Characterization of Antibacterial Proanthocyanidins of Dalbergia monetaria, an Amazonian Medicinal Plant, by UHPLC-HRMS/MS

Abstract

Dalbergia monetaria is an Amazonian plant whose bark is widely used to treat urinary tract infections. This paper describes a bio-guided study of ethanolic extracts from the bark and leaves of D. monetaria, in a search for metabolites active against human pathogenic bacteria. In vitro assays were performed against 10 bacterial strains, highlighting methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Fractioning of the extracts was performed using instrumental and classical techniques, and samples were characterized by UHPLC-HRMS/MS. Ethyl acetate fractions from bark and leaves showed similar antibacterial activities. EAFB is enriched in isoflavone C-glucosides and EAFL enriched in proanthocyanidins. Subfractions from EAFL presented higher activity and showed a complex profile of proanthocyanidins constructed by (epi)-cassiaflavan and (epi)-catechin units, including dimers, trimers and tetramers. The fragmentation pattern emphasized the neutral loss of cassiaflavan units by quinone-methide fission. Fraction SL7-6, constituted by (ent)-cassiaflavan-(ent)-cassiaflavan-(epi)-catechin isomers, showed the lowest MIC against the S. aureus and P. aeruginosa with values corresponding to 64 and 32 µg/mL, respectively. Cassiaflavan-proanthocyanidins have not been found previously in another botanical genus, except in Cassia, and the traditional medicinal use of D. monetaria might be related to the antibacterial activity of proanthocyanidins characterized in the species.

Key words

Dalbergia monetaria - Leguminosae - antibacterial activity - proanthocyanidin - mass spectroscopy - methicillin-resistant Staphylococcus aureus - Pseudomonas aeruginosa

