Correction: New cyclic glycolipids from Silene succulenta promote in vitro MCF-7 breast carcinoma cell apoptosis by cell cycle arrest and in silico mitotic Mps1/TTK inhibition.

[This corrects the article DOI: 10.1039/D3RA01793A.].

Acacia nilotica stem bark extract ameliorates obesity, hyperlipidemia, and insulin resistance in a rat model of high fat diet-induced obesity.

Background and aim: Acacia nilotica (A. nilotica) is an imperative plant with many medicinal uses. The current study aimed to investigate the protective effects of the stem bark of A. nilotica and its fractions in a high fat diet (HFD) rat model. Experimental procedure: Seventy-two male albino rats were randomly divided into 9 groups, 8 rats per each. Group 1 was the normal control and received standard balanced diet. All the remaining groups were fed HFD for 8 weeks to induce obesity. Group 2 served as the HFD control group, group 3 received orlistat (5 mg/kg/day), groups 4 and 5 received total extract of A. nilotica stem bark (250 and 500 mg/kg). Groups 6 and 7 received A. nilotica ethyl acetate fraction (250 and 500 mg/kg), while groups 8 and 9 received butanol fraction (250 and 500 mg/kg). Results and conclusion: Both doses of the ethyl acetate fraction of the stem bark of A. nilotica significantly decreased the body weight, blood glucose, lipid profile and improved insulin sensitivity. Levels of MDA, leptin and inflammatory cytokines were significantly decreased by the ethyl acetate fraction while adiponectin and HDL-C were significantly increased relative to the HFD control group. Both doses of the ethyl acetate fraction significantly abolished HDF induced oxidative stress and normalized the values of antioxidant enzymes. Furthermore, metabolic profiling of the ethyl acetate fraction was performed by UHPLC/Q-TOF-MS. In conclusion, the ethyl acetate fraction of A. nilotica stem bark possessed antioxidant, anti-inflammatory and insulin sensitizing properties in HFD rat model.

New cyclic glycolipids from Silene succulenta promote in vitro MCF-7 breast carcinoma cell apoptosis by cell cycle arrest and in silico mitotic Mps1/TTK inhibition.

In vitro anticancer screening of Silene succulenta Forssk. aerial parts (Caryophyllaceae) showed that the n-hexane fraction was a highly effective fraction against breast carcinoma cell lines (MCF-7) with IC50 = 15.5 µg mL-1. The bioactive-guided approach led to the isolation of two new cyclic glucolipids from the n-hexane fraction, identified as a 1,2'-cyclic ester of 11-oxy-(6'-O-acetyl-ß-d-glucopyranosyl) behenic acid (1) as a C-11 epimeric mixture and 11(R)-oxy-(ß-d-glucopyranosyl)-1,2'-cyclic ester of behenic acid (2). An in vitro cytotoxicity study showed the potential suppression of MCF-7 cells with IC50 values of 11.7 ± 0.04 and 6.6 ± 0.01 µg mL-1 for compounds 1 and 2, respectively, compared to doxorubicin (IC50 = 3.83 ± 0.01 µg mL-1). Accordingly, only cell cycle tracking for the most active compound (2) was assessed. The cell cycle investigation showed that compound 2 altered the cell cycle at G0/G1, S, and G2/M phases in MCF-7 treated cells. In addition, its powerful apoptotic ability resulted in a significant increase in the early and late stages of apoptosis. Moreover, molecular docking analysis, which was performed against the anticancer mitotic (or spindle assembly) checkpoint target Mps1 kinase, showed that the two new cyclic glycolipids (1 and 2) possess high binding affinity of -7.7 and - 7.6 kcal mol-1, respectively, compared to its ATP ligand. Overall, this report emphasizes that natural cyclic glycolipids can be used as potential antitumour breast cancer agents.

Pharmacological Activities and Characterization of Phenolic and Flavonoid Compounds in Solenostemma argel Extract.

Solenostemma argel is a desert medicinal plant indigenous to African countries. This research aims to study the pharmacological properties of Solenostemma argel plant. Aerial parts (leaves and flowers) of Solenostemma argel (Delile) Hayane were tested for antibacterial activity, antioxidant activity, anticancer, and anti-inflammatory activity. Phenolic and flavonoid contents of the plant were characterized. There was an increase in the antioxidant activity of Solenostemma argel extract from 12.16% to 94.37% by increasing concentration from10 µg/mL to 1280 µg/mL. The most sensitive organism was S. epidermidis with chloroform extract. The MTT assay revealed that methanolic extracts of Solenostemma argel showed potent cytotoxic effects on the A549, Caco-2, and MDAMB-231 cell lines, respectively. The anti-inflammatory activity increased by increasing the concentration of methanolic extract of Solenostemma argel, using indomethacin as a standard. Gallic acid was the most abundant phenolic acid, followed by synergic acid and p-coumaric acid, respectively. Catechin, quercetin, luteolin, kaempferol and rutin flavonoids were also found in the methanolic extract. GC-mass analysis showed that aerial parts of Solenostemma argel were rich in 2-(5-methyl-5 vinyl tetrahydro-2-furanyl)-2-propanol (11.63%), hexanoic acid methyl ester (10.93%), 3-dioxolane,4-methyl-2-pentadecyl (9.69%), phenol, 2-(1,1-dimethylethyl) (8.50%). It can be concluded that Solenostemma argel methanolic extract contain natural bioactive constituents with potential medicinal importance such as antioxidants, antimicrobial, anti-inflammatory, and anticancer activities.

