Abstract
The term copalchi has been used in the scientific literature to define a group of plants of the Rubiaceae and Euphorbiaceae families with extremely bitter stem-barks, useful for treating diabetes and malaria. In this review we summarized the most relevant chemical and pharmacological works carried out in the last century with the copalchis of the Rubiaceae family, namely Hintonia latiflora, H. standleyana and Exostema caribaeum. Their major components are 4-phenylcoumarins 5,7,3′,4′- or 5,7,4′-substituted with oxygenated functionalities, with the former having the most common pattern. These along with a few cucurbitacins are responsible for the antidiabetic properties of both Hintonia species. E. caribaeum contained mostly 4-phenylcoumarins, which apparently are the antimalarial constituents of these plants. Toxicological reports on these plants are discussed. The quality control procedures (chromatographic and molecular) developed for the three species are summarized. These will be valuable for their unequivocal identification, which in turn will avoid their partial adulteration or substitution. Future studies are required to solve the puzzle around the toxicity of the copalchis and for better understanding their pharmacological actions. Finally, establishment of their metabolomics profiles will provide a better knowledge of their secondary metabolism and help map their biosynthesis pathways.
Similar content being viewed by others
Abbreviations
- ATP:
-
Adenosine triphosphate
- AMPK 5′:
-
Adenosine monophosphate-activated protein kinase
- CD1 (ICR):
-
Institute of Cancer Research male mice
- CM:
-
Commercial mixture of copalchi
- COSY:
-
Homonuclear single-quantum correlation spectroscopy
- DNA:
-
Deoxyribonucleic acid
- FABMS:
-
Fast atom bombardment mass spectrometry
- HbA1c:
-
Glycosylated hemoglobin
- HMBC:
-
Heteronuclear multiple bond correlation spectroscopy
- HPLC:
-
High-performance liquid chromatography
- HSQC:
-
Heteronuclear single-quantum correlation spectroscopy
- IMN:
-
Instituto Médico Nacional
- IR:
-
Infrared spectroscopy
- ITS2 :
-
Internal transcribed spacer 2
- l-NAME:
-
l-N-Nitroarginine methyl ester
- MS:
-
Mass spectrometry
- NMR:
-
Nuclear magnetic resonance
- NP-SH:
-
Non-protein sulfhydryl endogenous
- psbA-trnH :
-
Internal transcribed spacer between the psbA and trnH chloroplast genes
- rbcL:
-
Ribulose bisphosphate carboxylase large
- rpl32-trnL :
-
Internal transcribed spacer between ribosomal protein L32 and tRNA-Leu chloroplast genes
- TLC:
-
Thin-layer chromatography
- TII-DM:
-
Type II diabetes mellitus
- UPLC:
-
Ultra-high-performance liquid chromatography
- UV:
-
Ultraviolet spectroscopy
References
Alarcón-Aguilar FA, Román-Ramos R (2006) Antidiabetic plants in Mexican and Central American Medicine. In: Soumyanath A (ed) Traditional medicines for modern times: antidiabetic plants, 1st edn. CRC Press, Boca Raton, pp 179–194
Anaya Dávila GMI (1991) Estudio etnobotánico del complejo quina en México. Dissertation, Universidad Nacional Autónoma de México
Andrade-Cetto A, Heinrich M (2005) Mexican plants with hypoglycaemic effect used in the treatment of diabetes. J Ethnopharmacol 99:325–348
Antih J (2018) Flore médicinale d’Amérique latine dans la médecine européenne: étude d’une sélection de plantes décrites entre le XVIème et le XVIIIème siècle. Dissertation, Université de Lorraine
