LC/MS-Based Metabolomics Reveals Chemical Variations of Two Broccoli Varieties in Relation to Their Anticholinesterase Activity: In vitro and In silico Studies.

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.

Evidence on the inhibitory effect of Brassica plants against Acinetobacter baumannii lipases: phytochemical analysis, in vitro, and molecular docking studies.

BACKGROUND: Infections caused by Acinetobacter baumannii are becoming a rising public health problem due to its high degree of acquired and intrinsic resistance mechanisms. Bacterial lipases penetrate and damage host tissues, resulting in multiple infections. Because there are very few effective inhibitors of bacterial lipases, new alternatives for treating A. baumannii infections are urgently needed. In recent years, Brassica vegetables have received a lot of attention since their phytochemical compounds have been directly linked to diverse antimicrobial actions by inhibiting the growth of various Gram-positive and Gram-negative bacteria, yeast, and fungi. Despite their longstanding antibacterial history, there is currently a lack of scientific evidence to support their role in the management of infections caused by the nosocomial bacterium, A. baumannii. This study aimed to address this gap in knowledge by examining the antibacterial and lipase inhibitory effects of six commonly consumed Brassica greens, Chinese cabbage (CC), curly and Tuscan kale (CK and TK), red and green Pak choi (RP and GP), and Brussels sprouts (BR), against A. baumannii in relation to their chemical profiles. METHODS: The secondary metabolites of the six extracts were identified using LC-QTOF-MS/MS analysis, and they were subsequently correlated with the lipase inhibitory activity using multivariate data analysis and molecular docking. RESULTS: In total, 99 metabolites from various chemical classes were identified in the extracts. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) revealed the chemical similarities and variabilities among the specimens, with glucosinolates and phenolic compounds being the major metabolites. RP and GP showed the highest antibacterial activity against A. baumannii, followed by CK. Additionally, four species showed a significant effect on the bacterial growth curves and demonstrated relevant inhibition of A. baumannii lipolytic activity. CK showed the greatest inhibition (26%), followed by RP (21%), GP (21%), and TK (15%). Orthogonal partial least squares-discriminant analysis (OPLS-DA) pinpointed 9 metabolites positively correlated with the observed bioactivities. Further, the biomarkers displayed good binding affinities towards lipase active sites ranging from -70.61 to -30.91 kcal/mol, compared to orlistat. CONCLUSION: This study emphasizes the significance of Brassica vegetables as a novel natural source of potential inhibitors of lipase from A. baumannii.

LC-MS/MS profiling of Tipuana tipu flower, HPLC-DAD quantification of its bioactive components, and interrelationships with antioxidant, and anti-inflammatory activity: in vitro and in silico approaches.

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-1ß, 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.

Combinative effects of akarkara root-derived metabolites on anti-inflammatory and anti-alzheimer key enzymes: integrating bioassay-guided fractionation, GC-MS analysis, and in silico studies.

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-1ß, 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.

A comprehensive analytical framework integrating liquid chromatography-tandem mass spectrometry metabolomics with chemometrics for metabolite profiling of lettuce varieties and discovery of antibacterial agents.

This study comprehensively characterized the metabolite profiles of six lettuce varieties and established the correlation between the elucidated profiles and their antivirulence effects. A total of 195 metabolites were annotated using LC-QTOF-MS/MS metabolomics assisted by molecular networking and integrated with chemometrics. Red varieties (red longifolia and lolla rosa) demonstrated higher chlorogenic and chicoric acids suggesting their antioxidant properties. In parallel, amino acids and disaccharides were enriched in romaine longifolia rationalizing its palatable taste and nutritional potential, while crispa, capitata, and lolla bionda presented a high ß-carboline alkaloid content. The antibacterial and antihemolytic potential of all varieties against methicillin-sensitive and methicillin-resistant Staphylococcus aureus was assessed and validated by prominent downregulation of α-hemolysin transcriptional levels in both strains. Moreover, correlation analysis revealed sesquiterpenes, ß-carboline alkaloids, amino acids, and oxy-fatty acids as the main bioactives. Results emphasize lettuce significance as a functional food and nutraceutical source, and highlight varieties naturally rich in antibacterial agents to adapt breeding programs.

