Phytochemistry and Pharmacology of the Genus Zanthoxylum (Rutaceae): A Review

Japheth    O.    Ombito
Abstract

Background: The genus Zanthoxylum (Rutaceae) represents an interesting source of bioactive compounds, and more than 220 accepted species of this genus are distributed in the warm temperate and subtropical regions of the world. Different plant parts of Zanthoxylum species have been used traditionally as medicines for various diseases affecting both humans and animals. Based on traditional knowledge, several phytochemical and pharmacological studies have been conducted.
Objective: This review aims to provide up-to-date information about the phytochemistry and pharmacology of the genus Zanthoxylum, covering literature published from January 2012 to mid-2019.
Methods: The traditional medicinal uses, phytochemical and pharmacological data about Zanthoxylum species were searched and obtained from scientific databases such as Google Scholar, PubMed, SciFinder and Web of Science. Information about the accepted number of Zanthoxylum species was obtained from the Global Biodiversity Information Facility and Plants of the World online databases.
Results: The genus Zanthoxylum (Rutaceae) is a rich source of structurally diverse secondary metabolites with promising pharmacological activities. Approximately 126 new secondary metabolites, including alkaloids, amides, lignans and neolignans, coumarins, peptides, terpenoids, and flavonoids have been isolated and identified from different Zanthoxylum species. The numerous studies have shown that compounds isolated from the genus Zanthoxylum exhibit pharmacological activities, including anti-inflammatory, antimicrobial, cytotoxic, larvicidal, antioxidant, anticancer/ antiproliferative, and antimycobacterial activities.
Conclusion: Zanthoxylum genus, a rich source of alkaloids, amides, lignans and neolignans, coumarins, peptides, terpenoids, and flavonoids, is an interesting genus with multiple pharmacological activities. This review summarises phytochemical and pharmacological studies conducted so far. The data collected from the available literature shows that plants of the genus Zanthoxylum have great pharmacological potential. However, the genus is not fully explored and many gaps in the knowledge still exist.
Keywords: Zanthoxylum, rutaceae, secondary metabolite, phytochemistry, pharmacology, flavonoids.
Graphical Abstract

[1] 
Fish, F.; Waterman, P.G. Chemosystematics in the Rutaceae II. The chemosystematics of the Zanthoxylum/Fagara complex. Taxon,  1973, 22, 177-203.
[http://dx.doi.org/10.2307/1218122] 
[2] 
Pirani, J.R. A new species and a new combination in Zanthoxylum (Rutaceae) from Brazil. Brittonia,  1993, 45, 154-158.
[http://dx.doi.org/10.2307/2807498] 
[3] 
Global Biodiversity Information Facility. Biodiversity occurrence dataGBIF Data Portal, 2018.
[4] 
Available from. http://www.plantsoftheworldonline.org/
[5] 
Patiño, L.O.J.; Prieto, R.J.A.; Cuca, S.L.E. Zanthoxylum genus as potential source of bioactive compounds.Bioactive Compounds in Phytomedicine; Rasooli, I., Ed.; InTech, 2012. 
[http://dx.doi.org/10.5772/26037] 
[6] 
Waterman, P.G. New combinations in Zanthoxylum L.(1753). Taxon,  1975, 24, 361-366.
[http://dx.doi.org/10.2307/1218347] 
[7] 
Waterman, P.G. A phytochemist in the African rain forest. Phytochemistry,  1985, 25, 3-17.
[http://dx.doi.org/10.1016/S0031-9422(00)94492-3] 
[8] 
Medhi, K.; Deka, M.; Bhau, B.S. The genus Zanthoxylum-a stockpile of biological and ethnomedicinal properties. Sci. Rep.,  2013, 2, 697-704.
[9] 
Ducci, F.; Malentacchi, L. Preliminary micropropagation trials of Zanthoxylum simulans. Ital. For. Mont.,  1993, 48, 45-53.
[10] 
Bitchagno, G.T.M.; Tankeo, S.B.; Tsopmo, A.; Mpetga, J.D.S.; Tchinda, A.T.; Fobofou, S.A.T.; Wessjohann, L.A.; Kuete, V.; Tane, P. Lemairones A and B: Two new antibacterial tetraflavonoids from the leaves of Zanthoxylum lemairei (Rutaceae). Phytochem. Lett.,  2015, 14, 1-7.
[http://dx.doi.org/10.1016/j.phytol.2015.08.012] 
[11] 
Zhang, Y.; Wang, D.; Yang, L.; Zhou, D.; Zhang, J. Purification and characterization of flavonoids from the leaves of Zanthoxylum bungeanum and correlation between their structure and antioxidant activity. PLoS One,  2014, 9(8)e105725
[http://dx.doi.org/10.1371/journal.pone.0105725] [PMID:  25157400] 
[12] 
Epifano, F.; Curini, M.; Marcotullio, M.C.; Genovese, S. Searching for novel cancer chemopreventive plants and their products: the genus Zanthoxylum. Curr. Drug Targets,  2011, 12(13), 1895-1902.
[http://dx.doi.org/10.2174/138945011798184128] [PMID:  21158710] 
[13] 
Talontsi, F.M.; Matasyoh, J.C.; Ngoumfo, R.M.; Chepkorir, R. Mosquito larvicidal activity of alkaloids from Zanthoxylum lemairei against the malaria vector Anopheles gambiae. Pestic. Biochem. Physiol.,  2011, 99, 82-85.
