Inhibitory activity of Enhydra fluctuans Lour. on calcium oxalate crystallisation through in silico and in vitro studies
The decoction of the whole plant of Enhydra fluctuans is used ethno medicinally by various tribes for the treatment of kidney stones and urinary problems. However, no scientific studies were carried out to delineate its influence on urinary stone formation and crystallisation. Hence, the present stu...
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Frontiers Media S.A.
2023-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.982419/full |
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| author | Bornika Chattaraj Arijit Nandi Anwesha Das Amit Sharma Yadu Nandan Dey Dharmendra Kumar Mogana R |
| author_facet | Bornika Chattaraj Arijit Nandi Anwesha Das Amit Sharma Yadu Nandan Dey Dharmendra Kumar Mogana R |
| author_sort | Bornika Chattaraj |
| collection | DOAJ |
| description | The decoction of the whole plant of Enhydra fluctuans is used ethno medicinally by various tribes for the treatment of kidney stones and urinary problems. However, no scientific studies were carried out to delineate its influence on urinary stone formation and crystallisation. Hence, the present study is proposed to investigate the effect of the aqueous extract of Enhydra fluctuans extract on in vitro crystallisation of calcium oxalate. The present study also evaluated. in silico studies of the metabolites with the target proteins present in the renal calcium oxalate stone matrix. The plant material was subjected to decoction to obtain an aqueous extract. The effect of the extract on calcium oxalate crystallization was evaluated by in vitro nucleation and aggregation assays. Further, the metabolites present in E. fluctuans were mined from the existing literature and their number was found to be 35. The selected 35 metabolites of E. fluctuans were subjected to molecular docking with the 5 proteins which are known to be responsible for calcium oxalate crystal growth. Results of in vitro studies indicated that the extract (50, 100, and 200 μg/mL) and standard drug cystone (1,000 μg/mL) exhibited an inhibitory role in the nucleation process where the percentage inhibitions were 52.69, 43.47, 21.98, and 31.67 μg/mL respectively. The results of molecular docking studies revealed that 2 out of 35 metabolites i.e. Baicalein-7-O-diglucoside and 4′,5,6,7-Tetrahydroxy-8-methoxy isoflavone-7-O-beta-D- galactopyranosyl-(1→3)-O-beta-D-xylopyranosyl-(1→4)- O-alpha-L-rhamnopyranoside showed modulatory effects on the four renal stone matrix-associated protein (Human CTP: Phosphoethanolamine Cytidylyltransferase (Protein Data Bank ID: 3ELB), UDP glucose: glycoprotein glucosyltransferase 2 (Gene: UGGT2) (AlphaFold) and RIMS-binding protein 3A (Gene: RIMBP3) (AlphaFold), and Ras GTPase activating-like protein (PDB: 3FAY) based on their docking scores which indicates that they may inhibit the crystallization process. Findings from this study show that Enhydra fluctuans may be effective in the prevention of the crystallization of calcium oxalate. However, further, in vivo studies as well as molecular studies are needed to be conducted to confirm and strengthen its anti-urolithiatic activity and to elucidate the possible mechanism of action involved therein. |
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| last_indexed | 2024-04-10T21:20:32Z |
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| spelling | doaj.art-43f3480069324d24ba0ad0d941fe8d9c2023-01-20T05:02:42ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-01-011310.3389/fphar.2022.982419982419Inhibitory activity of Enhydra fluctuans Lour. on calcium oxalate crystallisation through in silico and in vitro studiesBornika Chattaraj0Arijit Nandi1Anwesha Das2Amit Sharma3Yadu Nandan Dey4Dharmendra Kumar5Mogana R6Department of Pharmacology, Dr. B.C. Roy College of Pharmacy and Allied Health Sciences, Durgapur, IndiaDepartment of Pharmacology, Dr. B.C. Roy College of Pharmacy and Allied Health Sciences, Durgapur, IndiaDepartment of Pharmacy, Indira Gandhi National Tribal University, Lalpur, IndiaDepartment of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, IndiaDepartment of Pharmacology, Dr. B.C. Roy