Chemical compounds isolated from extracts and essential oils of the genus <i>Zanthoxylum</i> Linnaeus (Rutaceae) and its antimicrobial potential

Saraiva Filho, Daniel Eugenio; Sousa, Josenir Barreto de; Santos, Hélcio Silva dos; Fontenelle, Raquel Oliveira dos Santos

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Artigo • Hoehnea 47 • 2020 • https://doi.org/10.1590/2236-8906-88/2019 copy

Chemical compounds isolated from extracts and essential oils of the genus Zanthoxylum Linnaeus (Rutaceae) and its antimicrobial potential

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

This review covers the documentation of the isolated and biologically active chemical constituents of 20 species of the genus Zanthoxylum Linnaeus distributed all over the world. The species extracts and oils chemical constituents were isolated and characterized by different analytical methods. This review was carried out through the survey of the Master’s Dissertations, Doctoral Theses and mainly published scientific articles about the biological activity and phytochemical characterization of Zanthoxylum species, available at in the CAPES, PubMed, ScienceDirect, Scopus, Scielo and Google Scholar databases from 1985 to 2019. The species presented a diverse chemical composition in which alkaloids, terpenes and coumarins predominate. In addition, those chemical compounds perform different types of biological activity for the plant, such as larvicidal, anti-inflammatory, analgesic, antinociceptive, antioxidant, antibiotic, hepatoprotective, antiplasmodial, cytotoxic, antiproliferative, anthelmintic, antiviral and antifungal.

Keywords:
analytical methods; biological activity; chemical constituents; essential oil; Zanthoxylum

Espécies de Zanthoxylum	Parte Vegetal	Extrato/Óleo	Classes	Atividades Biológicas	Referências
Z. alatum	Folha	Aquoso, Metanólico	Terpenos	Atividade Antifúngica (Colletotrichum) e antibacteriana (Corynebacterium diptheriae)	(*Wazir et al. 2014Wazir, A., Mehjabeen, Jahan, N., Sherwani, S.K. & Ahmad, M. 2014. Antibacterial, Antifungal and antioxidant activities of some medicinal plants. Pakistan journal of pharmaceutical sciences 27: 2145-2152., Stappen et al. 2018*Stappen, I., Tabanca, N., Ali, A., Wanner, J., Lal, B., Jaitak, V., Wedge, D.E., Kaul, V.K., Schmidt, E. & Jirovetz, L. 2018. Antifungal and repellent activities of the essential oils from three aromatic herbs from western Himalaya. Open Chemistry 16: 306-316.)
Z. budrunga	Folha, raiz	Éter de petróleo, Hexânico, Etanólico	Alcaloides, terpenos, esteroides, flavonoides	Atividade antibacteriana (Bacillus cereus, B. subtilis, Shigella dysenteriae, Escherichia coli e Streptococcus aureus) e antifúngico Aspergillus fumigatus e Hensinela californica	(*Ahsan et al. 2014Ahsan, M., Haque, M.R., Hossain, M.B., Islam, S.N., Gray, A.I. & Hasan, C.M. 2014. Cytotoxic dimeric quinolone-terpene alkaloids from the root bark of Zanthoxylum rhetsa. Phytochemistry 103: 8-12., Islam et al. 2001Islam, A., Sayeed, A., Bhuiyan, M.S.A., Mosaddik, M.A., M.AU Islam, M. A.U. & Klan, A.M. 2001. Antimicrobial activity and cytotoxicity of Zanthoxylum budrunga. Fitoterapia 72: 428-430., Islam et al. 2014Islam, M.K., Biswas, N.N., Saha, S., Hossain, H., Jahan, I. A., Khan, T.A., Awang, K. & Shilpi, J.A. 2014a. Anti-nociceptive and antioxidant activity of Zanthoxylum budrunga Wall (Rutaceae) seeds. The Scientific World Journal 2014: 1-7., Rahman et al. 2005*Rahman, M.M., Islam, M.A., Khondkar, P. & Gray, A.I. 2005. Alkaloids and lignans from Zanthoxylum budrunga (Rutaceae). Biochemical Systematics and Ecology 33: 91-96.)
