Identification and metabolomic characterization of potent anti-MRSA phloroglucinol derivatives from Dryopteris crassirhizoma Nakai (Polypodiaceae)

Sumana Bhowmick; Manfred Beckmann; Jianying Shen; Luis A J Mur

doi:10.3389/fphar.2022.961087

Identification and metabolomic characterization of potent anti-MRSA phloroglucinol derivatives from Dryopteris crassirhizoma Nakai (Polypodiaceae)

Front Pharmacol. 2022 Oct 20:13:961087. doi: 10.3389/fphar.2022.961087. eCollection 2022.

Authors

Sumana Bhowmick^{1

2}, Manfred Beckmann², Jianying Shen³, Luis A J Mur²

Affiliations

¹ Department of Neurology, Stanford University School of Medicine, Stanford, CA, United States.
² Institute of Biological, Environmental and Rural Studies, Aberystwyth University, Aberystwyth, United Kingdom.
³ Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

Abstract

Traditional Chinese medicine (TCM) has been used to treat infectious diseases and could offer potential drug leads. This study evaluates the in vitro antimicrobial activities from commercially sourced Dryopteris crassirhizoma Nakai (Polypodiaceae) whose authenticity was confirmed by DNA barcoding based on the ribulose bisphosphate carboxylase (rbcL) gene. Powdered rhizomes were sequentially extracted using n-hexane, dichloromethane, ethyl acetate, and methanol at ambient temperature. The dried extracts at different concentrations were tested for antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium smegmatis. D. crassirhizoma extracts exhibited significant antimicrobial activities only against MRSA (minimum inhibitory concentration: 3.125 μg/ml n-hexane extract). Activity-led fractionations of D. crassirhizoma and characterization by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) targeted a fraction (A3), with two anti-MRSA phloroglucinol derivatives, flavaspidic acid AB and norflavaspidic acid AB-being greatly enriched in the latter. The impact of A3 on MRSA cells was examined using untargeted metabolomic analysis and compared to that of other established antibiotics (all treatments normalized to MIC₅₀ at 6 h). This suggested that norflavaspidic acid AB had distinctive effects, one of which involved targeting bioenergetic transformation, metabolism, and particularly acetyl-CoA, on MRSA cells. No cytotoxicity was observed for the norflavaspidic acid AB-enriched fraction against murine HepG2 cells. This study requires further experimental validation but can have indicated a naturally available compound that could help counter the threat of clinically relevant strains with antibiotic resistance.

Keywords: Dryopteris crassirhizoma; metabolomics; methicillin-resistant Staphylococcus aureus; natural products; phloroglucinols.

Grants and funding

SB was supported by an AberDoc Ph.D. scholarship from Aberystwyth University, United Kingdom.