Methyl jasmonate elicitation effect on the metabolic profile of cambial meristematic cells culture derived from sweet basil (Ocimum basilicum L.) in relation to antioxidant activity: Untargeted metabolomics study in a time-based approach.

The undifferentiated cambial meristematic cell (CMC) has been recognized as a value-added production platform for plant natural products in comparison to the dedifferentiated plant cell line (DDC). In a time-based approach at 0, 24, 48, and 72 h, the present study aimed at investigating the phytochemical metabolome of methyl jasmonate (MeJA)-elicited CMC cultures derived from sweet basil (Ocimum basilicum L.), including primary and secondary metabolites analyzed using GC/TOF-MS post-silylation and RP-UPLC-C18-FT-MS/MS, respectively, as well as the analysis of aroma composition using headspace SPME-GC-MS. The results revealed a stress response in primary metabolism manifested by an increase in amino and organic acids reaching their maximum levels after 48 (1.3-fold) and 72 (1.7-fold) h, respectively. In addition, phenolic acids (e.g., sagerinic acid, rosmarinic acid, and 3-O-methylrosmarinic acid) followed by flavonoid aglycones (e.g., salvigenin and 5,6,4'-trihydroxy-7,3'-dimethoxyflavone) were the most abundant with prominent increases at 48 (1.2-fold) and 72 (2.1-fold) h, respectively. The aroma was intensified by the elicitation along the time, especially after 48 and 72 h. Furthermore, multivariate data analyses, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) confirmed elicitation effect, especially post 48 and 72 h. The study further assessed the effect of MeJA elicitation on the antioxidant and polyphenolic content. The cultures at 48 h demonstrated a significant (p < 0.05) antioxidant activity concurrently with correlation with total polyphenolic content using Pearson's correlation. Our study provides new insights to the elicitation impact on primary and secondary metabolism, in addition to aroma profile, to orchestrate the stress response and in relation to antioxidant effect.

Impact of Eucalyptus maculata Hook resin exudate constituents on reducing COX-2 gene expression: In-vivo anti-inflammatory, molecular docking and dynamics studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Eucalyptus maculata Hook from the Myrtaceae family is a native Australian plant that is frequently cultivated in Egypt. Many Eucalyptus species, including E. maculata, were widely used by the Dharawal, the indigenous Australian people, for their anti-inflammatory properties. AIM OF THE STUDY: The purpose of this study was to determine the anti-inflammatory activity of the ethanol extract of E. maculata resin exudate, its methylene chloride and n-butanol fractions, as well as the isolated compounds. MATERIALS AND METHODS: the ethanol extract was partitioned by methylene chloride, and n-butanol saturated with water. The fractions were chromatographed to isolate pure compounds. In-vivo anti-inflammatory activity of the ethanol extract, the fractions at a dose of 200 mg/kg, and the isolated compounds (20 mg/kg) was estimated using carrageenan-induced rat paws edema method against indomethacin (20 mg/kg). The activity was supported by histopathological and biochemical parameters. RESULTS: Three isolated compounds were identified as aromadendrin (C1), 7-O-methyl aromadendrin (C2), and naringenin (C3). Our findings demonstrated that the tested fractions significantly reduced the paw edema starting from the 3rd to the 5th hour as compared to the positive control, compounds C2 and C3 showed the greatest significant reduction in paw edema. The ethanol extract, fractions, C2, and C3 demonstrated an anti-inflammatory potential through reducing the levels of TNF-α, IL-6, and PGE2, as well as COX-2 protein expression compared to the negative control. These results were supported by molecular docking, which revealed that the isolated compounds had high affinity to target COX-1 and COX-2 active sites with docking scores ranging from -7.3 to -9.6 kcal mol-1 when compared to ibubrofen (-7.8 and -7.4 kcal mol-1, respectively). Molecular dynamics simulations were also performed and confirmed the docking results. CONCLUSION: The results supported the traditional anti-inflammatory potency of E. maculata Hook, and the biochemical mechanisms underlying this activity were highlighted, opening up new paths for the development of potent herbal anti-inflammatory medicine. Finally, our findings revealed that E. maculata resin constituents could be considered as promising anti-inflammatory drug candidates.

