著者

神戸 敏江 土屋 香誉子 堀 誠 浴本 久雄 高橋 良和 竹内 富雄

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.17, no.4, pp.527-530, 1994-04-15 (Released:2008-04-10)

参考文献数

5

被引用文献数

1

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Several antitumor anthracyclines, including those in preclinical stages, were examined for their action in reversing tumorous phenotypes of H- or K-ras 3T3 cells (NIH3T3 cells transformed by human H- or K-ras oncogene) into normal phenotypes, such as flattened cell morphology, anchorage dependent cell growth, etc. (referred to as anti-ras activity). The study elucidated relationships between the chemical structure of anthracyclines and the anti-ras activity. The human tumor cell line T24, which has a mutated H-ras gene, responded to the anthracyclines, as did K- or H-ras 3T3 cells, in respect to the phenotypic alterations. Pirarubicin was more than 4 times as active as aclarubicin in inhibiting the growth of solid tumors of K-ras 3T3 cells in nude mice, possibly reflecting a difference in anti-ras activity between the two antibiotics.

著者

Masashi Kitamura Masako Aragane Kou Nakamura Kazuhito Watanabe Yohei Sasaki

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b16-00090, (Released:2016-04-27)

参考文献数

31

被引用文献数

1 23

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In many parts of the world, the possession and cultivation of Cannabis sativa L. are restricted by law. As chemical or morphological analyses cannot identify the plant in some cases, a simple yet accurate DNA-based method for identifying C. sativa is desired. We have developed a loop-mediated isothermal amplification (LAMP) assay for the rapid identification of C. sativa. By optimizing the conditions for the LAMP reaction that targets a highly conserved region of tetrahydrocannabinolic acid (THCA) synthase gene, C. sativa was identified within 50 min at 60-66 °C. The detection limit was the same as or higher than that of conventional PCR. The LAMP assay detected all 21 specimens of C. sativa, showing high specificity. Using a simple protocol, the identification of C. sativa could be accomplished within 90 min from sample treatment to detection without use of special equipment. A rapid, sensitive, highly specific, and convenient method for detecting and identifying C. sativa has been developed and is applicable to forensic investigations and industrial quality control.

著者

Ji Yin Zhou Shi Wen Zhou Ke Bin Zhang Jian Lin Tang Li Xia Guang Yi Ying Ying Xu Le Zhang Dan Dan Li

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.31, no.6, pp.1169-1176, 2008-06-01 (Released:2008-06-01)

参考文献数

37

被引用文献数

61 114

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Berberine is one of the main alkaloids of Rhizoma coptidis which has been used as a folk medicine to treat diabetes mellitus for more than 1400 years in China. To investigate the chronic effect of berberine on diabetic hyperlipidemic rats, fasted rats were intraperitoneally injected 35 mg/kg streptozotocin. Diabetic rats were admitted after 2 weeks and given a high-carbohydrate/high-fat diet to induce hyperlipidemia. The rats were divided into 7 groups at the end of week 16: normal and diabetic rats received no drug, 5 treatment groups were administered with either 75, 150, 300 mg/kg berberine, 100 mg/kg fenofibrate or 4 mg/kg rosiglitazone per day for 16 weeks, respectively. The blood glucose, hemoglobin A1c, lipid metabolic parameters and hepatic glycogen and triglyceride were measured, and histopathology and peroxisome proliferator-activated receptors (PPARs) α/δ/γ expression of liver were determined by hematoxylin eosin and immunohistochemical staining. Berberine reduced diabetic rats' body weight, liver weight and liver to body weight ratio. Berberine restored the increased blood glucose, hemoglobin A1c, total cholesterol, triglyceride, low density lipoprotein-cholesterol, apolipoprotein B and the decreased high density lipoprotein-cholesterol, apolipoprotein AI levels in diabetic rats to near the control ones. Berberine alleviated the pathological progression of liver and reverted the increased hepatic glycogen and triglyceride to near the control levels. Berberine increased PPARα/δ expression and reduced PPARγ expression in liver of diabetic rat to near the control ones. Berberine improved glucolipid metabolism both in blood and liver in diabetic rats possibly through modulating the metabolic related PPARα/δ/γ protein expression in liver.