Z. bungeanum	Folha, fruto	Etanólico, Metanólico	Alcaloides, terpenoides, flavonoides	Atividade antibacteriana (S. aureus e E. coli) e antifúngica (Leptosphaeria maculans, Bipolaris maydi)	(*Gong et al. 2009Gong, Y. Huang, Y. Zhou, L. Shi, X. Guo, Z. Wang, M. & Jiang, W. 2009. Chemical composition and antifungal activity of the fruit oil of Zanthoxylum bungeanum maxim. (Rutaceae) from China. Journal of Essential Oil Research 21: 174-178., Zhang et al. 2017*Yu, X. Q., Zheng, X.Y., Kan, J.Q. & Guo, J. 2009. Evaluation of specific quality of Zanthoxylum bungeanum Maxim and Zanthoxylum schinifolium Sieb. et Zucc. Food Science 30: 45-48.)
Z. chalybeum	Raiz	Metanólico	Alcaloides, flavonoides terpenos, taninos	Atividade antibacteriana (B. subtilis, M. luteus e S. aureus)	(*Anza et al. 2014Anza, M., Haile, E., Tadesse, S., Mammo, F. & Endale, M. 2014. A coniferyl alcohol derivative from the roots of Zanthoxylum chalybeum. Journal of Coastal Life Medicine 2: 970-974., Matu & Van Staden 2003Matu, E. N. & Van Staden, J. 2003. Antibacterial and anti-inflammatory activities of some plants used for medicinal purposes in Kenya. Journal of Ethnopharmacology 87: 35-41., Nantongo et al. 2018*Nantongo, J.S., Odoi, J.B., Abigaba, G. & Gwali, S. 2018. Variability of phenolic and alkaloid content in different plant parts of Carissa edulis Vahl and Zanthoxylum chalybeum Engl. BMC Research Notes 11: 1-5.)
Z. caribaeum	Folha	Etanólico	Terpenos	Atividade antibacteriana (S. enterica)	(*Nogueira et al. 2014aNogueira, J., Mourão, S.C., Dolabela, I.B., Santos, M.G., Mello, C.B., Kelecom, A., Mexas, R., Feder, D., Fernandes, C.P., Gonzalez, M.S. & Rocha, L. 2014a. Zanthoxylum caribaeum (Rutaceae) essential oil: chemical investigation and biological effects on Rhodnius prolixus nymph. Parasitology Research113: 4271-4279., Souza et al. 2017*Souza, J.G.L., Toledo, A.G., Santana, C.B., Dos Santos, C.G., Mallmann, A.P., Da Silva, J.P.B. & Pinto, F.G.S. 2017. Chemical composition and antibacterial activity of essential oil and leaf extracts of Zanthoxylum caribaeum Lam. against serotypes of Salmonella. Revista Brasileira de Saúde e Produção Animal 18: 446-453.)
