Skip to main content Accessibility help

Efficacy of combined treatment with albendazole and baicalein against eosinophilic meningitis induced by Angiostrongylus cantonensis in mice

  • Han-Jiang He (a1) (a2) (a3), Zhi-Yue Lv (a1) (a2), Zheng-Yu Li (a1) (a2), Li-Yan Zhang (a1) (a2), Qi Liao (a1) (a2), Huan-Qin Zheng (a1) (a2), Wei-Yang Su (a4), Shao-Qi Rao (a4), Xin-Bing Yu (a1) (a2) and Zhong-Dao Wu (a1) (a2)...


Angiostrongylus cantonensis infection causes eosinophilic meningitis in humans. Baicalein is a flavonoid originally isolated from the roots of Scutellaria baicalensis Georgi. In this study we evaluated the efficacy of the combination of albendazole and baicalein for treating eosinophilic meningitis in BALB/c mice. Therapeutic efficacy included the survival time, body weight, neurological function, leucocyte and eosinophil counts, eotaxin concentration, matrix metalloproteinase-9 (MMP-9) activity, larval recovery and histopathological examination. The results showed that the combination of albendazole and baicalein was more effective than either drug administered singly. Combination therapy increased the survival time, decreased body weight loss, neurological dysfunction, leucocyte response, eotaxin concentration and MMP-9 activity. Our results suggest that the combination of albendazole and baicalein may exhibit synergistic beneficial effects in the treatment of eosinophilic meningitis induced by A. cantonensis.


Corresponding author

*Fax: (86) 02087331588 E-mail:


