Biotransformation of the Phenolic Constituents from Licorice and Cytotoxicity Evaluation of Their Metabolites.
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ABSTRACT:
SUBMITTER: Xiao Y
PROVIDER: S-EPMC8465054 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A new phenolic compound, 2-O-?-laminaribiosyl-4-hydroxyacetophenone (1), was isolated from Cynanchi Wilfordii Radix (CWR, the root of Cynanchum wilfordii Hemsley), along with 10 known aromatic compounds, including cynandione A (2), bungeisides-C (7) and -D (8), p-hydroxyacetophenone (9), 2',5'-dihydroxyacetophenone (10), and 2',4'-dihydroxyacetophenone (11). The structure of the new compound (1) was elucidated using spectroscopic methods and chemical methods. The structure of cynandione A (2), including a linkage mode of the biphenyl parts that remained uncertain, was unambiguously confirmed using the 2D 13C-13C incredible natural abundance double quantum transfer experiment (INADEQUATE) spectrum. Additionally, health issues related to the use of Cynanchi Auriculati Radix (CAR, the root of Cynanchum auriculatum Royle ex Wight) instead of CWR have emerged. Therefore, constituents present in methanolic extracts of commercially available CWRs and CARs were examined using UV-sensitive high-performance liquid chromatography (HPLC), resulting in common detection of three major peaks ascribed to cynandione A (2), p-hydroxyacetophenone (9), and 2',4'-dihydroxyacetophenone (11). Thus, to distinguish between these ingredients, a thin-layer chromatography (TLC) method, combined with only UV irradiation detection, focusing on wilfosides C1N (12) and K1N (13) as marker compounds characteristic of CAR, was performed. Furthermore, we propose this method as a simple and convenient strategy for the preliminary distinction of CWR and CAR to ensure the quality and safety of their crude drugs.
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Project description:Neuraminidase (NA), a key enzyme in viral replication, is the first-line drug target to combat influenza. On the basis of a shape-focused virtual screening, the roots of Glycyrrhiza glabra (licorice) were identified as plant species with an accumulation of constituents that show 3D similarities to known influenza NA inhibitors (NAIs). Phytochemical investigation revealed 12 constituents identified as (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-(8-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-yl)-2-propen-1-one (1), 3,4-dihydro-8,8-dimethyl-2H,8H-benzo[1,2-b:3,4-b']dipyran-3-ol (2), biochanin B (3), glabrol (4), glabrone (5), hispaglabridin B (6), licoflavone B (7), licorice glycoside B (8), licorice glycoside E (9), liquiritigenin (10), liquiritin (11), and prunin (12). Eleven of these constituents showed significant influenza virus NA inhibition in a chemiluminescence (CL)-based assay. Additional tests, including (i) a cell-based cytopathic effect inhibition assay (general antiviral activity), (ii) the evaluation of cytotoxicity, (iii) the inhibition of the NA of Clostridium perfringens (CL- and fluorescence (FL)-based assay), and (iv) the determination of self-fluorescence and quenching, provided further perspective on their anti-influenza virus potential, revealing possible assay interference problems and false-positive results. Compounds 1, 3, 5, and 6 showed antiviral activity, most likely caused by the inhibition of NA. Of these, compounds 1, 3, and 6 were highly ranked in shape-focused virtual screening.
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Project description:Phytochemical analysis of the dichloromethane:methanol (1:1) extract of root parts of Prangos pabularia led to the isolation of twelve cytotoxic constituents, viz., 6-hydroxycoumarin (1), 7-hydroxycoumarin (2), heraclenol-glycoside (3), xanthotoxol (4), heraclenol (5), oxypeucedanin hydrate (6), 8-((3,3-dimethyloxiran-2-yl)methyl)-7-methoxy-2H-chromen-2-one (7), oxypeucedanin hydrate monoacetate (8), xanthotoxin (9), 4-((2-hydroxy-3-methylbut-3-en-1-yl)oxy)-7H-furo[3,2-g]chromen-7-one (10), imperatorin (11) and osthol (12). The isolates were identified using spectral techniques in the light of literature. 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity screening of the isolated constituents was carried out against six human cancer cell lines including lung (A549 and NCI-H322), epidermoid carcinoma (A431), melanoma (A375), prostate (PC-3) and Colon (HCT-116) cell lines. Osthol (12) exhibited the highest cytotoxicity with IC50 values of 3.2, 6.2, 10.9, 14.5, 24.8, and 30.2 µM against epidermoid carcinoma (A431), melanoma (A375), lung (NCI-H322), lung (A549), prostate (PC-3) and colon (HCT-116) cell lines respectively. Epidermoid carcinoma cell line A431 was sensitive to most of the compounds followed by lung (A549) cancer cell line. Finally a simple and reliable HPLC method was developed (RP-HPLC-DAD) and validated for the simultaneous quantification of these cytotoxic constituents in Prangos pabularia. The extract was analyzed using a reversed-phase Agilent ZORBAX eclipse plus column C18 (4.6×250 mm, 5 µm) at 250 nm wavelength using a gradient water-methanol solvent system at a flow rate of 0.8 ml/min. The RP-HPLC method is validated in terms of recovery, linearity, accuracy and precision (intra and inter-day validation). This method, because of shorter analysis time, makes it valuable for the commercial quality control of Prangos pabularia extracts and its future pharmaceutical preparations.
