Antiurolithic activity and biotransformation of galloylquinic acids by Aspergillus alliaceus ATCC10060, Aspergillus brasiliensis ATCC 16404, and Cunninghamella elegans ATCC 10028b
Graphical abstract
Introduction
Different species of Copaifera species (Fabaceae), such as C. lucens and C. langsdorffii are widely distributed in Brazil (Motta et al., 2017) and they possess promising biological activities mainly their use in the modulation of renal stones, also known as urolithiasis (Oliveira et al., 2013). The major secondary metabolites (Nogueira et al., 2015) in Copaifera leaves extracts were identified as galloylquinic acids (Fig. 1), and flavonoids (Brancalion et al., 2012; Nogueira et al., 2015), that contribute to their antiurolithic effect. We previously reported that the 3,4,5-tri-O-galloylquinic acid methyl ester (TGAME) inhibited calcium oxalate crystal growth in a Drosophila melanogaster model, and downregulated renal cell surface expression of annexin A1 (ANXA1), α-enolase and heat shock protein 90 (HSP90), which are potential calcium oxalate monohydrate (COM) binding receptors, and it also decreased cells crystal adhesion, a key factor in renal stones pathogenesis (Abd El-Salam et al., 2018). However, there is very little information on the metabolic pathway and pharmacokinetic of galloylquinic acids in Copaifera extracts. Therefore, studies on the metabolism of such phytochemicals by filamentous fungi are important for predicting their metabolic behavior and better understanding their biological effects. In this study, the n-butanolic fraction of C. lucens (BF) and gallic acid (GA) were cultured aerobically with Aspergillus alliaceus ATCC10060, Aspergillus brasiliensis ATCC 16404, and Cunninghamella elegans ATCC 10028b cultures for 60 h and 120 h. One major compound 3-O-methyl gallic acid (M1) was detected and identified in the fungal culture of Aspergillus alliaceus ATCC10060 by UPLC-MS/MS and 1H NMR. The two other fungal strains showed no apparent biotransformation. The resulting metabolite M1 and the BF were tested for their potential to inhibit COM crystal adherence to the surface of Madin-Darby Canine Kidney type I (MDCKI) cells as well as COM-binding proteins, using crystal binding assay and Western blot analysis, respectively. The compounds were also investigated for their ability to scavenge free radicals in a DPPH assay.
Section snippets
General
The analytical HPLC-UV analyses were undertaken by using Shimadzu LC-10ADvp (Japan) equipped with Shimadzu SPD-MICAvp photodiode array detector, using our previously described method (Abd El-Salam et al., 2018). Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS) analyses were performed on a Waters ACQUITY UPLC H-Class system coupled to the Xevo® TQ-S tandem quadrupole (Waters Corporation, Milford, MA, USA) mass spectrometer with a Z-spray source operating in the negative
Results and discussion
Due to the similarities between the microbial system and human metabolic pathways, biotransformation using filamentous fungi can be a useful tool in predicting the metabolic profiles of plant extracts (Hegazy et al., 2015). Several reports have highlighted the role of filamentous fungi and gut microbiota in the metabolism of phytochemicals, for instance He et al. studied before the biotransformation and in vitro metabolic profile of Polygonum capitatum bioactive extract (He et al., 2014). The
Conclusion
We report a possible metabolic pathway of plant extracts rich in galloylquinic acids which were biodegraded by the hydrolytic enzymes of filamentous fungi. The data could provide a foundation for further exploring the efficacy and pharmacokinetic profile of galloylquinic acids. Moreover, the results also corroborate our previous studies, suggesting that galloylquinic acids contribute to the antiurolithic activities of Copaifera extracts. These compounds may generate in vivo bioactive
Declaration of interest
No potential conflict of interest was reported by all authors.
Acknowledgment
This work was supported by The World Academy of Sciences (TWAS), Italy, and the National Council for Scientific and Technological Development (CNPq), Brazil (PhD Fellowship No. 190066/2014-8 to Mohamed Abd El-Salam). Biological studies were partially supported by the Mayo Clinic O’Brien Urology Research Center (NIH DK100227) and the Mayo Foundation for Medical Research.
References (12)
- et al.
Microbial biotransformation as a tool for drug development based on natural products from mevalonic acid pathway: a review
J. Adv. Res.
(2015) - et al.
Galloylquinic acid derivatives from Copaifera langsdorffii leaves display gastroprotective activity
Chem. Biol. Interact.
(2017) - et al.
Thin-layer chromatography of gallic acid, methyl gallate, pyrogallol, phloroglucinol, catechol, resorcinol, hydroquinone, catechin, epicatechin, cinnamic acid, p-coumaric acid, ferulic acid and tannic acid
J. Chromatogr., A
(1998) - et al.
The synthesized plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester inhibits calcium oxalate crystal growth in a Drosophila model, downregulates renal cell surface annexin A1 expression, and decreases crystal adhesion to cells
J. Med. Chem.
(2018) - et al.
Effect of hydroalcoholic extract from Copaifera langsdorffii leaves on urolithiasis induced in rats
Urol. Res.
(2012) - et al.
Biotransformation and in vitro metabolic profile of bioactive extracts from a traditional miao-nationality herbal medicine
Polygonum capitatum. Molecules
(2014)
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