Exploring the anti-osteoporosis potential of Petroselinum crispum (Mill.) Fuss extract employing experimentally ovariectomized rat model and network pharmacology approach.

One of the most prevalent secondary osteoporosis is ovariectomy-induced osteoporosis. Parsley (Petroselinum crispum) has potent estrogenic and antioxidant properties and was used traditionally in the treatment of amenorrhea and dysmenorrhea. The present study aimed to characterize parsley leaf extract (PLE) employing RP-HPLC-MS-MS/MS-based method and possible protective effect in ovariectomized (OVX)-induced osteoporosis in rats was assessed. Rats were randomly assigned into SHAM group, OVX group, PLE + OVX group (150 mg/kg/day, p.o), and estradiol benzoate (E2) + OVX group (30 µg/kg/day, s.c). After eight weeks following ovariectomy, biomarkers of bone strength, bone resorption, oxidative stress and histopathology were carried out. A network pharmacology approach investigated the key targets and potential mechanisms by of PLE metabolites against osteoporosis using databases: PubChem, BindingDB server, DisGeNET, ShinyGO, and KEGG Pathway. Moreover, FunRich 3.1.3, Cytoscape 3.10.0, and MOE 2019.0102 softwares were used for network pharmacology analysis and molecular docking studies. Flavones and hydroxycinnamic acid derivatives were predominant among 38 metabolites in PLE. It significantly restored bone strength and bone resorption biomarkers, osteocalcin (OST), oxidative stress biomarkers and histopathological alterations. The employed network pharmacology approach revealed that 14 primary target genes were associated with decreasing the severity of osteoporosis. Molecular docking revealed that cGMP-PKG signaling pathway has the highest fold enrichment and its downstream PDE5A. Luteolin, diosmetin, and isorhamnetin derivatives affected mostly osteoporosis targets. PLE exhibited protective action against ovariectomy-induced osteoporosis in rats and may be a promising therapy for premenopausal bone loss. cGMP-PKG signaling pathway could be a promising target for PLE in treating osteoporosis.

The potential roles of gossypol as anticancer agent: advances and future directions.

Gossypol, a polyphenolic aldehyde derived from cottonseed plants, has seen a transformation in its pharmaceutical application from a male contraceptive to a candidate for cancer therapy. This shift is supported by its recognized antitumor properties, which have prompted its investigation in the treatment of various cancers and related inflammatory conditions. This review synthesizes the current understanding of gossypol as an anticancer agent, focusing on its pharmacological mechanisms, strategies to enhance its clinical efficacy, and the status of ongoing clinical evaluations.The methodological approach to this review involved a systematic search across several scientific databases including the National Center for Biotechnology Information (NCBI), PubMed/MedLine, Google Scholar, Scopus, and TRIP. Studies were meticulously chosen to cover various aspects of gossypol, from its chemical structure and natural sources to its pharmacokinetics and confirmed anticancer efficacy. Specific MeSH terms and keywords related to gossypol's antineoplastic applications guided the search strategy.Results from selected pharmacological studies indicate that gossypol inhibits the Bcl-2 family of anti-apoptotic proteins, promoting apoptosis in tumor cells. Clinical trials, particularly phase I and II, reveal gossypol's promise as an anticancer agent, demonstrating efficacy and manageable toxicity profiles. The review identifies the development of gossypol derivatives and novel carriers as avenues to enhance therapeutic outcomes and mitigate adverse effects.Conclusively, gossypol represents a promising anticancer agent with considerable therapeutic potential. However, further research is needed to refine gossypol-based therapies, explore combination treatments, and verify their effectiveness across cancer types. The ongoing clinical trials continue to support its potential, suggesting a future where gossypol could play a significant role in cancer treatment protocols.

UPLC-MS Metabolome-Based Seed Classification of 16 Vicia Species: A Prospect for Phyto-Equivalency and Chemotaxonomy of Different Accessions.