Hide All
Chang, E.E., Chung, L.Y. & Yen, C.M. (2004) Kinetics of change in the eotaxin concentration in serum and cerebrospinal fluid of mice infected with Angiostrongylus cantonensis. Parasitology Research 92, 137141.
Chen, C.J., Raung, S.L., Liao, S.L. & Chen, S.Y. (2004) Inhibition of inducible nitric oxide synthase expression by baicalein in endotoxin/cytokine-stimulated microglia. Biochemical Pharmacology 67, 957965.
Chen, H.T. (1935) Un nouveau nematoda pulmonaire: Pulmonema cantonensis, n.g.m. 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.
Chen, K.M., Lee, H.H., Lu, K.H., Tseng, Y.K., Hsu, L.S., Chou, H.L. & Lai, S.C. (2004) Association of matrix metalloproteinase-9 and Purkinje cell degeneration in mouse cerebellum caused by Angiostrongylus cantonensis. International Journal for Parasitology 34, 11471156.
Chen, X.G., Li, H. & Lun, Z.R. (2005) Angiostrongyliasis, Mainland China. Emerging Infectious Diseases 11, 16451647.
Chen, Y.C., Chow, J.M. & Lin, C.W. (2006) Baicalein inhibition of oxidative-stress-induced apoptosis via modulation of ERKs activation and induction of HO-1 gene expression in rat glioma cells C6. Toxicology and Applied Pharmacology 216, 263273.
Cheng, Y., He, G., Mu, X., Zhang, T., Li, X., Hu, J., Xu, B. & Du, G. (2008) Neuroprotective effect of baicalein against MPTP neurotoxicity: behavioral, biochemical and immunohistochemical profile. Neuroscience Letters 441, 1620.
Diao, Z.L., Chen, X.H., Yin, C.H., Wang, J., Qi, H.Y. & Ji, A.P. (2009) Angiostrongylus cantonensis: effect of combination therapy with albendazole and dexamethasone on Th cytokine gene expression in PBMC from patients with eosinophilic meningitis. Experimental Parasitology 123, 15.
Eamsobhana, P., Yoolek, A., Punthuprapasa, P. & Yong, H.S. (2009) Thai Koi-Hoi snail dish and Angiostrongyliasis due to Angiostrongylus cantonensis: effects of food flavoring and alcoholic drink on the third-stage larvae in infected snail meat. Foodborne Pathogens and Disease 6, 401405.
He, H.J., Lv, Z.Y., Li, Z.Y., Yu, X.B. & Wu, Z.D. (2009) Infection of different host to Angiostrongylus cantonensis. Journal of Tropical Medicine 9, 171174.
Hong, T., Jin, G.B., Cho, S. & Cyong, J.C. (2002) Evaluation of the anti-inflammatory effect of baicalein on dextran sulfate sodium-induced colitis in mice. Planta Medica 68, 268271.
Huang, W.H., Lee, A.R. & Yang, C.H. (2006) Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis GEORGI. Bioscience, Biotechnology, and Biochemistry 70, 23712380.
Intapan, P.M., Niwattayakul, K., Sawanyawisuth, K., Chotmongkol, V. & Maleewong, W. (2007) Cerebrospinal fluid eotaxin and eotaxin-2 levels in human eosinophilic meningitis associated with angiostrongyliasis. Cytokine 39, 138141.
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.
Lai, C.H., Yen, C.M., Chin, C., Chung, H.C., Kuo, H.C. & Lin, H.H. (2007) HYPERLINK “” Eosinophilic meningitis caused by Angiostrongylus cantonensis after ingestion of raw frogs. American Journal of Tropical Medicine and Hygiene 76, 399402.
Lai, S.C. (2006) Chinese herbal medicine Yin-Chen-Extract as an adjunct to anthelmintic albendazole used against Angiostrongylus cantonensis-induced eosinophilic meningitis or meningoencephalitis. The American Journal of Tropical Medicine and Hygiene 75, 556562.
Lai, S.C., Twu, J.J., Jiang, S.T., Hsu, J.D., Chen, K.M., Chiaing, H.C., Wang, C.J., Tseng, C.K., Shyu, L.Y. & Lee, H.H. (2004) Induction of matrix metalloproteinase-9 in murine eosinophilic meningitis caused by Angiostrongylus cantonensis. Annals of Tropical Medicine and Parasitology 98, 715724.
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.
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.
Leppert, D., Leib, S.L., Grygar, C., Miller, K.M., Schaad, U.B. & Holländer, G.A. (2000) Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood–brain barrier damage and neurological sequelae. Clinical Infectious Disease 31, 8084.
Li, H.B. & Chen, F. (2005) Isolation and purification of baicalein, wogonin and oroxylin A from the medicinal plant Scutellaria baicalensis by high-speed counter-current chromatography. Journal of Chromatography A 1074, 107110.
Lin, C.C. & Shieh, D.E. (1996) The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin. The American Journal of Chinese Medicine 24, 3136.
Lv, S., Zhang, Y., Chen, S.R., Wang, L.B., Fang, W., Chen, F., Jiang, J.Y., Li, Y.L., Du, Z.W. & Zhou, X.N. (2009) Human angiostrongyliasis outbreak in Dali, China. PLoS Neglected Tropical Disease 3, e520.
Nakajima, T., Imanishi, M. & Yamamoto, K. (2001) Inhibitory effect of baicalein, a flavonoid in Scutellaria root on eotaxin production by human dermal fibroblasts. Planta Medica 67, 132135.
Ong, E.S., Len, S.M., Lee, A.C., Chui, P. & Chooi, K.F. (2004) Proteomic analysis of mouse liver for the evaluation of effects of Scutellariae radix by liquid chromatography with tandem mass spectrometry. Rapid Communications in Mass Spectrometry: RCM 18, 25222530.
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.
Pharmacopoeia Commission of the People's Republic of China (2000) Pharmacopoeia of the People's Republic of China. 7th edn.248 pp. Beijing, Chemical Industry Press.
Rosenberg, G.A., Kornfeld, M., Estrada, E., Kelley, R.O., Liotta, L.A. & Stetler-Stevenson, W.G. (1992) TIMP-2 reduces proteolytic opening of blood–brain barrier by type-IV collagenase. Brain Research 576, 203207.
Shih, P.C., Lee, H.H., Lai, S.C., Chen, K.M., Jiang, S.T. & Chen, Y.F. (2007) Efficacy of curcumin therapy against Angiostrongylus cantonensis-induced eosinophilic meningitis. Journal of Helminthology 81, 15.
Society of Japanese Pharmacopoeia (2001) Japanese Pharmacopoeia. 14th edn.907 pp. Tokyo, Hirokawa Shoten Press.
Tarragó, T., Kichik, N., Claasen, B., Prades, R., Teixidó, M. & Giralt, E. (2008) Baicalin, a prodrug able to reach the CNS, is a prolyl oligopeptidase inhibitor. Bioorganic and Medicinal Chemistry 16, 75167524.
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. The Journal of Antimicrobial Chemotherapy 41, 145147.
Wallace, G.D. & Rosen, L. (1966) Studies on eosinophilic meningitis. 2. Experimental infection of shrimp and crabs with Angiostrongylus cantonensis. American Journal of Epidemiology 84, 120131.
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.


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