[http://dx.doi.org/10.1016/j.pestbp.2010.11.003] 
[14] 
Matasyoh, J.C.; Talontsi, F.M.; Ngoumfo, R.M.; Chepkorir, R. Larvicidal activity of acridone alkaloids from Zanthoxylum leprieurii against the malaria vector Anopheles gambiae. Nat. Prod. J.,  2011, 1, 121-124.
[http://dx.doi.org/10.2174/2210315511101020121] 
[15] 
Huang, H.Y.; Ishikawa, T.; Peng, C.F.; Chen, S.; Chen, I.S. Secondary metabolites from the root wood of Zanthoxylum wutaiense and their antitubercular activity. Chem. Biodivers.,  2011, 8(5), 880-886.
[http://dx.doi.org/10.1002/cbdv.201000127] [PMID:  21560236] 
[16] 
Zondegoumba, E.N.T.; Dibahteu, W.L.; de Araujo, A.; Vidari, G.; Liu, Y.; Luo, S.; Li, S.; Junior, F.J.B.M.; Scotti, L.; Tullius, M. Cytotoxic and schistosomidal activities of extract, fractions and isolated compounds from Zanthoxylum leprieurii (Rutaceae). Int. J. Sci. Basic Appl. Res.,  2019, 44, 209-222.
[17] 
Kenmoe Djeukeu, C.; Kouam Kenmogne, A.; Guy Blaise Azebaze, A.; Belle Ebanda Kedi, P.; Vardamides, J.C.; Sewald, N.; Duplex Wansi, J. A new aromatic amide from the roots of Zanthoxylum tessmannii (Rutaceae). Chem. Biodivers.,  2019, 16(4)e1800590
[http://dx.doi.org/10.1002/cbdv.201800590] [PMID:  30834662] 
[18] 
Jie, Y.; Li, S.; Ho, C-T. Chemical composition, sensory properties and application of Sichuan pepper (Zanthoxylum genus). Food Sci. Hum. Wellness,  2019, 8, 115-125.
[http://dx.doi.org/10.1016/j.fshw.2019.03.008] 
[19] 
Tan, S-B.; Guo, T.; Tang, X-F.; Song, T-T.; Wang, Y. Chemical constituents of Zanthoxylum armatum. II. Chem. Nat. Compd.,  2018, 54, 1027-1028.
[http://dx.doi.org/10.1007/s10600-018-2543-4] 
[20] 
da Silva, T.A.; Henrique, C.Y.; Braguine, C.G.; Gonccedil, U.O.; Bastos, J.K.; Silva, M.L.A.; Cunha, W.R.; Januario, A.H.; Pauletti, P.M. Flavonoids and an alkaloid from Zanthoxylum naranjillo and their in vitro evaluation on the reproductive fitness of Schistosoma mansoni. J. Med. Plants Res.,  2012, 6, 5099-5102.
[http://dx.doi.org/10.5897/JMPR12.668] 
[21] 
Yuan, H.M.; Qiu, L.; Xie, Z.J.; Zou, L.; Zheng, J.; Fu, Q. Research progress on alkaloids constituents from Zanthoxylum and their pharmacological activities. Zhongguo Zhongyao Zazhi,  2015, 40(23), 4573-4584.
[PMID: 27141666] 
[22] 
Chruma, J.J.; Cullen, D.J.; Bowman, L.; Toy, P.H. Polyunsaturated fatty acid amides from the Zanthoxylum genus - from culinary curiosities to probes for chemical biology. Nat. Prod. Rep.,  2018, 35(1), 54-74.
[http://dx.doi.org/10.1039/C7NP00044H] [PMID:  29299588] 
[23] 
McGaw, L.J.; Lall, N.; Meyer, J.J.M.; Eloff, J.N. The potential of South African plants against Mycobacterium infections. J. Ethnopharmacol.,  2008, 119(3), 482-500.
[http://dx.doi.org/10.1016/j.jep.2008.08.022] [PMID:  18805475] 
[24] 
McGaw, L.J.; Eloff, J.N. Ethnoveterinary use of southern African plants and scientific evaluation of their medicinal properties. J. Ethnopharmacol.,  2008, 119(3), 559-574.
[http://dx.doi.org/10.1016/j.jep.2008.06.013] [PMID:  18620038] 
[25] 
Rochfort, S.; Parker, A.J.; Dunshea, F.R. Plant bioactives for ruminant health and productivity. Phytochemistry,  2008, 69(2), 299-322.
[http://dx.doi.org/10.1016/j.phytochem.2007.08.017 PMID: 17919666] 
[26] 
Bhatt, V.; Sharma, S.; Kumar, N.; Singh, B. A new lignan from the leaves of Zanthoxylum armatum. Nat. Prod. Commun.,  2017, 12(1), 99-100.
[http://dx.doi.org/10.1177/1934578X1701200128] [PMID:  30549837] 
[27] 
Nooreen, Z.; Kumar, A.; Bawankule, D.U.; Tandon, S.; Ali, M.; Xuan, T.D.; Ahmad, A. New chemical constituents from the fruits of Zanthoxylum armatum and its in vitro anti-inflammatory profile. Nat. Prod. Res.,  2019, 33(5), 665-672.
[http://dx.doi.org/10.1080/14786419.2017.1405404 PMID: 29161887] 
[28] 
Phuyal, N.; Jha, P.K.; Prasad Raturi, P.; Rajbhandary, S. Zanthoxylum armatum DC.: Current knowledge, gaps and opportunities in Nepal. J. Ethnopharmacol.,  2019, 229, 326-341.
