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.100, no.5, pp.315-322, 2006 (Released:2006-06-24)

参考文献数

41

被引用文献数

114 139

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Ca2+ is a central player in the excitation-contraction coupling of cardiac myocytes, the process that enables the heart to contract and relax. Mishandling of Ca2+ is a central cause of both contractile dysfunction and arrhythmias in pathophysiological conditions such as heart failure (HF). Upon electrical excitation, Ca2+ enters the myocytes via voltage-gated Ca2+ channels and induces further Ca2+ release from the sarcoplasmic reticulum (SR). This raises the free intracellular Ca2+ concentration ([Ca2+]i), activating contraction. Relaxation is driven by [Ca2+]i decline, mainly due to re-uptake into the SR via SR Ca2+-ATPase and extrusion via the sarcolemmal Na+/Ca2+ exchange, NCX. Intracellular Na+ concentration ([Na+]i) is a main regulator of NCX, and thus [Na+]i plays an important role in controlling the cytosolic and SR [Ca2+]. [Na+]i may have an even more important role in HF because NCX is generally upregulated. There are several pathways for Na+ entry into the cells, whereas the Na+/K+ pump (NKA) is the main Na+ extrusion pathway and therefore is essential in maintaining the transmembrane Na+ gradient. Phospholemman is an important regulator of NKA function (decreasing [Na+]i affinity unless it is phosphorylated). Here we discuss the interplay between Ca2+ and Na+ in myocytes from normal and failing hearts.

著者

Akihiko Wada Hiroki Yokoo Toshihiko Yanagita Hideyuki Kobayashi

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.99, no.4, pp.307-321, 2005 (Released:2005-12-17)

参考文献数

100

被引用文献数

104 122

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In addition to the well-documented mood-stabilizing effects of lithium in manic-depressive illness patients, recent in vitro and in vivo studies in rodents and humans have increasingly implicated that lithium can be used in the treatment of acute brain injuries (e.g., ischemia) and chronic neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, tauopathies, and Huntington’s disease). Consistent with this novel view, substantial evidences suggest that depressive illness is not a mere neurochemical disease, but is linked to gray matter atrophy due to the reduced number/size of neurons and glia in brain. Importantly, neurogenesis, that is, birth/maturation of functional new neurons, continues to occur throughout the lifetime in human adult brains (e.g., hippocampus); the neurogenesis is impaired by multiple not-fully defined factors (e.g., aging, chronic stress-induced increase of glucocorticoids, and excitotoxicity), accounting for brain atrophy in patients with depressive illness and neurodegenerative diseases. Chronic treatment of lithium, in agreement with the delayed-onset of mood-stabilizing effects of lithium, up-regulates cell survival molecules (e.g., Bcl-2, cyclic AMP-responsive element binding protein, brain-derived neurotrophic factor, Grp78, Hsp70, and β-catenin), while down-regulating pro-apoptotic activities (e.g., excitotoxicity, p53, Bax, caspase, cytochrome c release, β-amyloid peptide production, and tau hyperphosphorylation), thus preventing or even reversing neuronal cell death and neurogenesis retardation.

著者

Hitoshi Kaneko Kozo Nakanishi

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.95, no.2, pp.158-162, 2004 (Released:2004-06-23)

参考文献数

9

被引用文献数

92 115

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We are exposed to many external and internal stresses in this day and age. Stress weakens the function of immune systems in living organisms and disturbs homeostasis. As a result, stress induces various psychosomatic diseases. Thus, ways of reducing stress and thus protecting humans from disease must be developed. One such method is called “the prevention of Mibyou” in Kampo, the Chinese traditional medicine. Many studies have reported the direct effects of medical ginseng on damaged target organs and recovery from disease. It also increases immune potential and may maintain homeostasis of living organisms through the autonomic-endocrine systems. It is also thought to prevent the development of disease. We studied and considered the action of medical ginseng on living organisms that were exposed to various stresses such as cold environment and industrial work. Furthermore, we confirmed the preventive effects of medical ginseng on the common cold symptom complex, including flu, by clinical observation. Here, we report our experiences.

