Identification of cyclooxygenase-II inhibitory saponins from fenugreek wastes: Insights from liquid chromatography-tandem mass spectrometry metabolomics, molecular networking, and molecular docking.

INTRODUCTION: This research explores sustainable applications for waste generated from fenugreek (Trigonella foenum-graecum), a plant with both nutritional and medicinal uses. The study specifically targets waste components as potential sources of nutrients and bioactive compounds. OBJECTIVES: The focus is to conduct detailed metabolic profiling of fenugreek waste, assess its anti-inflammatory properties by studying its cyclooxygenase (COX) inhibitory effect, and correlate this effect to the metabolite fingerprint. MATERIALS AND METHODS: Ethanolic extracts of fenugreek fruit pericarp and a combination of leaves and stems were subjected to untargeted metabolic profiling using liquid chromatography-mass spectrometry integrated with online database searches and molecular networking as an effective dereplication strategy. The study also scrutinized the COX inhibitory capabilities of these extracts and saponin-rich fractions prepared therefrom. Molecular docking was employed to investigate the specific interactions between the identified saponins and COX enzymes. RESULTS: The analysis led to the annotation of 81 metabolites, among which saponins were predominant. The saponin-rich fraction of the fruit pericarp extract displayed the strongest COX-II inhibitory activity in the in vitro inhibition assay (IC50 value of 81.64 ± 3.98 µg/mL). The molecular docking study supported the selectivity of the identified saponins towards COX-II. The two major identified saponins, namely, proto-yamogenin 3-O-[deoxyhexosyl (1 → 2)] [hexosyl (1 → 4)] hexoside 26-O-hexoside and trigofenoside A, were predicted to have the highest affinity to the COX-II receptor site. CONCLUSION: In the present study, we focused on the identification of COX-II inhibitory saponins in fenugreek waste through an integrated approach. The findings offer valuable insights into potential anti-inflammatory and cancer chemoprotective applications of fenugreek waste.

Regulating microsomal triglyceride transfer protein with natural products for the treatment of hyperlipidaemia.

Hyperlipidaemia, characterised by elevated levels of lipids, particularly LDL-C, is a significant risk factor for atherosclerotic cardiovascular disease. While synthetic inhibitors of microsomal triglyceride transfer protein (MTP) have shown potential in lowering LDL-C, they are associated with adverse effects. This study explores a novel approach by screening natural products to identify plant extracts that down-regulate MTP gene expression, aiming to reduce hyperlipidaemia with fewer side effects. Modulating MTP expression, rather than direct inhibition, offers a promising avenue for lowering plasma lipids and mitigating cardiovascular risk. Various plant extracts were examined for their potential as MTP down-regulators, with Liquorice root and Pomegranate rind extracts demonstrating the highest efficacy. Additionally, the study assessed the total phenolic content of these extracts, revealing their -antioxidant capacity. This research provides a foundation for further investigation into bioactive molecules as potential anti-hyperlipidemic agents with improved safety profiles, addressing a critical need in cardiovascular disease prevention.

Oral and Topical Anti-Inflammatory Activity of Jatropha integerrima Leaves Extract in Relation to Its Metabolite Profile.

Jatropha integerrima Jacq., family: Euphorbiaceae, is used in India and subtropical Africa to treat different skin conditions. In this study we evaluated the anti-inflammatory activity of J. integerrima leaves extract (JILE) using rat paw edema model. The extract was administered orally (200 and 400 mg/kg) or applied topically as creams at 2.5, 5, and 10% strength. Four hours post-treatment, maximum reduction of edema volume by 63.09% was observed after oral administration of JILE (400 mg/kg) as compared to indomethacin with 60.43%. The extract anti-inflammatory effect was accompanied by a decrease in NO, prostaglandin PGE2, TNF-α and PKC levels by 19, 29.35, 16.9, and 47.83%, respectively. Additionally, topical applications of JILE showed dose dependent reduction in paw edema and resulted in normalized levels of PGE2, TNF-α, and PKC when used as 10% cream. Signs of inflammations were reduced or absent from paw tissue of animals receiving JILE either orally or topically. Finally, liquid chromatography/mass spectrometry analysis of JILE resulted in the annotation of 133 metabolites including 24 diterpenoids, 19 flavonoids, 10 phenolic acid conjugates, 8 cyclic peptides, 6 phytosterols, 4 sesquiterpenes, and 4 coumarins. Several of the annotated metabolites have known anti-inflammatory activity including vitexin, isovitexin, fraxitin, scopeltin, stigmasterol, and many diterpenoidal derivatives.