Arévalo R (1897) Estudio sobre la corteza de Copalchi. In: Cortina CG (ed) Nueva recopilación de Monografías Mexicanas y Tesis Inaugurales de Materia Médica, vol 2. Oficina Tipográfica de la Secretaría de Fomento, Mexico City, pp 66–70
Argotte-Ramos R, Ramírez-Avila G, Rodríguez-Gutiérrez MDC, Ovilla-Muñoz M, Lanz-Mendoza H, Rodríguez MH, González-Cortazar M, Alvarez L (2006) Antimalarial 4-phenylcoumarins from the stem bark of Hintonia latiflora. J Nat Prod 69:442–444
Argueta AV, Cano LM, Rodarte ME (eds) (1994) Atlas de las plantas de la medicina tradicional Mexicana. Instituto Nacional Indigenista, Mexico City, p 1786
Beametz D, Egasse E (1889) Les Plantes médicinales indigènes et exotiques, leurs usages thérapeutiques, pharmaceutiques et industriel. Doin, Paris, p 635
Beltrán-Rodríguez L, Manzo-Ramos F, Martínez-Ballesté A, Blancas J, Maldonado-Almanza B (2017) Wild medicinal species traded in the Balsas Basin, Mexico: risk analysis and recommendations for their conservation. J Ethnobiol 37:743–764
Bhanu S, Saroja T, Seshadri TR, Mukerjee SK (1972) Conversion of 4-phenylcoumarins into xanthones. Biogenetic implications. Indian J Chem 10:577–580
Borhidi A (2012) Rubiáceas de México, 2nd edn. Akadémiai Kiadó, Budapest
Borhidi A, Diego-Pérez N (2002) Introducción a la taxonomía de la familia Rubiaceae en la flora de México. Acta Bot Hung 44:237–280
Bremer B, Andreasen K, Olsson D (1995) Subfamilial and tribal relationships in the Rubiaceae based on rbcL sequence data. Ann Missouri Bot Gard 82:383–397
Bruguera M, Herrera S, Lázaro E, Madurga M, Navarro M, De Abajo FJ (2007) Hepatitis aguda asociada al consumo de Copalchi. A propósito de 5 casos. Gastroenterol Hepatol 30:66–68
Bye R, Linares E (2016) Traditional markets in Mesoamerica: a mosaic of history and traditions. In: Lira R, Casas A, Blancas J (eds) Ethnobotany of Mexico, 1st edn. Springer, New York, pp 151–178
Capasso F (1993) Toxikologisches Gutachten uber Sucontral®. Universitat Neapel, Naples
Castillejos-Ramirez EV (2013) Pruebas de composición e identidad de la droga cruda Exostema caribaeum (Rubiaceae). Dissertation, Universidad Nacional Autónoma de México
Cristians S, Guerrero-Analco JA, Pérez-Vásquez A, Palacios-Espinosa F, Ciangherotti C, Bye R, Mata R (2009) Hypoglycemic activity of extracts and compounds from the leaves of Hintonia standleyana and H. latiflora: potential alternatives to the use of the stem bark of these species. J Nat Prod 72:408–413
Cristians S, Bye R, Navarrete A, Mata R (2013) Gastroprotective effect of Hintonia latiflora and Hintonia standleyana aqueous extracts and compounds. J Ethnopharmacol 145:530–535
Cristians S, Bye R, Nieto-Sotelo J (2018) Molecular markers associated with chemical analysis: a powerful tool for quality control assessment of copalchi medicinal plant complex. Front Pharmacol 9:1–12
De Lanessan JL (1886) Les Plantes utiles des colonies françaises, ouvrage publié sous la direction. Imprimerie nationale, Paris, p 990
Déciga-Campos M, Guerrero-Analco JA, Quijano L, Mata R (2006) Antinociceptive activity of 3-O-β-d-glucopyranosyl-23,24-dihydrocucurbitacin F from Hintonia standleyana (Rubiaceae). Pharmacol Biochem Behav 83:334–342