[http://dx.doi.org/10.1016/j.jep.2018.08.010] [PMID:  30166217] 
[29] 
Chen, J-J.; Yang, C-K.; Kuo, Y-H.; Hwang, T-L.; Kuo, W-L.; Lim, Y-P.; Sung, P-J.; Chang, T-H.; Cheng, M-J. New coumarin derivatives and other constituents from the stem bark of Zanthoxylum avicennae: Effects on neutrophil pro-inflammatory responses. Int. J. Mol. Sci.,  2015, 16(5), 9719-9731.
[http://dx.doi.org/10.3390/ijms16059719] [PMID:  25938967] 
[30] 
Wang, Y.; Liao, Z-B.; Cao, R.; Li, H.; Wei, A-Z.; Gao, J-M. Isolation, structural characterization and neurotrophic activity of alkylamides from Zanthoxylum bungeanum. Nat. Prod. Commun.,  2017, 12, 1121-1124.
[http://dx.doi.org/10.1177/1934578X1701200730] 
[31] 
Chakthong, S.; Ampaprom, R.; Inparn, S.; Phetkul, U.; Chusri, S.; Limsuwan, S.; Voravuthikunchai, S.P. New alkylamide from the stems of Zanthoxylum nitidum. Nat. Prod. Res.,  2019, 33(2), 153-161.
[http://dx.doi.org/10.1080/14786419.2018.1440218 PMID: 29457506] 
[32] 
Zhao, L-N.; Guo, X-X.; Liu, S.; Feng, L.; Bi, Q-R.; Wang, Z.; Tan, N-H. (±)-Zanthonitidine A, a pair of enantiomeric furoquinoline alkaloids from Zanthoxylum nitidum with antibacterial activity. Nat. Prod. Bioprospect.,  2018, 8(5), 361-367.
[http://dx.doi.org/10.1007/s13659-018-0169-7] [PMID:  29855857] 
[33] 
Cui, H.Z.; Choi, H.R.; Choi, D.H.; Cho, K.W.; Kang, D.G.; Lee, H.S. Aqueous extract of Zanthoxylum schinifolium elicits contractile and secretory responses via β1-adrenoceptor activation in beating rabbit atria. J. Ethnopharmacol.,  2009, 126(2), 300-307.
[http://dx.doi.org/10.1016/j.jep.2009.08.025] [PMID:  19703535] 
[34] 
Li, W.; Sun, Y.N.; Yan, X.T.; Yang, S.Y.; Kim, E-J.; Kang, H.K.; Kim, Y.H. Coumarins and lignans from Zanthoxylum schinifolium and their anticancer activities. J. Agric. Food Chem.,  2013, 61(45), 10730-10740.
[http://dx.doi.org/10.1021/jf403479c] [PMID:  24144361] 
[35] 
Wang, J-F.; Deng, Y-H.; Yang, S-H.; Liu, Y-Q.; Wang, Y-H.; Pan, W-W.; Zhou, X-J. Characterization and biological evaluation of six new dimeric lignans with an unusual α,β-unsaturated ketone motif from Zanthoxylum simulans. Bioorg. Med. Chem. Lett.,  2014, 24(19), 4667-4671.
[http://dx.doi.org/10.1016/j.bmcl.2014.08.042] [PMID:  25205192] 
[36] 
Yao-Kouassi, P.A.; Caron, C.; Ramiarantsoa, H.; Prost, É.; Harakat, D.; Le Magrex-Debar, É.; Gangloff, S.C.; Coffy, A.A.; Zèches-Hanrot, M. New nitro-benzo [c] phenanthridine and indolopyridoquinazoline alkaloids from Zanthoxylum atchoum. C. R. Chim.,  2015, 18, 891-897.
[http://dx.doi.org/10.1016/j.crci.2015.01.005] 
[37] 
Kokwaro, J.O. Medicinal plants of East Africa; East African Literature Bureau: Nairobi, Kenya, 1976. 
[38] 
Kokwaro, J.O. Medicinal plants of East Africa; University of Nairobi press, 2009. 
[39] 
Adesina, S.K. Extractives from Zanthoxylum lemairie root and stem. Pharmazie,  1997, 52, 720-724.
[40] 
Ngane, A.N.; Biyiti, L.; Zollo, P.H.A.; Bouchet, P. Evaluation of antifungal activity of extracts of two Cameroonian rutaceae: Zanthoxylum leprieurii Guill. et Perr. and Zanthoxylum xanthoxyloides Waterm. J. Ethnopharmacol.,  2000, 70(3), 335-342.
[http://dx.doi.org/10.1016/S0378-8741(99)00188-9] [PMID:  10837996] 
[41] 
Wine-show, S.; Ian-Lih, T.; Che-Ming, T.; Ih-Sheng, C. Nor-neolignan and phenyl propanoid from Zanthoxylum ailanthoides. Phytochemistry,  1994, 36, 213-215.
[http://dx.doi.org/10.1016/S0031-9422(00)97039-0] 
[42] 
Xiong, Q.B.; Shi, D.W. Morphological and histological studies of Chinese traditional drug “hua jiao” (pericarpium zanthoxyli) and its allied drugs. Yao Xue Xue Bao,  1991, 26(12), 938-947.
[PMID: 1823995] 
[43] 
Kohno, K.; Soemori, H.; Takahashi, K. Flora of the Ryukyus (including Amami Islands, Okinawa Islands, and Sakishima Archipelago)(Added and Corrected) Flora of the Ryukyus (including Amami Islands, Okinawa Islands, and Sakishima Archipelago)(Added and Corrected), 1975. Appl. Entomol. Zool.,  2004, 39, 119-125.
