Skip to main content Accessibility help

Efficacy of albendazole combined with a marine fungal extract (m2-9) against Angiostrongylus cantonensis-induced meningitis in mice

  • Z.-Y. Li (a1) (a2), R. Sun (a1) (a2), J. Li (a3), Y.-X. Song (a3), Y.-C. Lin (a3), X. Zeng (a1) (a2), H.-J. He (a1) (a2), J. Wei (a1) (a2), F. Yang (a1) (a2), H.-Q. Zheng (a1) (a2), Z.-Y. Lv (a1) (a2) and Z.-D. Wu (a1) (a2)...


The pathogenesis of angiostrongyliasis, resulting from Angiostrongylus cantonensis invasion of the human central nervous system, remains elusive. Anthelmintics are usually used to kill worms, although dead worms in the brain may cause severe inflammation which will lead to central nervous system damage. Therefore, combination therapy with anthelmintics and anti-inflammatory drugs in the treatment of human angiostrongyliasis needs further study. To evaluate the efficacy of albendazole combined with a marine fungal extract (m2-9) in A. cantonensis infection, BALB/c mice infected by the third-stage larvae of A. cantonensis were divided into three groups: mice treated with albendazole or m2-9 alone or in combination from day 5 post-inoculation (PI). Several efficacy parameters were recorded, including weight change, worm recovery, neurological function, behavioural analysis, eosinophil and leucocyte counts. The results showed that combination therapy increased body weight, reduced worm burden, improved learning ability, memory and action, decreased neurological dysfunction and leucocyte response in these mice. The combination of albendazole and m2-9 treatment significantly decreased leucocyte response and increased the frequency of rearing, compared to infected mice treated with either drug alone. Therefore, m2-9 is a natural product with potentially significant therapeutic value for angiostrongyliasis and is worthy of further study.


