Kazutaka maeyama
Department of Pharmacology, Informational Biomedicine, School of Medicine, Ehime University Japan

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EFEK SENYAWA FLAVONOIDS DARI KEMUNING (Murraya paniculata [L.] Jack.) TERHADAP PELEPASAN HISTAMIN DARI KULTUR SEL MAST Nugroho, Agung Endro; Riyanto, Sugeng; Sukari, Mohamad Aspollah; Maeyama, Kazutaka
Majalah Obat Tradisional Vol 15, No 1 (2010)
Publisher : Faculty of Pharmacy, Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (503.985 KB) | DOI: 10.14499/mot-TradMedJ15iss1pp%p

Abstract

Murraya paniculata [L.] Jack. merupakan tanaman yang tumbuh di Indonesia, dikenal dengan nama Kemuning. Penelitian mengenai tanaman ini telah banyak dilakukan, terutama isolasi senyawa aktifnya. Tanaman ini mempunyai kandungan senyawa aktif, diantaranya senyawa turunan flavonoid. Pada penelitian, tiga senyawa flavonoid yang diisolasi dari M. paniculata diuji aktivitasnya terhadap pelepasan histamin dari kultur sel mast yaitu sel RBL-2H3. Ketiga senyawa tersebut adalah 3,3’,4’,5,5’,7–heksametoksiflavon; 3,3’,4’,5,5’,6,7-heptametoksiflavon; dan 3,3’,4’,5,5’,6,7,8-oktametoksiflavon. Induktor pelepasan histamin yang digunakan adalah DNP24-BSA dan thapsigargin. Keduanya berturut-turut menginduksi secara imunologis dan non-imunologis. Hasil penelitian menunjukkan bahwa senyawa heptametoksiflavon dan heksametoksiflavon cenderung tidak mempengaruhi pelepasan histamin dari sel mast. Namun, oktametoksiflavon dapat meningkatkan pelepasan histamin dari sel mast baik tanpa induksi maupun terinduksi dengan DNP24-BSA atau thapsigargin. Senyawa tersebut mampun meningkatkan pelepasan histamin hingga 50%. Dari hasil tersebut, penambahan gugus polimetoksi pada struktur flavonoid berpotensi dapat menghasilkan efek pelepasan histamin dari sel mast.  
Comparison of Cytotoxic and Antiproliferative Effects of Benzylidenecyclopentanone Analogues of Curcumin on RBL-2H3 Cells Nugroho, Agung Endro; ., Sardjiman; Maeyama, Kazutaka
Indonesian Journal of Biotechnology Vol 15, No 2 (2010)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (253.862 KB)

Abstract

Curcumin is a natural yellow pigment isolated from the rhizomes of Curcuma longa L. (turmeric), and has several pharmacological effects and no toxicity in both in animal and human clinical study. However, the problem of curcumin is its stability because of its active methylene moiety. Modification of this moiety to cyclopentanone is expected to increase the stability. Previous study reported that benzylidenecyclopentanone analogues of curcumin showed inhibitory effect on histamine release from RBL-2H3 (rat basophilic leukemia) cells, a tumor analog of mast cells. One of them, the hydroxy-methoxy analog (PGV-0), showed more potent effect than that of curcumin. In the present study, some benzylidenecyclopentanone analogues of curcumin were evaluated for their effects on the viability and proliferation of RBL-2H3 cells. Viable cells were counted under a light microscope with a cells-counting chamber or using the cell viability reagent WST-1. The results showed that mast cell viability and histamine content were not affected by curcumin and benzylidene cyclopentanone for 30 min incubation, however, impaired for overnight incubation. The hydroxy-dimethyl benzylidene analog (PGV-1) strongly decreased the mast cells viability for overnight incubation, and its effect was highest among the other analogues. In the proliferation study, this compound also strongly inhibited the proliferation of mast cells, whereas curcumin and hydroxy-methoxy benzylidene analog inhibited the proliferation slightly. There were no inhibitory effects on mast cells proliferation treated by dibenzylidene; dihydroxybenzylidene; and hydroxy-diethylbenzylidene cyclopentanone.Keywords : viability, proliferation, curcumin, benzylidene cyclopentanone, RBL-2H3 cells
Comparison of Cytotoxic and Antiproliferative Effects of Benzylidenecyclopentanone Analogues of Curcumin on RBL-2H3 Cells Nugroho, Agung Endro; Sardjiman, S.; Maeyama, Kazutaka
Indonesian Journal of Biotechnology Vol 15, No 2 (2010)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (253.862 KB) | DOI: 10.22146/ijbiotech.7822