[http://dx.doi.org/10.1303/aez.2004.119] 
[44] 
Singh, T.P.; Singh, O.M. Phytochemical and pharmacological profile of Zanthoxylum armatum DC.-an overview. Indian J. Nat. Prod. Resour.,  2011, 2, 275-285.
[45] 
Xiang, L.; Liu, Y.; Xie, C.; Li, X.; Yu, Y.; Ye, M.; Chen, S. The chemical and genetic characteristics of Szechuan Pepper (Zanthoxylum bungeanum and Z. armatum) cultivars and their suitable habitat. Front. Plant Sci.,  2016, 7, 467.
[http://dx.doi.org/10.3389/fpls.2016.00467] [PMID:  27148298] 
[46] 
Thuy, T.T.; Porzel, A.; Ripperger, H.; Van Sung, T.; Adam, G. Bishordeninyl terpene alkaloids from Zanthoxylum avicennae. Phytochemistry,  1999, 50, 903-907.
[http://dx.doi.org/10.1016/S0031-9422(98)00612-8] 
[47] 
Fonge, B.A.; Egbe, E.A.; Fongod, A.G.N.; Focho, D.A.; Tchetcha, D.J.; Nkembi, L.; Tacham, W.N. Ethnobotany survey and uses of plants in the Lewoh-Lebang communities in the Lebialem highlands, South West Region, Cameroon. J. Med. Plants Res.,  2012, 6, 855-865.
[48] 
Huang, S.; Zhao, L.; Zhou, X.L.; Ying, M.; Wang, C.J.; Weng, J. New alkylamides from pericarps of Zanthoxylum bungeanum. Chin. Chem. Lett.,  2012, 23, 1247-1250.
[http://dx.doi.org/10.1016/j.cclet.2012.09.022] 
[49] 
Schmidt, E.; Lotter, M.; McCleland, W. Trees and shrubs of Mpumalanga and Kruger national park; Jacana Media, 2002. 
[50] 
Calderwood, J.M.; Finkelstein, N.; Fish, F. Constituents of the stem and root barks of Fagara capensis (Thunb.). Phytochemistry,  1970, 9, 675.
[http://dx.doi.org/10.1016/S0031-9422(00)85715-5] 
[51] 
Tran, G.  Knob wood (Zanthoxylum chalybeum). Feedipedia, a programme by INRA, CIRAD, AFZ and FAO.,. 2015.
[52] 
Matu, E.N.; van Staden, J. Antibacterial and anti-inflammatory activities of some plants used for medicinal purposes in Kenya. J. Ethnopharmacol.,  2003, 87(1), 35-41.
[http://dx.doi.org/10.1016/S0378-8741(03)00107-7 PMID: 12787952] 
[53] 
Kamikawa, T.; Hanaoka, Y.; Fujie, S.; Saito, K.; Yamagiwa, Y.; Fukuhara, K.; Kubo, I. SRS-A antagonist pyranoquinolone alkaloids from east African Fagara plants and their synthesis. Bioorg. Med. Chem.,  1996, 4(8), 1317-1320.
[http://dx.doi.org/10.1016/0968-0896(96)00110-1] [PMID:  8879553] 
[54] 
Nguta, J.M.; Mbaria, J.M.; Gakuya, D.W.; Gathumbi, P.K.; Kiama, S.G. Antimalarial herbal remedies of Msambweni, Kenya. J. Ethnopharmacol.,  2010, 128(2), 424-432.
[http://dx.doi.org/10.1016/j.jep.2010.01.033] [PMID:  20096761] 
[55] 
Betti, J.L. Medicinal plants sold in Yaoundé markets, Cameroon. Afr. Study Monogr.,  2002, 23, 47-64.
[56] 
Lamaty, G.; Menut, C.; Bessiere, J.M.; Aknin, M. Aromatic plants of tropical Central Africa. II. A comparative study of the volatileconstituents of Zanthoxylum leprieurii (Guill. et Perr.) Engl. and Zanthoxylum tessmannii Engl. leaves and fruit pericarps from the Cameroon. Flavour Frag. J., 1989, 4, 203-205.. 
[57] 
Oliver-Bever, B. Medicinal plants in tropical West Africa. I. Plants acting on the cardiovascular system. J. Ethnopharmacol.,  1982, 5(1), 1-72.
[http://dx.doi.org/10.1016/0378-8741(82)90021-6] [PMID:  7033667] 
[58] 
Somanabandhu, A.; Ruangrungsi, N.; Lange, G.L.; Organ, M.G. Constituents of the stem bark of Zanthoxylum limonella. J. Sci. Soc. Thailand,  1992, 18, 181-185.
[http://dx.doi.org/10.2306/scienceasia1513-1874.1992.18.181] 
[59] 
Tringali, C. Bioactive compounds from natural sources: Isolation, Characterization and biological properties; CRC Press: Boca Raton, Florida, 2000. 
[http://dx.doi.org/10.1201/9781482289268] 
[60] 
Kan, W.S. Essential oil composition of fruits and leaves of Zanthoxylum nitidum grown in upper Assam region of India. Pharmacognosy Res.,  1970, 1, 148-151.
[61] 
Bhattacharya, S.; Zaman, K. Essential oil composition of fruits and leaves of Zanthoxylum nitidum grown in upper Assam region of India. Pharmacognosy Res.,  2009, 1, 148-151.