College of Pharmacy and Allied Health Sciences, Durgapur, IndiaNarayan Institute of Pharmacy, Gopal Narayan Singh University, Sasaram, IndiaDepartment of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, UCSI Education SDN.BHD, UCSI University, Kuala Lumpur, MalaysiaThe decoction of the whole plant of Enhydra fluctuans is used ethno medicinally by various tribes for the treatment of kidney stones and urinary problems. However, no scientific studies were carried out to delineate its influence on urinary stone formation and crystallisation. Hence, the present study is proposed to investigate the effect of the aqueous extract of Enhydra fluctuans extract on in vitro crystallisation of calcium oxalate. The present study also evaluated. in silico studies of the metabolites with the target proteins present in the renal calcium oxalate stone matrix. The plant material was subjected to decoction to obtain an aqueous extract. The effect of the extract on calcium oxalate crystallization was evaluated by in vitro nucleation and aggregation assays. Further, the metabolites present in E. fluctuans were mined from the existing literature and their number was found to be 35. The selected 35 metabolites of E. fluctuans were subjected to molecular docking with the 5 proteins which are known to be responsible for calcium oxalate crystal growth. Results of in vitro studies indicated that the extract (50, 100, and 200 μg/mL) and standard drug cystone (1,000 μg/mL) exhibited an inhibitory role in the nucleation process where the percentage inhibitions were 52.69, 43.47, 21.98, and 31.67 μg/mL respectively. The results of molecular docking studies revealed that 2 out of 35 metabolites i.e. Baicalein-7-O-diglucoside and 4′,5,6,7-Tetrahydroxy-8-methoxy isoflavone-7-O-beta-D- galactopyranosyl-(1→3)-O-beta-D-xylopyranosyl-(1→4)- O-alpha-L-rhamnopyranoside showed modulatory effects on the four renal stone matrix-associated protein (Human CTP: Phosphoethanolamine Cytidylyltransferase (Protein Data Bank ID: 3ELB), UDP glucose: glycoprotein glucosyltransferase 2 (Gene: UGGT2) (AlphaFold) and RIMS-binding protein 3A (Gene: RIMBP3) (AlphaFold), and Ras GTPase activating-like protein (PDB: 3FAY) based on their docking scores which indicates that they may inhibit the crystallization process. Findings from this study show that Enhydra fluctuans may be effective in the prevention of the crystallization of calcium oxalate. However, further, in vivo studies as well as molecular studies are needed to be conducted to confirm and strengthen its anti-urolithiatic activity and to elucidate the possible mechanism of action involved therein.https://www.frontiersin.org/articles/10.3389/fphar.2022.982419/fullcalcium oxalatecrystallizationEnhydra fluctuansAsteraceaemolecular dockingkidney stones |
| spellingShingle | Bornika Chattaraj Arijit Nandi Anwesha Das Amit Sharma Yadu Nandan Dey Dharmendra Kumar Mogana R Inhibitory activity of Enhydra fluctuans Lour. on calcium oxalate crystallisation through in silico and in vitro studies Frontiers in Pharmacology calcium oxalate crystallization Enhydra fluctuans Asteraceae molecular docking kidney stones |
| title | Inhibitory activity of Enhydra fluctuans Lour. on calcium oxalate crystallisation through in silico and in vitro studies |
| title_full | Inhibitory activity of Enhydra fluctuans Lour. on calcium oxalate crystallisation through in silico and in vitro studies |
| title_fullStr | Inhibitory activity of Enhydra fluctuans Lour. on calcium oxalate crystallisation through in silico and in vitro studies |
| title_full_unstemmed | Inhibitory activity of Enhydra fluctuans Lour. on calcium oxalate crystallisation through in silico and in vitro studies |
| title_short | Inhibitory activity of Enhydra fluctuans Lour. on calcium oxalate crystallisation through in silico and in vitro studies |
| title_sort | inhibitory activity of enhydra fluctuans lour on calcium oxalate crystallisation through in silico and in vitro studies |
| topic | calcium oxalate crystallization Enhydra fluctuans Asteraceae molecular docking kidney stones |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.982419/full |
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