Targeting Natural Plant Metabolites for Hunting SARS-CoV-2 Omicron BA.1 Variant Inhibitors: Extraction, Molecular Docking, Molecular Dynamics, and Physicochemical Properties Study.

(1) Background: SARS-CoV-2 Omicron BA.1 is the most common variation found in most countries and is responsible for 99% of cases in the United States. To overcome this challenge, there is an urgent need to discover effective inhibitors to prevent the emerging BA.1 variant. Natural products, particularly flavonoids, have had widespread success in reducing COVID-19 prevalence. (2) Methods: In the ongoing study, fifteen compounds were annotated from Echium angustifolium and peach (Prunus persica), which were computationally analyzed using various in silico techniques. Molecular docking calculations were performed for the identified phytochemicals to investigate their efficacy. Molecular dynamics (MD) simulations over 200 ns followed by molecular mechanics Poisson-Boltzmann surface area calculations (MM/PBSA) were performed to estimate the binding energy. Bioactivity was also calculated for the best components in terms of drug likeness and drug score. (3) Results: The data obtained from the molecular docking study demonstrated that five compounds exhibited remarkable potency, with docking scores greater than -9.0 kcal/mol. Among them, compounds 1, 2 and 4 showed higher stability within the active site of Omicron BA.1, with ΔGbinding values of -49.02, -48.07, and -67.47 KJ/mol, respectively. These findings imply that the discovered phytoconstituents are promising in the search for anti-Omicron BA.1 drugs and should be investigated in future in vitro and in vivo research.

Conducting the RBD of SARS-CoV-2 Omicron Variant with Phytoconstituents from Euphorbia dendroides to Repudiate the Binding of Spike Glycoprotein Using Computational Molecular Search and Simulation Approach.

(1) Background: Natural constituents are still a preferred route for counteracting the outbreak of COVID-19. Essentially, flavonoids have been found to be among the most promising molecules identified as coronavirus inhibitors. Recently, a new SARS-CoV-2 B.1.1.529 variant has spread in many countries, which has raised awareness of the role of natural constituents in attempts to contribute to therapeutic protocols. (2) Methods: Using various chromatographic techniques, triterpenes (1-7), phenolics (8-11), and flavonoids (12-17) were isolated from Euphorbia dendroides and computationally screened against the receptor-binding domain (RBD) of the SARS-CoV-2 Omicron variant. As a first step, molecular docking calculations were performed for all investigated compounds. Promising compounds were subjected to molecular dynamics simulations (MD) for 200 ns, in addition to molecular mechanics Poisson-Boltzmann surface area calculations (MM/PBSA) to determine binding energy. (3) Results: MM/PBSA binding energy calculations showed that compound 14 (quercetin-3-O-ß-D-glucuronopyranoside) and compound 15 (quercetin-3-O-glucuronide 6″-O-methyl ester) exhibited strong inhibition of Omicron, with ΔGbinding of -41.0 and -32.4 kcal/mol, respectively. Finally, drug likeness evaluations based on Lipinski's rule of five also showed that the discovered compounds exhibited good oral bioavailability. (4) Conclusions: It is foreseeable that these results provide a novel intellectual contribution in light of the decreasing prevalence of SARS-CoV-2 B.1.1.529 and could be a good addition to the therapeutic protocol.

Perioperative total intravenous anesthesia in a child with Walker-Warburg syndrome: A case report.

Purpose: Walker-Warburg syndrome is a rare autosomal recessive congenital muscular dystrophy presenting with hydrocephalus, type II lissencephaly, cerebellar malformation, and ocular anomalies. Here, we describe the use of perioperative total intravenous anesthesia in a pediatric patient with Walker-Walburg syndrome. Clinical Features: A 2-month-old girl with Walker-Walburg syndrome was admitted for urgent ventriculoperitoneal shunt insertion. Anesthesia was induced using intravenous atropine (100 µg), ketamine (10 mg), and fentanyl (15 µg). The patient was monitored for various clinical parameters based on American Society of Anesthesiologists standards. Anesthesia was maintained using intermittent doses of 0.5 mg intravenous midazolam and 5-10 µg fentanyl in incremental boluses. The postoperative course was uneventful. Conclusions: To our knowledge, no published cases have reported the use of total intravenous anesthesia in patients with Walker-Walburg syndrome who have potential risks for anesthetic-induced malignant hyperthermia. This report described the key features, potential anesthetic management plan, and current literature review of Walker-Walburg syndrome.