Modulatory Effect of Pyrus pyrifolia Fruit and its Phenolics on Key Enzymes against Metabolic Syndrome: Bioassay-Guided Approach, HPLC Analysis, and In Silico Study.

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-ß-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.

Unveiling the functional components and antivirulence activity of mustard leaves using an LC-MS/MS, molecular networking, and multivariate data analysis integrated approach.

Plant extracts have recently received increased attention as alternative sources of antimicrobial agents in the fight against multidrug-resistant bacteria. Non-targeted metabolomics liquid chromatography-quadrupole time-of-flight tandem mass spectrometry, molecular networking, and chemometrics were used to evaluate the metabolic profiles of red and green leaves of two Brassica juncea (L.) varieties, var. integrifolia (IR and IG) and var. rugosa (RR and RG), as well as to establish a relationship between the elucidated chemical profiles and antivirulence activity. In total, 171 metabolites from different classes were annotated and principal component analysis revealed higher levels of phenolics and glucosinolates in var. integrifolia leaves and color discrimination, whereas fatty acids were enriched in var. rugosa, particularly trihydroxy octadecadienoic acid. All extracts demonstrated significant antibacterial activity against Staphylococcus aureus and Enterococcus faecalis, presenting the IR leaves the highest antihemolytic activity against S. aureus (99 % inhibition), followed by RR (84 %), IG (82 %), and RG (37 %) leaves. Antivirulence of IR leaves was further validated by reduction in alpha-hemolysin gene transcription (∼4-fold). Using various multivariate data analyses, compounds positively correlated to bioactivity, primarily phenolic compounds, glucosinolates, and isothiocyanates, were also identified.

Unveiling metabolome heterogeneity and new chemicals in 7 tomato varieties via multiplex approach of UHPLC-MS/MS, GC-MS, and UV-Vis in relation to antioxidant effects as analyzed using molecular networking and chemometrics.

Tomatoes show diverse phytochemical attributes that contribute to their nutritive and health values. This study comprehensively dissects primary and secondary metabolite profiles of seven tomato varieties. UHPLC-qTOF-MS assisted molecular networking was used to monitor 206 metabolites, 30 of which were first-time to be reported. Flavonoids, as valuable antioxidants, were enriched in light-colored tomatoes (golden sweet, sun gold, and yellow plum) versus high tomatoside A, an antihyperglycemic saponin, in cherry bomb and red plum varieties. UV-Vis analysis revealed similar results with a strong absorbance corresponding to rich phenolic content in light varieties. GC-MS unveiled monosaccharides as the main contributors to samples' segregation, found abundant in San Marzano tomato accounting for its sweet flavor. Fruits also demonstrated potential antioxidant activities in correlation to their flavonoids and phospholipids. This work provides a complete map of tomatoes' metabolome heterogeneity for future breeding programs and a comparative approach utilizing different metabolomic platforms for tomato analysis.

Chemometric discrimination of Hylocereus undulatus from different geographical origins via their metabolic profiling and antidiabetic activity.

Hylocereus spp. known as dragon fruit is an exotic fruit that belongs to the Cactaceae family. LC-QTOF-MS and multivariate statistical tools were established to analyze differences in the composition of dragon fruit peel and pulp from Egypt, Germany, Philippines, and China. The α-glucosidase inhibitory effects of different extracts were carried out along with the anti-glycation end products (AGE) using BSA-fructose, BSA-methylglyoxal, and arginine-methylglyoxal assays. In addition, the total antioxidant capacity was investigated as a complementary mechanism to AGE formation. Principal component analysis revealed that dragon fruits from China and Egypt were the most distinct among all samples due to betalains content. Orthogonal projection to latent structures-discriminant analysis identified 16 compounds highly correlated to the antiglycation activity such as betanin, γ-aminobutyric acid, neobetanin, and portulacaxanthin II. Pulp extracts were more active than peels as inhibitors of α-glucosidase. While peels were more active as AGE formation inhibitors and as antioxidants.

