Exploring the ethnopharmacological significance of Cynara scolymus bracts: Integrating metabolomics, in-Vitro cytotoxic studies and network pharmacology for liver and breast anticancer activity assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver and breast cancers are the most dominant cancer types with high occurrence rates. Artichoke (Cynara scolymus L.) has been reputed for its traditional use in alleviating many liver and gallbladder ailments beside its anticancer activity against various types of cancer cells. AIM OF THE STUDY: To demonstrate detailed chemical matrices of the different plant parts and evaluate their cytotoxic activities aiming to unveil the relationship between these activities and the intrinsic metabolites using metabolomic studies, in-vitro experiments and network pharmacology. MATERIALS AND METHODS: Chemical profiling of extracts from the different plant parts (stems, leaves, bracts and receptacles) was performed using HPLC/QqQ/MS followed by unsupervised chemometric studies. In-vitro cytotoxic potentials of the extracts were evaluated on breast and liver cancer cell line then an OPLS study using linear regression was conducted. Consequently, a network pharmacology analysis on the most bioactive plant organ was applied. RESULTS: Unsupervised chemometric analysis revealed that kaempferol-3-O-α-L-rhamnopyranoside-7-O-ß-D-galacturonopyranoside, chrysoeriol-7-rutinoside and 1-caffeoylquinic acid were responsible for the segregation of the bract (CSB) segregated from the rest of the plant organs. Interestingly, CSB extract possessed the highest potential in-vitro cytotoxic activity against both liver and breast cancer cells (IC50 = 1.65 and 1.77 µg/mL). As expected, the aforementioned biomarkers were observed to be the discriminatory cytotoxic metabolites in the constructed supervised chemometric model. Network pharmacology analysis on CSB revealed 27 liver cancer-related metabolites of which, 1-caffeoylquinic acid was the most enriched one contributing to 13% of the total interactions. Furthermore, 38 target genes were involved, the most enriched of which were Aldo-keto reductase family 1 member B1 (AKR1B10) and interleukin-2 (IL-2). KEGG pathway analysis unveiled 23 significantly related pathways including metabolic pathways that possessed the lowest p-value (1.6E-5). CONCLUSION: The findings demonstrated that CSB is a significant source of cytotoxic metabolites against breast cancer and liver cancer cell lines, hence, drawing attention to the pharmaceutical and medicinal value of this negligible plant organ and paving the route for insightful research into its exact pharmacological cytotoxic mechanisms.

Exploring the dynamics of bioactive metabolites changes in barley grains (Hordeum vulgare L.) during roasting: Insights from UPLC-QqQ-MS/MS analysis combined to chemometrics.

This investigation delves into the dynamic metabolic shifts within barley grains during the roasting process, employing UPLC-QqQ-MS/MS analysis. The complex spectrum of metabolites before and after roasting is revealed. The resulting data, unveils substantial transformations in chemical composition during roasting. A total of 62 chromatographic peaks spanning phenolic compounds, flavones, Millard Reaction Products, amino acids, lignans, vitamins, folates, and anthocyanins were annotated. Leveraging UPLC-QqQ-MS/MS analysis, we scrutinized the intricate metabolite profile before and after roasting where the roasting process was found to trigger dynamic changes across diverse metabolite classes particularly Millard Reaction Products, produced through the Maillard reaction, with dihydro-5-methyl-5H-cyclopentapyrazine, maltol and hydroxy maltol emerging as discerning markers of roasting progression. Amino acids and sugars showed degradation, while beta-glucan, a signature barley sugar, experienced notable decline. Folate derivatives witnessed pronounced reduction, aligning with the heat sensitivity of folates. Harnessing the power of multivariate data analysis, the consequences of roasting materialize through distinct clusters in PCA and OPLS-DA plots. Noteworthy, roasting duration governs the trajectory of metabolic divergence, culminating in the identification of roasting-specific markers. Epigallocatechin, procyanidin B, 10-HCO-H4 folate, and hordatine A emerge as pivotal discriminators. Orthogonal Projection to Latent Structure (OPLS) analysis linked anti-inflammatory activity with 30-min, 1-hour, and 1.5-hour roasted samples, with hordatine B in addition to some Millard Reaction Products being correlated with pro-inflammatory marker downregulation.. This study encapsulates the intricate metabolic metamorphosis ignited by roasting in barley grains, offering a holistic comprehension of their potential health-enhancing attributes. Key metabolites act as poignant indicators of these transformations, substantiating the complex interplay between roasting and the barley grain metabolome.

Metabolomics and chemometrics depict the changes in the chemical profile of white lupine (Lupinus albus L.) bioactive metabolites during seed germination.