A new cycloartane triterpene and other phytoconstituents from the aerial parts of Euphorbia dendroides.

New cycloartane-type triterpene 23 R/S-3ß-hydroxycycloart-24-ene-23-methyl ether 1a,b (as an C-23 epimeric mixture), along with ten known compounds, including 1 steroid, 3 fatty acids and 6 triterpenoids were isolated from the aerial parts of Euphorbia dendroides L. (Euphorbiaceae). The known compounds (2-11) were identified using 1 D & 2 D-NMR spectra and by comparison with data reported in the literature as well as using GC-MS for the isolated fatty acids. The new compound 1 (a,b) was elucidated by comprehensive 1 D & 2 D NMR experiments as well as LR & HR-FAB-MS. In addition, the isolated cycloartane-type triterpenoids have been tested for in vitro cytotoxicity against different cell lines. The new compound 1 (a,b) exhibited good to weak selective cytotoxic activities against HepG2, Huh-7, KLM-1, 1321N1 and HeLa cell lines with IC50 values of 20.67 ± 0.72, 16.24 ± 0.53, 22.59 ± 0.94, 25.99 ± 0.31 and 40.50 ± 3.14 µM, respectively.

Chemical constituents from Limonium tubiflorum and their in silico evaluation as potential antiviral agents against SARS-CoV-2.

Wild plants growing in the Egyptian deserts are facing abiotic stress, which can lead to interesting & safe natural products possessing potential chemical profiles. Consequently, our study was designed to assess the phytochemical composition of the aerial parts of Limonium tubiflorum (family Plumbaginaceae) growing wild in Egypt for the first time. In addition, in silico screening and molecular dynamic simulation of all isolated phytoconstituents were run against the main protease (Mpro) and spike glycoprotein SARS-CoV-2 targets which displayed a crucial role in the replication of this virus. Our findings showed that the phytochemical investigation of 70% ethanol extract of L. tubiflorum aerial parts afforded six known flavonoids; myricetin 3-O-(2''-galloyl)-ß-d-galactopyranoside (1), myricetin 3-O-(2''-galloyl)-α-l-rhamnopyranoside (2), myricetin 3-O-(3''-galloyl)-α-l-rhamnopyranoside (3), myricetin 3-O-ß-d-galactopyranoside (5), apigenin (6), myricetin (7), along with two known phenolic acid derivatives; gallic acid (4) and ethyl gallate (8). Docking studies revealed that compounds (1) & (2) were the most effective compounds with binding energies of -17.9664 & -18.6652 kcal mol-1 against main protease and -18.9244 & -18.9272 kcal mol-1 towards spike glycoprotein receptors, respectively. The molecular dynamics simulation experiment agreed with the docking study and reported stability of compounds (1) and (2) against the selected targets which was proved by low RMSD for the tested components. Moreover, the structure-activity relationship revealed that the presence of the galloyl moiety is necessary for enhancement of the activity. Overall, the galloyl substructure of myricetin 3-O-glycoside derivatives (1 and 2) isolated from L. tubiflorum may be a possible lead for developing COVID-19 drugs. Further, in vitro and in vivo assays are recommended to support our in silico studies.

Ent-trachylobane-3ß-hydroperoxide, a new diterpene from the root bark of Chrozophora oblongifolia (Fam.; Euphorbiaceae).

New ent-trachylobane-3ß-hydroperoxide (5) together with four known compounds, ricinine (1), trimethoxy ellagic acid (2), dimethoxy ellagic acid (3) and aleurotolic acid (4) were isolated from the methylene chloride fraction of the root bark of Chrozophora oblongifolia. The structures of these secondary metabolites were elucidated by using different spectroscopic techniques, 1H NMR, 13C NMR, HSQC, HMBC, 1H-1H COSY, NOESY, HR-ESI-MS, EI-MS and comparison with published data. Ent-trachylobane-3ß-hydroperoxide showed moderate cytotoxic activity by MTT assay method against human breast cancer cells (MCF-7) and human hepatocyte-derived carcinoma cells (Huh-7) with IC50 values of 24.53 and 34.13 µM, in comparison with IC50 values of 23.47 µM and 15.82 µM for 5-fluorouracil respectively.

Validation of Antidiabetic Potential of Gymnocarpos decandrus Forssk.

