Medicinal plants have been exploited for therapeutic purposes since the dawn of civilization and have long been acknowledged essential to human health. The purpose of this research is to examine the scientific evidence for using the therapeutic herbal plants Thalictrum foliolosum DC. and Cordia dichotoma G. Forst. to treat hepatitis illness. The fundamental explanation for the therapeutic relevance of these plants is phytochemicals, which were evaluated qualitatively and quantitatively in three separate extracts with different solvent properties (methanol-polar, chloroform-non-polar, and aqueous-polar as one of the bases of traditional use). Flavonoids, phenols, tannins, saponins, and alkaloids were all evaluated for their presence in plant extracts, and it was observed that methanolic extract had the highest content of phytochemicals among different extracts whereas, the aqueous extract showed least amount of phytochemicals. Additionally, the antioxidant activity of these plants was also evaluated and methanolic extract was revealed with potential antioxidant activity, as also evidenced by the lowest half inhibitory concentration (IC50) values in the DPPH, ABTS, and high %inhibition in μM Fe equivalent of FRAP assays. Following that, the dominant phytochemicals were investigated using ultra-high performance liquid chromatography from the selected plants. Furthermore, default docking algorithms were used to appraise the dominant phytoconstituents for their in-silico investigation, in which rutin was found with the highest binding affinity (8.2 kcal/mol) and interaction with receptor which is further involved in causing jaundice. The receptor is infact an enzyme that is sphingomyelin phosphodiesterase Leptospira interrogans (PDB: 5EBB) which is holded back in its position by rutin and do not interact with Leptospira inferrogans spp which causes jaundice. Overall, the study suggested that these herbs have significant therapeutic properties, and their in-silico analysis strongly recommends further clinical investigations to get insight into the mechanisms of action in curing variety of diseases.
- MeSH
- Antioxidants pharmacology analysis MeSH
- Cordia * MeSH
- Flavonoids pharmacology analysis MeSH
- Phytochemicals analysis MeSH
- Humans MeSH
- Methanol MeSH
- Plant Extracts chemistry MeSH
- Rutin MeSH
- Molecular Dynamics Simulation MeSH
- Thalictrum * MeSH
- Jaundice * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Metabolic syndrome (MetS) belongs to the serious health complications expanding in cardiovascular diseases, obesity, insulin resistance, and hyperglycemia. In this study, hypertriacylglycerolemic rats fed a high-fat-fructose diet (HFFD) were used as an experimental model of MetS to explore the effect of tested compounds. Effects of a new prospective pyridoindole derivative coded SMe1EC2 and the natural polyphenol rutin were tested. Endothelial nitric oxide synthase (NOS3) and nuclear factor kappa B (NF-?B) expression were assessed in the left ventricle immunohistochemically and left ventricle activity was monitored in isolated perfused rat hearts. NOS3 activity in the left ventricle decreased markedly as a result of a HFFD. NOS3 expression was upregulated by both substances. NF-?B expression was increased in the MetS group in comparison to control rats and the expression further increased in the SMe1EC2 treatment. This compound significantly improved the coronary flow in comparison to the control group during reperfusion of the heart followed after ischemia. Further, it tended to increase left ventricular systolic pressure, heart product, rate of maximal contraction and relaxation, and coronary flow during baseline assessment. Moreover, the compound SMe1EC2 decreased the sensitivity of hearts to electrically induced ventricular fibrillation. Contrary to this rutin decreased coronary flow in reperfusion. Present results suggest that despite upregulation of NOS3 by both substances tested, pyridoindole SMe1EC2 rather than rutin could be suitable in treatment strategies of cardiovascular disorders in MetS-like conditions.
- MeSH
- Biometry MeSH
- Fructose adverse effects MeSH
- Indoles pharmacology therapeutic use MeSH
- Metabolic Syndrome drug therapy enzymology etiology MeSH
- Myocardium metabolism MeSH
- NF-kappa B metabolism MeSH
- Rats, Wistar MeSH
- Drug Evaluation, Preclinical MeSH
- Pyridines pharmacology therapeutic use MeSH
- Rutin pharmacology therapeutic use MeSH
- Heart drug effects MeSH
- Nitric Oxide Synthase Type III metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Hemorrhoids * therapy MeSH
- Conservative Treatment MeSH
- Humans MeSH
- Rutin therapeutic use MeSH
- Check Tag
- Humans MeSH
Aqueous solutions of ionic liquids (ILs) with surface active properties were used as extraction solvents, taking advantage of their impressive solvation properties, in a green microwave-assisted solid-liquid extraction method (IL-MA-SLE) for the extraction of flavonoids from passion fruit and mango leaves. The extraction method was combined with high-performance liquid chromatography and photodiode-array detection (HPLC-PDA) and optimized by response surface methodology using the Box-Behnken experimental design. Under optimum conditions, the extraction efficiency of six structurally different IL-based surfactants was evaluated. Thus, imidazolium-, guanidinium- and pyridinium-type ILs with different tailorable characteristics, such as side chain length and multicationic core, were assessed. The decylguanidinium chloride ([C10Gu+][Cl-]) IL-based surfactant was selected as key material given its superior performance and its low cytotoxicity, for the determination of flavonoids of several samples of Passiflora sp. and Mangifera sp. leaves from the Canary Islands, and using as target analytes: rutin, quercetin and apigenin. The analysis of 50 mg of plant material only required 525 µL of the low cytotoxic IL-based surfactant solution at 930 mM, 10.5 min of microwave irradiation at 30 °C and 50 W, which involves a simpler, faster, more efficient and greener method in comparison with other strategies reported in the literature for obtaining bioactive compounds profiles from plants.