著者

Guo-Sheng Li Xu-Han Liu Hua Zhu Lan Huang Ya-Li Liu Chun-Mei Ma Chuan Qin

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.34, no.5, pp.644-654, 2011-05-01 (Released:2011-05-01)

参考文献数

41

被引用文献数

10 28

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The diabetic “lipotoxicity” hypothesis presents that fat-induced visceral white adipose tissue insulin resistance plays a central role in the pathogenesis of type 2 diabetes. Berberine, a hypolipidemic agent, has been reported to have antidiabetic activities. The molecular mechanisms for this property are, however, not well clarified. Therefore in this study type 2 diabetic hamsters were induced by high-fat diet with low-dose streptozotocin. Then, we investigated the gene expression alterations and explored the molecular mechanisms underlying the therapeutic effect of berberine on fat-induced visceral white adipose tissue insulin resistance in diabetic hamsters by microarray analysis followed by real-time reverse transcription-polymerase chain reaction (RT-PCR) confirmation. Type 2 diabetic hamsters exhibited hyperglycemia and relative hyperinsulinemia, glucose intolerance, insulin resistance, intra-adipocyte lipid accumulation, significant increase in body weight and visceral white adipose tissue weight, abnormal serum adipokines levels, and deleterious dyslipidemia. Furthermore, they had increased sterol regulatory element-binding proteins (SREBPs) expression and decreased liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) expression in visceral white adipose tissue. After 9-week berberine treatment, fat-induced insulin resistance and diabetic phenotype in type 2 diabetic hamsters were significantly improved. Compared with diabetic hamsters, expression of LXRs and PPARs significantly increased and SREBPs significantly decreased in visceral white adipose tissue from berberine-treated diabetic hamsters. These results suggest that altered visceral white adipose tissue LXRs, PPARs, and SREBPs transcriptional programs are involved in the therapeutic mechanisms of berberine on fat-induced visceral white adipose tissue insulin resistance in type 2 diabetic hamsters.

著者

Yong-Qiang Shan Yan-Ping Zhu Jing Pang Yan-Xiang Wang Dan-Qing Song Wei-Jia Kong Jian-Dong Jiang

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.36, no.10, pp.1562-1569, 2013-10-01 (Released:2013-10-01)

参考文献数

41

被引用文献数

11 40

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This study was designed to improve the absorption and hypoglycemic efficacy of berberine (BBR), which is a substrate of P-glycoprotein (P-gp), by combination with a P-gp inhibitor tetrandrine (Tet). Flow cytometry and LC-MS/MS were used to determine the cellular efflux or retention of chemicals. Pharmacokinetic study was performed in ICR mice following oral administration of the study compounds. The hypoglycemic efficacies of the compounds were evaluated in diabetic KK-Ay mice. In the in vitro experiments, Tet significantly inhibited the efflux and increased the uptake of P-gp substrates rhodamine-123 as well as BBR in MCF7/DOX cells and Caco-2 intestinal cells. Meanwhile, Tet greatly reduced the expression of P-gp in Caco-2 cells. The inhibition of BBR efflux by Tet was translated into improved pharmacokinetics in vivo. When co-administered, Tet dose-dependently increased the average maximum concentration (Cmax) and area under concentration–time curve (AUC0–24) of BBR in mice. Tet itself had no impact on glucose metabolism. However, it greatly potentiated the hypoglycemic efficacy of BBR in diabetic KK-Ay mice. In addition, we found that Tet had moderate inhibitory effect on the catalytic activity of CYP3A4, which played a role in the bio-transformation of BBR, and this may also take part in the improvement of the pharmacokinetics of BBR. In summary, combination with P-gp inhibitors such as Tet can improve the pharmacokinetics and hypoglycemic efficacy of BBR greatly; this implicates a feasible strategy for exploring the therapeutic effects of BBR and other pharmaceuticals which are substrates of P-gp.

