Passent M. Abdel Baki

Asparagus officinalis L. spears offer substantial potential as a functional food due to their rich nutritional profile and bioactive compounds.

Background: Over the past centuries, Aloe species have been traditionally used in managements of infectious ailments. However, no scientific investigation has been conducted into their mechanistic actions behind their antimicrobial activities. The main purpose of this study is to investigate the anti-virulence activities of Aloe marlothii A. Berger (AM) and Aloe striata Haw (AS) leaves and roots against Pseudomonas aeruginosa based on biofilm, pyocyanin and motility assays. Besides, the metabolic profiling of their different organs was evaluated via HPLC–MS/MS analysis. A molecular docking study of marker compounds into a LasR target was conducted to gain an insight into the bioactive metabolites involved into mechanism of action. Results: A. marlothii roots (AMR) and A. striata leaves (ASL) displayed significant activity against P. aeruginosa at 0.5 MIC via decreasing the biofilm development, pyocyanin production, swarming and swimming motilities. HPLC–MS/MS analysis led to the identification of one hundred metabolites belonging to different chemical classes. Additionally, it revealed the richness of AMR and ASL with anthraquinones and anthrones. Molecular docking of tentatively identified anthraquinones and anthrones was performed, revealing that chrysophanol-8-O-glucoside and 6-malonylnataloin revealed superior binding affinities and stabilities within the pocket of LasR system, compared to TP-4. Conclusions: These findings give sound evidence for the use of AMR and ASL as effective anti-virulence agents against P. aeruginosa.

Phytochemical characterization, and biological assessment of the neuroprotective activities of Achillea santolina L. methanolic extract (AS), its methylene chloride fraction (MF), butanol fraction (BF) and their isolated compounds were investigated. Twenty-two compounds were identified and quantified in AS using HPLC. Luteolin and kaempferol were isolated from MF. Isovitexin and kaempferol 3-O-glucoside were isolated from BF. The anti-inflammatory activity of the isolated compounds was determined by employing cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitory assays. Neuroprotective activities of AS, MF and BF were investigated against monosodium glutamate (MSG) induced neurotoxicity in rats. Brain damage amended significantly as indicated by the decreased lactate dehydrogenase and tumor necrosis factor. Brain oxidative status was restored as indicated by increased glutathione and decreased lipid peroxidation. AS, MF and BF markedly attenuated histopathological alterations in cerebral cortex and downregulated expression of COX-2, IL-1B, IL-10 genes. The affinity of the isolated compounds for Human Heme Oxygenase-1, 5-LOX, Kelch-like ECH-associated protein and COX-2 was studied. Molecular dynamics simulation and ADME study proved that isovitexin has stable conformations and binding patterns with the active sites of the studied enzymes. For the first time, the neuroprotective potential of AS, fractions and isolated compounds was determined supported by anti-inflammatory study.

Background: Fabaceae plays a crucial role in African traditional medicine as a source of large number of important folk medication, agriculture and food plants. In a search of potential antioxidant and anti-inflammatory candidates derived from locally cultivated plants, the flowers of Tipuana tipu (Benth.) Lillo growing in Egypt were subjected to extensive biological and phytochemical studies. The impact of the extraction technique on the estimated biological activities was investigated. Methods: The flowers were extracted using different solvents (aqueous, methanol, water/methanol (1:1), methanol/methylene chloride (1:1), and methylene chloride). The different extracts were subjected to antioxidant (DPPH, ABTS, and FRAP) and anti-inflammatory (COX-2 and 5-LOX) assays. The methanol extract was assessed for its inhibitory activity against iNOS, NO production, and pro-inflammatory cytokines (NF-KB, TNF-R₂, TNF-α, IL-1β, and IL-6) in LPS-activated RAW 264.7 macrophages. The composition-activity relationship of the active methanol extract was further investigated using a comprehensive LC–QTOF-MS/MS analysis. The major identified phenolic compounds were further quantified using HPLC-DAD technique. The affinity of representative compounds to iNOS, COX-2, and 5-LOX target active sites was investigated using molecular docking and molecular dynamics simulations. Results: The methanol extract exhibited the highest radical scavenging capacity and enzyme inhibitory activities against COX-2 and 5-LOX enzymes with IC₅₀ values of 10.6 ± 0.4 and 14.4 ± 1.0 µg/mL, respectively. It also inhibited iNOS enzyme activity, suppressed NO production, and decreased the secretion of pro-inflammatory cytokines. In total, 62 compounds were identified in the extract including flavonoids, coumarins, organic, phenolic, and fatty acids. Among them 18 phenolic compounds were quantified by HPLC-DAD. The highest docking scores were achieved by kaempferol-3-glucoside and orientin. Additionally, molecular dynamics simulations supported the docking findings. Conclusion: The flower could be considered a potentially valuable component in herbal medicines owing to its unique composition and promising bioactivities. These findings encourage increased propagation of T. tipu or even tissue culturing of its flowers for bioprospecting of novel anti-inflammatory drugs. Such applications could be adopted as future approaches that benefit the biomedical field.

