Radioiodination of andrographolide and its biodistribution in mice for inflammatory tracer

Jutti Levita, Cahya Nova A., As’ari Nawawi, Slamet Ibrahim

Abstract


Andrographolide,  a  bioactive  component  of  Andrographis  paniculata (Burm.F)  Nees,  is  the  major  lactone  diterpenoidal  bicyclic  constituent  in  this plant  which  has  proven  to  exert  anti-inflammatory  activity  in  vitro  which  was occurred via  several mechanism, e.g inhibition of inducible nitric oxide synthase (iNOS),  inhibition  of  radical  oxygen  species,  and  inhibition  of  NF-kappaB activation. The labeling with radionuclide is often used for therapy, detection and quantification of metabolites in the body. Even though the metabolites are very low  in  concentration  they  can  be  detected  by  the  energy  they  emitted. Radionuclide  can  be  used as  radiotracer  to  detect  whether  drug  really interacts with  its  target.  The  objective  of  this  research  is  to  synthesize 131I-labelled andrographolide  and  to  study  its  biodistribution  in  mice  to  understand  the location  of  its  organ  target.  Indirect  radioiodination  of  andrographolide  was

carried  out  by  using  bromine  as  the  leaving  group  and  followed  by  fast iodination  at  40oC,  yielded  72.6  %  purity  of  the  labeled  compound.  Iodination was occurred through proton substitution at C-12. Then the andrographolide-131I was  injected  into  lateral  vein  of  mice’s  tail  to  study  its  biodistribution.  The compound  was  distributed  in  all organs  with the  highest  accumulation  occurred in  the  stomach  (16.87  %/gram  organ).  The  result  showed  that  inducing  the animals  with  LPS  caused  inflammation  in  the  stomach  and  increased  the production  of  prostaglandin  as  proven  by  the  distribution  of  the  radioligand  in that organ.

Key words: andrographolide, radioiodination, anti-inflammatory, biodistribution


Full Text:

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References


Chiou, W-F., Chen, C-F., and Lin, J-J., 2000, Mechanisms of Suppression of Inducible Nitric Oxide Synthase (iNOS) Expression in RAW 264.7 Cells by Andrographolide, British J. of Pharmacology, 129: 1553-1560

Coenen, H. H., Mertens, J., and Maziere, B., 2006, Radioiodination Reactions for Radiopharmaceuticals, Compendium for Effective Synthesis Strategies, Springer, Dordrecht, The Netherlands. ISBN 1-4020-4561-1

Eary, J. F., and Brenner, W., 2007, Nuclear Medicine Therapy, Informa Healthcare, NewYork, USA.

ISBN 0-8247-2876-9

Erbsloh-Moller, B., Dumas, A., Roth, B., Svakianakis, G. N., and Bourgoignie, J. J., 1991, Furosemide-131I-hippuran renography after angiotensin-converting enzyme inhibition for the diagnosis of renovascular hypertension, Am. J. Med., 90(1): 23-29

Fabiola, G. F., Damodharan, L., Pattabhi, V., and Nagarajan, K., 2001, Cyclooxygenase-2 – An Attractive Target for Fruitful Drug Design, Current Science, 80(1): 26-34

Hidalgo, M. A., Romero, A., Figueroa, J., Cortes, P., Concha, I. I., Hancke, J. L., and Burgos, R.A., 2005, Andrographolide Interferes with Binding of Nuclear Factor-kappaB to DNA in HL-60-derived Neutrophilic Cells, British J. of Pharmacology, 144: 680-685

Levita, J., Nawawi, A., Mutholib, A., and Ibrahim, S., 2010, Andrographolide Inhibits COX-2 Expression in Human Fibroblast Cells Due to Its Interaction with Arginine and Histidine in Cyclooxygenase Site, J. Applied Sci. 10(14): 1481-1484 ISSN 1812-5654

Shen, Y. C., Chen, C. F., and Chiou, W. F., 2002, Andrographolide Prevents Oxygen Radical Production by Human Neutrophils: Possible Mechanism Involved in Its Antiinflammatory Effect, British J. of Pharmacology, 135: 399-406

Wiart, C., 2006, Ethnopharmacology of Medicinal Plants, Asia and the Pacific, Humana Press Inc., Totowa, New Jersey, USA. ISBN 1-58829-748-9

Xia, Y-F., Ye, B-Q., Li, Y-D., Wang, J-G., He, X-J., Lin, X., Yao, X., Ma, D., Slungaard., A., Hebbel., R.P., Key, N.S., and Geng, J-G., 2004, Andrographolide Attenuates Inflammation by Inhibition of NF-kappaB Activation through Covalent Modification of Reduced Cysteine62 of p50, The Jo. of Immunology, 4207-4217




DOI: http://dx.doi.org/10.14499/indonesianjpharm0iss0pp258-265

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