著者

Nobuaki Egashira Kazuhide Hayakawa Megumi Osajima Kenichi Mishima Katsunori Iwasaki Ryozo Oishi Michihiro Fujiwara

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.105, no.2, pp.211-214, 2007 (Released:2007-10-17)

参考文献数

11

被引用文献数

45 64

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We investigated the involvement of γ-aminobutyric acidA (GABAA) receptors in the neuroprotective effect of γ-glutamylethylamide (theanine), a component of Japanese green tea, following a 4-h middle cerebral artery (MCA) occlusion in mice. Theanine (1 mg/kg) reduced the size of the cerebral infarct and alterations of NeuN, GFAP, and Iba 1 expression levels at 24 h after MCA occlusion. This neuroprotective effect of theanine was prevented by bicuculline (GABAA-receptor antagonist, 10 mg/kg) but not 3-mercaptopropionic acid (glutamate decarboxylase inhibitor). These results suggest that the neuroprotective effect of theanine is mediated, at least in part, by GABAA receptors.

著者

Masato Yasui

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.96, no.3, pp.260-263, 2004 (Released:2004-11-20)

参考文献数

22

被引用文献数

28 36

---

The discovery of the water channel aquaporin has greatly expanded our understanding of the regulation of the water permeability of biological membranes. The atomic structure of aquaporin-1 (AQP1) demonstrated how aquaporin is freely permeated by water but not protons and provided marked insight into several human disorders. Eleven mammalian aquaporins have been identified, each with a distinct distribution, and these are selectively permeated by water or water plus glycerol. Aquaporins are suspected in numerous pathological conditions involving fluid transport such as brain edema. Knowledge of aquaporin structure may provide insight into the development of new therapeutics through appropriate drug design.

著者

Masaru Kunitomo Yu Yamaguchi Satomi Kagota Noriko Yoshikawa Kazuki Nakamura Kazumasa Shinozuka

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.110, no.3, pp.354-361, 2009 (Released:2009-07-17)

参考文献数

50

被引用文献数

26 36

---

Cigarette smoking is a major risk factor for cardiovascular disease. The induction of oxidative stress by smoking plays a key role in the progression of atherosclerosis. However, the underlying mechanisms are not fully understood. In the present study, we investigated whether long-term smoking can accelerate the progression of atherosclerosis and whether oxidative stress is implicated in its pathogenesis. Apolipoprotein E–deficient spontaneously hyperlipidemic mice, a model of atherosclerosis, were exposed to the gas-phase of smoke, from which tar and nicotine had been removed, for 15 min a day, 6 days a week, for 16 weeks. Exposure to cigarette smoke significantly increased the serum levels of oxidative stress markers such as thiobarbituric acid–reactive substances, oxidatively modified low-density lipoproteins, and 3-nitrotyrosine, but it did not affect serum cholesterol and triglyceride levels. Exposure to smoke also accelerated the accumulation of total cholesterol levels in the aorta that was accompanied by an increase in 3-nitrotyrosine levels of the atherosclerotic mice. These changes in the serum and aorta that progressed with exposure to smoke were prevented by vitamin E administration. Our data suggest that chronic cigarette smoking promotes and aggravates atherosclerosis and that the antioxidant vitamin E exerts an anti-atherogenic effect via reduction of oxidative stress.

著者

Tomohiro Okuda Dongying Zhang He Shao Nobuyuki Okamura Naoko Takino Tatsunori Iwamura Eiko Sakurai Takeo Yoshikawa Kazuhiko Yanai

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.111, no.2, pp.167-174, 2009 (Released:2009-10-15)