Broccoli is commonly consumed as food and as medicine. However, comprehensive metabolic profiling of two broccoli varieties, Romanesco broccoli (RB) and purple broccoli (PB), in relation to their anticholinergic activity has not been fully disclosed. A total of 110 compounds were tentatively identified using UPLC-Q-TOF-MS metabolomics. Distinctively different metabolomic profiles of the two varieties were revealed by principal component analysis (PCA). Furthermore, by volcano diagram analysis, it was found that PB had a significantly higher content of phenolic acids, flavonoids, and glucosinolates, indicating the different beneficial health potentials of PB that demonstrated higher antioxidant and anticholinergic activities. Moreover, Pearson’s correlation analysis revealed 18 metabolites, mainly phenolic and sulfur compounds, as the main bioactive. The binding affinity of these biomarkers to the active sites of acetyl- and butyryl-cholinesterase enzymes was further validated using molecular docking studies. Results emphasize the broccoli significance as a functional food and nutraceutical source and highlight its beneficial effects against Alzheimer’s disease.

Background: In the last few decades, the use of plant extracts and their phytochemicals as candidates for the management of parasitic diseases has increased tremendously. Irises are aromatic and medicinal plants that have long been employed in the treatment of different infectious diseases by traditional healers in many cultures. This study aims to explore the potential of three common Iris species (I. confusa Sealy, I. pseudacorus L. and I. germanica L.) against infectious diseases. Their in vitro antiprotozoal potency against Plasmodium falciparum, Trypanosoma brucei brucei, T. b. rhodesiense, T. cruzi and Leishmania infantum beside their cytotoxicity on MRC-5 fibroblasts and primary peritoneal murine macrophages were examined. Methods: The secondary metabolites of the tested extracts were characterized by UPLC-HRMS/MS and Pearsons correlation was used to correlate them with the antiprotozoal activity. Results: Overall, the non-polar fractions (NPF) showed a significant antiprotozoal activity (score: sc 2 to 5) in contrast to the polar fractions (PF). I. confusa NPF was the most active extract against P. falciparum [IC₅₀ of 1.08 μg/mL, selectivity index (S.I. 26.11) and sc 5] and L. infantum (IC₅₀ of 12.7 μg/mL, S.I. 2.22 and sc 2). I. pseudacorus NPF was the most potent fraction against T. b. rhodesiense (IC₅₀ of 8.17 μg/mL, S.I. 3.67 and sc 3). Monogalactosyldiacylglycerol glycolipid (18:3/18:3), triaceylglycerol (18:2/18:2/18:3), oleic acid, and triterpenoid irridals (spirioiridoconfal C and iso-iridobelamal A) were the top positively correlated metabolites with antiplasmodium and antileishmanial activities of I. confusa NPF. Tumulosic acid, ceramide sphingolipids, corosolic, maslinic, moreollic acids, pheophytin a, triaceylglycerols, mono- and digalactosyldiacylglycerols, phosphatidylglycerol (22:6/18:3), phosphatidylcholines (18:1/18:2), and triterpenoid irridal iso-iridobelamal A, were highly correlated to I. pseudacorus NPF anti- T. b. rhodesiense activity. The ADME study revealed proper drug likeness properties for certain highly corelated secondary metabolites. Conclusion: This study is the sole map correlating I. confusa and I. pseudacorus secondary metabolites to their newly explored antiprotozoal activity.