Z. chiloperone	Caule, folha	Hexânico,	Alcaloides	Atividade antiplasmodial (P. faciparum), tripanocida (Trypanossoma cruzi)	(*Cebrián-Torrejón et al. 2011Cebrián-Torrejón, G., Spelman, K., Leblanc, K., Muñoz-Durango, K., Gutiérrez, S.T., Ferreira, M.E., Arias, A.R., Figadère, B., Fournet, A., Maciuk, A., Grellier, P., Cech, N.B. & Poupon, E. 2011.The antiplasmodium effects of a traditional South American remedy: Zanthoxylum chiloperone var. Angustifolium against chloroquine resistant and chloroquine sensitive strains of Plasmodium falciparum. Brazilian Journal of Pharmacognosy 21: 652-661., Ferreira et al. 2007Ferreira, M.E., Nakayama, H., Arias, A.R., Schinini, A., Bilbao, N.F., Serna, E., Lagoutte, D., Soriano-Agatón, F., Pouponb, E., Hocquemiller, R. & Fournet, A. 2007. Effects of canthin-6-one alkaloids from Zanthoxylum chiloperone on Trypanosoma cruzi - infected mice. Journal of Ethnopharmacology 109: 258-263., Ferreira et al. 2011*Ferreira, M.E., Cebrián-Torrejón, G., Corrales, A.S., Bilbao, N.V., Rolón, M., Gomez, C.V., Leblanc, K., Yaluf, G., Schinini, A., Torres, S., Serna, E., Arias, A.R., Poupon, E. & Fournet, A. 2011. Zanthoxylum chiloperone leaves extract: First sustainable Chagas disease treatment. Journal of Ethnopharmacology133: 986-993.,
		Etanólico			*Hamuy et al. 2013*Hamuy, R., Vera, B.N., Ferreira, M.E., Acosta, N. & Lopez, E. 2013. Determinacion de la sensibilidad in vitro de diferentes cepas de Trypanosoma cruzi al benznidazol y al extracto de hoja de la planta Zanthoxylum chiloperone. Mem. Inst. Invest. Cienc. Salud 9: 16-25.)
Z. djalma-batistae	Galhos	Hexânico	Terpenos	Atividade antileishmanial (L. donovani)	(*Lima et al. 2015b*Lima, R.B.S., Rocha, S.L.F., Melo, M.R.S., Costa, J,S., Picanço, N.S., Lima, E.S., Vasconcellos, M.C., Boleti, A.P.A., Santos, J.M.P., Amorim, R.C.N., Chaves, F.C.M., Coutinho, J.P., Tadei, W.P., Krettli, A.U. & Pohlit, A.M. 2015b. In vitro and in vivo anti-malarial activity of plants from the Brazilian Amazon. Malaria Journal 14: 1-14.)
Z. ekmanii	Folha e raiz	Etanólico	Alcaloides, terpenos	Atividade antimalárica	(*Facundo et al. 2003Facundo, V.A., Rezende, C.M., Pinto, A.C. & Morais, S.M. 2003. Essential oil of Zanthoxylum ekmanii (Urb.) Alain. Leaves. Journal of Essential Oil Research 15: 402-403., Facundo et al. 2005*Facundo, V.A., Pinto, S.A.S., Filho, R.B., Pinto, A.C. & Rezende, C.M. 2005. Constituintes químicos de Zanthoxylum ekmanii (URB.) alain. Química Nova 28: 224-225.)
Z. fagara	Fruto e caule	Etanólico, Aquoso	Terpenos, alcalóides, cumarinas, flavonoides, lignanas	Atividade antifúngica (C. acutatum, S. cerevisiae e Microsporum canis), antibacteriana (B. subtilis e Vibrio cholerae)	(*Amaro-Luis et al. 1988Amaro-Luis, J.M., Fronczek, F.R., Massanet, G., Pando, E., Rodriguez-Luis, F., Watkins, S. F. & Zubía, E. 1988. Meridinol, a lignan from Zanthoxylum fagara. Phytochemistry 27: 3933-3935., Diéguez-Hurtado et al. 2003Diéguez-Hurtado, R., Garrido-Garrido, G., Prieto-González, S., Iznaga, Y., Gonzalez, Molina-Torres, J., M. Curini, M.F., Epifano, F. & Marcotullio, M.C. 2003. Antifungal activity of some Cuban Zanthoxylum species. Fitoterapia 74: 384-386., Prieto et al. 2011Prieto, J.A., Patiño, O.J., Delgado, W.A., Moreno, J.P. & Cuca, L.E. 2011. Chemical composition, insecticidal, and antifungal activities of fruit essential oils of three colombian Zanthoxylum species. Chilean journal of agricultural research 71: 73-82., Macías et al. 2010*Macías, V.V.E., Ericsson, D.C.B. & Cuca, L.E. 2010. Novel furocarbazole a lkaloids and antibacterial activity of ethanol extract from Zanthoxylum fagara (L.) Sargent. Revista Colombiana de Química 39: 333-341.)
