Analgesic, antipyretic, anti-inflammatory and toxic effects of andrographolide derivatives in experimental animals
Andrographolide (1) and 14-deoxy-11,12-didehydroandrographolide (2) are active constituents of Andrographis paniculata (Burm. f.), family Acanthaceae. A. paniculata extracts are reported to have antiviral, antipyretic, immunostimulant and anticancer activities. In this study, 1 and its 14-acetyl- (4) and 3,19-isopropylidenyl- (3) derivatives, as well as 2 and its 3,19-dipalmitoyl-derivative (5), were intraperitoneally tested for their analgesic, antipyretic, anti-inflammatory and acute toxicity effects in animal models. Analgesic effects were tested in mice using hot plate and writhing tests to distinguish the central and peripheral effects, respectively. The results showed that, at 4 mg/kg, all tested substances have significant analgesic effects, and the highest potency was seen with 3, 4 and 5. Increasing the dose of 3 and 5 to 8 mg/kg did not increase the analgesic effect. In the writhing test, 3 and 5, but not 1, showed significant results. In a baker’s yeast-induced fever model, 3 and 5 significantly reduced rats’ rectal temperature (p < 0.05). In a carrageenan-induced inflammation model, 1, 3 and 5 significantly reduced rats’ paw volume. Doses of 3 and 5 up to 100 mg/kg did not show any serious toxic effects. From this study, 3 and 5 are the most interesting derivatives, showing much greater potency than their parent compounds. These could be further developed as analgesic, antipyretic and anti-inflammatory agents, without any serious toxicity.
Key wordsAndrographolide derivatives Antipyretic Analgesic Anti-inflammatory Acute toxicity
Unable to display preview. Download preview PDF.
- Deng, W. L., Nie, R. J., and Liu, J. Y., Comparison of pharmacological effect of four andrographolides. Yaoxue Tongbao, 17, 195–198 (1982).Google Scholar
- Fujita, T., Fujitani, R., Takeda, Y., Takaishi, Y., Yamada, T., Kido, M., and Miura, I., On the triterpenoids of Andrographis paniculata: X-ray crystallographic analysis of andrographolide and structure determination of new minor diterpenoids. Chem. Pharm. Bull., 32, 2117–2125 (1984).Google Scholar
- Han, G. Du, G.-J., and Xu, Q.-T., Yang, S.-S., Studies of andrographolide maleate monoester and its antipyretic and antiinflammatory activities. Zhongguo Yaoxue Zazhi, 40, 628–631(2005).Google Scholar
- Kumar, V., Abbas, A. K., Fausto N. (Eds.), Robbins and Cotran Pathologic Basis of Disease, 7th ed. Elsevier Saunders: Philadelphia, (2005).Google Scholar
- Madav, S., Tripathi, C., Tandan, S. K., and Mishra, S., Analgesic, antipyretic, and antiulcerogenic effects of andrographolide. Ind. J. Pharm. Sci. 57, 121–125 (1995).Google Scholar
- Madav, S., Tandon, S. K., Lal, J., and Tripathi, C., Anti-inflammatory of andrographolide. Fitoterapia, 67, 452–458 (1996).Google Scholar
- Nasrallah H. A. et al, Efficacy and safety of three doses of paliperidone palmitate, an investigational long acting injectable antipsychotic, in schizophrenia. APA Meeting; Abstract NR4-036 (2008).Google Scholar
- Panossian, A., Hovhannisyan, A., Mamikonyan, G., Abrahamian, H., Hambardzumyan, E., Gabrielian, E. Goukasova, G., Wikman, G., and Wagner, H., Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human. Phytomedicine, 7, 351–364 (2000).PubMedGoogle Scholar
- Thamlikitkul, V. Dechatiwongse, T., Theerapong, S., Chantrakul, C., Boonroj, P., and Punkrut, W., Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis. J. Med. Assoc. Thailand 74, 437–442 (1991).Google Scholar
- Tomazetti, J., Avila, D. S., Ferreira, A. P., Martins, J. S. Souza, F. R., Royer, C., Rubin, M. A., Oliveira, M. R., Bonacorso, H. G., Martins, M. A., Zanatta, N., and Mello, C. F., Baker yeast-induced fever in young rats: Characterization and validation of an animal model for antipyretics screening. J. Neurosci. Methods, 147, 29–35 (2005).PubMedCrossRefGoogle Scholar
- 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., Andrographolide attenuates inflammation by inhibition of NF-kB Activation through covalent modification of reduced cysteine 62 of p50. J. Immunol., 173, 4207–4217 (2004).PubMedGoogle Scholar