Déciga-Campos M, Rivero-Cruz I, Arriaga-Alba M, Castañeda-Corral G, Angeles-López GE, Navarrete A, Mata R (2007) Acute toxicity and mutagenic activity of Mexican plants used in traditional medicine. J Ethnopharmacol 110:334–342
Dibble CE, Anderson AJO (1963) History of the things of new Spain: Book 11, earthly things. The University of Utah, Salt Lake City, p 613
Farmacopea Herbolaria de los Estados Unidos Mexicanos (FHEUM) (2013) Secretaría de Salud, 2nd edn. Mexico City, p 193
Flores-Jiménez N, Rojas-Lemus M, Fortoul TI, Zepeda-Rodríguez A, López-Camacho PY, Anacleto-Santos J, Malagón-Gutiérrez F, Basurto-Islas G, Rivera-Fernández N (2018) Histopathological alterations in mice under sub-acute treatment with Hintonia latiflora methanolic stem bark extract. Histol Histopathol 33:1299–1309
Garcia M (2010) A folk remedy for NIDDM: evidence of antihyperglycemic effects of H. latiflora. California Digital Library, UCLA, California, pp 1–11
Guerrero-Analco JA (2007) Compuestos antihiperglicémicos y antinociceptivos de la especie Hintonia standleyana Bullock (Rubiaceae). Una contribución a la determinación de los parámetros de inocuidad, calidad y eficacia de la droga cruda. Dissertation, Universidad Nacional Autónoma de México
Guerrero-Analco JA, Hersch-Martínez P, Pedraza-Chaverri J, Navarrete A, Mata R (2005) Antihyperglycemic effect of constituents from Hintonia standleyana in streptozotocin-induced diabetic rats. Planta Med 71:1099–1105
Guerrero-Analco J, Medina-Campos O, Brindis F, Bye R, Pedraza-Chaverri J, Navarrete A, Mata R (2007) Antidiabetic properties of selected Mexican copalchis of the Rubiaceae family. Phytochemistry 68:2087–2095
Heinrich M, Anagnostou S (2017) From pharmacognosia to DNA-based medicinal plant authentication-pharmacognosy through the centuries. Planta Med 83:1110–1116
Hernández F (1943) Historia de las plantas de Nueva España, Instituto de Biología, Universidad Nacional Autónoma de México, vol 2. Imprenta Universitaria, Mexico City (Books 3 and 4)
Hersch P (2008) La industrialización químico-farmacéutica mexicana y la flora: el caso de laboratorios Garcol. Bol Soc Quim Mex 1:5–12
Ivanova NV, Kuzmina ML, Braukmann TWA, Borisenko AV, Zakharov EV (2016) Authentication of herbal supplements using next-generation sequencing. PLoS ONE 11:1–24
Kaiser H, Geyer H (1955) Zur Pharmakologie der Rinde von Coutarea latiflora D.C. Arch Pharm 288:595–608
Korec R, Sensch KH, Zoukas T (2000) Effects of the neoflavonoid coutareagenin, one of the antidiabetic active substances of Hintonia latiflora, on streptozotocin-induced diabetes mellitus in rats. Drug Res 50:122–128
Korecova M, Hladikova M (2014) Treatment of mild and moderate type-2 diabetes: open prospective trial with Hintonia latiflora extract. Eur J Med Res 19:16
Korecova M, Hladícova M, Korec R (2006) Hintonia latiflora in type 2 diabetes-A clinical long-term study [Hintonia latiflora bei typ-2-diabetes. Klinische langzeitstudie]. Z Phytother 27:272–278
Landa E (1913) Estudio del Copalchi de Jojutla (Coutarea latiflora). Anales del Instituto Medico Nacional 12:146–158
Linares E, Bye R (1987) A study of four medicinal plants complexes of Mexico and adjacent United States. J Ethnopharmacol 19:153–183
Loaeza A (1907) Informes de trabajos realizados del mes de enero al mes de noviembre de 1907. Anales del Instituto Medico Nacional 9(178):246