著者

Sayaka Masada-Atsumi Yukie Kumeta Yutaka Takahashi Takashi Hakamatsuka Yukihiro Goda

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.37, no.3, pp.454-460, 2014-03-01 (Released:2014-03-01)

参考文献数

23

被引用文献数

5 18 3

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Despite the increasing sales of black cohosh (the dried rhizome and root of Cimicifuga racemosa L.) in the world herbal market, these products have continuous adulteration issues. The botanical authenticity of the black cohosh products is the first important step for ensuring their quality, safety and efficacy. In this study, we genetically identified the botanical sources of 10 black cohosh products and 5 Cimicifuga Rhizome crude drugs of Japanese Pharmacopoeia grade, and analyzed the metabolic profiling of 25 black cohosh products using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Consequently, we found that C. dahurica and possibly C. foetida are misused as sources of the black cohosh products and in some cases, the extracts of black cohosh were adulterated with the plant materials of C. dahurica. We demonstrated that these three species can be distinguished by three marker compounds in a specific mass range. These results must be helpful in establishing regulations for the safe use of the black cohosh products.

著者

Raimundo Pajón GONZÁLEZ Albert LEYVA Manoel Odorico MORAES

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.24, no.10, pp.1097-1101, 2001 (Released:2002-06-28)

参考文献数

38

被引用文献数

17 23 47

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The discovery that angiogenesis is a key condition for the growth of a tumor beyond a millimeter or two, brings about a new approach in the treatment of tumors using drugs able to inhibit the formation of new blood vessels. Also, it has been realized that antiangiogenic drugs can be useful in the treatment of other pathological processes, now classified as angiogenesis-dependent diseases. Initially, cartilage was considered as a possible natural source of antiangiogenic compounds due to its known avascular nature. To date, a number of in vitro and in vivo studies have suggested the existence of antiangiogenic and antitumor compounds in bovine and shark cartilage. However, the potential usefulness of shark cartilage in the treatment of cancer and other angiogenesis-dependent diseases have not been totally accepted due to (i) unsatisfactory patient outcome in clinical trials that have used shark cartilage in cancer patients, (ii) the lack of data that correlates bioavailability with pharmacological effects using oral shark cartilage. Thus, the objective of this review is to describe the main basic and clinical investigations reported in the literature, in which the antiangiogenic and/or antitumor properties of shark cartilage or of its extracts were evaluated. Possible explanations for conflicting results are discussed as well.

著者

Ji-young Lee Jun-Gu Oh Jin Sook Kim Kwang-Won Lee

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.37, no.7, pp.1162-1167, 2014-07-01 (Released:2014-07-01)

参考文献数

24

被引用文献数

1 14

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Advanced glycation end-products (AGEs) have been implicated in the development of diabetic complications. We report the antiglycating activity of chebulic acid (CA), isolated from Terminalia chebula on breaking the cross-links of proteins induced by AGEs and inhibiting the formation of AGEs. Aminoguanidine (AG) reduced 50% of glycated bovine serum albumin (BSA) with glycolaldehyde (glycol-BSA)-induced cross-links of collagen at a concentration of 67.8±2.5 mM, the level of CA required for exerting a similar antiglycating activity was 38.8±0.5 µM. Also, the breaking activity on collagen cross-links induced by glycol-BSA was potent with CA (IC50=1.46±0.05 mM), exhibiting 50-fold stronger breaking activity than with ALT-711, a well-known cross-link breaker (IC50=72.2±2.4 mM). IC50 values of DPPH· scavenging activity for CA and ascorbic acid (AA) were 39.2±4.9 and 19.0±1.2 µg dry matter (DM) mL−1, respectively, and ferric reducing and antioxidant power (FRAP) activities for CA and AA were 4.70±0.06 and 11.4±0.1 mmol/FeSO4·7H2O/g DM, respectively. The chelating activities of CA, AG and ALT711 on copper-catalyzed oxidation of AA were compared, and in increasing order, ALT-711 (IC50 of 1.92±0.20 mM)<CA (IC50 of 0.96±0.07 mM)<AG (0.47±0.05 mM). Thus, CA could be a breaker as well as an inhibitor of AGE cross-linking, the activity of which may be explained in large part by its chelating and antioxidant activities, suggesting that CA may constitute a promising antiglycating candidate in intervening AGE-mediated diabetic complications.