Role of telepharmacy in pharmacist counselling to coronavirus disease 2019 patients and medication dispensing errors.

INTRODUCTION: Remote pharmacist interventions have achieved much more attention during the coronavirus disease 2019 (COVID-19) outbreak, since they reduce the risk of transmission and can potentially increase the access of vulnerable populations, such as patients with COVID-19, to pharmaceutical care. This study aimed to examine differences in rates and types of pharmacist interventions related to COVID-19 and medication dispensing errors (MDEs) across community pharmacies with and without telepharmacy services. METHODS: This was a prospective, disguised, observational study conducted over four months (from March 2020 to July 2020) in 52 community pharmacies (26 with and 26 without telepharmacy) across all seven states of the United Arab Emirates using proportionate random sampling. A standardised data-collection form was developed to include information about patient status, pharmacist interventions and MDEs. RESULTS: The test (telepharmacy) group pharmacies provided pharmaceutical care to 19,974 patients, of whom 6371 (31.90%) and 1213 (6.07%) were probable and confirmed cases of COVID-19, respectively. The control group pharmacies provided care to 9151 patients, of whom 1074 (11.74%) and 33 (0.36%) were probable and confirmed cases of COVID-19, respectively. Rates of MDEs and their subcategories, prescription-related errors and pharmacist counselling errors across pharmacies with telepharmacy versus those without remote services were 15.81% versus 19.43% (p < 0.05), 5.38% versus 10.08% (p < 0.05) and 10.42% versus 9.35% (p > 0.05), respectively. DISCUSSION: This is one of the first studies to provide high-quality evidence of the impact of telepharmacy on COVID-19 patients' access to pharmaceutical care and on medication dispensing safety.

Green Biosynthesis of Silver Nanoparticles Using Annona glabra and Annona squamosa Extracts with Antimicrobial, Anticancer, Apoptosis Potentials, Assisted by In Silico Modeling, and Metabolic Profiling.

Annona glabra L. (AngTE) and Annona squamosa L. (AnsTE) fruits have been widely used in cancer treatment. Accordingly, their extracts were used to synthesize silver nanoparticles via a biogenic route (Ang-AgNPs) and (Ans-AgNPs), respectively. Chemical profiling was established using UPLC-QTOF-MS/MS. All species were tested for anticancer activity against human cervical cancer cells (HeLa), prostate adenocarcinoma metastatic (PC3), and ovary adenocarcinoma (SKOV3) using sulphorhodamine B assay. Apoptosis was determined using Annexin flow cytometry along with cell cycle analysis and supported by a molecular docking. The antibacterial and synergistic effect when combined with gentamicin were evaluated. A total of 114 compounds were tentatively identified, mainly acetogenins and ent-kaurane diterpenes. AnsTE and Ans-AgNPs had the most potent cytotoxicity on HeLa and SKOV3 cells, inducing a significant apoptotic effect against all tumor cells. The AnsTE and Ans-AgNPs significantly arrested PC3, SKOV3, and HeLa cells in the S phase. The nanoparticles demonstrated greater antibacterial and antifungal activities, as well as a synergistic effect with gentamicin against P. aeruginosa and E. coli. Finally, a molecular docking was attempted to investigate the binding mode of the identified compounds in Bcl-2 proteins' receptor, implying that the fruits and their nanoparticles are excellent candidates for treating skin infections in patients with ovarian or prostatic cancer.

Ferocactus herrerae Fruits: Nutritional Significance, Phytochemical Profiling, and Biological Potentials.