Abstract

Curcumin is a natural yellow pigment isolated from the rhizomes of Curcuma longa L. (turmeric), and has several pharmacological effects and no toxicity in both in animal and human clinical study. However, the problem of curcumin is its stability because of its active methylene moiety. Modification of this moiety to cyclopentanone is expected to increase the stability. Previous study reported that benzylidenecyclopentanone analogues of curcumin showed inhibitory effect on histamine release from RBL-2H3 (rat basophilic leukemia) cells, a tumor analog of mast cells. One of them, the hydroxy-methoxy analog (PGV-0), showed more potent effect than that of curcumin. In the present study, some benzylidenecyclopentanone analogues of curcumin were evaluated for their effects on the viability and proliferation of RBL-2H3 cells. Viable cells were counted under a light microscope with a cells-counting chamber or using the cell viability reagent WST-1. The results showed that mast cell viability and histamine content were not affected by curcumin and benzylidene cyclopentanone for 30 min incubation, however, impaired for overnight incubation. The hydroxy-dimethyl benzylidene analog (PGV-1) strongly decreased the mast cells viability for overnight incubation, and its effect was highest among the other analogues. In the proliferation study, this compound also strongly inhibited the proliferation of mast cells, whereas curcumin and hydroxy-methoxy benzylidene analog inhibited the proliferation slightly. There were no inhibitory effects on mast cells proliferation treated by dibenzylidene; dihydroxybenzylidene; and hydroxy-diethylbenzylidene cyclopentanone.Keywords : viability, proliferation, curcumin, benzylidene cyclopentanone, RBL-2H3 cells
DUAL EFFECTS OF FLAVONOID QUERCETIN ON RAT BASOPHILIC LEUKEMIA (RBL-2H3) CELLS : INHIBITS HISTAMINE RELEASE AND REDUCES CELL GROWTH Ikawati, Zullies; Wallgard, Elizabeth; Maeyama, Kazutaka
INDONESIAN JOURNAL OF PHARMACY Vol 13 No 2, 2002
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (130.619 KB) | DOI: 10.14499/indonesianjpharm0iss0pp55-64

Abstract

The dual effects of the flavonoid quercetin on rat basophilic leukemia cells (RBL-2H3), tumor analog mast cells, was studied. Quercetin is known as an anti-inflammatory drug that inhibits mast cell secretion of histamine. This study aims to investigate the consequences of varying incubation times with quercetin on 2H3 cells to histamine release inhibitory action and the effects of long time incubation to the morphology of the cells. The effect of quercetin on histamine synthesis was also observed. The histamine release from the cells was inhibited by quercetin as expected, but the ability of secretion was rapidly recovered when quercetin was removed before challenging. Incubation up to 6 hours decreased the inhibitory action, but longer than 6 hours increased the inhibitory activity. In long time incubation, the cells exhibited cell damage, decreased cell growth, morphological changes, and detachment from the underlying surface in proportion with the concentration of quercetin. The instant and reversible inhibitory effects of quercetin appear to represent a first phase of actions, while reduced cell growth, elevated cell damage and morphological changes seem to be connected to a second phase. Consequently, quercetin could be considered as a compound that acts dually on RBL-2H3 cells.Key words : quercetin, histamine, RBL-2H3 cells
Econazole depleted calcium release-activated calcium (CRAC) current through blockade of voltage-dependent Ca 2+ channels Nugroho, Agung Endro; Purnomo, Hari; Maeyama, Kazutaka
INDONESIAN JOURNAL OF PHARMACY Vol 22 No 2, 2011
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (349.21 KB) | DOI: 10.14499/indonesianjpharm0iss0pp128-136

