Introduction: The increase in multidrug resistance and lack of efficacy in malaria therapy has propelled the urgent discovery of new antiplasmodial drugs, reviving the screening of secondary metabolites from traditional medicine. In plant metabolomics, NMR-based strategies are considered a golden method providing both a holistic view of the chemical profiles and a correlation between the metabolome and bioactivity, becoming a corner stone of drug development from natural products.
Objective: Create a multivariate model to identify antiplasmodial metabolites from 1H NMR data of two African medicinal plants, Keetia leucantha and K. venosa.
Methods: The extracts of twigs and leaves of Keetia species were measured by 1H NMR and the spectra were submitted to orthogonal partial least squares (OPLS) for antiplasmodial correlation.
Results: Unsupervised 1H NMR analysis showed that the effect of tissues was higher than species and that triterpenoids signals were more associated to Keetia twigs than leaves. OPLS-DA based on Keetia species correlated triterpene signals to K. leucantha, exhibiting a higher concentration of triterpenoids and phenylpropanoid-conjugated triterpenes than K. venosa. In vitro antiplasmodial correlation by OPLS, validated for all Keetia samples, revealed that phenylpropanoid-conjugated triterpenes were highly correlated to the bioactivity, while the acyclic squalene was found as the major metabolite in low bioactivity samples.
Conclusion: NMR-based metabolomics combined with supervised multivariate data analysis is a powerful strategy for the identification of bioactive metabolites in plant extracts. Moreover, combination of statistical total correlation spectroscopy with 2D NMR allowed a detailed analysis of different triterpenes, overcoming the challenge posed by their structure similarity and coalescence in the aliphatic region.
Keywords: In vitro antiplasmodial activity; Keetia leucantha; Keetia venosa; NMR-based metabolomics; STOCSY; Triterpenes.
Conflict of interest statement
The authors declare that they have no conflict of interest.
In vivo antimalarial activity of Keetia leucantha twigs extracts and in vitro antiplasmodial effect of their constituents.J Ethnopharmacol. 2013 Aug 26;149(1):176-83. doi: 10.1016/j.jep.2013.06.018. Epub 2013 Jun 19. J Ethnopharmacol. 2013. PMID: 23792125
1H NMR-based metabolomics of antimalarial plant species traditionally used by Vha-Venda people in Limpopo Province, South Africa and isolation of antiplasmodial compounds.J Ethnopharmacol. 2019 Jan 10;228:148-155. doi: 10.1016/j.jep.2018.07.022. Epub 2018 Jul 23. J Ethnopharmacol. 2019. PMID: 30048730
Optimization and validation of extraction and quantification methods of antimalarial triterpenic esters in Keetia leucantha plant and plasma.J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Jan 1;1104:109-118. doi: 10.1016/j.jchromb.2018.11.003. Epub 2018 Nov 4. J Chromatogr B Analyt Technol Biomed Life Sci. 2019. PMID: 30448629
Translational Metabolomics of Head Injury: Exploring Dysfunctional Cerebral Metabolism with Ex Vivo NMR Spectroscopy-Based Metabolite Quantification.In: Kobeissy FH, editor. Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. Boca Raton (FL): CRC Press/Taylor & Francis; 2015. Chapter 25. Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. 2015. PMID: 26269925 Free Books & Documents. Review.
Antimalarial activity of medicinal plants from the Democratic Republic of Congo: A review.J Ethnopharmacol. 2015 Jul 1;169:76-98. doi: 10.1016/j.jep.2015.03.075. Epub 2015 Apr 8. J Ethnopharmacol. 2015. PMID: 25862959 Review.
Cited by 1 article
Bioactivity-Guided Fractionation and NMR-Based Identification of the Immunomodulatory Isoflavone from the Roots of Uraria crinita (L.) Desv. ex DC.Foods. 2019 Nov 3;8(11):543. doi: 10.3390/foods8110543. Foods. 2019. PMID: 31684126 Free PMC article.
- Abreu AC, Coqueiro A, Sultan AR, Lemmens N, Kim HK, Verpoorte R, et al. Looking to nature for a new concept in antimicrobial treatments: Isoflavonoids from Cytisus striatus as antibiotic adjuvants against MRSA. Scientific Reports. 2017;7(1):3777. doi: 10.1038/s41598-017-03716-7. - DOI - PMC - PubMed
- Beaufay C, Bero J, Quetin-Leclercq J. Natural antimicrobial agents; sustainable development and biodiversity. Cham: Springer; 2018. Antimalarial terpenic compounds isolated from plants used in traditional medicine (2010–July 2016) pp. 247–268.