Effects of pentagamavunon-0 on histaminemediated hyperresponsive airway in asthmatic models : in-vitro in-vivo

Agung Endro Nugroho, Hemmy Prasetyo, Djoko Suhardjono, Mulyono Zhang Be, Shuang Liu, Supardjan A. Margono, Kazutaka Maeyama


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


Full Text:

PDF 90-99


Barnes P. J., Chung K. F., and Page C. P., 1998, Inflammatory mediators of asthma: an update, Pharmacol. Rev., 50, 515–596.

Barnes P. J., and Liew F. Y., 1995, Nitric oxide and asthmatic inflammation, Immunol. Today, 16, 128–130.

Bochner B. S., and Busse W. W., 2005, Allergy and Asthma, J. Allergy Clin. Immunol., 115, 953-959.

Brunton L., Parker K., Blumenthal, and Buxton L., 2008, Pharmacotherapy of Asthma, In Goodman and Gliman’s Manual of Pharmacology and Therapeutics, The McGraw-Hill Companies Inc, Singapore. 464.

Di Bello M. G., Masini E., Ioannides C., Ndisang J.F., Raspanti S., Sacchi T. B., and Mannaioni P. F., 1998. Histamine release from rat mast cells induced by the metabolic activation of drugs of abuse into free radicals. Inflamm. Res. 47, 3, 122-130.

Hogan S. P., Koskinen A., Matthaei K. I., Young I. G., and Foster P. S., Interleukin-5-producing CD4+ T cells play a pivotal role in aeroallergen-induced eosinophilia, bronchial hyperreactivity, and lung damage in mice. Am J Respir Crit Care Med1998; 157, 210–8.

Holt P. G., Macaubas C., Stumbles P. A., and Sly P. D., 1999, The role of allergy in the development of asthma. Nature. 402, B12–7.

Kay A. B., 1991, Asthma and Inflammation, J. Allergy Clin. Immunol., 87, 893-910.

Kodak, 1961, Film-forming photosensitive polymers. Chem. Abstrs. 55, 11154h.

Liu S., Chihara K., and Maeyama K., 2005, The contribution of mast cells to the late-phase of allergic asthma in rats, Inflamm. Res., 54, 221-228.

Lomask M., 2006, Further exploration of the Penh parameter, Exp Toxicol Pathol., 57 (Suppl)2, 13-20.

Mannaioni P. F., Bello M. G. D., Raspanti S., Mugnai L., Romano V., and Masini E., 1996. Free radical mediated release of histamine from rat mastcells induced by drugs of abuse. Inflamm. Res. 45(suppl.1), S25-S26.

Masini E., Palmerani B., Gambassi F., Pistelli A., Giannella E., Occupati B., Ciuffi M., Sacchi B., and Mannaioni P. F., 1990., Histamine release from rat mast cells induced by metabolic activation of polyunsaturated fatty acidsinto free radicals. Biochem Pharmacol. 39, 5, 879-889.

Nugroho A. E., Sardjiman and Maeyama K., 2008, Inhibitory effect of 2,5-bis(4-hydroxy-3- methoxy benzylidene) cyclopentanone on mast cell histamine mediated-rat paw edema, 61th Annual Japanese Pharmacological SocietySouthwest Regional Meeting, Proceeding, Yonago Japan.

Nugroho, A. E., Ikawati, Z., Sardjiman, and Maeyama, K., 2009, Effects of benzylidenecyclopentanone analogues of curcumin on histamine release from mast cells, Biological Pharmaceutical Bulletin, 32, 5, 842-849.

O’Byrne P. M, 1998, Allergen-induced airway hyperresponsiveness, J. Allergy Clin. Immunol., 81, 119-127.

Rang, H. P., Dale, M. M., and Ritter, J. M., 2003, Pharmacology, 4th Ed., Churchill Livingstone, Melbourne.

Robinson A. T. W. , Phillips R. S., Severin A., Moncada S., and Liew F. Y., 1993, The role of TH1 and TH2 cells in a rodent malaria infection, Science, 260, 1931– 1934.

Sardjiman, 2000, Synthesis of a new series of curcumin analogues, biological activities and qualitative structure-activity relationships. Dissertation, Gadjah Mada University.

Sayah M. E, Filho V. C, Yunes R. A, Pinheiro T. R, and Calixto J. B, 1998, Action of Polygodial, a sesquiterpene isolated from Drymis winteri, in the guinea-pig ileum and trachea in vitro, European Journal of Pharmacology, 344 : 215-221.

Suzuki M., Nakamura T., Iyoki S., Fujiwara A., Watanabe Y., Mohri K., Isobe K., Ono K., and Yano S., 2005, Elucidation of anti-allergic activities of curcumin-related compounds with a special reference to their anti-oxidative activities. Biol Pharm Bull., 28, 8, 1438-1443.

Yamatodani A., Fukuda H., Wada H., Iwaeda T., and Watanabe T., 1985., High-performance liquid chromatographic determination of plasma and brain histamine without previous purification of biological samples : cation-exchange chromatography coupled with post-column derivatization fluorometry. J Chromatogr.344, 115-123.

DOI: http://dx.doi.org/10.14499/indonesianjpharm0iss0pp90-99


  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Indonesian J Pharm indexed by:

analytics View My Stats