参考文献数

26

被引用文献数

17 27

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Histamine H3 receptors inhibit the release of not only histamine itself, but also other neurotransmitters including dopamine. Previous papers have reported that histaminergic neurons inhibit psychostimulant-induced behavioral changes. To examine whether deficiency in histamine H3 receptors influences psychostimulant-induced behavioral sensitization and reward, we examined locomotor activity, conditioned place preference (CPP), and c-Fos expression in histamine H3 receptor–gene knockout mice (H3KO) and their wild-type (WT) counterparts before and after treatment with methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA). The increase in locomotion induced by treatment with METH or MDMA was lower in histamine H3KO mice than in WT mice, while the locomotor sensitization was developed by METH or MDMA in both strains. However, no significant difference in METH- and MDMA-induced preference scores of CPP between histamine H3KO mice and WT mice was observed. Following treatment with METH, the number of c-Fos–positive neurons in the the caudate-putamen of histamine H3KO mice was lower than that in the caudate-putamen of WT mice. In contrast, there was no significant difference in the number of the psychostimulant-induced c-Fos–positive cells in the nucleus accumbens between the two strains of mice. These findings suggest that deficiency in histamine H3 receptors may have inhibitory effects on psychostimulant-induced increase in locomotion, but insignificant effects on the reward.

著者

Yuki Takada-Takatori Toshiaki Kume Yasuhiko Izumi Tetsuhiro Niidome Takeshi Fujii Hachiro Sugimoto Akinori Akaike

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.112, no.3, pp.265-272, 2010 (Released:2010-03-19)

参考文献数

24

被引用文献数

4

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We have previously shown that chronic donepezil treatment induces nicotinic acetylcholine receptor up-regulation and enhances the sensitivity of the neurons to the neuroprotective effect of donepezil. Further analyses revealed that the nicotinic receptor is involved in this enhancement. In this study, we examined whether nicotinic receptor stimulation is sufficient to make neurons more sensitive to donepezil. We treated primary cultures of rat cortical neurons with nicotine and confirmed that chronic nicotine treatment induced nicotinic receptor up-regulation and made the neurons more sensitive to the neuroprotective effects of donepezil. Analyses with receptor antagonists and kinase inhibitors revealed that the effects of chronic nicotine treatment are mediated by nicotinic receptors and their downstream effectors including phosphatidylinositol 3-kinase. In contrast to chronic donepezil treatment that enhanced the level of nicotine-induced Ca2+ influx, chronic nicotine treatment did not significantly alter the level of Ca2+ influx.

著者

Toshiaki Kume Ryo Ito Ryota Taguchi Yasuhiko Izumi Hiroshi Katsuki Tetsuhiro Niidome Yuki Takada-Takatori Hachiro Sugimoto Akinori Akaike

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.109, no.1, pp.110-118, 2009 (Released:2009-01-17)

参考文献数

41

被引用文献数

10 12

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We investigated the effect of serofendic acid, a neuroprotective substance derived from fetal calf serum, on the morphological changes in cultured cortical astrocytes. Cultured astrocytes developed a stellate morphology with several processes following exposure to dibutylyl cAMP (dbcAMP), a membrane-permeable cAMP analog; 8-Br-cGMP, a membrane-permeable cGMP analog; or phorbol-12-myristate-13-acetate (PMA), a protein kinase C activator. Serofendic acid significantly accelerated the stellation induced by dbcAMP- and 8-Br-cGMP. In contrast, the PMA-induced stellation was not affected by serofendic acid. Next, we attempted to elucidate the mechanism underlying the dbcAMP-induced stellation and explore the site of action of serofendic acid. Both the stellation induced by dbcAMP and the promotional effect of serofendic acid were partially inhibited by KT5720, a specific protein kinase A (PKA) inhibitor. Furthermore, serofendic acid failed to facilitate the stellation induced by Y-27632, an inhibitor of Rho-associated kinase (ROCK). These results indicate that serofendic acid promotes dbcAMP- and 8-Br-cGMP-induced stellation and the promotional effect on dbcAMP-induced stellation is mediated at least partly by the regulation of PKA activity and not by controlling ROCK activity.

著者

Ichiro Takada Miyuki Suzawa Shigeaki Kato

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.123, no.2, pp.207, 2013 (Released:2013-10-19)

被引用文献数

1

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

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.