著者

Bahar Ahmed Adnan Jathlan Al-Rehaily Tawfeq Abdullah Al-Howiriny Khaled Abdelatee El-Sayed Mohammad Shamim Ahmad

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.26, no.4, pp.462-467, 2003 (Released:2003-04-01)

参考文献数

17

被引用文献数

21 48

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Five iridoid glycosides, including the two new compounds scropolioside-D2 (1) and harpagoside-B (2), were isolated from the aerial parts of Scrophularia deserti DEL (Scrophulariaceae). Their structures were elucidated on the basis of spectral data to be 6-O-[2″,4″-di-O-acetyl-3″-O-trans-cinnamoyl)-α-L-rhamnopyranosyl]-8α-hydroxymethyl-1α,5β,6α,7α,9β-pentahydro-7(8)-epoxy-2-oxaind-3-ene-1-O-β-D-glucopyranoside-6′-O-acetate (1) and 5-O-β-hydroxy-8-O-β-trans-cinnamoyl-8α-methyl-1,6,7,9-tetrahydro-2-oxaind-3-ene-1-O-β-D-glucopyranoside (2), respectively. In addition, three more iridoid glycosides, scropolioside-D (3), koelzioside (4), and 8-O-acetyl-harpagide (5), were also isolated and characterized from this source. The biological activity and the structure activity relationship of the compounds were also studied, and scropolioside-D (3) and harpagoside-B (2) were found to possess significant antidiabetic and antiinflammatory activity, respectively.

著者

Seong Soo Joo Yeong Min Yoo Byung Woo Ahn Sang Yun Nam Yun-Bae Kim Kwang Woo Hwang Do Ik Lee

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.31, no.7, pp.1392-1396, 2008-07-01 (Released:2008-07-01)

参考文献数

26

被引用文献数

26 77

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Considering the importance of inflammation and apoptosis in neurodegenerative conditions, the potential suppressive effects of the Rg3, a by-product obtained during the steaming of red ginseng, may indicate that Rg3 could provide a beneficial therapeutic approach to treating or preventing neurodegenerative disease. We investigated the effect of Rg3 on Aβ42-mediated microglial activation and inflammation-mediated neurotoxicity in murine BV-2 microglial and Neuro-2a neuroblastoma cells, respectively. Rg3 effectively reduced inflammatory cytokine expression in Aβ42-treated BV-2, and inhibited the binding of NF-κB p65 to its DNA consensus sequences, and significantly reduced the expression of TNF-α in activated microglia. Pretreatment with Rg3 increased the survival rate of Neuro-2a exposed to TNF-α. These observations suggest that Rg3 reduced neurotoxicity by inhibiting chronic inflammation through the suppression of activated microglia. In addition, the expression of pro-inflammatory cytokines in BV-2 stimulated by Aβ42 was decreased but not eliminated by Rg3 when binding to the macrophage scavenger receptor type A (MSRA) was blocked with fucoidan. This implies that the inflammatory response may not be exclusively triggered via MSRA. More interestingly, iNOS was almost completely inhibited in the presence of Rg3 when MSRA binding was blocked with fucoidan. Moreover, Rg3 increased the expression of MSRA in BV-2 transfected with siRNA targeting MSRA mRNA, and this increased MSRA expression may play a role in the phagocytosis of Aβ42 peptides. Our results indicate that inhibition of the inflammatory repertoire of microglia, neuroprotection, and increased MSRA expression induced by Rg3 may at least partly explain its therapeutic effects in chronic neurodegenerative diseases.