Z. hyemale	Caule, folha	Metanólico, Aquoso	Alcaloide	Atividade bacteriostática (S. epidermidis)	(Simionatto 2004Simionatto, U. 2004. Estudo dos constituintes químicos de óleos voláteis de plantas medicinais do Rio Grande do Sul : Isolamento , determinação e modificação estrutural e atividade Biológica. RS - Brasil. Tese de Doutorado, Universidade Federal de Santa Maria, Santa Maria., Zanon 2010Zanon, G. 2010. Análise fitoquímica e estudo das atividades antimicrobiana, antioxidante e de inibição da enzima acetilcolinesterase das espécies Zanthoxylum rhoifolium e Zanthoxylum hyemale. RS - Brasil. Dissertação de Mestrado, Universidade Federal de Santa Maria, Santa Maria.)
Z. monophyllum	Fruto, caule	Etanólico, Aquoso	Terpenos, alcaloides	Atividade antifúngica (Fusarium oxysporum e A. fumigados), antibacteriana (S. aureus)e antiplasmodial (Plasmodium falciparum)	(*Ladino et al. 2011Guy, I., Charles, B., Hélène, G., Fournet, A., Ferreira, M.E. & Arias, A.R. 2001b. Essential Oils from Leaves of Two Paraguayan Rutaceae: Zanthoxylum hyemale A. St. Hil. and Z. naranjilo Griseb. Jessent. Oil Res 13: 200-201., Prieto et al. 2011Prieto, J.A., Patiño, O.J., Delgado, W.A., Moreno, J.P. & Cuca, L.E. 2011. Chemical composition, insecticidal, and antifungal activities of fruit essential oils of three colombian Zanthoxylum species. Chilean journal of agricultural research 71: 73-82., Rodríguez-Guzmán et al. 2011*Rodríguez-Guzmán, R., Johansmann, F.L.C., Radwan, M.M., Burandt, C.L. & Ross, S.A. 2011. Chemical constituents, antimicrobial and antimalarial activities of Zanthoxylum monophyllum. Planta Medica 77: 1542-1544.)
Z. naranjillo	Folha	Hexânico	Lignanas	Atividade antiplasmodial (P. falciparum) e tripanocida (T. cruzi)	(*Bastos et al. 1999Bastos, J. K., Albuquerque, S. & Silva, M.L.A. 1999. Evaluation of the trypanocidal activity of lignans isolated from the leaves of Zanthoxylum naranjillo. Planta Medica 65: 541-544., Braguine et al. 2009Braguine, C., Costa, E.S., Magalhães, L.G., Rodrigues, V., Silva-Filho, A.A., Bastos, J.K., Silva, M.L.A., Cunha, W.R., Januário, A.H. & Pauletti, P.M. 2009. Schistosomicidal evaluation of Zanthoxylum naranjillo and its isolated compounds against Schistosoma mansoni adult worms. Zeitschrift fur Naturforschung 64: 793-797., Saraiva et al. 2007Saraiva, J., Veja, C., Rolon, M., Da Silva, R., Silva, M.l.A., Donate, P.M., Bastos, J.K., Gomez-Barrio, A. & Albuquerque, S. 2007. In vitro and in vivo activity of lignan lactones derivatives against Trypanossoma cruzi. Parasitology Research 100: 791-795., Gansane et al. 2010*Gansane, A., Sanon, S., Ouattara, P.L., Hutter, S., Ollivier, E., Azas, N., Traore, A., Traore, A.S., Guissou, I.P., Nebie, I. & Sirima, B.S. 2010. Antiplasmodial activity and cytotoxicity of semi purified fractions from Zanthoxylum zanthoxyloides Lam. Bark of Trunk.International Journal of Pharmacology6: 921-925.)