The current study reports for the first time the nutritional, fruit volatiles, phytochemical, and biological characteristics of Ferocactus herrerae J. G. Ortega fruits. The nutritional analysis revealed that carbohydrate (20.6%) was the most abundant nutrient followed by dietary fibers (11.8%), lipids (0.9%), and proteins (0.8%). It was rich in vitamins, minerals, essential, and non-essential amino acids. Gas chromatography-mass spectrometry (GC-MS) analysis of the headspace-extracted volatiles showed that 3-methyl octadecane (35.72 ± 2.38%) was the major constituent detected. Spectrophotometric determination of total phenolic and flavonoid contents of the fruit methanolic extract (ME) showed high total phenolic [9.17 ± 0.87 mg/g gallic acid equivalent (GAE)] and flavonoid [4.99 ± 0.23 mg/g quercetin equivalent (QE)] contents. The ME was analyzed using high-performance liquid chromatography with ultraviolet (HPLC-UV), which allowed for both qualitative and quantitative estimation of 16 phenolic compounds. Caffeic acid was the major phenolic acid identified [45.03 ± 0.45 mg/100 g dried powdered fruits (DW)] while quercitrin (52.65 ± 0.31 mg/100 g DW), was the major flavonoid detected. In-vitro assessment of the antioxidant capacities of the ME revealed pronounced activity using three comparative methods; 2, 2-diphenyl-1-picrylhydrazyl (DPPH) (132.06 ± 2.1 µM Trolox equivalent (TE) /g), 2,2'-azino-di(3-ethylbenzthiazoline-6-sulfonic acid (ABTS), (241.1 ± 5.03 uM TE/g), and ferric reducing antioxidant power (FRAP) (258.9 ± 1.75 uM TE/g). Besides, remarkable anti-inflammatory [COX-1 (IC50 = 20.2 ± 1.1 µg/mL) and COX-2 (IC50 = 9.8 ± 0.64 µg/mL)] and acetylcholinesterase inhibitory (IC50 = 1.01 ± 0.39 mg/mL) activities were observed. Finally, our results revealed that these fruits could be used effectively as functional foods and nutraceuticals suggesting an increase in their propagation.

Lepidium meyenii (Maca) Roots: UPLC-HRMS, Molecular Docking, and Molecular Dynamics.

Lepidium meyenii or Maca is widely cultivated as a health care food supplement due to its nutritional and medicinal properties. Although there are a few in-depth studies evaluating Maca antihypertensive effects, the correlations between the chemical constituents and bioactivity of the plant have not been studied before. Thus, the roots were extracted using different solvents (aqueous, methanol, 50% methanol, and methylene chloride) and investigated for their antihypertensive and antioxidant activities through several in vitro assays. The methanolic extract exhibited the best renin and angiotensin converting enzyme (ACE) inhibitory activities with IC50 values of 24.79 ± 1.3 ng/mL and 22.02 ± 1.1 ng/mL, respectively, along with the highest antioxidant activity. In total, 120 metabolites from different classes, e.g., alkylamides, alkaloids, glucosinolates, organic acids, and hydantoin derivatives, were identified in the methanolic extract using ultrahigh-performance liquid chromatography/high-resolution mass spectrometry (UPLC/HRMS). Molecular docking simulations were used to investigate the potential binding modes and the intermolecular interactions of the identified compounds with ACE and renin active sites. Glucotropaeolin, ß-carboline alkaloids, succinic acid, and 2,4-dihydroxy-3,5-cyclopentyl dienoic acid showed the highest affinity to target the ACE with high docking scores (S ranging from -35.32 to -22.51 kcal mol-1) compared to lisinopril (S = -36.64 kcal mol-1). Interestingly, macamides displayed the greatest binding affinity to the active site of renin with docking scores (S ranging from -22.47 to -28.25 kcal mol-1). Further, ß-carbolines achieved docking scores comparable to that of the native ligand (S ranging from -13.50 to -20.06 kcal mol-1). Molecular dynamics simulations and MMPBSA were also carried out and confirmed the docking results. Additionally, the computational ADMET study predicted that the compounds attaining promising docking results had proper pharmacokinetics, drug-likeness characteristics, and safe toxicological profiles. Ultimately, our findings revealed that Maca roots could be considered a promising candidate as an antihypertensive drug.

Impact of anthocyanin on genetic stability in mammary adenocarcinoma-induced mice treated with methotrexate.