- MeSH
- Flavonoids chemistry isolation & purification MeSH
- Ionic Liquids chemistry MeSH
- Plant Leaves chemistry MeSH
- Mangifera chemistry MeSH
- Microwaves MeSH
- Passiflora chemistry MeSH
- Surface-Active Agents chemistry MeSH
- Plant Extracts chemistry MeSH
- Solvents chemistry MeSH
- Rutin chemistry MeSH
- Publication type
- Journal Article MeSH
Rutinosidases (α-l-rhamnopyranosyl-(1-6)-β-d-glucopyranosidases, EC 3.2.1.168, CAZy GH5) are diglycosidases that cleave the glycosidic bond between the disaccharide rutinose and the respective aglycone. Similar to many retaining glycosidases, rutinosidases can also transfer the rutinosyl moiety onto acceptors with a free -OH group (so-called transglycosylation). The recombinant rutinosidase from Aspergillus niger (AnRut) is selectively produced in Pichia pastoris. It can catalyze transglycosylation reactions as an unpurified preparation directly from cultivation. This enzyme exhibits catalytic activity towards two substrates; in addition to rutinosidase activity, it also exhibits β-d-glucopyranosidase activity. As a result, new compounds are formed by β-glucosylation or rutinosylation of acceptors such as alcohols or strong inorganic nucleophiles (NaN3). Transglycosylation products with aliphatic aglycones are resistant towards cleavage by rutinosidase, therefore, their side hydrolysis does not occur, allowing higher transglycosylation yields. Fourteen compounds were synthesized by glucosylation or rutinosylation of selected acceptors. The products were isolated and structurally characterized. Interactions between the transglycosylation products and the recombinant AnRut were analyzed by molecular modeling. We revealed the role of a substrate tunnel in the structure of AnRut, which explained the unusual catalytic properties of this glycosidase and its specific transglycosylation potential. AnRut is attractive for biosynthetic applications, especially for the use of inexpensive substrates (rutin and isoquercitrin).
- MeSH
- Aspergillus niger enzymology MeSH
- Disaccharides chemistry metabolism MeSH
- Fungal Proteins chemistry metabolism MeSH
- Glycoside Hydrolases chemistry metabolism MeSH
- Glycosylation MeSH
- Hydrolysis MeSH
- Catalytic Domain MeSH
- Recombinant Proteins metabolism MeSH
- Rutin chemistry metabolism MeSH
- Molecular Docking Simulation MeSH
- Substrate Specificity MeSH
- Publication type
- Journal Article MeSH
Rutinosidases (α-l-rhamnosyl-β-d-glucosidases) catalyze the cleavage of the glycosidic bond between the aglycone and the disaccharide rutinose (α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranose) of specific flavonoid glycosides such as rutin (quercetin 3-O-rutinoside). Microbial rutinosidases are part of the rutin catabolic pathway, enabling the microorganism to utilize rutin and related plant phenolic glycosides. Here, we report the first three-dimensional structure of a rutinosidase determined at 1.27-Å resolution. The rutinosidase from Aspergillus niger K2 (AnRut), a member of glycoside hydrolase family GH-5, subfamily 23, was heterologously produced in Pichia pastoris. The X-ray structure of AnRut is represented by a distorted (β/α)8 barrel fold with its closest structural homologue being an exo-β-(1,3)-glucanase from Candida albicans (CaExg). The catalytic site is located in a deep pocket with a striking structural similarity to CaExg. However, the entrance to the active site of AnRut has been found to be different from that of CaExg - a mostly unstructured section of ~ 40 residues present in CaExg is missing in AnRut, whereas an additional loop of 13 amino acids partially covers the active site of AnRut. NMR analysis of reaction products provided clear evidence for a retaining reaction mechanism of AnRut. Unexpectedly, quercetin 3-O-glucoside was found to be a better substrate than rutin, and thus, AnRut cannot be considered a typical diglycosidase. Mutational analysis of conserved active site residues in combination with in silico modeling allowed identification of essential interactions for enzyme activity and helped to reveal further details of substrate binding. The protein sequence of AnRut has been revised. DATABASES: The nucleotide sequence of the rutinosidase-encoding gene is available in the GenBank database under the accession number MN393234. Structural data are available in the PDB database under the accession number 6I1A. ENZYME: α-l-Rhamnosyl-β-d-glucosidase (EC 3.2.1.168).