Z. petiolare	Folha	Óleo essencial	Terpenos	Atividade antifúngica Trichophyton rubrum)	(*Arruda et al. 1994Arruda, M.S.P., Fernandes, J.B., Vieira, P.C., Fatima, M. & Pirani, J.R. 1994. Protolimonoid and lignans from Zanthoxylum petiolare. Phytochemistry 36: 1303-1306., Arruda et al. 1992Arruda, M.S.P., Fernandes, J.B., Silva, F.G.F., Paula C. Vieira, P.C. & Pirani, J.R. 1992. Quinolone alkaloids from Zanthoxylum acutifoliuim. Plrytockemistry 31: 3617-3619., Mesquita, 2018*Mesquita, M.C.A. 2018. Atividade antifúngica e composição química do óleo essencial de Zanthoxylum petiolare A. St. -Hil. & Tul (RUTACEAE). CE - Brasil. Monografia, Universidade do Vale do Acaraú, Sobral.)
Z. quinduense	Caule	Etanólico	Alcaloides	Atividade antibacteriana (S. aureus, E. faecalis, S. typhimurium)	(*Ladino et al. 2011*Guy, I., Charles, B., Hélène, G., Fournet, A., Ferreira, M.E. & Arias, A.R. 2001b. Essential Oils from Leaves of Two Paraguayan Rutaceae: Zanthoxylum hyemale A. St. Hil. and Z. naranjilo Griseb. Jessent. Oil Res 13: 200-201.)
Z. riedeliano	Folha	Metanólico	Lignanas, terpenos	Atividade antibacteriana (Streptococcus agalactiae e Flavobacterium columnare)	(*Castro et al. 2008*Castro, S.B.R. Leal, C.A.G., Freire, F.R., Carvalho, D.A., Oliveira, D.F. & Figueiredo, H.C.P. 2008. Antibacterial activity of plant extracts from Brazil against fish pathogenic bacteria. Brazilian Journal of Microbiology 39: 756-760.)
Z. rhoifolium	Folha, caule	Etanólico	Alcaloides, taninos, flavonoides	Atividade antibacteriana (E. coli e Staphylococcus aureus) e antifúngica (Candida albicans)	(*Costa et al. 2010Costa, J.G.M., Campos, A.R., Brito, S.A., Pereira, C.K.B., Souza, E.O. & Rodrigues, F.F.G. 2010. Biological screening of araripe basin medicinal plants using Artemia salina Leach and pathogenic bacteria. Pharmacognosy Magazine 6: 331-335., Gonzaga et al. 2003Gonzaga, W.D.A., Weber, A.D., Giacomelli, S.R., Simionatto, E., Dalcol, I.I., Dessoy, E.C.M. & Morel, A.D. 2003. Composition and antibacterial activity of the essential oils from Zanthoxylum rhoifolium. Planta Medica 69: 773-775., Tavares et al. 2014Tavares, D.L.C., Zanon, G., Weber, A.D., Neto, A.T., Mostardeiro, C.P., Cruz, I.B.M., Oliveira, R.M., Ilha, V., Dalcol, I.I. & Morel, A.F. 2014. Structure-activity relationship of benzophenanthridine alkaloids from Zanthoxylum rhoifolium having antimicrobial activity. PLoS ONE 9: 1-10., Zanon 2010Zanon, G. 2010. Análise fitoquímica e estudo das atividades antimicrobiana, antioxidante e de inibição da enzima acetilcolinesterase das espécies Zanthoxylum rhoifolium e Zanthoxylum hyemale. RS - Brasil. Dissertação de Mestrado, Universidade Federal de Santa Maria, Santa Maria., Melo Neto et al. 2016*Neto, B.M., Leitão, J.M.S.R., Oliveira, L.G.C., Santos, S.E.M., Carneiro, S.M.P., Rodrigues, K.A.F., Chaves, M.H., Arcanjo, D.D.R. & Carvalho, F.A.A. 2016. Inhibitory effects of Zanthoxylum rhoifolium lam. (Rutaceae) against the infection and i.fectivity of macrophages by Leishmania amazonensis. Anais da Academia Brasileira de Ciências 88: 1851-1861.)