The current study attempts to illustrate how the chemical and biological profile of white lupine seeds varies throughout the course of various germination days using UHPLC-QqQ-MS combined to chemometrics. Abscisic acid showed maximum level in the un-germinated seeds and started to decline with seed germination accompanied by an increase in the levels of gibberellins which were undetectable in un-germinated seeds. Coumaronochromones were the most prevalent constituents detected in un-germinated seeds while day 2 sprouts showed significant accumulation of flavones. The levels of alkaloids showed significant increase upon germination of the seeds reaching its maximum in day 14 sprouts. The OPLS model coefficients plot indicated that lupinalbin D and F, apigenin hexoside, kaempferol hexoside, albine, and hydoxylupanine showed strong positive correlation to the alpha amylase inhibitory activity of the tested samples while lupinalbin A, lupinisoflavone, lupinic acid and multiflorine were positively correlated to the inhibition of alpha glycosidase activity. The results obtained indicated that seed germination has a profound effect on the chemical profile as well as the in-vitro antidiabetic activity of lupine seeds.

Profiling of acetylcholinesterase inhibitory alkaloids from some Crinum, Habranthus and Zephyranthes species by GC-MS combined with multivariate analyses and in silico studies.

Acetylcholinesterase (AChE) inhibitors remain the class of drugs used for the treatment of Alzheimer disease (AD). For the aim of discovering new sources of potent AChE inhibitors, a combined AChE-inhibitory activity together with alkaloid profiles by GC-MS, combined with multivariate statistical analysis for biomarkers determination and in silico studies were attempted. Strategy was applied on leaves, roots and bulbs of six aquatic and terrestrial Amaryllidaceae species. Thirty alkaloids were identified and the AChE inhibitory activities of the extracts were tested by in-vitro Ellman method. Principal bioactive markers were discovered by correlating AChE inhibitory activity with chemical fingerprints via PLS and OPLS modeling which revealed that galanthamine, lycoramine, caranine, tazettine and N-demethylgalanthamine were the most bio-significant markers. Furthermore, the molecular docking was performed to illustrate binding orientations of the top scoring alkaloids in the active site of human acetylcholinesterase. Suggested strategy revealed that, beside galanthamine, caranine, N-demethylgalanthamine, and lycoramine are promising AChE inhibitors.

Chemical profiling and biological screening with potential anti-inflammatory activity of Callisia fragrans grown in Egypt.

The ethanolic extract of Callisia fragrans aerial parts showed a significant strong in vivo anti-inflammatory and in vitro antioxidant activities with a high in vivo gastrointestinal safety profile and a very low in vitro cytotoxicity on peripheral blood mononuclear cells (PBMCs) with an IC50 > 1000 µg/ml. The alcoholic extract of C. fragrans has been analysed by HPLC coupled to multiple-stage Linear Ion-Trap and Orbitrap High-Resolution mass spectrometry in negative electrospray ionisation mode (LC-ESI/LTQOrbitrap/MS/MSn). By this approach, it was possible to putatively identify 13 compounds, mainly organic acids, flavonoids, one steroid and one hydroxy-coumarin. Luteolin 6-C-glucopyranosyl-7-O-glucopyranoside, luteolin-8-C-glucopyranosyl-7-O-rhamnopyranoside, luteolin-6-C-glucoside and isoorientin 7-O-[6''-feruloyl]-glucoside were detected for the first time in C. fragrans and family Commelinaceae.[Figure: see text].

Effect of ontogeny on the content of the hallucinogenic alkaloids atropine and scopolamine in the different organs of some Solanaceae plants.

The content of atropine and scopolamine is known to vary with ontogeny and plant organs selected which makes it necessary to define the optimal stage for harvesting of each plant organ. The present study aims at investigating the effect of ontogeny on the accumulation of atropine and scopolamine in the leaves, stems, roots, flowers and fruits of the Solanaceae plants Burgmansia suaveolens Bercht. & J.Presl, Datura stramonium L., D. arborea L., D. inoxia Mill. and Hyoscyamus albus L. Results showed that the highest content of atropine and scopolamine was observed during the flowering stage of most organs. H. albus L. leaves collected during flowering stage exhibited the highest content of atropine (746.66 ug/g) followed by the pre-flowering leaves of D. stramonium L. and the flowering stage stems of H. albus L. while D. inoxia Mill. pre-flowering leaves and flowering stems had significantly higher content of scopolamine among all the tested extracts with a concentration of 555.04 ug/g and 244.26 ug/g, respectively.

Cornigerin, a new sesqui-lignan from the hepatoprotective fractions of Cynara cornigera L.

The ethanol extract of Cynara cornigera L. was fractionated and the fractions were subjected to hepatoprotective assays using Wistar albino rats at a dose of 500 and 250mg/kg. The liver injury was induced in rats using carbon tetrachloride. Biochemical parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin were estimated as reflections of the liver condition, with silymarin as a positive control. Phytochemical investigation and chromatographic separation of the hepatoprotective fractions led to the isolation of a new sesqui-lignan namely cornigerin (1), along with eight known compounds: apigenin (2), luteolin (3), ß-sitosterol glycoside (4), apigenin 7-O-ß-D-glucopyranoside (5), luteolin-7-O-ß-D-glucopyranoside (6), apigenin-7-O-rutinoside (7), cynarin 1,5-di-O-caffeoylquinic acid (8), and apigenin-7-O-ß-D-glucuronide (9). This is the first report for the isolation of 8 and 9 from this plant.