Background: Anacyclus pyrethrum L. (Akarkara root), a valuable Ayurvedic remedy, is reported to exhibit various pharmacological activities. Akarkara root was subjected to bioassay-guided fractionation, to isolate its active constituents and discover their potential bioactivities, followed by computational analysis. Methods: The methanol extract and its fractions, methylene chloride, and butanol, were assessed for their antioxidant, anti-inflammatory, and anticholinergic potentials. The antioxidant activity was determined using DPPH, ABTS, FRAP, and ORAC assays. The in vitro anticholinergic effect was evaluated via acetyl- and butyryl-cholinesterase inhibition, while anti-inflammatory effect weas determined using COX-2 and 5-LOX inhibitory assays. The methylene chloride fraction was subjected to GC/MS analysis and chromatographic fractionation to isolate its major compounds. The inhibitory effect on iNOS and various inflammatory mediators in LPS-activated RAW 264.7 macrophages was investigated. In silico computational analyses (molecular docking, ADME, BBB permeability prediction, and molecular dynamics) were performed. Results: Forty-one compounds were identified and quantified and the major compounds, namely, oleamide (A1), stigmasterol (A2), 2E,4E-deca-2,4-dienoic acid 2-phenylethyl amide (A3), and pellitorine (A4) were isolated from the methylene chloride fraction, the most active in all assays. All compounds showed significant in vitro antioxidant, anticholinergic and anti-inflammatory effects. They inhibited the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in activated RAW macrophages. The isolated compounds showed good fitting in the active sites of acetylcholinesterase and COX-2 with high docking scores. The ADME study revealed proper pharmacokinetics and drug likeness properties for the isolated compounds. The isolated compounds demonstrated high ability to cross the BBB and penetrate the CNS with values ranging from 1.596 to -1.651 in comparison with Donepezil (-1.464). Molecular dynamics simulation revealed stable conformations and binding patterns of the isolated compounds with the active sites of COX-2 and acetyl cholinesterase. Conclusions: Ultimately, our results specify Akarkara compounds as promising candidates for the treatment of inflammatory and neurodegenerative diseases.

This study aims to isolate the active constituents of Pyrus pyrifolia Nakai fruits using a bioassay-guided fractionation approach, test their activity in vitro against key enzymes for metabolic disorders, and support it with molecular docking simulations. The antioxidant potential of the methanolic extract (ME), its polar (PF), and non-polar fractions (NPF), along with the inhibitory activity against α-glucosidase, α-amylase, lipase, angiotensin I converting enzyme (ACE), renin, inducible nitric oxide synthase (iNOS), and xanthine oxidase (XO) were assessed. The PF exhibited the highest antioxidant and enzyme inhibitory activity. Purification of PF yielded rutin, isoquercitrin, isorhamnetin-3-O-β-D-glucoside, chlorogenic acid, quercetin, and cinnamic acid. HPLC-UV analysis of the PF allowed for the quantification of 15 phenolic compounds, including the isolated compounds. Cinnamic acid was the most powerful antioxidant in all assays and potent enzyme inhibitor against the tested enzymes (α-glucosidase, α-amylase, lipase, ACE, renin, iNOS, and XO). Additionally, it showed high affinity to target α-glucosidase and ACE active sites with high docking scores (calculated total binding free energy (ΔGbind) -23.11 kcal/mol and − 20.03 kcal/mol, respectively]. A 20-ns molecular dynamics simulation using MM-GBSA analysis revealed a stable conformation and binding patterns in a stimulating environment of cinnamic acid. Interestingly, the isolated compounds’ dynamic investigations including RMSD, RMSF, and Rg demonstrated a stable ligand − protein complex to the active site of iNOS with ΔGbind ranging from − 68.85 kcal/mol to -13.47 kcal/mol. These findings support the notion that P. pyrifolia fruit is a functional food with multifactorial therapeutic agents against metabolic syndrome-associated diseases.