[62] 
Yang, S.Y.; Tai, B.H.; Song, S.B.; Li, W.; Yan, X.T.; Sun, Y.N.; Thao, N.P.; Kim, Y.H. NF-κB activation and PPAR transactivational effects of a new aliphatic acid amide from pericarps of Zanthoxylum piperitum. Bull. Korean Chem. Soc.,  2014, 35, 2361.
[http://dx.doi.org/10.5012/bkcs.2014.35.8.2361] 
[63] 
Yang, G.Z.; Hu, Y.; Yang, B.; Chen, Y. Lignans from the bark of Zanthoxylum planispinum. Helv. Chim. Acta,  2009, 92, 1657-1664.
[http://dx.doi.org/10.1002/hlca.200900055] 
[64] 
Irvine, F.R.  Woody plants of Ghana; Oxford University Press, 1961. 
[65] 
Arun, K.; Paridhavi, M. An ethnobotanical, phytochemical and pharmacological utilization of widely distributed species Zanthoxylum: A comprehensive overview. Int. J. Pharm. Invent.,  2012, 2, 24-35.
[66] 
Fernandes, C.C. Vieira, P.C.; Silva, V.C.d.; Dall’Oglio, E.L.; Silva, L.E.d.; Sousa Jr, P.T.d. 6-Acetonyl-N-methyl-dihydrodecarine, a new alkaloid from Zanthoxylum riedelianum. J. Braz. Chem. Soc.,  2009, 20, 379-382.
[http://dx.doi.org/10.1590/S0103-50532009000200025] 
[67] 
Moccelini, S.K.; Silva, V.C.d.; Ndiaye, E.A.; Sousa, P.T.d., Jr; Vieira, P.C. Phytochemical study from root barks of Zanthoxylum rigidum Humb. & Bonpl. ex Willd (Rutaceae). Quim. Nova,  2009, 32, 131-133.
[http://dx.doi.org/10.1590/S0100-40422009000100025] 
[68] 
Adesina, S.K. Three new amides from Zanthoxylum rubescens. Planta Med.,  1989, 55(3), 324-326.
[http://dx.doi.org/10.1055/s-2006-962021] [PMID:  17262432] 
[69] 
Penali, L.; Mulholland, D.A.; Tano, K.D.; Cheplogoi, P.K.; Randrianarivelojosia, M. Low antiplasmodial activity of alkaloids and amides from the stem bark of Zanthoxylum rubescens (Rutaceae). Parasite,  2007, 14(2), 161-164.
[http://dx.doi.org/10.1051/parasite/2007142161] [PMID:  17645189] 
[70] 
Adesina, S.K. The Nigerian Zanthoxylum: Chemical and biological values. Afr. J. Tradit. Complement. Altern. Med.,  2005, 2, 282-301.
[http://dx.doi.org/10.4314/ajtcam.v2i3.31128] 
[71] 
Fish, F.; Waterman, P.G. Alkaloids from two Nigerian species of Fagara. J. Pharm. Pharmacol.,  1971, 23, 132S-135S.
[http://dx.doi.org/10.1111/j.2042-7158.1971.tb08780.x PMID: 4401447] 
[72] 
Chen, I-S.; Wu, S-J.; Tsai, I-L.; Wu, T-S.; Pezzuto, J.M.; Lu, M.C.; Chai, H.; Suh, N.; Teng, C-M. Chemical and bioactive constituents from Zanthoxylum simulans. J. Nat. Prod.,  1994, 57(9), 1206-1211.
[http://dx.doi.org/10.1021/np50111a003] [PMID:  7798955] 
[73] 
Mbaze, L.M.; Poumale, H.M.P.; Wansi, J.D.; Lado, J.A.; Khan, S.N.; Iqbal, M.C.; Ngadjui, B.T.; Laatsch, H. α-Glucosidase inhibitory pentacyclic triterpenes from the stem bark of Fagara tessmannii (Rutaceae). Phytochemistry,  2007, 68(5), 591-595.
[http://dx.doi.org/10.1016/j.phytochem.2006.12.015 PMID: 17270224] 
[74] 
Odebiyi, O.O.; Sofowora, E.A. Antimicrobial alkaloids from a Nigerian chewing stick (Fagara zanthoxyloides). Planta Med.,  1979, 36(3), 204-207.
[http://dx.doi.org/10.1055/s-0028-1097271] [PMID:  482432] 
[75] 
Rios, M.Y.; Córdova-Albores, L.C.; Ramírez-Cisneros, M.Á.; King-Díaz, B.; Lotina-Hennsen, B.; León Rivera, I.; Miranda-Sánchez, D. Phytotoxic potential of Zanthoxylum affine and its major compound linarin as a possible natural herbicide. ACS Omega,  2018, 3(11), 14779-14787.
[http://dx.doi.org/10.1021/acsomega.8b02020] [PMID:  30555988] 
[76] 
Samita, F.N.; Sandjo, L.P.; Ndiege, I.O.; Hassanali, A.; Lwande, W. Zanthoxoaporphines A-C: Three new larvicidal dibenzo[de,g]quinolin-7-one alkaloids from Zanthoxylum paracanthum (Rutaceae). Beilstein J. Org. Chem.,  2013, 9, 447-452.
[http://dx.doi.org/10.3762/bjoc.9.47] [PMID:  23504306] 
[77] 
Sandjo, L.P.; Kuete, V.; Tchangna, R.S.; Efferth, T.; Ngadjui, B.T. Cytotoxic benzophenanthridine and furoquinoline alkaloids from Zanthoxylum buesgenii (Rutaceae). Chem. Cent. J.,  2014, 8(1), 61.
