Identification and metabolomic characterization of potent anti-MRSA phloroglucinol derivatives from Dryopteris crassirhizoma Nakai (Polypodiaceae)
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 ba...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.961087/full |
| _version_ | 1797804446529355776 |
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| author | Sumana Bhowmick Sumana Bhowmick Manfred Beckmann Jianying Shen Luis A. J. Mur |
| author_facet | Sumana Bhowmick Sumana Bhowmick Manfred Beckmann Jianying Shen Luis A. J. Mur |
| author_sort | Sumana Bhowmick |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T05:37:17Z |
| format | Article |
| id | doaj.art-28527080b7dc4a999248668c9ecdc83a |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-13T05:37:17Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-28527080b7dc4a999248668c9ecdc83a2023-06-14T05:42:53ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.961087961087Identification and metabolomic characterization of potent anti-MRSA phloroglucinol derivatives from Dryopteris crassirhizoma Nakai (Polypodiaceae)Sumana Bhowmick0Sumana Bhowmick1Manfred Beckmann2Jianying Shen3Luis A. J. Mur4Department of Neurology, Stanford University School of Medicine, Stanford, CA, United StatesInstitute of Biological, Environmental and Rural Studies, Aberystwyth University, Aberystwyth, United KingdomInstitute of Biological, Environmental and Rural Studies, Aberystwyth University, Aberystwyth, United KingdomArtemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Biological, Environmental and Rural Studies, Aberystwyth University, Aberystwyth, United KingdomTraditional 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.961087/fullnatural productsphloroglucinolsDryopteris crassirhizomametabolomicsmethicillin-resistant Staphylococcus aureus |
| spellingShingle | Sumana Bhowmick Sumana Bhowmick Manfred Beckmann Jianying Shen Luis A. J. Mur Identification and metabolomic characterization of potent anti-MRSA phloroglucinol derivatives from Dryopteris crassirhizoma Nakai (Polypodiaceae) Frontiers in Pharmacology natural products phloroglucinols Dryopteris crassirhizoma metabolomics methicillin-resistant Staphylococcus aureus |
| title | Identification and metabolomic characterization of potent anti-MRSA phloroglucinol derivatives from Dryopteris crassirhizoma Nakai (Polypodiaceae) |
| title_full | Identification and metabolomic characterization of potent anti-MRSA phloroglucinol derivatives from Dryopteris crassirhizoma Nakai (Polypodiaceae) |
| title_fullStr | Identification and metabolomic characterization of potent anti-MRSA phloroglucinol derivatives from Dryopteris crassirhizoma Nakai (Polypodiaceae) |
| title_full_unstemmed | Identification and metabolomic characterization of potent anti-MRSA phloroglucinol derivatives from Dryopteris crassirhizoma Nakai (Polypodiaceae) |
| title_short | Identification and metabolomic characterization of potent anti-MRSA phloroglucinol derivatives from Dryopteris crassirhizoma Nakai (Polypodiaceae) |
| title_sort | identification and metabolomic characterization of potent anti mrsa phloroglucinol derivatives from dryopteris crassirhizoma nakai polypodiaceae |
| topic | natural products phloroglucinols Dryopteris crassirhizoma metabolomics methicillin-resistant Staphylococcus aureus |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.961087/full |
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