BACKGROUND: Genetic instability leads to genome mutations, changes in nucleotide sequences, rearrangements, and gains or losses of part of the chromosomes. This instability can initiate and develop cancer. This study evaluated genomic stability in methotrexate and anthocyanin-treated mammary adenocarcinoma model. Seventy albino mice were divided into seven groups: negative control, anthocyanin, methotrexate, Ehrlich's solid tumor; Ehrlich's solid tumor and methotrexate; Ehrlich's solid tumor and anthocyanin; and Ehrlich's solid tumor, methotrexate, and anthocyanin groups. RESULTS: Tumor weight and size were evaluated. Serum arylesterase activity was low in all the induced tumors and those treated with anthocyanin, methotrexate, or both. Poly[adenosine diphosphate (ADP)-ribose] polymerase activity was high, and glutathione S-transferase activity was low in the tumors treated with anthocyanin, methotrexate, or both, compared with that of the untreated tumor. There was an increase in DNA damage in the mice with solid tumors and those injected with methotrexate or methotrexate and anthocyanin, compared with that in the untreated mice. CONCLUSIONS: There was a decrease in genetic instability and DNA damage in the tumor-bearing mice treated with anthocyanin, with a concomitant increase in nuclear poly[adenosine diphosphate (ADP)-ribose] polymerase activity, compared with those of the untreated group. Anthocyanin exerted positive effects in the treatment of mammary adenocarcinoma.

Assessment of a new strategy for catalyzing deprescribing in community pharmacies.

BACKGROUND: Although community pharmacists have been actively engaged in patient care, their role in deprescribing is still restricted. OBJECTIVES: This study aimed to assess the effectiveness of a new educational approach designed to catalyze deprescribing in community pharmacies. METHODS: In this 4-month, randomized, controlled trial, 108 community pharmacies in Egypt were randomly and equally distributed to either the active or the control groups. Participants from the active group pharmacies received 31 deprescribing-related clinical case scenarios, designed according to the available deprescribing guideline and clinical experiences of an expert panel members, and delivered through WhatsApp. Then participants from both groups reported the incidence of potentially inappropriate medicines (PIMs), the frequency of deprescribing opportunities, and related pharmacist interventions. RESULTS: Pharmacists from the active group reported a considerably higher incidence of PIMs (20.87%) than that reported by pharmacists from the control group (5.03%). In addition, they made 1326 deprescribing-related interventions, of which 1022 (77.07%) were accepted and 641 (48.34%) were significant interventions. The proportions of cessation of drug therapy, reducing the dose, and persuasion of patients to accept deprescribing pharmacist interventions in the active group were 37.85%, 22.09%, and 10.63%, respectively. In contrast, 150 of 268 deprescribing-related interventions (55.97%) in the active group were accepted. The clinical value and type of deprescribing decision were statistically significant determinants for the acceptance of deprescribing decisions. The mean time needed to persuade the patient about deprescribing and the cost saved per patient across the active and the control groups were 5.09 ± 3.54 minutes versus 10.03 ± 6.19 minutes and 17.88 ± 9.60 U.S. dollars versus 4.49 ± 2.44 U.S. dollars, respectively. CONCLUSION: The intervention proposed improved the frequency and clinical value of deprescribing decisions.

A novel educational approach for improving medication-related problems in community pharmacies.

BACKGROUND: Community pharmacists have the responsibilities of identifying and resolving medication-related problems (MRPs), thereby improving patient safety. OBJECTIVES: To deliver a series of clinical case scenarios using WhatsApp and assess the impact of this method on the ability of pharmacists to identify MRPs. METHODS: This study was conducted in 104 community pharmacies in the United Arab Emirates (UAE) over a period of six months. Recruited pharmacies were randomly allocated to either intervention or control groups using a 1:1 allocation ratio. Senior experts in clinical pharmacy created a series of clinical case scenarios based on their clinical practice and based on previous published studies related to MRPs. WhatsApp®, a well-known messenger application, which has been proven to be an efficient platform to improve communication between learners and educators, was used to deliver clinical scenarios-based educational interventions to pharmacists. Then, pharmacists from both groups filled a standardized data reporting form. The clinical importance of pharmacist recommendations was assessed by a multidisciplinary expert panel. RESULTS: The total number of patients with MRPs across the intervention and control groups was 492 versus 194 (p = 0.01). While the number of MRPs identified, the mean time needed to resolve MRPs for patients with major polypharmacy, and physicians' acceptance of pharmacist recommendations across the intervention and control groups were 492 versus 194, 1589 versus 255, 6.82 (±3.86) versus 10.78 (±6.38), and 1065/1284 (82.94%) versus 125/201 (62.18%), respectively, all with p < 0.05. Efficacy-related problems (27.56%) and safety-related problems (28.44%) were the most commonly identified MRPs by pharmacists in the intervention group. Clinically significance of pharmacist recommendations was a significant predictive factor for physicians' acceptance of pharmacist recommendations. CONCLUSION: Clinical case scenarios delivered by WhatsApp may be useful for improving the ability of pharmacists to identify MRPs and for shortening the mean time needed to resolve MRPs.