著者

Makoto Kajizono Hikaru Sada Yuhko Sugiura Yoshihiko Soga Yoshihisa Kitamura Junji Matsuoka Toshiaki Sendo

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.38, no.12, pp.1850-1855, 2015-12-01 (Released:2015-12-01)

参考文献数

46

被引用文献数

3 47

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Zoledronic acid and denosumab are two antiresorptive drugs currently in use for treating osteoporosis. They have different mechanisms of action, but both have been shown to delay the onset of skeletal-related events in patients with advanced cancer. However, medication-related osteonecrosis of the jaw (MRONJ) has been reported in cancer patients treated with zoledronic acid or denosumab. We studied 155 patients with several types of advanced cancer who were treated with zoledronic acid or denosumab in our hospital during the period from April 2010 through March 2013. Thirteen of these 155 patients (8.4%) developed MRONJ. MRONJ development was significantly associated with the number of zoledronic acid or denosumab infusions (p<0.001) and the duration of zoledronic acid or denosumab therapy (p<0.001). Logistic regression analysis showed that diabetes [odds ratio (OR)=6.699, 95% confidence interval (CI), 1.435–31.277, p=0.016], anemia [OR=14.559, 95% CI, 2.161–98.069, p=0.006], and pus discharge [OR=6.491, 95% CI, 1.514–27.835, p=0.012] significantly increased the risk of developing MRONJ. However, the risk of MRONJ was significantly lower [OR=0.137, 95% CI, 0.020–0.944, p=0.043] when patients received periodical dentistry maintenance. Diabetes, anemia, and pus discharge may also play roles in its development. These findings suggest that the active inclusion of dentistry maintenance in bisphosphonate or denosumab treatment of cancer patients can reduce MRONJ development.

著者

Ryogo Umetsu Junko Abe Natsumi Ueda Yamato Kato Toshinobu Matsui Yoko Nakayama Yasutomi Kinosada Mitsuhiro Nakamura

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.38, no.11, pp.1689-1699, 2015-11-01 (Released:2015-11-01)

参考文献数

38

被引用文献数

1 23

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Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of depression worldwide. SSRIs are suspected to increase the risk of suicidal ideation and behavior (suicidality) in children, adolescents, and young adults. We examined the association between SSRI therapy and suicidality by applying a logistic regression model to age-stratified data from the Food and Drug Administration (FDA) Adverse Event Reporting System database. We attempted to mitigate the effect of patient-related factors by data subsetting. We selected case reports for SSRIs as referred to in the World Health Organization Anatomical Therapeutic Chemical classification code N06AB. The association between SSRIs and “suicidal events” or “self-harm events” was calculated as a reporting odds ratio (ROR) and adjusted for covariates by logistic regression. For subjects <18 years old (y.o.) the adjusted RORs (95% confidence interval) of SSRI therapy with suicidal events were 9.58 (8.97–10.23) in the whole data analysis and 4.64 (4.15–5.19) in the subset analysis; those with self-harm events were 31.40 (27.71–35.58) and 16.31 (13.12–20.29), respectively. Although the adjusted RORs were lower in the subset analyses than in the whole data analyses, both analyses indicated associations between SSRI treatment and suicidal and self-harm events. In both analyses these associations were stronger in the <18 y.o. group than other age groups. Children and adolescents should be closely monitored for the occurrence of suicidality when they are prescribed SSRIs. In addition, we found that data subsetting might mitigate the effect of an intrinsic risk among patients taking the suspected drug.