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Project description:Licorice has been shown to affect the activities of several cytochrome P450 enzymes. This study aims to identify the key constituents in licorice which may affect these activities. Bioactivity assay was combined with metabolic profiling to identify these compounds in several complex licorice extracts. Firstly, the inhibition potencies of 40 pure licorice compounds were tested using an liquid chromatography/tandem mass spectrometry cocktail method. Significant inhibitors of human P450 isozymes 1A2, 2C9, 2C19, 2D6, and 3A4 were then selected for examination of their structural features by molecular docking to determine their molecular interaction with several P450 isozymes. Based on the present in vitro inhibition findings, along with our previous in vivo metabolic studies and the prevalence of individual compounds in licorice extract, we identified several licorice constituents, viz., liquiritigenin, isoliquiritigenin, together with seven isoprenylated flavonoids and arylcoumarins, which could be key components responsible for the herb-drug interaction between cytochrome P450 and licorice. In addition, hydrophilic flavonoid glycosides and saponins may be converted into these P450 inhibitors in vivo. These studies represent a comprehensive examination of the potential effects of licorice components on the metabolic activities of P450 enzymes.
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Project description:Bacillus licheniformis strain TAB7 is a bacterium used as a commercial deodorizing agent for compost in Japan. In this work, its ability to biotransform the following monocyclic phenolic compounds was assessed: ferulate, vanillate, p-coumarate, caffeate, protocatechuate, syringate, vanillin, and cinnamate (a precursor for some phenolic compounds). These compounds are abundant in composting material and are reported to have allelopathic properties. They come from sources such as plant material decomposition or agro-industrial waste. Biotransformation assays were carried out in LB supplemented with 0.2 mg/mL of an individual phenolic compound and incubated for up to 15 days followed by extraction and HPLC analysis. The results showed that TAB7 could biotransform ferulate, caffeate, p-coumarate, vanillate, protocatechuate, and vanillin. It, however, had a poor ability to transform cinnamate and syringate. LC-MS/MS analysis showed that ferulate was transformed into 4-vinylguaiacol as the final product, while caffeate was transformed into 4-ethylcatechol. TAB7 genome analysis suggested that, while TAB7 may not mineralize phenolic compounds, it harbored genes possibly encoding phenolic acid decarboxylase, vanillate decarboxylase, and some protocatechuate degradation pathway enzymes, which are involved in the catabolism of phenolic compounds known to have negative allelopathy on some plants. The results thus suggested that TAB7 can reduce such phenolic compounds in compost.
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Project description:This study aimed to provide scientific data on the anti-Alzheimer's disease (AD) effects of phenolic compounds from Drynariae Rhizoma (DR) extract using a multi-component approach. Screening of DR extracts, fractions, and the ten phenolic compounds isolated from DR against the key AD-related enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and monoamine oxidase-B (MAO-B) confirmed their significant inhibitory activities. The DR extract was confirmed to have BACE1-inhibitory activity, and the ethyl acetate and butanol fractions were found to inhibit all AD-related enzymes, including BACE1, AChE, BChE, and MAO-B. Among the isolated phenolic compounds, compounds (2) caffeic acid 4-O-β-D-glucopyranoside, (6) kaempferol 3-O-rhamnoside 7-O-glucoside, (7) kaempferol 3-o-b-d-glucopyranoside-7-o-a-L-arabinofuranoside, (8) neoeriocitrin, (9) naringin, and (10) hesperidin significantly suppressed AD-related enzymes. Notably, compounds 2 and 8 reduced soluble Amyloid Precursor Protein β (sAPPβ) and β-secretase expression by over 45% at a concentration of 1.0 μM. In the thioflavin T assay, compounds 6 and 7 decreased Aβ aggregation by approximately 40% and 80%, respectively, and degraded preformed Aβ aggregates. This study provides robust evidence regarding the potential of DR as a natural therapeutic agent for AD, highlighting specific compounds that may contribute to its efficacy.