Dismantling Parkinson's disease with herbs: MAO-B inhibitory activity and quantification of chemical constituents using HPLC-MS/MS of Egyptian local market plants.

Withania somnifera, Angelica sinensis, Glycyrrhiza glabra, and Simmondsia chinensis were acquired from the Egyptian market, profiled for their chemical constituents, screened for the in-vitro MAO-B inhibitory activity and evaluated for the total phenolic content. Thirty compounds were characterized in the selected herbs using HPLC-MS/MS. In-vitro MAO-B inhibitory activity and total phenolic content of the acquired herbs were compared with those of a prepared herbal formula consisting of a mixture of equal amounts of the four mentioned herbs. The most potent MAO-B inhibitory activity was exerted by the methanol extract of the prepared formula (IC50 of 712.19 ± 13.90 ng/mL) compared to selegiline (IC50 of 581.69 ± 11.35 ng/mL). The highest value of the total phenolic content was shown by Angelica sinensis methanolic extract (76.15 ± 0.1 mg/g) followed by Glycyrrhiza glabra methanolic extract (65.74 ± 0.1 mg/g), then the mixture's methanolic extract of the four herbs (37.04 ± 0.1 mg/g).

Impact of Washingtonia robusta Leaves on Gamma Irradiation-Induced Hepatotoxicity in Rats and Correlation with STING Pathway and Phenolic Composition.

Exposure to ionizing radiation usually results in cellular oxidative damage and may induce liver toxicity. The efficiency of the ethanol extracts of Washingtonia filifera (EWF) and Washingtonia robusta (EWR) leaves in alleviating γ-radiation-induced oxidative hepatotoxicity was herein explored. Proximate and macronutrient composition of the leaves was determined to establish reliable quality control criteria. Colorimetric estimation of total phenolic (TPC) and flavonoid (TFC) contents revealed their occurrence in larger amounts in EWR. In vitro evaluation of the antioxidant capacity by 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) assays confirmed higher efficiency of EWR designating a close correlation with phenolic composition. Four phenolics, viz., naringenin, kaempferol, quercetin, and gallic acid, were isolated from EWR. In vivo assessment of the extracts' antioxidant potential was performed on γ-irradiated (7.5 Gy) female rats. EWR was found more efficient in restoring the elevated liver index, ALT, albumin, cholesterol, and reactive oxygen species (ROS) levels. Both extracts ameliorated the increase in the stimulator of interferon gene (STING) expression. Bioactivity was confirmed by immuno-histochemical examination of inflammatory and apoptotic biomarkers (TNF-α, IL-6 and caspase-3) and histopathological architecture. In addition, the interactions of the isolated compounds with STING were assessed in silico by molecular docking. Therefore, Washingtonia robusta leaves might be suggested as a valuable nutritional supplement to alleviate radiotherapy-induced hepatotoxicity.

Phenolic Constituents of Chrysophyllum oliviforme L. Leaf Down-Regulate TGF-ß Expression and Ameliorate CCl4-Induced Liver Fibrosis: Evidence from In Vivo and In Silico Studies.

The prevalence of hepatic diseases globally and in Egypt particularly necessitates an intensive search for natural hepatoprotective candidates. Despite the traditional use of Chrysophyllum oliviforme L. and C. cainito L. leaves in the treatment of certain ailments, evidence-based reports on their bioactivities are limited. In this work, in vivo and in silico studies were conducted to evaluate their methanol extracts potential to alleviate liver damage in CCl4-intoxicated rats, in addition to their antioxidant activity and identifying the molecular mechanisms of their phenolic constituents. The extracts restored the altered total cholesterol (TC), triglycerides (TG), high-density lipoproteins (HDL), alanine aminotransferase ALT, aspartate aminotransferase AST, total protein, and albumin. Histopathological architecture, DNA fragmentation, and mRNA expression level of TGF-ß1 also confirmed the anti-fibrotic activity of the two extracts. The total phenolic content (TPC) in C. oliviforme ethanol extract exceeded that in C. caimito. Additionally, the malondialdehyde (MDA), reduced glutathione (GSH), and total antioxidant capacity (TAC) levels assured the antioxidant potential. Seven phenolics; quercetin, isoquercitrin, myricetin, kaempferol, and caffeic, trans-ferulic, and gallic acids were isolated from the ethanol extract of C. oliviforme. The molecular docking of isolated compounds revealed a low binding energy (kcal/mol with TGF-ß1, thus confirming the hepatoprotctive activity of the extracts. In conclusion, the C. oliviforme leaves could be considered as potent safe raw material for the production of herbal formulations to alleviate hepatic toxicity after preclinical safety study.