Shedding the light on Pharmacists' roles during COVID-19 global pandemic.

INTRODUCTION: (Background)The role of pharmacists revolves around providing the highest levels of care to society and ensuring the provision of medicine to all patients. However, with the spread of coronavirus disease 2019 (COVID -19), pharmacists as a very important part of healthcare professionals' team are responsible for fighting against the disease regardless of their setting of practice. The role of pharmacists will undergo a little change to extend and include other roles in order to ensure the safety of the community and limit the virus spread. Also, they will be required to obtain information from reliable sources, and to be up to date, so they can be reliable advisors to the community and raise their awareness. OBJECTIVES: The purpose of this review is to highlight community and hospital pharmacists' roles during (COVID-19) global pandemic, and to clearly illustrate how they are contributing to maintain pharmacy services continuity, supporting other healthcare professionals, and facilitating the patient's education. SUMMARY: Clinical pharmacists provide direct patient care through monitoring adverse drug reactions, ensuring individualized treatment, performing evidence-based practice, and evaluating drugs in clinical trials. On the other hand, community pharmacists which are the most accessible healthcare providers by the community increase their awareness regarding the preventive measures, balance medicines supply and demand, provide drive-thru and home delivery services, offer telehealth counselling, psychological support, refer suspected COVID-19 patients, and provide vaccination when available. CONCLUSION: Innovative pharmacists' roles have emerged to adapt to changes during COVID-19 pandemic, however, they may be needed in the post COVID-19 world as well.

The effectiveness of pharmacist-based coaching inimproving breast cancer-related health behaviors: A randomized controlled trial

Background: Although pharmacists are trusted and easily accessible by the public, their role in changing health behaviours related to breast cancer has been rarely investigated. Objective: To investigate the effectiveness of pharmacist-based coaching in improving BC-related health behaviors and knowledge in females, and to measure the comfort level toward this program. Methods: This was a randomized controlled study carried out in community pharmacies in Egypt. Pharmacies included were asked to enroll 240 females into a trial, then equally allocate them into either active or control arms, and provide 12 weekly face-to-face coaching sessions to those assigned to the active arm. Pharmacists were also asked to survey females and fill a standardized data collection form at baseline, in the middle of coaching, at the end of coaching, and three months after coaching. Results: The proportions of doing high physical activity, practicing healthy diet, and practicing breast self-exam three months after the end of coaching programme across the active and control arms were 52.17% versus 17.09% (p=0.002), 62.60% versus 28.20% (p=0.003), and 81.73% versus 23.07% (p=0.005), respectively. The mean scores of knowledge on BC symptoms, risk factors, and detection methods three months after coaching across the active and control arms were 4.10±2.47 versus 2.72±1.19 (p=0.038), 4.25±2.20 versus 3.28±1.48 (p=0.020), and .34±1.80 versus 1.72±0.68 (p=0.001) respectively. While most of the females participated in the active arm were comfortable toward the financial 94.78% and social 88.69% sides of the program, more than one-third (34.78%) of the participants were uncomfortable toward the competency of coaches. Conclusion: Despite the need for some modifications, BC-related health behaviors and knowledge can be improved through pharmacist-based health coaching (AU)