Z. syncarpum	Folha	Etanólico	Taninos, flavonoide, esteroides, alcaloides	Atividade leishmanicida (Leishmania infantum chagasi) e antiplasmodial (P. falciparum)	(*Ross et al. 2004Ross, S.A., Sultana, G.N.N., Burandt, C.L., ElSohly, M.A., Marais, J.P.J. & Ferreira, D. 2004. Syncarpamide, a New Antiplasmodial (+)-Norepinephrine Derivative from Zanthoxylum syncarpum. Journal of Natural Products 67: 88-90., Silva et al. 2014*Silva, A.A.S., Júnior, J.M.F., Silva, M.G.V. & Morais, S. M. 2014. Estudo fitoquímico e atividades biológicas do limãozinho (Zanthoxylum syncarpum Tull.). Revista Brasileira de Higiene e Sanidade Animal 8: 37-53.)
Z. stelligerum	Raiz	Metanólico	Alcaloide, cumarinas, esteroides	Atividade antibacteriana (S. aureus e M. luteus) e antifúngica (Candida sp.)	(*Silva et al. 2009Silva, C.V., Reis, A.L.V., Ferrer, S.R., Guerreiro, H.M.N., Barros, T.F. & Velozo, E.S. 2009. Avaliação da atividade antimicrobiana de duas espécies de Rutaceae do Nordeste brasileiro. Brazilian Journal of Pharmacognosy 20: 355-360., Hohlemwerger et al. 2012*Hohlemwerger, S.V.A., Sales, E.M., Santos, C.R., Silva, V.E. & Silva, G. M.L. 2012. Alcaloides das cascas das raízes de Zanthoxylum spp. Química Nova 35: 2173-2176.)
Z. scandens	Caule	Metanólico	Alcaloides	Atividade antiviral	(*Cheng et al. 2008Cheng, M.J., Lin, C.F, Chang, H.S. & Chen, I.S. 2008. Chemical constituents from the stem bark of Zanthoxylum sacandens. Journal of the Chilean Chemical Society 53: 1631-1634., Nguyen et al. 2002*Nguyen, Q.A., Van-Dufat, H.T., Michel, S., Tillequin, F., Dumontet, V.M. & Sévenet, T. 2002. A new phenylpropanoid ester from the bark of Zanthoxylum scandens (Rutaceae). Zeitschrift fur Naturforschung 57: 986-989.)
Z. schinifolium	Fruto. folha	Metanólico, Aquoso	Terpenos	Atividade antibacteriana (S. epidermidis e M. tuberculosis) e antiviral	(*Diao et al. 2013Diao, W.R., Hu, Q.P., Feng, S.S., Li, W.Q. & Xu, J.G. 2013. Chemical composition and antibacterial activity of the essential oil from green huajiao (Zanthoxylum schinifolium) against selected foodborne pathogens. Journal of Agricultural and Food Chemistry, 61: 6044-6049., Kim et al. 2018Kim, S., Seo, H., Mahmud, H.A.l., Islam, M.I., Leeb, B.E., Choc, M.L. & Song, H.Y. 2018. In vitro activity of collinin isolated from the leaves of Zanthoxylum schinifolium against multidrug- and extensively drug-resistant Mycobacterium tuberculosis. Phytomedicine 46: 104-110., Choi, 2016Choi, H.J. 2016. Evaluation of Antiviral Activity of Zanthoxylum Species Against Picornaviruses. Osong Public Health and Research Perspectives, 7: 400-403., Hu et al. 2016*Hu, L., Wang, K., Wang, Z., Liu, J., Wang, K., Zhang, J., Luo, Z., Xue, Y., Zhang, Y. & Zhang, Y. 2016. A new megastigmane sesquiterpenoid from Zanthoxylum schinifolium Sieb. et Zucc. Molecules 21: 1-7.)