Abstract

Econazole  is  an  azole  antifungal  agent  which  can  block  the  calcium release-activated  calcium  (CRAC)  current  in  human  leukaemic  T  cell  line.  The phenomenon  is  also  possible  to  occur  in  mast  cell  such  as  RBL-2H3  (rat basophilic  leukemia)  cells,  a  tumor  analog  of  mast  cells.  In  the  study,  we investigated  effect  of  econazole  on 45Ca2+ uptake  into  the  cells  in  response  to thapsigargin, an ATP-dependent Ca2+ (SERCA) inhibitor, by direct measurement of  radiolabelled  Ca2+ uptake  in  cells.  The  mechanism  underlying  this  effect  of econazole  was  studied  using  molecular  modelling.  In present  study,  econazole inhibited 45Ca2+ influx  into  mast  cells  in  absence  of  mast  cells  inducer, thapsigargin.  Moreover,  econazole  potently  suppressed  the 45Ca2+ influx induced  by  thapsigargin.  It  was  supported  that  econazole  also  inhibited  Ca2+-induced  tracheal  contraction.  The  increase  of  Ca2+ was  stimulated  by  the opening of voltage-dependent Ca2+ channels activated by KCl-induced membrane depolarization. Based on molecular docking study, score of interaction (equal to  energy  of  interaction)  of  3FGO,  a  main  protein  target  on  Ca2+ -ATPase,  with native ligan, thapsigargin and econazole were -76.941, -117.205, and -92.277, respectively.  The  interaction  of  thapsigargin  and  Ca2+ -ATPase  was  more  stable than  this  of  econazole  and  Ca2+ -ATPase.   It  suggests  that  it  would  be  difficult for  econazole  to  block  the  interaction  of  thapsigargin  with  Ca2+ -ATPase  to increase  intracellular  Ca2+.In  conclusion,  econazole  inhibited  the  increase  of intracellular Ca2+involving the blokade of voltage-dependent Ca2+ channels, but not involving the Ca2+ -ATPase pathway.Key words :econazole, Ca2+ -ATPase, CRAC current, thapsigargin 
The effects of PGV-1 and PGV-2 on the b-hexosaminidase release from intraceluller calcium ion-induced mast cells Nugroho, Agung Endro; ., Sardjiman; Maeyama, Kazutaka
INDONESIAN JOURNAL OF PHARMACY Vol 20 No 4, 2009
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (239.931 KB) | DOI: 10.14499/indonesianjpharm0iss0pp207-216

Abstract

PGV-1 or 2,5-bis(4-hydroxy-3,5-dimethylbenzylidene)cyclopentanone and PGV-2 or 2,5-bis(4-hydroxy-3,5 diethylbenzylidene)cyclopentanone are two benzylidene cyclopentanone analogues of curcumin. In our study, we investigated the effects of these compounds on the b-hexoaminidase enzyme release from mast cell culture (RBL-2H3 cell line). Thapsigargin and ionomycin were used as intracellular calcium ion stimulants for inducing b-hexoaminidase enzyme release from mast cells. The release of b-hexoaminidase enzyme was determined by colorimetric methods with substrate, p-nitrophenyl-2-acetamido-2-deoxy-b-D-glucopyranocide, and a microplate reader at 405 nm. In present study, treatment of 0.5 mM thapsigargin or 1 mM ionomycin could stimulate the release of b-hexoaminidase enzyme from RBL-2H3 cells by 43.91 ± 1.30 % and 52.93 ± 2.07 %, respectively. PGV-1 and PGV-2 showed inhibitory effects on the b-hexoaminidase enzyme release from RBL-2H3 cells induced by the increase of intraceluller calcium ion in dose dependent manner. At the dose of 100 mM, PGV-1 and PGV-2, respectively, inhibited the b-hexoaminidase enzyme release by 73.51 ± 8.69 % and 66.42 ± 8.63 % on thapsigargin experiments; and by 89.73 ± 3.23 % and 38.57 ± 5.32 % on ionomycin experiments. The IC50 values of their effects on the b-hexoaminidase enzyme release from RBL-2H3 cells, respectively, were 22.20 mM and 22.27 mM on thapsigargin experiment; and 22.77 mM and >100 mM on ionomycin experiment. Based on the results, the inhibitory effect of PGV-1 and PGV-2 on the b-hexoaminidase enzyme release from RBL-2H3 cells involving mechanisms related to the alteration on activation processes of intracellular calcium ion on mast cells.Key words : Curcumin, PGV-1, PGV-2, mast cells, b-hexoaminidase enzyme
The cytotoxic and antiproliferative effects of gamavuton-0 in rat basophilic Leukemia cells Nugroho, Agung Endro; ., Sardjiman; Maeyama, Kazutaka
INDONESIAN JOURNAL OF PHARMACY Vol 20 No 2, 2009
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (219.677 KB) | DOI: 10.14499/indonesianjpharm0iss0pp84-90