[http://dx.doi.org/10.1186/s13065-014-0061-4] [PMID:  25349626] 
[78] 
Tangjitjaroenkun, J.; Chantarasriwong, O.; Chavasiri, W. Chemical constituents of the stems of Zanthoxylum limonella Alston. Phytochem. Lett.,  2012, 5, 443-445.
[http://dx.doi.org/10.1016/j.phytol.2012.04.001] 
[79] 
Wangensteen, H.; Ho, G.T.T.; Tadesse, M.; Miles, C.O.; Moussavi, N.; Mikolo, B.; Malterud, K.E. A new benzophenanthridine alkaloid and other bioactive constituents from the stem bark of Zanthoxylum heitzii. Fitoterapia,  2016, 109, 196-200.
[http://dx.doi.org/10.1016/j.fitote.2016.01.012] [PMID:  26802607] 
[80] 
Wansi, J.D.; Tcho, A.T.; Toze, F.A.A.; Nahar, L.; Martin, C.; Sarker, S.D. Cytotoxic acridone and indoloquinazoline alkaloids from Zanthoxylum poggei. Phytochem. Lett.,  2016, 17, 293-298.
[http://dx.doi.org/10.1016/j.phytol.2016.08.010] 
[81] 
Wouatsa, V.N.A.; Misra, L.; Kumar, S.; Prakash, O.; Khan, F.; Tchoumbougnang, F.; Venkatesh, R.K. Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylum species. Chem. Cent. J.,  2013, 7, 125.
[http://dx.doi.org/10.1186/1752-153X-7-125] [PMID:  23866063] 
[82] 
Yang, Z-D.; Zhang, D-B.; Ren, J.; Yang, M-J. Skimmianine, a furoquinoline alkaloid from Zanthoxylum nitidum as a potential acetylcholinesterase inhibitor. Med. Chem. Res.,  2012, 21, 722-725.
[http://dx.doi.org/10.1007/s00044-011-9581-9] 
[83] 
Luo, X.; Pedro, L.; Milic, V.; Mulhovo, S.; Duarte, A.; Duarte, N.; Ferreira, M-J.U. Antibacterial benzofuran neolignans and benzophenanthridine alkaloids from the roots of Zanthoxylum capense. Planta Med.,  2012, 78(2), 148-153.
[http://dx.doi.org/10.1055/s-0031-1280289] [PMID:  22002848] 
[84] 
Samad, A.; Badshah, S.; Khan, D.; Ali, F.; Amanullah, M.; Hanrahan, J. New prenylated carbazole alkaloids from Zanthoxylum armatum. J. Asian Nat. Prod. Res.,  2014, 16(12), 1126-1131.
[http://dx.doi.org/10.1080/10286020.2014.967228] [PMID:  25355272] 
[85] 
Devkota, K.P.; Wilson, J.; Henrich, C.J.; McMahon, J.B.; Reilly, K.M.; Beutler, J.A. Isobutylhydroxyamides from the pericarp of Nepalese Zanthoxylum armatum inhibit NF1-defective tumor cell line growth. J. Nat. Prod.,  2013, 76(1), 59-63.
[http://dx.doi.org/10.1021/np300696g] [PMID:  23268719] 
[86] 
Guetchueng, S.T.; Nahar, L.; Ritchie, K.J.; Ismail, F.M.; Evans, A.R.; Sarker, S.D. Zanthoamides G-I: Three new alkamides from Zanthoxylum zanthoxyloides. Phytochem. Lett.,  2018, 26, 125-129.
[http://dx.doi.org/10.1016/j.phytol.2018.05.031] 
[87] 
Omosa, L.K.; Mbogo, G.M.; Korir, E.; Omole, R.; Seo, E-J.; Yenesew, A.; Heydenreich, M.; Midiwo, J.O.; Efferth, T. Cytotoxicity of fagaramide derivative and canthin-6-one from Zanthoxylum (Rutaceae) species against multidrug resistant leukemia cells. Nat. Prod. Res.,  2019, 1-8.
[http://dx.doi.org/10.1080/14786419.2019.1587424 PMID: 30896260] 
[88] 
Siddhanadham, A.S.; Yejella, R.P.; Prava, R.; Reddy, J.; Sama, A.K. Isolation, characterization and biological evaluation of two new lignans from methanolic extract of bark of Zanthoxylum armatum. Int. J. Pharmacogn. Phytochem. Res.,  2017, 9, 395-399.
[89] 
Tantapakul, C.; Phakhodee, W.; Ritthiwigrom, T.; Yossathera, K.; Deachathai, S.; Laphookhieo, S. Antibacterial compounds from Zanthoxylum rhetsa. Arch. Pharm. Res.,  2012, 35(7), 1139-1142.
[http://dx.doi.org/10.1007/s12272-012-0703-9] [PMID:  22864735] 
[90] 
Tian, J-M.; Wang, Y.; Xu, Y-Z.; Yu, Z-C.; Wei, A-Z.; Zhang, W-M.; Gao, J-M. Characterization of isobutylhydroxyamides with NGF-potentiating activity from Zanthoxylum bungeanum. Bioorg. Med. Chem. Lett.,  2016, 26(2), 338-342.
[http://dx.doi.org/10.1016/j.bmcl.2015.12.015] [PMID:  26707398] 
[91] 
Wang, Y.; Li, C-H.; Luo, B.; Sun, Y.N.; Kim, Y.H.; Wei, A-Z.; Gao, J-M. Isobutylhydroxyamides from Zanthoxylum bungeanum and their suppression of NO production. Molecules,  2016, 21(10), 1416.