著者

Quan Feng Liu Jang Ho Lee Young-Mi Kim Soojin Lee Yoon Ki Hong Soojin Hwang Youngje Oh Kyungho Lee Hye Sup Yun Im-Soon Lee Songhee Jeon Young-Won Chin Byung-Soo Koo Kyoung Sang Cho

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b15-00459, (Released:2015-10-10)

参考文献数

58

被引用文献数

3 37

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Alzheimer’s disease (AD) is the most common neurodegenerative disorder, characterized by progressive neuronal loss with amyloid β-peptide (Aβ) plaques. Despite several drugs currently used to treat AD, their beneficial effects on AD progress remains under debate. Here, we established a rapid in vivo screening system using Drosophila AD models to assess the neuroprotective activities of medicinal plants that have been used in traditional Chinese medicine. Among 23 medicinal plants tested, the extracts from five plants, Coriandrum sativum, Nardostachys jatamansi, Polygonum multiflorum (P. multiflorum), Rehmannia glutinosa, and Sorbus commixta (S. commixta), showed protective effects against the Aβ42 neurotoxicity. We further characterized the neuroprotective activity of ethanol extracts from P. multiflorum and S. commixta. Aβ42-expressing flies that we used showed AD neurological phenotypes, such as decreased survival and motility and increased cell death and reactive oxygen species level. However, feeding these flies extracts from P. multiflorum or S. commixta showed strong suppression of such phenotypes. Similar results were observed in human cells, so that the treatment of P. multiflorum and S. commixta extracts increased the viability of Aβ-treated SH-SY5Y cells. Moreover, 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside, one of the main constituents of P. multiflorum, also showed similar protective activity against Aβ42 cytotoxicity in both Drosophila and human cells. Taken together, our results suggest that both P. multiflorum and S. commixta have therapeutic potential for the treatment of neurodegenerative diseases, such as AD.

著者

Hiroshi Fukasawa Madoka Nakagomi Naoko Yamagata Hiroshi Katsuki Kohichi Kawahara Kazuyoshi Kitaoka Takami Miki Koichi Shudo

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.35, no.8, pp.1206-1212, 2012-08-01 (Released:2012-08-01)

参考文献数

69

被引用文献数

17 75

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Tamibarotene (Am80), a synthetic retinoid approved in Japan for treatment of acute promyelocytic leukemia (APL), is a retinoic acid receptor (RAR) agonist with high specificity for RARα and RARβ over RARγ. Temporarily and spatially specific expression of RARs suggests their pivotal roles in the adult brain. Am80 is considered to be a promising candidate drug for treatment of Alzheimer’s disease (AD) because of its transcriptional controls of multiple target genes involved in etiology and pathology of AD. In APP23 AD model mice, administration of Am80 decreased the deposition of insoluble amyloid-β(42). In senescence-accelerated mice (SAMP8), Am80 ameliorated the decrease of cortical acetylcholine, as well as reducing anxiety in behavioral tests and improving the sleep deficit. Am80 also effected a significant improvement of memory in the rat scopolamine-induced memory deficit model. Like other retinoids, Am80 also has an immunomodulatory effect and reduces secretion of proinflammatory cytokines and chemokines by astrocytes and microglia surrounding amyloid-β plaques. In a rat experimental autoimmune encephalomyelitis model, Am80 reduced inflammatory cytokines and showed significant efficacy. Retinoids also promote differentiation of neural stem cells, and Am80 improved the recovery of spinal cord-injured rats. Am80 may also improve vascular factors involved in onset and/or progression of AD. Am80 has been in clinical use for treatment of APL in Japan since 2005, and has been reported to have fewer side effects than other retinoids. We have recently started a clinical study to evaluate the efficacy and safety of Am80 for the treatment of Alzheimer’s disease.

著者

Noriaki Nagai Atsushi Takeda Yuri Itanami Yoshimasa Ito

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.35, no.12, pp.2230-2237, 2012-12-01 (Released:2012-12-01)