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Project description:Vanillin is valuable and popular flavor used in foods and cosmetics. Many bacteria species have the ability to decarboxylate substituted cinnamic acids in order to form vanillin. However, the phenolic biotransformation including vanillin production in a common fungus, the Aspergillus luchuensis, which is used in distilled beverages, has not yet been clarified. This study focused on elucidating the vanillin production due to phenolic biotransformation in A. luchuensis during fermentation. The phenolic metabolites were extracted by a solid phase column and they were determined using on LC/MS and LC/MS/MS in a selective ion mode. As a result, ferulic acid, vanillin and vanillic acid, were detected in the rice koji fermentationed by A. luchuensis and also fermentated with yeast. In addition, the accurate molecular formula of vanillin glucoside (C14H17O8, 313.0927, (M-H)- and its production ions was also determined by HRESI-mass spectrometry. Based on the results including the phenolic metabolites and related genes found in A. luchuensis genome, this study proposed the vanillin production mechanism due to the side chain cleavage of ferulic acid through Coenzyme A (CoA) and feruloyl-CoA hydratase/lyase, to form vanillin and acetyl-COA. In this study, another possible vanillin production pathway also was proposed due to the neutral hexose hydrolysis of vanillin glucoside. The subsequent dehydrogenation of vanillin produced vanillic acid. In addition, vanillin was detected in the distilled alcohol indicating its contribution to the aroma profile of beverages. It has been unknown that the vanillin in the distilled solution is derived from the vanillin produced during rice-koji and/or moromi mash fermentations.
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Project description:Regulatory T cells (Treg) play a critical role to control immune responses and to prevent autoimmunity, thus selective increase of Treg cells in vivo has broad therapeutic implications for autoimmune and inflammatory diseases. Licorice is a well-known herbal medicine used worldwide for over thousands of years, and accumulating evidence has shown its immunomodulatory potential. However, it is not clear whether licorice could regulate the induction and function of Treg cells. Here we found licorice extract could promote Treg cell induction, and then we used a rational approach to isolate its functional fractions and constituents. The results showed that two constituents, isoliquiritigenin and naringenin, promoted Treg cell induction both in vitro and in vivo. The effective fractions and two constituents of licorice also enhanced immune suppression of Treg cells, and they further reduced severity of DSS-induced colitis in mice. This study suggested that promotion of regulatory T cell induction could be an underlying mechanism of the historically and widely used herbal medicine licorice, providing its two effective molecules against autoimmune and inflammatory diseases.
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Project description:Licorice botanicals are produced from the roots of Glycyrrhiza species (Fabaceae), encompassing metabolites of both plant and rhizobial origin. The composition in both primary and secondary metabolites (1°/2°Ms) reflects the physiologic state of the plant at harvest. Interestingly, the relative abundance of 1°Ms vs 2°Ms in licorice extracts remains undetermined. A centrifugal partition chromatography (CPC) method was developed to purify liquiritin derivatives that represent major bioactive 2°Ms and to concentrate the polar 1°Ms from the crude extract of Glycyrrhiza uralensis. One objective was to determine the purity of the generated reference materials by orthogonal UHPLC-UV/LC-MS and qHNMR analyses. The other objectives were to evaluate the presence of 1°Ms in purified 2°Ms and define their mass balance in a crude botanical extract. Whereas most impurities could be assigned to well-known 1°Ms, p-hydroxybenzylmalonic acid, a new natural tyrosine analogue, was also identified. Additionally, in the most polar fraction, sucrose and proline represented 93% (w/w) of all qHNMR-quantified 1°Ms. Compared to the 2°Ms, accounting for 11.9% by UHPLC-UV, 1°Ms quantified by qHNMR defined an additional 74.8% of G. uralensis extract. The combined orthogonal methods enable the mass balance characterization of licorice extracts and highlight the relevance of 1°Ms, and accompanying metabolites, for botanical quality control.
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Project description:The method of drying licorice is an important factor affecting the quality of the final product. To determine the best processing method of licorice postharvest, we investigated the interaction of increasing aridity between the endophytic microorganisms and the accumulation of metabolites. Samples from the roots of licorice growing along an aridity gradient during the natural drying process were collected, and the metabolic components, the content of the main active substances and the dynamic changes of the endophytic microbial community were assessed. The glycyrrhizic acid and liquiritin contents decreased slightly or remained flat during natural drying, whereas those of liquiritigenin and isoliquiritigenin increased slightly. Moreover, the Shannon index of endophytic microbial diversity of licorice was the highest in the fresh period and showed a downward trend during the drying process. When the licorice were fresh, Cladosporiaceae and Burkholderiaceae were the dominant family present, but after drying, Nectriaceae and Enterobacteriaceae were the dominant families. A similar trend was also found in which the differential metabolites of licorice were reduced during natural drying. Furthermore, correlation analysis between dominant families and differential metabolites showed that there was a correlation between the two. Therefore, fresh processing is an effective drying method to ensure the quality of licorice. This study revealed the relationship of endophytic microbiota and changes in the licorice metabolites during different stages of drying, which provided a scientific basis for the drying method of licorice.
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