Abstract

Gamavuton-0 (GVT-0), also named as 1,5-bis(4’-hydroxy-3’- methoxyphenyl)-1,4-pentadiene-3 one is a 1,5-diphenyl-1,4-pentadiene-3-one analog of curcumin by modifying the center site of curcumin leading to 1,4-pentadiene-3-ones to maintain the hydroxy moiety at aromatic rings which are responsible for its biological activities. Curcumin has been reported to have potent anticarcinogenic effects. Besides, curcumin was found to induce apoptosis in human Leukemia cells. In our study, we investigated the cytotoxic and antiproliferative effects of gamavuton-0 in rat basophilic leukemia cells. Cell viability was determined by WST-1 assay. In brief, tetrazolium salts were cleaved to formazan by cellular enzymes of viable cells, determined by colorimetric methods with a microplate (ELISA) reader at 450 nm.In the present study, we evaluated cytotoxic and proliferative effects of GVT-0 in rat basophilic leukemia cells. In the study, GVT-0 induced rat basophilic leukemia cells death in a dose dependent manner after overnight incubation. GVT-0 also impaired the content of histamine and b-hexoaminidase enzyme in cells. However, the cytotoxic effect of GVT-0 (IC50 : 43,67 mM) was less potent than this of curcumin (IC50 : 29,14 mM). GVT-0 (1 mM) also showed a significant inhibition of cell growth after 48 and 72 hr. Its fact indicates that GVT-0 could prolong the cells doubling time. These results provide useful information to guide the development of new synthetic compounds for the treatment of cancer diseases.Key words : gamavuton-0, curcumin, cancer, cytotoxic, antiproliferative,
Effects of pentagamavunon-0 on histaminemediated hyperresponsive airway in asthmatic models : in-vitro in-vivo Nugroho, Agung Endro; Prasetyo, Hemmy; Suhardjono, Djoko; Be, Mulyono Zhang; Liu, Shuang; Margono, Supardjan A.; Maeyama, Kazutaka
INDONESIAN JOURNAL OF PHARMACY Vol 21 No 2, 2010
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (285.397 KB) | DOI: 10.14499/indonesianjpharm0iss0pp90-99

Abstract

Asthma  is  a  chronic  inflammatory  airway  disease  involving  reversible airway  constriction  and  airway  hyperresponsiveness  (AHR)  to  allergens,  airway edema,  and  increased  mucus  secretion  tumor  cells.  To  date,  exploration  of antiasthmatic  drug  is  still  being  studied  both  from natural  products  or  sinthetic processes.  One of the sinthetic compound is pentagamavunon-0  (PGV-0)  which possesses anti-inflammatory and inhibitory effects on histamine release from rat mast cells. The aim of the study is to look at the effects of PGV-0 on histaminemediated hyperresponsive airway in asthmatic models (in vitro and in vivo studies).  In  vitro  study  was  conducted  using  isolated  organ  technique  with isotonic  transducer.  The  results  have  shown  that  PGV-0  could  not  inhibit  the contraction  of  isolated  guinea  pig  trachea  induced  by  histamine.  PGV-0 did not change  the  pD2 and  Emax  values  of  histamine  on  trachea  smooth  muscle.  The finding  indicates  that  PGV-0  does  not  have  affinity and  intrinsic  activity  on  H-1 histaminergic  receptor  in  trachea  smooth  muscle.  In vivo  study,  we  sensitized the  rats  with  ovalbumin  (OVA)  to  develop  the  airway hyperreactivity  to histamine.  Histamine  level  in  bronchoalveolar  lavage  fluid  (BALF)  and  airway tissue  were  determined  using  HPLC-fluorometry.  Multiple  exposures  of ovalbumin  significantly  histamine  level  in  BALF  by  74.51±5.33  pmol/mL  or 6-times  higher  than  this  of  control  saline  group.  Oral  administration  of  PGV-0 (40  mg/kg  BW)  significantly  decreased  the  histamine accumulation  in  BALF  to 30  %  of  the  value  of  control  group  in  asthmatic  rats.  Besides,  PGV-0 significantly  prevented  the  histamine  decrease  in  asthmatic  rats  to  37.8  % trachea, and 34.2 % in bronchus. However, PGV-0 did not succeed to prevent the histamine decrease in the lung of asthmatic rats.  The result of the study may provide useful information for further discovering pharmacological synthetic compound for treatment of allergic inflammatory asthma.Key words: asthma, curcumin, pentamavunon-0, histamine, airway hyperresponsiveness 
EFEK SENYAWA FLAVONOIDS DARI KEMUNING (Murraya paniculata [L.] Jack.) TERHADAP PELEPASAN HISTAMIN DARI KULTUR SEL MAST Nugroho, Agung Endro; Riyanto, Sugeng; Sukari, Mohamad Aspollah; Maeyama, Kazutaka
Majalah Obat Tradisional Vol 15, No 1 (2010)
Publisher : Faculty of Pharmacy, Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (503.985 KB) | DOI: 10.22146/tradmedj.8066