Loaeza A (1908) Informes de trabajos realizados del mes de enero al mes de junio de 1908. Anales del Instituto Medico Nacional 10:154–155
Martínez-Pérez A, López PA, Gil-Muñoz A, Cuevas-Sánchez JA (2012) Plantas silvestres útiles y prioritarias identificadas en la Mixteca Poblana, México. Acta Botanica Mexicana 98:73–98
Mata R, Calzada F, García MR, Reguero MT (1987) Chemical studies on Mexican plants used in traditional medicine, III. New 4-phenylcoumarins from Exostema caribaeum. J Nat Prod 50:866–871
Mata R, Calzada F, García MR (1988) Chemical studies on Mexican plants used in traditional medicine, IV. Additional 4-phenylcoumarins from Exostema caribaeum. J Nat Prod 51:851–856
Mata R, Del Rayo Camacho M, Cervera E, Bye R, Linares E (1990) Secondary metabolites from Hintonia latiflora. Phytochemistry 29:2037–2040
Mata R, Del Rayo Camacho M, Mendoza S, Del Carmen Cruz M (1992) A phenylstyrene from Hintonia latiflora. Phytochemistry 31:3199–3201
Mata R, Acevedo L, Méndez-Bautista DI, Guerrero-Analco JA, Rivero BE, Rodríguez JM (2008) Development and validation of liquid chromatography method for quantification of the active markers of Hintonia standleyana and Hintonia latiflora crude drugs. Pharm Biol 46:105–110
Mata R, Navarrete A, Cristians S, Hersch P, Bye RA (2009) Copalchi. Hintonia latiflora [Sessé et Mociño ex DC.] Bullock (Rubiaceae) Pruebas de control de calidad (identidad y composición), eficacia y seguridad. In Plantas Medicinales de México. Monografía científica. Sentido Giratorio, Mexico City, p 29
Mata R, Cristians S, Escandón-Rivera S, Juárez-Reyes K, Rivero-Cruz I (2013) Mexican antidiabetic herbs: valuable sources of inhibitors of α-glucosidases. J Nat Prod 76:468–483
McVaugh R (2000) Botanical Results of the Sessé & Mociño Expedition (1787–1803): a guide to relevant scientific names of plants. Hunt Institute for Botanical Documentation, Pittsburgh, p 226, 463, 471
Mishra P, Kumar A, Nagireddy A, Mani DN, Shukla AK, Tiwari R, Sundaresan V (2016) DNA barcoding: an efficient tool to overcome authentication challenges in the herbal market. Plant Biotechnol J 14:8–21
Monroy-Ortiz C, García-Moya E, Romero-Manzanares A, Sánchez-Quintanar C, Luna-Cavazos M, Uscanga-Mortera E, Flores-Guido JS, González-Romero V (2013) Plants of local interest for medicinal and conservation purposes in Morelos, Mexico. Stud Ethno-Med 7:13–26
Noster S, Kraus L (1990) In vitro antimalarial activity of Coutarea latiflora and Exostema caribaeum extracts on Plasmodium falciparum. Panta Med 56:63–65
Paris and Bastien (1960) Apropos of the hypoglycemic action of 2 drugs named “copalchi”: Coutarea latiflora (Rubiaceae) and Croton niveus (Euphorbiaceae). Ann Pharm Fr 18:205–219
Pérez-Vásquez A, Castillejos-Ramírez E, Cristians S, Mata R (2014) Developmet of UHPLC-PDA method for the simultaneous quantification of 4-phenylcoumarins and chlorogenic acid in Exostema caribaeum stem bark. J Nat Prod 77:516–520
Phillips SJ, Anderson R, Schapire RE (2006) Maximum entropy modeling of species geographic distributions. Ecol Mod 190:231–259
Pinto A, Capasso A, Sorrentino L (1997) Experimental animal studies on the hypoglycemic effects of a Copalchi extract. Arzneim Forsch 47:829–833
Raclariu AC, Heinrich M, Ichim MC, De Boer H (2018) Benefits and limitations of DNA barcoding and metabarcoding in herbal product authentication. Phytochem Anal 29:123–128