• References

• 1 de Carvalho AEM. A synopsis of the genus Dalbergia (Fabaceae: Dalbergieae) in Brazil. Brittonia 1997; 49: 87-109
• 2 Sarquis RSF, Sarquis IR, Sarquis IR, Fernandes CP, Silva GA, Silva RBL, Jardim MAG, Sánchez-Ortíz BL, Carvalho JCT. The use of medicinal plants in the riverside community of the Mazagão River in the Brazilian Amazon, Amapá, Brazil: ethnobotanical and ethnopharmacological studies. Evid Based Complement Alternat Med 2019; 2019: 6087509
• 3 Coelho-Ferreira MR, da Silva MFF. A fitofarmacopéia da comunidade pesqueira de Marudá, Litoral Paraense. Bol Mus Para Emílio Goeldi, sér Ciências Naturais 2005; 1: 31-43
• 4 Leão RBA, Coelho-Ferreira MR, Jardim MAG. Levantamento de plantas de uso terapêutico no município de Santa Bárbara do Pará, Estado do Pará, Brasil. Rev Bras Farmacogn 2007; 88: 21-25
• 5 Nunes DS, Haag A, Hans BJ. Inhaltsstoffe der Rinde von Dalbergia monetaria L. Drei neue Isoflavon-C-glucoside. Liebigs Ann 1989; 1989: 331-335
• 6 Nunes DS, Haag A, Bestmann HJ. Two proanthocyanidins from the bark of Dalbergia monetaria . Phytochemistry 1989; 28: 2183
• 7 de Moura PH, Lucas FC, Tavares-Martins AC, Lobato GD, Gurgel ES. Etnobotânica de chás terapêuticos em Rio Urubueua de Fátima, Abaetetuba–Pará, Brasil. Biotemas 2016; 29: 77-88
• 8 Bonkat G, Pickard R, Bartoletti R, Bruyère F, Geerlings SE, Wagenlehner F, Wullt B. EAU guidelines on urological infections. Available at: https://uroweb.org/wp-content/uploads/Urological-Infections-2017-pocket.pdf Accessed November 15, 2019
• 9 Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol 2015; 13: 269-284
• 10 Nielubowicz GR, Mobley HLT. Host-pathogen interactions in urinary tract infection. Nat Rev Urol 2010; 7: 430-441
• 11 Levison ME, Kaye D. Treatment of complicated urinary tract infections with an emphasis on drug-resistant gram-negative uropathogens. Curr Infect Dis Rep 2013; 15: 109-115
• 12 Williams G, Craig JC. Long-term antibiotics for preventing recurrent urinary tract infection in children. Cochrane Database Syst Rev 2019; (04) CD001534
• 13 Nathan C, Cars O. Antibiotic resistance–problems, progress and prospects. N Engl J Med 2014; 371: 1061-1063
• 14 WHO (World Health Organization). Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. WHO Drug Inf 2017; 31: 46-51
• 15 Veiga VF, Pinto AC, Maciel MAM. Medicinal plants: Safe cure?. Quim Nova 2005; 28: 519-528
• 16 Sharifi-Rad M, Ozcelik B, Altn G, Dakaya-Dikmen C, Martorell M, Ramrez-Alarcn K, Alarcn-Zapata P, Morais-Braga MFB, Carneiro JN, Leal ALAB, Coutinho HDM, Gyawali R, Tahergorabi R, Ibrahim SA, Sahrifi-Rad R, Sharopov F, Salehi B, Contreras MM, Segura-Carretero A, Sen S, Acharya K, Sharifi-Rad J. Salvia spp. plants – from farm to food applications and phytopharmacotherapy. Trends Food Sci Technol 2018; 80: 242-263
• 17 Salehi B, Krochmal-Marczak B, Skiba D, Patra JK, Das SK, Das G, Popović-Djordjević JB, Kostić AŽ, Anil Kumar NV, Tripathi A, Al-Snafi AE, Arserim-Uçar DK, Konovalov DA, Csupor D, Shukla I, Azmi L, Mishra AP, Sharifi-Rad J, Sawicka B, Martins N, Taheri Y, Fokou PVT, Capasso R, Martorell M. Convolvulus plant–a comprehensive review from phytochemical composition to pharmacy. Phytother Res 2020; 34: 315-328
• 18 Zhang S, Li L, Cui Y, Luo L, Li Y, Zhou P, Sun B. Preparative high-speed counter-current chromatography separation of grape seed proanthocyanidins according to the degree of polymerization. Food Chem 2017; 219: 399-440
• 19 Hatano T, Yamashita A, Hashimoto T, Ito H, Kubo N, Yoshiyama M, Shimura S, Itoh Y, Okuda T, Yoshida T. Flavan dimers with lipase inhibitory activity from Cassia nomame . Phytochemistry 1997; 46: 893-900
• 20 Coetzee J, Mciteka L, Malan E, Ferreira D. Structure and synthesis of the first procassinidin dimers based on epicatechin, and gallo- and epigallocatechin. Phytochemistry 2000; 53: 795-804
• 21 Nakamura S, Xu F, Ninomiya K, Nakashima S, Oda Y, Morikawa T, Muraoka O, Yoshikawa M, Matsuda H. Chemical structures and hepatoprotective effects of constituents from Cassia auriculata leaves. Chem Phar Bull 2014; 62: 1026-1031
• 22 Sobeh M, Mahmoud MF, Abdelfattah MAO, Cheng H, El-Shazly AM, Wink M. A proanthocyanidin-rich extract from Cassia abbreviata exhibits antioxidant and hepatoprotective activities in vivo . J Ethnopharmacol 2018; 213: 38-47
• 23 Wang H, Ye YH, Wang HH, Liu J, Liu YJ, Jiang BW. HPLC-QTOF-MS/MS profiling, antioxidant, and α‐glucosidase inhibitory activities of Pyracantha fortuneana fruit extracts. J Food Biochem 2019; 43: e12821
• 24 Mohn T, Plitzko I, Hamburger MA. Phytochemistry: a comprehensive metabolite profiling of Isatis tinctoria leaf extracts. Phytochemistry 2009; 70: 924-934
• 25 Otify A, George C, Elsayed A, Farag MA. Mechanistic evidence of Passiflora edulis (Passifloraceae) anxiolytic activity in relation to its metabolite fingerprint as revealed via LC-MS and chemometrics. Food Funct 2015; 6: 3807-3817
• 26 Rodríguez-Medina I, Beltrán-Debón R, Molina VM, Alonso-Villaverde C, Joven J, Menéndez JA, Segura-Carretero A, Fernández-Gutiérrez A. Direct characterization of aqueous extract of Hibiscus sabdariffa using HPLC with diode array detection coupled to ESI and ion trap MS. J Sep Sci 2009; 32: 3441-3448
• 27 Lee SY, Ismail IS, Ang EL, Abas F. Antioxidant, α-glucosidase inhibitory activities, and HPLC quantitative analysis of phenolic compounds isolated from Neptunia oleracea Lour. Int Food Res J 2019; 26: 679-688
• 28 Hammerstone JF, Lazarus SA, Mitchell AE, Rucker R, Schmitz HH. Identification of procyanidins in cocoa (Theobroma cacao) and chocolate using high-performance liquid chromatography/mass spectrometry. J Agric Food Chem 1999; 47: 490-496
• 29 Friedrich W, Eberhardt A, Galensa R. Investigation of proanthocyanidins by HPLC with electrospray ionization mass spectrometry. R Eur Food Res Technol 2000; 211: 56-64
• 30 Lee IS, Yu SY, Jung SH, Lee YR, Lee YM, Kim JH, Sun H, Kim JS. Proanthocyanidins from Spenceria ramalana and their effects on AGE formation in vitro and hyaloid-retinal vessel dilation in larval zebrafish in vivo . J Nat Prod 2013; 76: 1881-1888
• 31 Dzotam JK, Simo IK, Bitchagno G, Celik I, Sandjo LP, Tane P, Kuete V. In vitro antibacterial and antibiotic modifying activity of crude extract, fractions and 3′,4′,7-trihydroxyflavone from Myristica fragrans Houtt against MDR Gram-negative enteric bacteria. BMC Complement Altern Med 2018; 15: 1-9
• 32 Xie Y, Yang W, Tang F, Chen X, Ren L. Antibacterial activities of flavonoids: structure-activity relationship and mechanism. Curr Med Chem 2015; 22: 132-149
• 33 Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev 2012; (10) CD001321
• 34 Leal ICR, dos Santos KRN, Júnior II, Antunes OAC, Porzel A, Wessjohann L, Kuster RM. Ceanothane and lupane type triterpenes from Zizyphus joazeiro–an anti-staphylococcal evaluation. Planta Med 2010; 76: 47-52
• 35 CLSI (Clinical and Laboratory Standards Institute). M100-S26. Performance Standards for antimicrobial Susceptibility Testing; Twenty-Fifth informational Supplement. Pennsylvania, USA: Wayne; 2016: 168-179
• 36 Isenberg HD. Antimicrobial susceptibility testing: a critical evaluation. J Antimicrob Chemother 1988; 22: 73-86
• 37 Hall BG, Acar H, Nandipati A, Barlow M. Growth rates made easy. Mol Biol Evol 2013; 31: 232-238