参考文献数

42

被引用文献数

3 8

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Non-steroidal anti-inflammatory drugs (NSAIDs) comprise one of the most frequently used classes of medicines in the world; however, NSAIDs have significant side effects, such as gastroenteropathy, and rheumatoid arthritis patients taking NSAIDs are more susceptible to NSAID-induced gastric lesions as compared to patients with other diseases. In Asian countries, loxoprofen has been used clinically for many years as a standard NSAID. We demonstrate the preventive effect of the co-administration of water containing magnesium ion (magnesium water, 1–200 µg/kg) on the ulcerogenic response to loxoprofen in adjuvant-induced arthritis (AA) rats. Oral administration of loxoprofen (100 mg/kg) caused hemorrhagic lesions in the gastric mucosa of AA rats 14 d after adjuvant injection, and, following loxoprofen administration, the lesion score of AA rats was significantly higher than that of normal rats. The expression of inducible nitric oxide synthase (iNOS) mRNA and nitric oxide (NO) production in the gastric mucosa of AA rats were also increased by the administration of loxoprofen, and the increase in lesions and NO were prevented by the administration of aminoguanidine, an iNOS inhibitor. The co-administration of magnesium water decreased the ulcerogenic response to loxoprofen in AA rats. In addition, the co-administration of magnesium water attenuated the increase in iNOS mRNA expression and NO production in AA rats receiving loxoprofen. These results suggest that the oral co-administration of magnesium water to AA rats has a potent preventive effect on the ulcerogenic response to loxoprofen, probably by inhibiting the rise in iNOS and NO levels in the gastric mucosa.

著者

Takayoshi Mamiya Takamasa Asanuma Mitsuo Kise Yukihiko Ito Aya Mizukuchi Hiromichi Aoto Makoto Ukai

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.27, no.7, pp.1041-1045, 2004 (Released:2004-07-10)

参考文献数

21

被引用文献数

30 44

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We evaluated the effects of pre-germinated brown rice (hatsuga genmai, PGR) on learning and memory and compared them with those of polished rice or cornstarch. In mice that were fed pellets of polished rice or PGR for two weeks, the learning ability in the Morris water maze test was significantly enhanced compared with mice that were fed cornstarch pellets. In the Y-maze test, the intake of food pellets for two weeks failed to affect spontaneous alternation behavior. β-Amyloid25—35 (Aβ25—35: 3 nmol/mouse, i.c.v.) protein impaired spontaneous alternation behavior in mice that were fed pellets of cornstarch or polished rice. In contrast, PGR pellets prevented the Aβ25—35-induced impairment of spontaneous alternation behavior. These results suggest that polished rice and PGR have facilitating effects on spatial learning. In particular, it is surmised that PGR may prevent Alzheimer's disease associated with Aβ.

著者

Shigeyuki Ohta Sayaka Sakaguchi Yuki Kobayashi Norikazu Mizuno Kenji Tago Hiroshi Itoh

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.38, no.4, pp.594-600, 2015-04-01 (Released:2015-04-01)

参考文献数

26

被引用文献数

1 24

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GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) and is highly expressed in parts of tumor cells. The involvement of GPR56 in tumorigenesis has been reported. We generated agonistic monoclonal antibodies against human GPR56 and analyzed the action and signaling pathway of GPR56. The antibodies inhibited cell migration through the Gq and Rho pathway in human glioma U87-MG cells. Co-immunoprecipitation analysis indicated that the interaction between the GPR56 extracellular domain and transmembrane domain was potentiated by agonistic antibodies. These results demonstrated that functional antibodies are invaluable tools for GPCR research and should open a new avenue for therapeutic treatment of tumors.

著者

Manabu Murakami Hidetoshi Niwa Tetsuya Kushikata Hiroyuki Watanabe Kazuyoshi Hirota Kyoichi Ono Takayoshi Ohba

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.37, no.5, pp.834-839, 2014-05-01 (Released:2014-05-01)

参考文献数

20

被引用文献数

7 34

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The effects of inhalation anesthesia (2% isoflurane, sevoflurane, or enflurane) and intraperitoneal anesthesia with pentobarbital (65 mg/kg) were compared in rats using an electrocardiogram (ECG) and determination of blood oxygen saturation (SPO2) levels. Following inhalation anesthesia, heart rate (HR) and SPO2 were acceptable while pentobarbital anesthesia decreased HR and SPO2 significantly. This indicates that inhalation anesthesia is more preferable than pentobarbital anesthesia when evaluating cardiovascular factors. Additionally, pentobarbital significantly increased HR variability (HRV), suggesting a regulatory effect of pentobarbital on the autonomic nervous system, and resulted in a decreased response of the baro-reflex system. Propranolol or atropine had limited effects on ECG recording following pentobarbital anesthesia. Taken together, these data suggest that inhalation anesthesia is suitable for conducting hemodynamic analyses in the rat.

著者

Young-Hoon Song Soo-Jin Jeong Hee-Young Kwon Bonglee Kim Sung-Hoon Kim Dong-Youl Yoo

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.35, no.7, pp.1022-1028, 2012-07-01 (Released:2012-07-01)

参考文献数

33

被引用文献数

13 39

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Although ursolic acid isolated from Oldenlandia diffusa (Rubiaceae) was known to have anticancer activities in prostate, breast and liver cancers, the underlying mechanism of ursolic acid in ovarian cancer cells was not investigated so far. In the present study, the apoptotic mechanism of ursolic acid was elucidated in SK-OV-3 ovarian cancer cells by 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay, cell cycle analysis and Western blotting. Ursolic acid exerted cytotoxicity against SK-OV-3 and A2780 ovarian cancer cells with IC50 of ca. 50 and 65 µM, respectively. Apoptotic bodies were observed in ursolic acid treated SK-OV-3 cells. Also, ursolic acid significantly increased ethidium homodimer stained cells and sub-G1 apoptotic portion in SK-OV-3 cells. Consistently, Western blotting revealed that ursolic acid effectively cleaved poly(ADP-ribose) polymerase (PARP), caspase-9 and -3, suppressed the expression of survival genes such as c-Myc, Bcl-xL and astrocyte elevated gene (AEG)-1, and upregulated phosphorylation of extracellular signal-regulated kinase (ERK) in SK-OV-3 cells. Interestingly, ursolic acid suppressed β-catenin degradation as well as enhanced phosphorylation of glycogen synthase kinase 3 beta (GSK 3β). Furthermore, GSK 3β inhibitor SB216763 blocked the cleavages of caspase-3 and PARP induced by ursolic acid and proteosomal inhibitor MG132 disturbed down-regulation of β-catenin, activation of caspase-3 and decreased mitochondrial membrane potential (MMP) induced by ursolic acid in SK-OV-3 cells. Overall, our findings suggest that ursolic acid induces apoptosis via activation of caspase and phosphorylation of GSK 3β in SK-OV-3 cancer cells as a potent anti-cancer agent for ovarian cancer therapy.

著者

Kensuke Yamamura Junichi Kitagawa Masayuki Kurose Shinichiro Sugino Hanako Takatsuji Rahman Md Mostafeezur Hossain Md Zakir Yoshiaki Yamada

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.33, no.11, pp.1786-1790, 2010-11-01 (Released:2010-11-01)

参考文献数

47

被引用文献数

14 39

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Swallowing involves several motor processes such as bolus formation and intraoral transport of a food bolus (oral stage) and a series of visceral events that occur in a relatively fixed timed sequence but are to some degree modifiable (pharyngeal stage or swallow reflex). Reflecting the progressive aging of society, patients with swallowing disorders (i.e., dysphagia) are increasing. Therefore, there is expanding social demand for the development of better rehabilitation treatment of dysphagic patients. To date, many dysphagia diets have been developed and are available commercially to help bring back the pleasure of mealtimes to dysphagia patients. Texture modification of food to make the food bolus easier to swallow with less risk of aspiration is one of the important elements in dysphagia diets from the viewpoint of safety assurance. However, for the further development of dysphagia diets, new attempts based on new concepts are needed. One of the possible approaches is to develop dysphagia diets that facilitate swallow initiation. For this approach, an understanding of the mechanisms of swallow initiation and identification of factors that facilitate or suppress swallow initiation are important. In this review, we first summarize the neural mechanisms of swallowing and effects of taste and other inputs on swallow initiation based on data mainly obtained from experimental animals. Then we introduce a recently established technique for eliciting swallowing using electrical stimulation in humans and our ongoing studies using this technique.