Corresponding author


Hide All
Aiello, A., D'Esposito, M., Fattorusso, E., Menna, M., Muller, W.E., Perović-Ottstadt, S. & Schröder, H.C. (2006) Novel bioactive bromopyrrole alkaloids from the Mediterranean sponge Axinella verrucosa. Bioorganic & Medicinal Chemistry 14, 1724.
Alicata, J.E. (1965) Occurrence of Angiostrongylus cantonensis in Madagascar, Mauritius, Ceylon, and Sarawak. Journal of Parasitology 51, 937.
Andersen, R.J. & Williams, D.E. (2000) Pharmaceuticals from the sea. pp. 55in (Eds) Chemistry in the marine environment. Cambridge, The Royal Society of Chemistry Press.
Bittencourt, F.S., Figueiredo, J.G., Mota, M.R., Bezerra, C.C., Silvestre, P.P., Vale, M.R., Nascimento, K.S., Sampaio, A.H., Nagano, C.S., Saker-Sampaio, S., Farias, W.R., Cavada, B.S., Assreuy, A.M. & de Alencar, N.M. (2008) Antinociceptive and anti-inflammatory effects of a mucin-binding agglutinin isolated from the red marine alga Hypnea cervicornis. Naunyn-Schmiedeberg's Archive of Pharmacology 377, 139148.
Bugni, T.S. & Ireland, C.M. (2004) Marine derived fungi: a chemically and biologically diverse group of microorganisms. Natural Product Reports 21, 143163.
Chen, H.T. (1935) Un nouveau nematode pulmonaire, Pulmonema cantonensis n.g., n. sp. des rats de Canton. Annals of Parasitology 13, 312317.
Chen, K.M. & Lai, S.C. (2007) Biochemical and pathological evaluation of albendazole/thalidomide co-therapy against eosinophilic meningitis or meningoencephalitis induced by Angiostrongylus cantonensis. Journal of Antimicrobial Chemotherapy 59, 264276.
Courtois, A., Simon-Colin, C., Boisset, C., Berthou, C., Deslandes, E., Guézennec, J. & Bordron, A. (2008) Floridoside extracted from the red alga Mastocarpus stellatus is a potent activator of the classical complement pathway. Marine Drugs 6, 407417.
Cross, J.H. (1978) Clinical manifestations and laboratory diagnosis of eosinophilic meningitis syndrome associated with angiostrongyliasis. Southeast Asian Journal of Tropical Medicine and Public Health 9, 161170.
Dang, H.T., Lee, H.J., Yoo, E.S., Shinde, P.B., Lee, Y.M., Hong, J., Kim, D.K. & Jung, J.H. (2008) Anti-inflammatory constituents of the red alga Gracilaria verrucosa and their synthetic analogues. Journal of Natural Products 71, 232240.
Faulkner, D.J. (2002) Marine natural products. Natural Product Reports 19, 148.
Gelis, S., Spratt, D.M. & Raidal, S.R. (2011) Neuroangiostrongyliasis and other parasites in tawny frogmouths (Podargus strigoides) in south-eastern Queensland. Australian Veterinary Journal 89, 4750.
Hsieh, H.C. (1959) Outline of parasitic zoonoses in Taiwan. Formosan Science 13, 99108.
Hwang, K.P. & Chen, E.R. (1988) Larvicidal effect of albendazole against Angiostrongylus cantonensis in mice. American Journal of Tropical Medicine and Hygiene 39, 191195.
Ina, A., Hayashi, K., Nozaki, H. & Kamei, Y. (2007) Pheophytin a, a low molecular weight compound found in the marine brown alga Sargassum fulvellum, promotes the differentiation of PC12 cells. International Journal of Developmental Neuroscience 25, 6368.
John, D.T. & Martinez, A.J. (1975) Animal model of human disease. Central nervous system infection with the nematode Angiostrongylus cantonensis. Animal model: eosinophilic meningoencephalitis in mice infected with Angiostrongylus cantonensis. The American Journal of Pathology 80, 345348.
König, G.M. & Wright, A.D. (1996) Marine natural products research: current directions and future potential. Planta Medica 62, 193211.
Lai, S.C., Chen, K.M., Chang, Y.H. & Lee, H.H. (2008) Comparative efficacies of albendazole and the Chinese herbal medicine long-dan-xie-gan-tan, used alone or in combination, in the treatment of experimental eosinophilic meningitis induced by Angiostrongylus cantonensis. Annals of Tropical Medicine and Parasitology 102, 143150.
Laird, D.W. & van Altena, I.A. (2006) Tetraprenyltoluquinols from the brown alga Cystophora fibrosa. Phytochemistry 67, 944955.
Lan, K.P., Wang, C.J., Lai, S.C., Chen, K.M., Lee, S.S., Hsu, J.D. & Lee, H.H. (2004) The efficacy of therapy with albendazole in mice with parasitic meningitis caused by Angiostrongylus cantonensis. Parasitology Research 93, 311317.
Lee, H.H., Chou, H.L., Chen, K.M. & Lai, S.C. (2004) Association of matrix metalloproteinase-9 in eosinophilic meningitis of BALB/c mice caused by Angiostrongylus cantonensis. Parasitology Research 94, 321328.
Li, X., Lee, S.M., Choi, H.D., Kang, J.S. & Son, B.W. (2003) Microbial transformation of terreusinone, an ultraviolet-A (UV-A) protecting dipyrroloquinone, by Streptomyces sp. Chemical & Pharmaceutical Bulletin 51, 14581459.
Liberra, K. & Lindequist, U. (1995) Marine fungi – a prolific resource of biologically active natural products? Pharmazie 50, 583588.
Maldonado, A. Jr, Simões, R.O., Oliveira, A.P., Motta, E.M., Fernandez, M.A., Pereira, Z.M., Monteiro, S.S., Torres, E.J. & Thiengo, S.C. (2010) First report of Angiostrongylus cantonensis (Nematoda: Metastrongylidae) in Achatina fulica (Mollusca: Gastropoda) from Southeast and South Brazil. Memórias do Instituto Oswaldo Cruz 105, 938941.
Mayer, A.M. & Gustafson, K.R. (2004) Marine pharmacology in 2001–2: antitumour and cytotoxic compounds. European Journal of Cancer 40, 26762704.
Oh, D.C., Gontang, E.A., Kauffman, C.A., Jensen, P.R. & Fenical, W. (2008) Salinipyrones and pacificanones, mixed-precursor polyketides from the marine actinomycete Salinispora pacifica. Journal of Natural Products 71, 570575.
Parra, A., McGirt, M.J., Sheng, H., Laskowitz, D.T., Pearlstein, R.D. & Warner, D.S. (2002) Mouse model of subarachnoid hemorrhage associated cerebral vasospasm: methodological analysis. Neurological Research 24, 510516.
Pietra, F. (1997) Secondary metabolites from marine microorganisms: bacteria, protozoa, algae and fungi. Achievements and prospects. Natural Product Reports 14, 453464.
Ponomarenko, L.P., Kalinovsky, A.I., Afiyatullov, S.Sh., Pushilin, M.A., Gerasimenko, A.V., Krasokhin, V.B. & Stonik, V.A. (2007) Spongian diterpenoids from the sponge Spongia (Heterofibria) sp. Journal of Natural Products 70, 11101113.
Sawanyawisuth, K. & Sawanyawisuth, K. (2008) Treatment of angiostrongyliasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 102, 990996.
Tu, W.C. & Lai, S.C. (2006) Angiostrongylus cantonensis: efficacy of albendazole–dexamethasone co-therapy against infection-induced plasminogen activators and eosinophilic meningitis. Experimental Parasitology 113, 815.
Venkatesan, P. (1998) Albendazole. Journal of Antimicrobial Chemotherapy 41, 145147.
Wang, J., Qi, H., Diao, Z., Zheng, X., Li, X., Ma, S., Ji, A. & Yin, C. (2010) An outbreak of angiostrongyliasis cantonensis in Beijing. Journal of Parasitology 96, 377381.
Wang, L.C., Jung, S.M., Chen, C.C., Wong, H.F., Wan, D.P. & Wan, Y.L. (2006) Pathological changes in the brains of rabbits experimentally infected with Angiostrongylus cantonensis after albendazole treatment: histopathological and magnetic resonance imaging studies. Journal of Antimicrobial Chemotherapy 57, 294300.
Wang, Q.P., Lai, D.H., Zhu, X.Q., Chen, X.G. & Lun, Z.R. (2008) Human angiostrongyliasis. Lancet Infectious Diseases 8, 621630.
Yii, C.Y. (1976) Clinical observations on eosinophilic meningitis and meningoencephalitis caused by Angiostrongylus cantonensis on Taiwan. American Journal of Tropical Medicine and Hygiene 25, 233249.

Efficacy of albendazole combined with a marine fungal extract (m2-9) against Angiostrongylus cantonensis-induced meningitis in mice

  • Z.-Y. Li (a1) (a2), R. Sun (a1) (a2), J. Li (a3), Y.-X. Song (a3), Y.-C. Lin (a3), X. Zeng (a1) (a2), H.-J. He (a1) (a2), J. Wei (a1) (a2), F. Yang (a1) (a2), H.-Q. Zheng (a1) (a2), Z.-Y. Lv (a1) (a2) and Z.-D. Wu (a1) (a2)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed