| In vitro: |
| J Mol Struct . 2022 Apr 15;1254:132369. | | Potential of phytocompounds from Brassica oleracea targeting S2-domain of SARS-CoV-2 spike glycoproteins: Structural and molecular insights[Pubmed: 35034979] | | By 24th Sep. 2021, there are more than 229 million COVID-19 cases worldwide, the researchers are tirelessly working to discover and develop an efficient drug molecule against this devastative viral infection. This study aims to evaluate the inhibitory efficiency of the organic acids and phenolic compounds present in Brassica oleracea (Tronchuda Cabbage) against spike glycoprotein in SARS-CoV-2. Thirty-seven phytocompounds are screened on the basis of their molecular weight (<500 g/mol) and 14 ligands are docked using Autodock Vina and Autodock4 (version 4.2.6). The stability of the top five docked complexes was analyzed using classical molecular dynamics (MD) simulation. ADMET analysis is performed for the top five compounds and their targets are identified using SwissTargetPrediction. Phytoactives from B. oleracea namely Astragalin, 3-p-coumaroylquinic acid, 4-p-coumaroylquinic acid and sinapoyl-D-glucoside showed high binding affinities and free energy of binding during molecular docking and MD simulation studies (～ 8.5-9.0 kcal/mol) for the spike glycoprotein trimer of SARS-CoV2. The ADMET analysis revealed that these phytocompounds have good solubility in the aqueous phase and that they don't penetrate the blood brain barrier. Moreover, there is no P-gp substrate inhibition, CYP1A2 inhibition, CYP2C19 inhibition, CYP2C9 inhibition, CYP2D6 inhibition and CYP3A4 inhibition observed for these compounds. Additionally, zero PAINS alerts were reported. These findings from molecular docking and MD simulation studies suggest that astragalin and coumaroylquinic acids from Tronchuda cabbage possess potential inhibitory capacity against spike glycoprotein trimer of SARS-CoV-2 and could be further taken up as lead targets for drug discovery. | | Eur J Nutr . 2011 Oct;50(7):507-522. | | Intestinal transit and systemic metabolism of apple polyphenols[Pubmed: 21184087] | | Background: Apples are the most widely consumed fruits in Germany and various other countries. Positive health effects of apple-derived polyphenols in vivo depend on their absorption, metabolism, distribution, and elimination from the body after consumption. Data on the metabolism of these polyphenols in humans are scarce. In order to study the intestinal transit and metabolism of apple polyphenols in humans, a variety of experiments were carried out.
Methods: Polyphenols were incubated with saliva (for 5 min), simulated gastric or duodenal juice (4 or 10 h, respectively), or rat hepatocytes (4 h) under aerobic conditions, and with ileostomy fluid under aerobic conditions for 10 h. The polyphenol profile in human serum (8 h later) and renal elimination in urine (24 h later) were also investigated after consumption of 1 L apple juice. Polyphenols and their metabolites were identified and quantified by high-performance liquid chromatography with diode array detection (HPLC-DAD), HPLC-electrospray ionization-tandem mass spectrometry (ESI-MS/MS), and gas chromatography (GC)-MS.
Results: In the presence of native saliva or ileostomy fluid, β-glycosides of phloretin and quercetin were hydrolyzed, to varying degrees depending on the sugar moiety, and to much lesser degrees in the presence of antibiotics. In the gastric milieu, almost complete degradation of procyanidin B(2) to (-)-epicatechin was observed. In the presence of artificial duodenal juice flavan-3-ol epimerization occurred. Quercetin was completely converted to phloroglucinol, 3,4-dihydroxybenzoic acid, and 2,4,6-trihydroxybenzoic acid. Formation of isomeric products of hydroxycinnamic acid esters and their corresponding methyl esters was also observed, and similar results were obtained after incubation with rat hepatocytes. Products of phase II metabolism, two phloretin O-glucuronides and eight (methyl) quercetin O-glucuronides, were identified in the hepatocyte samples. Following enzymatic hydrolysis, 5-caffeoylquinic acid, 4-p-coumaroylquinic acid, caffeic acid, (-)-epicatechin, phloretin, and quercetin were recovered in both serum and urine (5.3% and 3.5% of the amounts consumed, respectively). In addition, 19.5% of the polyphenols consumed were identified in the urine in the form of hydroxylated phenolic and hippuric acids.
Conclusion: The findings relating to the absorption, metabolism, and systemic availability of polyphenols in vivo should contribute to our understanding of their biological effects, and the characterization of newly formed metabolites should facilitate further studies. |
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