Seeds of domesticated Vicia (vetch) species (family Fabaceae-Faboideae) are produced and consumed worldwide for their nutritional value. Seed accessions belonging to 16 different species of Vicia-both domesticated and wild taxa-were subjected to a chemotaxonomic study using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) analyzed by chemometrics. A total of 89 metabolites were observed in the examined Vicia accessions. Seventy-eight out of the 89 detected metabolites were annotated. Metabolites quantified belonged to several classes, viz., flavonoids, procyanidins, prodelphinidins, anthocyanins, stilbenes, dihydrochalcones, phenolic acids, coumarins, alkaloids, jasmonates, fatty acids, terpenoids, and cyanogenics, with flavonoids and fatty acids amounting to the major classes. Flavonoids, fatty acids, and anthocyanins showed up as potential chemotaxonomic markers in Vicia species discrimination. Fatty acids were more enriched in Vicia faba specimens, while the abundance of flavonoids was the highest in Vicia parviflora. Anthocyanins allowed for discrimination between Vicia hirsuta and Vicia sepium. To the best of our knowledge, this is the first report on employing UPLC-MS metabolomics to discern the diversity of metabolites at the intrageneric level among Vicia species.

Metabolic Profiling of the Oil of Sesame of the Egyptian Cultivar 'Giza 32' Employing LC-MS and Tandem MS-Based Untargeted Method.

Sesame (Sesamum indicum L.) is a global oil crop. Sesame oil has been regarded as functional oil with antioxidant properties in several in vivo studies but little is known about its minor fraction. In this line, this study figures out the profile of the polar fraction of Egyptian cultivar Giza 32 sesame oil (SG32 oil) employing reversed-phase high-performance liquid chromatography coupled with diode array detection and electrospray ionization-quadrupole-time-of-flight-mass spectrometry and tandem MS. The characterization of the sesame oil metabolites depended on the observation of their retention time values, accurate MS, and MS/MS data, with UV spectra, and compared with relevant literature and available standards. Remarkably, 86 metabolites were characterized and sub-grouped into phenolic acids, lignans, flavonoids, nitrogenous compounds, and organic acids. From the characterized metabolites, 72 compounds were previously characterized in SG32 cake, which presented antioxidant properties, and hence it could contribute to SG32 oil antioxidant properties. Further studies are required to state the presence of such phenolics in commercial sesame oils and what of these compounds resist oil refining.

Methanolic extracts of a selected Egyptian Vicia faba cultivar mitigate the oxidative/inflammatory burden and afford neuroprotection in a mouse model of Parkinson's disease.

Vicia faba L. is a legume from the family Fabaceae. Ancient Egyptians consumed fava beans thousands of years ago and they are still one of the most popular foods in Egypt. The current study examined the anti-Parkinson effect of 80% methanolic extracts of seeds or sprouts of the fava 'Sakha 3 'cultivar which has been selected based on the total phenol content among three cultivars tested. In addition, the extracts were characterized by reversed-phase high-performance liquid chromatography coupled with diode array detection and quadrupole-time-of-flight-mass spectrometry (RP-HPLC-DAD-QTOF-MS). Three doses (200, 400, and 600 mg/kg) of 80% methanol extracts of seeds or sprouts of the Sakha 3 cultivar were evaluated in rotenone-Parkinsonian mice from behavioral, biochemical, and histopathological aspects. The extract of fava sprouts (600 mg/kg dose) showed the most beneficial effect. It improved motor activity, enhanced striatal dopamine level, and decreased the striatal malondialdehyde, as well as the expression of the inflammatory markers, compared with the rotenone control group and groups receiving lower therapeutic doses of the extracts or L-Dopa. In addition, these findings were supported by a histopathological investigation which indicated that mice treated with the 600-mg/kg dose of the sprout extract showed a low number of degenerated neurons. The application of RP-HPLC-DAD-QTOF-MS and mass/mass spectroscopy enabled the metabolic profiling of the sprouts and seeds of the 'Sakha 3' cultivar. It is obvious that germination increased the amounts of phenolic acids, saponins, and aromatic amino acids, together with a dramatic increase in flavonoids. In conclusion, the 80% methanolic extract of sprouts of the fava "Sakha 3" cultivar may be a promising candidate for treating Parkinsonism if appropriate safety data are available.