[http://dx.doi.org/10.3390/molecules21101416] [PMID:  27782100] 
[92] 
Guo, T.; Tang, X-F.; Chang, J.; Wang, Y. A new lignan glycoside from the stems of Zanthoxylum armatum DC. Nat. Prod. Res.,  2017, 31(1), 16-21.
[http://dx.doi.org/10.1080/14786419.2016.1205064 PMID: 27438679] 
[93] 
Guo, T.; Xie, H.; Deng, Y-X.; Pan, S-L. A new lignan and other constituents from Zanthoxylum armatum DC. Nat. Prod. Res.,  2012, 26(9), 859-864.
[http://dx.doi.org/10.1080/14786419.2011.617748] [PMID:  22007685] 
[94] 
Peng, C-Y.; Liu, Y-Q.; Deng, Y-H.; Wang, Y-H.; Zhou, X-J. Lignans from the bark of Zanthoxylum simulans. J. Asian Nat. Prod. Res.,  2015, 17(3), 232-238.
[http://dx.doi.org/10.1080/10286020.2014.978303] [PMID:  25379867] 
[95] 
Su, G-y.; Wang, K-w.; Wang, X-y.; Wu, B. Bioactive lignans from Zanthoxylum planispinum with cytotoxic potential. Phytochem. Lett.,  2015, 11, 120-126.
[http://dx.doi.org/10.1016/j.phytol.2014.12.004] 
[96] 
Cebrián-Torrejón, G.; Assad Kahn, S.; Lagarde, N.; Castellano, F.; Leblanc, K.; Rodrigo, J.; Molinier-Frenkel, V.; Rojas de Arias, A.; Ferreira, M.E.; Thirant, C.; Fournet, A.; Figadère, B.; Chneiweiss, H.; Poupon, E. Antiproliferative activity of trans-avicennol from Zanthoxylum chiloperone var. angustifolium against human cancer stem cells. J. Nat. Prod.,  2012, 75(2), 257-261.
[http://dx.doi.org/10.1021/np2004165] [PMID:  22304006] 
[97] 
Cho, J-Y.; Hwang, T-L.; Chang, T-H.; Lim, Y-P.; Sung, P-J.; Lee, T-H.; Chen, J-J. New coumarins and anti-inflammatory constituents from Zanthoxylum avicennae. Food Chem.,  2012, 135, 17-23.
[http://dx.doi.org/10.1016/j.foodchem.2012.04.025] 
[98] 
Guetchueng, S.T.; Nahar, L.; Ritchie, K.J.; Ismail, F.M.D.; Wansi, J.D.; Evans, A.; Sarker, S.D. Kaurane diterpenes from the fruits of Zanthoxylum leprieurii (Rutaceae). Rec. Nat. Prod.,  2017, 11, 304-309.
[99] 
Hu, L.; Wang, K.; Wang, Z.; Liu, J.; Wang, K.; Zhang, J.; Luo, Z.; Xue, Y.; Zhang, Y.; Zhang, Y. A new megastigmane sesquiterpenoid from Zanthoxylum Schinifolium Sieb. et Zucc. Molecules,  2016, 21(3), 383.
[http://dx.doi.org/10.3390/molecules21030383] [PMID:  27007360] 
[100] 
Teshima, S.; Kawakami, S.; Sugimoto, S.; Matsunami, K.; Otsuka, H.; Shinzato, T. Aliphatic glucoside, zanthoionic acid and megastigmane glucosides: Zanthoionosides A–E from the leaves of Zanthoxylum ailanthoides. Chem. Pharm. Bull. (Tokyo),  2017, 65(8), 754-761.
[http://dx.doi.org/10.1248/cpb.c17-00211] [PMID:  28768929] 
[101] 
Vyry Wouatsa, N.A.; Misra, L.N.; Venkatesh Kumar, R.; Darokar, M.P.; Tchoumbougnang, F. Zantholic acid, a new monoterpenoid from Zanthoxylum zanthoxyloides. Nat. Prod. Res.,  2013, 27(21), 1994-1998.
[http://dx.doi.org/10.1080/14786419.2013.811662] [PMID:  23802991] 
[102] 
dos S. Beirigo, P.m.J.; Torquato, H.F.V.; dos Santos, C.H.C.; Carvalho, M.r.G.d.; Castro, R.N.; Paredes-Gamero, E.J.; de Sousa Jr, P.T.; Jacinto, M.J.; da Silva, V.C. [1-8-NαC]-Zanriorb A1, a proapoptotic orbitide from leaves of Zanthoxylum riedelianum. J. Nat. Prod.,  2016, 79, 1454-1458.
[103] 
Ribeiro, T.A.N.; da Silva, L.R.; de Sousa Júnior, P.T.; Castro, R.N.; De Carvalho, M.G. A new cyclopeptide and other constituents from the leaves of Zanthoxylum rigidum Humb. & Bonpl. ex Willd.(Rutaceae). Helv. Chim. Acta,  2012, 95, 935-939.
[http://dx.doi.org/10.1002/hlca.201100476] 
[104] 
Talontsi, F.M.; Facey, P.; Tatong, M.D.K.; Tofazzal Islam, M.; Frauendorf, H.; Draeger, S.; Tiedemann, Av.; Laatsch, H. Zoosporicidal metabolites from an endophytic fungus Cryptosporiopsis sp. of Zanthoxylum leprieurii. Phytochemistry,  2012, 83, 87-94.