Metabolite profiling driven analysis of Salsola species and their anti-acetylcholinesterase potential.

Over 100 species of the genus Salsola are distributed in dry, arid parts of Asia, Europe and Africa, of which many species are recognised as antifungal, anticancer, antihypertensive and anthelmintic agents. Egyptian Salsola received scant characterisation of either its phytochemical composition or its biological effects. In this study, the metabolite profiles of two Salsola species viz. S. vermiculata and S. tetrandra were characterised in the aerial portions and root via ultra-performance liquid chromatography high-resolution qTOF-MS and NMR. Identified metabolites belonged to various classes including hydroxycinnamic acid conjugates, flavonoids, oxygenated fatty acids and alkaloids. Principal component analysis of derived biochemical profiles was also used for species and/or organs classification. Roots were enriched in hydroxycinnamic acid conjugates, whereas flavonoids were more abundant in aerial parts with kaempferol derivatives as major flavonoids in S. tetrandra versus quercetin in S. vermiculata. The root of S. vermiculata exhibited strong anti-acetylcholinesterase activity relative to eserine standard.

Four butyrolactones and diverse bioactive secondary metabolites from terrestrial Aspergillus flavipes MM2: isolation and structure determination.

The chemical constituents and biological activities of the terrestrial Aspergillus flavipes MM2 isolated from Egyptian rice hulls are reported. Seven bioactive compounds were obtained, of which one sterol: ergosterol (1), four butyrolactones: butyrolactone I (2), aspulvinone H (3), butyrolactone-V (6) and 4,4'-diydroxypulvinone (7), along with 6-methylsalicylic acid (4) and the cyclopentenone analogue; terrien (5). Structures of the isolated compounds were deduced by intensive studies of their 1D & 2D NMR, MS data and comparison with related structures. The strain extract and the isolated compounds (1-7) were biologically studied against number of microbial strains, and brine shrimp for cytotoxicity. In this article, the taxonomical characterization of A. flavipes MM2 along with its upscale fermentation, isolation and structural assignment of the obtained bioactive metabolites, and evaluate their antimicrobial and cytotoxic activities were described.

Acaricidal activity of Swietenia mahogani and Swietenia macrophylla ethanolic extracts against Varroa destructor in honeybee colonies.

The acaricidal (miticidal) activity of 90% ethanolic extracts of leaves and stem bark of Swietenia mahogani and Swietenia macrophylla were tested against Varroa destructor mite. Four concentrations were used over two different time intervals under laboratory and field conditions. In general, it was noticed that the acaricidal effect based on mortality and LC(50) of all tested extracts against the Varroa mite was concentration and time dependant. The acaricidal action against Varroa mites was relatively the least for the S. macrophylla stem bark extract at 500 ppm concentration after 48 h while it reached 100% and 95% in case of S. mahogani bark and S. macrophylla leaves, respectively. The% infestation with Varroa in colonies treated with the different extracts at various time intervals showed that the rate of infestation decreased to 0.0% after 12 days from the beginning of treatments with 500 ppm of S. mahogani leaves extract compared to 0.79% decrease after treatment with Mitac, a reference drug (60 mg/colony). The rate of infestation in case of treatments with S. mahogani bark, S. macrophylla leaves and S. macrophylla bark was decreased to 0.11%, 2.41% and 1.08%, respectively. The highest reduction was observed with S. mahogani leaves extract followed by S. mahogani bark. All the tested extracts showed less or no effect on honey bees at the different concentrations and at different bioassay times. This study suggested that the use of natural plant extracts or their products as ecofriendly biodegradable agents could be of high value for the control of Varroa mite.