Z. tingoassuiba	Folha, raiz	Hexânico, diclorometano, Aquoso	Alcaloides, lignanas, terpenos	Atividade antibacteriana (S. aureus e M. luteus), antifúngica (T. mentagrophytes e M. gypseum) e antiprotozoário (T. cruzi e L. amazonenses)	(*Costa et al. 2017bCosta, R.S., Lins, M.O., Le, H.M., Barros, T.F. & Velozo, E.S. 2017b. In vitro antibacterial effects of Zanthoxylum tingoassuiba root bark extracts and two of its alkaloids against multiresistant Staphylococcus aureus. Brazilian Journal of Pharmacognosy 27: 195-198., Detoni et al. 2009Detoni, C.B., Cabral-Albuquerque, E.C.M., Hohlemweger, S.V.A., Sampaio, C., Barros, T.F. & Velozo, E.S. 2009. Essential oil from Zanthoxylum tingoassuiba loaded into multilamellar liposomes useful as antimicrobial agents. Journal of Microencapsulation 26: 684-691., Hohlemwerger et al. 2012Hohlemwerger, S.V.A., Sales, E.M., Santos, C.R., Silva, V.E. & Silva, G. M.L. 2012. Alcaloides das cascas das raízes de Zanthoxylum spp. Química Nova 35: 2173-2176.,Costa et al. 2018*Costa, R.S., Souza-Filho, O.P., Júnior-Otávio, C.S.D., Silva, J.J., Hyaric, M.L., Santos, M.A. V. & Velozo, E.S. 2018. In vitro antileishmanial and antitrypanosomal activity of compounds isolated from the roots of Zanthoxylum tingoassuiba. Brazilian Journal of Pharmacognosy 28: 551-558.)
Z. usambarense	Raiz, caule	Metanólico	Alcaloides	Atividade antibacteriana (B. subtilis, M. luteus e S. aureus), antiplasmodial (P. falciparum)	(*He et al. 2002He, W., Van, P.L., De Kimpe, N., Verbruggen, L., Anthonissen, K., Flaas, M.V., Bosselaers, J., Mathenge, S.G. & Mudida, F.P. 2002. Chemical constituents and biological activities of Zanthoxylum usambarense. Phytotherapy Research 16: 66-70., Kirira et al. 2006Kirira, P.G., Rukunga, G.M., Wanyonyi, A.W., Muregi, F.M., Gathirwa, J.W., Muthaurab, C. N., Omarc, S.A., Tolob, F., Mungaid, G.M. & Ndiege, I. 2006. Anti-plasmodial activity and toxicity of extracts of plants used in traditional malária therapy in Meru and Kilifi Districts of Kenya. Journal of Ethnopharmacology 106: 403-407., Matu & Van Staden 2003Matu, E. N. & Van Staden, J. 2003. Antibacterial and anti-inflammatory activities of some plants used for medicinal purposes in Kenya. Journal of Ethnopharmacology 87: 35-41.,Were et al. 2010*Were, P.S., Kinyanjui, P., Gicheru, M.M., Mwangi, E. & Ozwara, H.S. 2010. Prophylactic and curative activities of extracts from Warburgia ugandensis Sprague (Canellaceae) and Zanthoxylum usambarense (Engl.) Kokwaro (Rutaceae) against Plasmodium knowlesi and Plasmodium berghei. Journal of Ethnopharmacology 130: 158-162.)

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