Gymnocarpos decandrus Forssk. is a well-known grazing wild plant. This study targets scientific validation of its claimed antidiabetic activity and exploring its bioactive metabolites. Chromatographic purification of G. decandrus ethanol extract (GDEE) allowed isolation of vitexin (C1), protocatechuic acid (C2) and quercetin (C3). HPLC-PDA-MS/MS enabled identification of nineteen metabolites; 13 flavonoids, 5 saponins, and 1 phenolic acid in G. decandrus and four in the genus Gymnocarpos for the first time. The antidiabetic potential was evaluated via testing the Coxsackie B4 virus and α-glucosidase inhibitory potentials. C3 exhibited its potent antiviral activity through blocking of the virus attachment (96.28%, SI 4.41) and virus inactivation before adsorption (91.47%, SI 4.78). GDEE and C1-C3 showed dose dependent α-glucosidase inhibitory activity with IC50 of 733.9, 293.3, 118.1 and 69.1 µg/mL, respectively. Our study represents the sole complete map for G. decandrus secondary metabolites and presents it as promising drug for diabetes management.

Global metabolic changes induced by arbuscular mycorrhizal fungi in oregano plants grown under ambient and elevated levels of atmospheric CO2.

Symbiotic plant-microorganisms interaction is a promising approach to avoid the environmental hazards of synthetic fertilizers and pesticides. Among these, arbuscular mycorrhizal fungi (AMF) are known to improve the growth and quality of many plant species; however the detailed metabolic mechanisms behind such beneficial effects are far from complete. Further, elevated levels of atmospheric CO2 (eCO2) could affect such AMF-plant association. Herein, we have investigated the individual and synchronous impact of AMF and eCO2 (620 ppm) on nutrient uptake, growth, photosynthesis, respiration, and levels of primary and secondary metabolites in oregano (Oreganum vulgare), an economically important herbal plant. Enhanced AMF colonization rate and a better mycelial growth were observed in roots of oregano grown under eCO2. Both AMF and eCO2 treatments significantly enhanced the growth and photosynthesis of oregano plants, however much improvements were observed by their synchronous application. eCO2 further increased the AMF-induced dark respiration and accumulation of macro and microelements. Hierarchical clustering analysis of individual primary and secondary metabolites revealed a metabolite-dependent response toward AMF and eCO2. The synchronous application of AMF and eCO2 resulted in promoted accumulation of the majority of the detected sugars, organic acids, amino acids, unsaturated fatty acids, phenolic acids and flavonoids, as compared with the sole treatments. Moreover, AMF and eCO2 acted synergistically in improving the antioxidant capacity and anti-lipid peroxidation activity of oregano. Therefore, this study suggests that AMF treatment induces a global metabolic change in oregano, the effect that is strengthened under eCO2.

A new flavonol glycoside and other flavonoids from the aerial parts of Taverniera aegyptiaca.

Isolation of flavonoids from the aerial parts of Taverniera aegyptiaca Bioss. (Fabaceae) led to identification of one new flavonol glycoside, isorhamnetin-3-O-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranoside (1), along with eleven compounds, which previously have not been isolated from this plant quercetin-3-O-α-l-rhamnopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)-ß-d-galactopyranoside] (2), isorhamnetin-3-O-α-l-arabinopyranoside (3), quercetin-3-O-α-l-rhamnopyranosyl-(1→6)-ß-d-glucopyranoside (4), isorhamnetin-3-O-α-l-rhamnopyranosyl-(1→6)-ß-d-glucopyranoside (7), isorhamnetin 3-O-α-l-rhamnopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)-ß-d-galactopyranoside] (8), isorhamnetin 3-O-α-l-rhamnopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)-ß-d-glucopyranoside] (9), kaempferol 3-O-α-l-rhamnopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)-ß-d-galactopyranoside] (10), isorhamnetin (11), 4,4'-dihydroxy-2'-methoxychalcone (12), formononetin (13) and calycosin (15)] and some compounds already known from this plant [quercetin-3-O-robinobioside (5), isorhamnetin-3-O-robinobioside (6), afrormosin (14) and odoratin (16)].

Metformin, an Anthropogenic Contaminant of Seidlitzia rosmarinus Collected in a Desert Region near the Gulf of Aqaba, Sinai Peninsula.

A phytochemical investigation of Seidlitzia rosmarinus collected along the shoreline of the Gulf of Aqaba in the remote southern desert region of the Sinai peninsula has revealed the presence of the registered drug metformin (4). However, analysis of the 14C content revealed the drug to be an anthropogenic contaminant. Consequently, natural product researchers should be aware that compounds isolated from plants might originate from environmental contamination rather than biosynthesis. The new natural product N-(4-hydroxyphenylethyl)-α-chloroferuloylamide was isolated as a mixture of the E and Z isomers along with a number of other well-established secondary metabolites.