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Mexican copalchis of the Rubiaceae family: more than a century of pharmacological and chemical investigations

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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.

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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

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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.

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  1. Facultad de Química, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico

    Isabel Rivero-Cruz, Berenice Ovalle-Magallanes & Rachel Mata

  2. Jardín Botánico, Instituto de Biología, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico

    Sol Cristians

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  1. Isabel Rivero-Cruz
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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

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