Comparative metabolite profiling and antioxidant potentials of seeds and sprouts of three Egyptian cultivars of Vicia faba L.

Fava beans are considered basic food in Egypt and all over the world. They are a source of many bioactive secondary metabolites. Since there are many Egyptian cultivars of fava beans, this study addresses comparative chemical profiling of three Egyptian cultivars of fava beans namely Sakha 3, Nubaria 3, and Giza 843. The study also focuses on the effect of germination on the chemical profile of phenolic compounds and saponins. Sixty-five metabolites were characterized based on their UV spectra, accurate MS, and MS/MS data using RP-HPLC-DAD-ESI-QTOF-MS, including 37 metabolites reported for the first time in fava beans. The observed metabolites are phenolic compounds (flavonoids and phenolic acids), saponins, alkaloids, amino acids, nucleosides, organic acids, sugars, and a jasmonate. In fact, upon quantifying the area of metabolites in their chromatographic profiles, it was remarkable that germination increased the quantities of flavonoids, phenolic acids, and saponins. Moreover, the yield (%) of extracts, TPC, and DPPH increased upon sprouting. The TPC and the relative amounts of flavones, saponins, and amino acids showed a good positive correlation with DPPH. These findings elucidated the first report on the metabolic profiling of these cultivars as well as their antioxidant activities.

Phenolic Compounds from Sesame Cake and Antioxidant Activity: A New Insight for Agri-Food Residues' Significance for Sustainable Development.

Agri-food residues represent a rich source of nutrients and bioactive secondary metabolites, including phenolic compounds. The effective utilization of these by-products in food supplements and the nutraceuticals industry could provide a way of valorization in the transition to becoming more sustainable. In this context, the present study describes the phenolic profiling of sesame (Sesamum indicum L.) cake using reversed-phase high-performance liquid chromatography coupled to diode array detection and quadrupole-time-of-flight-mass spectrometry. Compounds were characterized based on their retention time, UV spectra, accurate mass spectrometry (MS) and MS/MS data along with comparison with standards, whenever possible, and the relevant literature. The characterized compounds (112 metabolites) belong to several classes, namely, phenolic acids (hydroxybenzoic acids and hydroxycinnamic acids), flavonoids, and lignans. Moreover, organic acids and some nitrogenous compounds were characterized. The total phenol content and the antioxidant activity of the cake extract were determined. This study provides useful information for the valorization of by-products from the sesame oil industry.

Red onion scales ameliorated streptozotocin-induced diabetes and diabetic nephropathy in Wistar rats in relation to their metabolite fingerprint.

AIM: The present study was designed to investigate the effect of red onion scales extract (ROS) against diabetic nephropathy, in relation to its metabolic profiling. METHODS: Four groups of male Wistar rats were assigned as follows; 1st untreated group, 2nd group (animals with diabetes) treated with streptozotocin (STZ, 50 mg/kg) IP, 3rd group co-treated with ROS (150 mg/kg + STZ, 50 mg/kg) and 4th group co-treated with ROS by a dose (300 mg/kg + STZ, 50 mg/kg) daily. After four weeks, random and fasting blood glucose (FBG) levels, serum insulin, advanced glycation end products (AGEs), urea, uric acid and inflammatory and fibrotic gene expression were evaluated. Moreover, histopathological examination of the renal tissues was performed. In addition, the metabolic profiling of ROS was performed via RP-HPLC-DAD-QTOF-MS and -MS/MS. RESULTS: The metabolic profiling of ROS revealed that protocatechuic acid and cyanidin-3-O-glucoside were the predominant compounds among 32 metabolites identified in the extract. ROS treated groups showed improvement of FBG and AGEs levels, whereas serum insulin level showed significant elevation. In addition, down-regulation of inflammatory mRNA expression associated with the hyperglycemic condition and amelioration in histopathological alterations in kidney tissues were observed. CONCLUSION: This study displayed the presence of 32 phenolic compounds in the ethanolic extract of ROS, a common by-product of the industrial production of onion in Egypt. This study proved the therapeutic potential of ROS as antidiabetic agent and its preventive effect against diabetic nephropathy. Therefore, this study represents a perspective of the utilization of food waste products.