[http://dx.doi.org/10.1016/j.phytochem.2012.06.006 PMID: 22883958] 
[105] 
Yao-Kouassi, P.A.; Caron, C.; Aké-Assi, E.; Martinez, A.; Le Magrex-Debar, E.; Gangloff, S.C.; Zèches-Hanrot, M. A new cycloheptapeptide from Zanthoxylum mezoneurispinosum Aké Assi (Rutaceae). Mediterr. J. Chem.,  2014, 3, 1013-1020.
[http://dx.doi.org/10.13171/mjc.3.5.2014.10.10.16.08] 
[106] 
Hu, J.; Shi, X.; Mao, X.; Chen, J.; Li, H. Cytotoxic mannopyranosides of indole alkaloids from Zanthoxylum nitidum. Chem. Biodivers.,  2014, 11(6), 970-974.
[http://dx.doi.org/10.1002/cbdv.201300381] [PMID:  24934682] 
[107] 
Zhu, L-J.; Ren, M.; Yang, T-C.; Qiao, C.; Chen, B-B.; Han, Z-Z.; Wang, S-H.; Wen, P.; Zhang, X. Four new alkylamides from the roots of Zanthoxylum nitidum. J. Asian Nat. Prod. Res.,  2015, 17(7), 711-716.
[http://dx.doi.org/10.1080/10286020.2015.1049161 PMID: 26096179] 
[108] 
Chen, J.; Zhang, T.; Zhang, Q.; Liu, Y.; Li, L.; Si, J.; Zou, Z.; Hua, H. Isobutylhydroxyamides from Sichuan pepper and their protective activity on PC12 cells damaged by corticosterone. J. Agric. Food Chem.,  2018, 66(13), 3408-3416.
[http://dx.doi.org/10.1021/acs.jafc.7b06057] [PMID:  29534566] 
[109] 
Li, W.; Yang, S.Y.; Yan, X.T.; Sun, Y.N.; Song, S.B.; Kang, H.K.; Kim, Y.H. NF-κB inhibitory activities of glycosides and alkaloids from Zanthoxylum schinifolium stems. Chem. Pharm. Bull. (Tokyo),  2014, 62(2), 196-202.
[http://dx.doi.org/10.1248/cpb.c13-00759] [PMID:  24492590] 
[110] 
Anza, M.; Haile, E.; Tadesse, S.; Mammo, F.; Endale, M. A coniferyl alcohol derivative from the roots of Zanthoxylum chalybeum. J. Coast. Life Med.,  2014, 2, 970-974.
[111] 
Bhatt, V.; Kumar, V.; Singh, B.; Kumar, N. A new geranylbenzofuranone from Zanthoxylum armatum. Nat. Prod. Commun.,  2015, 10(2), 313-314.
[http://dx.doi.org/10.1177/1934578X1501000225] [PMID:  25920270] 
[112] 
Williams, C.A.; Harborne, J.B., Eds.; Methods in plant biochemistry. Biflavonoids; Academic Press: San Diego, CA, USA, 1989, pp. 357-388.
[113] 
Taylor, W.I.; Battersby, A.R., Eds.; Oxidative coupling of phenols; M; Dekker, 1967, Vol. 1, . 
[114] 
Yang, S-H.; Liu, Y-Q.; Wang, J-F.; Wang, Y-H.; Pan, W-W.; Sheng, W-B.; Cai, R.; Zhou, X-J. Isoquinoline alkaloids from Zanthoxylum simulans and their biological evaluation. J. Antibiot. (Tokyo),  2015, 68(4), 289-292.
[http://dx.doi.org/10.1038/ja.2014.139] [PMID:  25269466] 
[115] 
Li, D.X.; Liu, M.; Zhou, X.J. A new dimeric lignan from Zanthoxylum simulans. Zhongguo Zhongyao Zazhi,  2015, 40(14), 2843-2848.
[PMID:  26666037] 
[116] 
Su, G.Y.; Cheng, Y.C.; Wang, K.W.; Wang, X.Y.; Wu, B. An unusual tetrahydrofuran lignan from the roots of Zanthoxylum planispinum and the potential anti‐inflammatory effects. Chem. Biodivers.,  2017, 14(1)e1600214
[http://dx.doi.org/10.1002/cbdv.201600214] [PMID:  27585089] 
[117] 
Moncada, S.; Palmer, R.M.; Higgs, E.A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol. Rev.,  1991, 43(2), 109-142.
[PMID: 1852778] 
[118] 
Fang, Y-Z.; Yang, S.; Wu, G. Free radicals, antioxidants, and nutrition. Nutrition,  2002, 18(10), 872-879.
[http://dx.doi.org/10.1016/S0899-9007(02)00916-4 PMID: 12361782] 
[119] 
Cos, P.; Vlietinck, A.J.; Berghe, D.V.; Maes, L. Anti-infective potential of natural products: how to develop a stronger in vitro ‘proof-of-concept’. J. Ethnopharmacol.,  2006, 106(3), 290-302.
[http://dx.doi.org/10.1016/j.jep.2006.04.003] [PMID:  16698208] 
[120] 
Guo, T.; Dai, L-P.; Tang, X-F.; Song, T-T.; Wang, Y.; Zhao, A-H.; Cao, Y-Y.; Chang, J. Two new phenolic glycosides from the stem of Zanthoxylum armatum DC. Nat. Prod. Res.,  2017, 31(20), 2335-2340.
Cite As
The Natural Products Journal

Phytochemistry and Pharmacology of the Genus Zanthoxylum (Rutaceae): A Review

Abstract

Graphical Abstract