- MeSH
- Aspergillus niger enzymology MeSH
- Fungal Proteins chemistry genetics metabolism MeSH
- Glycoside Hydrolases chemistry genetics metabolism MeSH
- Catalytic Domain MeSH
- Protein Conformation MeSH
- Crystallography, X-Ray MeSH
- Models, Molecular MeSH
- Mutation MeSH
- Oxidation-Reduction MeSH
- Rutin chemistry metabolism MeSH
- Amino Acid Sequence MeSH
- Sequence Homology MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Troxerutin (TRX) has a beneficial effect on blood viscosity and platelet aggregation, and is currently used for the treatment of chronic varicosity. Recently, TRX can improve lipid abnormalities, glucose intolerance and oxidative stress in high-fat diet-induced metabolic disorders. In this study, we tested the effect of TRX on metabolic syndrome-associated disorders using a non-obese model of metabolic syndrome-the Hereditary Hypertriglyceridaemic rats (HHTg). METHODS: Adult male HHTg rats were fed standard diet without or with TRX (150 mg/kg bwt/day for 4 weeks). RESULTS: Compared to untreated rats, TRX supplementation in HHTg rats decreased serum glucose (p<0.05) and insulin (p<0.05). Although blood lipids were not affected, TRX decreased hepatic cholesterol concentrations (p<0.01) and reduced gene expression of HMGCR, SREBP2 and SCD1 (p<0.01), involved in cholesterol synthesis and lipid homeostasis. TRX-treated rats exhibited decreased lipoperoxidation and increased activity of antioxidant enzymes SOD and GPx (p<0.05) in the liver. In addition, TRX supplementation increased insulin sensitivity in muscles and epididymal adipose tissue (p<0.05). Elevated serum adiponectin (p<0.05) and decreased muscle triglyceride (p<0.05) helped improve insulin sensitivity. Among the beneficial effects of TRX were changes to cytochrome P450 family enzymes. Hepatic gene expression of CYP4A1, CYP4A3 and CYP5A1 (p<0.01) decreased, while there was a marked elevation in gene expression of CYP1A1 (p<0.01). CONCLUSION: Our results indicate that TRX improves hepatic lipid metabolism and insulin sensitivity in peripheral tissues. As well as ameliorating oxidative stress, TRX can reduce ectopic lipid deposition, affect genes involved in lipid metabolism, and influence the activity of CYP family enzymes.
- MeSH
- Glucose metabolism MeSH
- Glycogen metabolism MeSH
- Hydroxyethylrutoside analogs & derivatives therapeutic use MeSH
- Hypolipidemic Agents therapeutic use MeSH
- Rats, Inbred Strains MeSH
- Insulin Resistance MeSH
- Muscle, Skeletal metabolism MeSH
- Rats MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Metabolic Syndrome drug therapy MeSH
- Lipid Metabolism drug effects MeSH
- Disease Models, Animal MeSH
- Oxidative Stress drug effects MeSH
- Transcriptome drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Quercetin is a flavonoid largely employed as a phytochemical remedy and a food or dietary supplement. We present here a novel biocatalytic methodology for the preparation of quercetin from plant-derived rutin, with both substrate and product being in mostly an undissolved state during biotransformation. This "solid-state" enzymatic conversion uses a crude enzyme preparation of recombinant rutinosidase from Aspergillus niger yielding quercetin, which precipitates from virtually insoluble rutin. The process is easily scalable and exhibits an extremely high space-time yield. The procedure has been shown to be robust and was successfully tested with rutin concentrations of up to 300 g/L (ca 0.5 M) at various scales. Using this procedure, pure quercetin is easily obtained by mere filtration of the reaction mixture, followed by washing and drying of the filter cake. Neither co-solvents nor toxic chemicals are used, thus the process can be considered environmentally friendly and the product of "bio-quality." Moreover, rare disaccharide rutinose is obtained from the filtrate at a preparatory scale as a valuable side product. These results demonstrate for the first time the efficiency of the "Solid-State-Catalysis" concept, which is applicable virtually for any biotransformation involving substrates and products of low water solubility.
- MeSH
- Aspergillus niger enzymology genetics MeSH
- Biocatalysis * MeSH
- Disaccharides chemistry metabolism MeSH
- Fungal Proteins genetics metabolism MeSH
- Glycoside Hydrolases genetics metabolism MeSH
- Pichia genetics metabolism MeSH
- Industrial Microbiology methods MeSH
- Quercetin chemistry metabolism MeSH
- Rutin chemistry metabolism MeSH
- Publication type
- Journal Article MeSH
- Keywords
- HHTg potkani,
- MeSH
- Anticholesteremic Agents MeSH
- Antioxidants MeSH
- Flavonoids therapeutic use MeSH
- Hydroxyethylrutoside * analogs & derivatives pharmacology therapeutic use MeSH
- Insulin Resistance MeSH
- Rats MeSH
- Lipids analysis blood MeSH
- Metabolic Syndrome drug therapy MeSH
- Oxidative Stress drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Keywords
- troxerutin,
- MeSH
- Animal Experimentation MeSH
- Metabolic Syndrome * drug therapy blood MeSH
- Ovariectomy adverse effects MeSH
- Oxidative Stress drug effects MeSH
- Postmenopause * blood drug effects MeSH
- Rats, Wistar MeSH
- Rutin * analogs & derivatives pharmacology therapeutic use MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