Abstract

Murraya paniculata [L.] Jack. merupakan tanaman yang tumbuh di Indonesia, dikenal dengan nama Kemuning. Penelitian mengenai tanaman ini telah banyak dilakukan, terutama isolasi senyawa aktifnya. Tanaman ini mempunyai kandungan senyawa aktif, diantaranya senyawa turunan flavonoid. Pada penelitian, tiga senyawa flavonoid yang diisolasi dari M. paniculata diuji aktivitasnya terhadap pelepasan histamin dari kultur sel mast yaitu sel RBL-2H3. Ketiga senyawa tersebut adalah 3,3’,4’,5,5’,7–heksametoksiflavon; 3,3’,4’,5,5’,6,7-heptametoksiflavon; dan 3,3’,4’,5,5’,6,7,8-oktametoksiflavon. Induktor pelepasan histamin yang digunakan adalah DNP24-BSA dan thapsigargin. Keduanya berturut-turut menginduksi secara imunologis dan non-imunologis. Hasil penelitian menunjukkan bahwa senyawa heptametoksiflavon dan heksametoksiflavon cenderung tidak mempengaruhi pelepasan histamin dari sel mast. Namun, oktametoksiflavon dapat meningkatkan pelepasan histamin dari sel mast baik tanpa induksi maupun terinduksi dengan DNP24-BSA atau thapsigargin. Senyawa tersebut mampun meningkatkan pelepasan histamin hingga 50%. Dari hasil tersebut, penambahan gugus polimetoksi pada struktur flavonoid berpotensi dapat menghasilkan efek pelepasan histamin dari sel mast.  
Evaluasi Pewarnaan Alcian Blue Terhadap Sel Mast Jaringan Ikat dari Preparat Beku Jaringan Kulit Kaki Tikus Nugroho, Agung Endro; Maeyama, Kazutaka
PHARMACY: Jurnal Farmasi Indonesia (Pharmaceutical Journal of Indonesia) Jurnal Pharmacy, Vol. 08 No. 02 Agustus 2011
Publisher : Fakultas Farmasi, Universitas Muhammadiyah Purwokerto

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (3700.146 KB)

Abstract

Alcian blue merupakan pewarna golongan phthalosianin tembaga yang digunakan dalam pewarnaan asam mukopolisakarida dan proteoglikan jaringan ikat. Alcian blue mengandung empat gugus tetrametillisothiouronium yang bermuatan positif (tetrakationik) yang berikat secara elektrostatik dengan muatan negatif dari glikoaminoglikan (heparin). Alcian blue tidak mewarnai semua sel mast. Hal ini kemungkinan karena sisi anionik dari heparin terlindungi oleh protein, atau ikatan kompleks dalam granul sel mast sangat kuat. Safranin sering digunakan sebagai pewarna lanjutan sebagai kombinasi alcian blue dengan safranin untuk mewarnai articular cartilage proteoglikan pada pengamatan histologi.Pewarna tunggal aclian blue terhadap sel mast jaringan ikat memberikan warna biru langit hingga hijau, sedangkan pewarna alcian blue-safranin memberikan warna biru langit hingga hijau, sedangkan pewarnaan alcian blue-safranin memberikann variasi warna yaitu biru, merah dan campuran kedua warna tersebut. Sel mast akan teramati cukup jelas pada pewarnaan toluidine blue dibandingkan dengan pewarnaan alcian blue. Namun, pada pewarnaan alcian blue terutama alcian blue-safranin, jumlah sel mast jaringan ikat yang teramati lebih banyak dibandingkan pewarnaan toluidine blue.