Infraspecific Chemical Variability and Biological Activity of Casearia sylvestris from Different Brazilian Biomes

Abstract

Casearia sylvestris is an outstanding representative of the Casearia genus. This representability comes from its distinctive chemical profile and pharmacological properties. This species is widespread from North to South America, occurring in all Brazilian biomes. Based on their morphology, 2 varieties are recognized: C. sylvestris var. sylvestris and C. sylvestris var. lingua. Despite the existence of data about their chemical composition, a deeper understanding of the specialized metabolism correlation and variation in respect to environmental factors and its repercussion over their biological activities was still pending. In this study, an UHPLC-DAD-based metabolomics approach was employed for the investigation of the chemical variation of 12 C. sylvestris populations sampled across 4 Brazilian biomes and ecotones. The correlation between infraspecific chemical variability and the cytotoxic and antioxidant activities was achieved by multivariate data analysis. The analyses showed that C. sylvestris var. lingua prevailed at Cerrado areas, and it was correlated with lower cytotoxic activity and high level of glycosylated flavonoids. Among them, narcissin and isorhamnetin-3-O-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranoside showed good correlation with the antioxidant activity. Conversely, C. sylvestris var. sylvestris prevailed at the Atlantic Forest areas, and it was associated with high cytotoxic activity and high content of clerodane diterpenoids. Different casearins showed good correlation (R²  = 0.3 – 0.70) with the cytotoxic activity. These findings highlighted the great complexity among different C. sylvestris populations, their chemical profile, and the related biological activities. Consequently, it can certainly influence the medicinal properties, as well as the quality and efficacy, of C. sylvestris phytomedicines.

Key words

Casearia sylvestris - Salicaceae - clerodane diterpenoids - glycosylated flavonoids - biological activities - plant ecophysiology - metabolomics - multivariate data analysis