Reguero MT, Mata R, Bye R, Linares E, Delgado G (1987) Chemical studies on Mexican plants used in traditional medicine, II: cucurbitacins from Hintonia latiflora. J Nat Prod 50:315–316
Reher G, Kraus L (1984) New neoflavonoid from Coutarea latiflorea. J Nat Prod 47:172
Reyes-García T, Maradiaga-Ceceña FS, Catalán-Heverástico C, Jiménez-Hernández J (2012) Flora Leñosa del municipio de Cocula, Guerrero, México. Polibotánica 34:21–49
Rivera N, López PY, Rojas M, Fortoul TI, Reynada DY, Reyes AJ, Rivera E, Beltrán HI, Malagón F (2014) Antimalarial efficacy, cytotoxicity, and genotoxicity of methanolic stem bark extract from Hintonia latiflora in a Plasmodium yoelii yoelii lethal murine malaria model. Parasitol Res 113:1529–1536
Roca B (2003) Rhabdomyolysis and hemolysis after use of Coutarea latiflora. Am J Med 115:677
Rodriguez-Nozal R, Gonzalez-Bueno A (1995) Real Academia Médica matritense y expediciones botánicas ilustradas. Una conexión fármaco-terapéutica. Acta Hisp Med Sci Hist Illus 15:375–399
Rojas A, Hernández L, Pereda-Miranda R, Mata R (1992) Screening for antimicrobial activity of crude drug extracts and pure natural products from Mexican medicinal plants. J Ethnopharmacol 35:275–283
Romero-Cerecero O, Reyes-Morales H, Aguilar-Santamaría L, Huerta-Reyes M, Tortoriello-García J (2009) Use of medicinal plants among patients with diabetes mellitus type 2 in Morelos, Mexico. B Latinoam Caribe PL 8:380–388
Sahagún B (1988) Historia general de las cosas de Nueva España. Primera versión íntegra del texto castellano del manuscrito conocido como Códice Florentino. Alianza Editorial Quinto Centenario, Madrid
Sánchez-Viesca F (1969) The structure of exostemin, a new 4-phenylcoumarin isolated from Exostema caribaeum. Phytocehmistry 8:1821–1823
Slijepčević M, Kraus L (1997) The diabetic mouse as an experimental model for measuring the blood glucose-lowering effects of plant extracts and insulin preparations. A Therapeutic 23:47–58
Stranczinger S, Szentpéteri JL, Borhidi A (2006) Sequence differentiation between some DNA regions of Hintonia latiflora and Hintonia standleyana. Acta Bot Hung 48:435–440
Terrés J (1913) Estudio del complejo Copalchi de Jojutla (Coutarea latiflora). Anales del Instituto Medico Nacional 12:109
Vierling C, Baumgartner CM, Bollerhey M, Erhardt WD, Stampfl A, Vierling W (2014) The vasodilating effect of a Hintonia latiflora extract with antidiabetic action. Phytomedicine 21:1582–1586
Wang B, Li N, Liu T, Sun J, Wang X (2017) Synthesis and biological evaluation of novel neoflavonoid derivatives as potential antidiabetic agents. RSC Adv 7:34448–34460
Wurtz AS, Vial T, Isoard B, Saillard E (2002) Possible hepatoxicity from Copaltra, an herbal medicine. Ann Pharmacother 36:941–942
Acknowledgements
This work was supported by Grants from CONACyT A1_S_11226, DGAPA IN217516 and PAIP-UNAM 5000-9140. We like to thank Virginia Evangelista-Oliva for their technical assistance in the actual and potential distribution maps.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Rivero-Cruz, I., Cristians, S., Ovalle-Magallanes, B. et al. Mexican copalchis of the Rubiaceae family: more than a century of pharmacological and chemical investigations. Phytochem Rev 18, 1435–1455 (2019). https://doi.org/10.1007/s11101-019-09618-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11101-019-09618-y