Publikationsverlauf

Eingereicht: 28. Juni 2020

Angenommen nach Revision: 26. Oktober 2020

Artikel online veröffentlicht:
21. Dezember 2020

• References

• 1 Croteau R, Kutchan TM, Lewis NG. Natural Products (secondary Metabolites–chapter 24). In: Buchanan B, Gruissem W, Jones R. eds. Biochemistry & molecular Biology of Plants. Rockville: American Society of Plant Physiologists; 2000: 1367
• 2 Dewick PM. Medicinal natural Products: A biosynthetic Approach. 3rd edition. Chichester: Wiley; 2009
• 3 Weckwerth W, Loureiro ME, Wenzel K, Fiehn O. Differential metabolic networks unravel the effects of silent plant phenotypes. PNAS 2004; 101: 7809-7814
• 4 Morgenthal K, Weckwerth W, Steuer R. Metabolomic networks in plants: transitions from pattern recognition to biological interpretation. Biosystems 2006; 83: 108-117
• 5 Moore BD, Andrew RL, Külheim C, Foley WJ. Explaining intraspecific diversity in plant secondary metabolites in an ecological context. New Phytol 2014; 201: 733-750
• 6 Sharma A, Cardoso-Taketa A, Choi YH, Verpoorte R, Villareal ML. A comparison on the metabolic profiling of the Mexican anxiolytic and sedative plant Galphimia glauca four years later. J Ethnopharmacol 2012; 141: 964-974
• 7 Cavallari MM, Gimenes MA, Billot C, Torres RB, Cavalheiro AJ, Bouvet JM. Population genetic relationships between Casearia sylvestris (Salicaceae) varieties occurring sympatrically and allopatrically in different ecosystems in south-east Brazil. Ann Bot 2010; 106: 627-636
• 8 Sleumer HO. Flora Neotropica (Monograph Number 22–Flacourtinaceae). New York: The New York Botanic Garden; 1980
• 9 Marquete R, Mansano VF. O gênero Casearia no Brasil. Rev Biol Trop 2016; 13: 69-249
• 10 Klein RM, Sleumer HO. Flacourtiaceae. In: Reitz R. ed. Flora Ilustrada Catarinense. Itajaí: Herbário Barbosa Rodrigues; 1984: 96
• 11 Ferreira PMP, Costa-Lotufo LV, Moraes M, Barros FWA, Martins AMA, Cavalheiro AJ, Bolzani VS, Santos AG, Pessoa C. Folk uses and pharmacological properties of Casearia sylvestris: a medicinal review. An Acad Bras Ciênc 2011; 83: 1373-1384
• 12 Anhesine NB, Bueno PCP, Torres RB, Lopes NP, Cavalheiro AJ. Non-polar and polar chemical profiling of six Casearia species (Salicaceae). Biochem Syst Ecol 2019; 87: 103954
• 13 Marmitt DJ, Bitencourt S, Silva AC, Rempel C, Goettert MI. Scientific production of plant species included in the Brazilian national list of medicinal plants of interest to the unified health system (RENISUS) from 2010 to 2013. J Chem Pharm Sci 2016; 82: 123-132
• 14 Carvalho PRF, Furlan M, Young MCM, Kingston DGI, Bolzani VS. Acetylated DNA-damage clerodane diterpenes from Casearia sylvestris . Phytochemistry 1998; 49: 1659-1662
• 15 Santos AG, Ferreira PMP, Vieira Junior GM, Perez CC, Tininis AG, Silva GH, Bolzani VS, Costa-Lotufo LV, Pessoa CO, Cavalheiro AJ. Casearin X, its degradation product and other clerodane diterpenes from leaves of Casearia sylvestris: evaluation of cytotoxicity against normal and tumor human cells. Chem Biodivers 2007; 7: 205-215
• 16 Carvalho ES, Santos AG, Cavalheiro AJ. Identificação de diterpenos clerodânicos em diferentes órgãos de Casearia sylvestris Sw. Rev Ciênc Farm Básica Apl 2009; 30: 277-284
• 17 Wang W, Ali Z, Li X, Smillie TA, Guo D, Khan IA. New clerodane diterpenoids from Casearia sylvestris . Fitoterapia 2009; 80: 404-407
• 18 Da Silva SL, Chaar JS, Yano T. Chemotherapeutic potential of two gallic acid derivative compounds from leaves of C. sylvestris Sw (Flacourtiaceae). Eur J Pharmacol 2009; 608: 76-83
• 19 Da Silva SL, Calgarotto AK, Chaar J, Marangoni S. Isolation and characterization of ellagic acid derivatives isolated from Casearia sylvestris Sw. aqueous extract with anti-Pla2 activity. Toxicon 2008; 52: 655-666
• 20 Bueno PCP, Passareli F, Anhesine NB, Torres RB, Cavalheiro AJ. Flavonoids from Casearia sylvestris Sw. variety lingua (Salicaceae). Biochem Syst Ecol 2016; 68: 23-26
• 21 Bueno PCP, Pereira FMV, Torres RB, Cavalheiro AJ. Development of a comprehensive method for analysing clerodane-type diterpenes and phenolic compounds from Casearia sylvestris Swartz (Salicaceae) based on ultra-high-performance liquid chromatography combined with chemometric tools. J Sep Sci 2015; 38: 1649-1656
• 22 Ferreira PMP, Militao GCG, Lima DJB, Costa NDJ, Machado KC, Santos AG, Cavalheiro AJ, Bolzani VS, Silva DHS, Pessoa CO. Morphological and biochemical alterations activated by antitumor clerodane diterpenes. Chem Biol Interact 2014; 222: 112-125
• 23 Xia L, Guo Q, Tu P, Chai X. The genus Casearia: a phytochemical and pharmacological overview. Phytochem Rev 2014; 14: 99-135
• 24 Itokawa H, Totsuka N, Takeya K, Watanabe K, Obata E. Antitumor principles from Casearia sylvestris Sw. (Flacourtiaceae), structure elucidation of new clerodane diterpenes by 2D NMR spectroscopy. Chem Pharm Bull 1998; 36: 1585-1588
• 25 Santos AG, Ferreira PMP, Vieira Júnior GM, Perez CC, Tininis AG, Silva GH, Bolzani VS, Costa-Lotufo LV, Pessoa C, Cavalheiro AJ. Casearin X, its degradation product and other clerodane diterpenes from leaves of Casearia sylvestris: evaluation of cytotoxicity against normal and tumour human cells. Chem Biodivers 2010; 7: 205-215
• 26 Napolitano DR, Mineo JR, Souza MA, Paula JE, Espindola LS, Espindola FS. Down-modulation of nitric oxide production in murine macrophages treated with crude plant extracts from the brazilian cerrado. J Ethnopharmacol 2005; 99: 37-41
• 27 Wolfender J, Nuzillard J, Van der Hooft JJJ, Renault J, Bertrand S. Accelerating metabolite identification in natural product research: toward an ideal combination of liquid chromatography−high-resolution tandem mass spectrometry and NMR profiling, in slico databases, and chemometrics. Anal Chem 2019; 91: 704-742
• 28 Ribeiro SM, Fratucelli EDO, Bueno PCP, Castro MKV, Francisco AA, Cavalheiro AJ, Klein MI. Antimicrobial and antibiofilm activities of Casearia sylvestris extracts from distinct brazilian biomes against Streptococcus mutans and Candida albicans . BMC Complement Altern Med 2019; 19: 308
• 29 Danuello A, Castro RC, Pilon AC, Bueno PCP, Pivatto M, Vieira Junior GM, Carvalho FQ, Oda FB, Perez CJ, Lopes NP, Santos AG, Ifa DR, Cavalheiro AJ. Fragmentation study of clerodane diterpenes from Casearia species by tandem mass spectrometry (QToF and Ion Trap). Rapid Commun Mass Spectrom 2020; 34: e8781
• 30 Mayr E. Systematics and the Origin of Species, from the Viewpoint of a Zoologist. Cambridge: Harvard University Press; 2009
• 31 Biswal B, Joshi PN, Raval MK, Biswal UC. Photosynthesis, a global sensor of environmental stress in green plants: stress signalling and adaptation. Curr Sci 2011; 101: 47-56
• 32 Givnish TJ. Adaptation to sun and shade: a whole-plant perspective. Aust J Plant Physiol 1988; 15: 63-92
• 33 Ruban AV. Plants in light. Commun Intreg Biol 2009; 1: 50-55
• 34 Qureshi MI, Qadir S, Zolla L. Proteomics-based dissection of stress-responsive pathways in plants. J Plant Physiol 2007; 164: 1239-1260
• 35 Nijveldt RJ, Nood E, Hoorn DEC, Boelens PG, Norren K, Leeuwen PAM. Flavonoids: a review of probable mechanisms of action and potential application. Am J Clin Nutr 2001; 74: 418-425