Neuroprotective activity of Colocasia esculenta (L.) Schott leaves against monosodium glutamate-induced excitotoxicity in rats: phytochemical and molecular docking study.

Colocasia esculenta (L.) Schott is a food crop with long history of use in treatment of various disorders including neurological diseases. The methanolic leaves extract (ME) and its n-butanol fraction (n-BF) demonstrated significant in vivo neuroprotective activity in monosodium glutamate induced excitotoxicity in rats. Sixteen and fifteen polyphenolic compounds were identified in n-BF and ME, respectively, using HPLC. Phytochemical investigation of n-BF followed by 1D (1H and 13C NMR) spectroscopic analyses led to isolation and identification of daucosterol (1), thermopsoside (2) and chrysoeriol 7-O-ß-D-neohesperidoside (3) for the first time from genus Colocasia, in addition to orientin (4). LC/MS/MRM analysis of fraction V obtained from n-BF revealed identification of 13 polyphenolic compounds. Molecular docking of isolated compounds confirmed binding of all compounds at the target pocket with higher energy than crystallised ligand. The current study evaluated and confirmed the mechanistic aspects of neuroprotective activity of C. esculenta leaves for the first time.

Antimicrobial, antiproliferative activities and molecular docking of metabolites from Alternaria alternata.

Endophytic fungi allied to plants have sparked substantial promise in discovering new bioactive compounds. In this study, propagation of the endophytic fungus Alternaria alternata HE11 obtained from Colocasia esculanta leaves led to the isolation of Ergosterol (1), ß-Sitosterol (2), Ergosterol peroxide (3), in addition to three dimeric naphtho-γ-pyrones, namely Fonsecinone A (4), Asperpyrone C (5), and Asperpyrone B (6), which were isolated from genus Alternaria for the first time. Structures of the isolated compounds were established on the basis of extensive 1D and 2D NMR and, MS measurements. The ethyl acetate extract, as well as compounds 1, 3, 4 and 6 were evaluated for their antimicrobial activity using agar well-diffusion and broth microdilution assays. Molecular docking study was carried out to explore the pharmacophoric moieties that governed the binding orientation of antibacterial active compounds to multidrug efflux transporter AcrB and the ATP binding site to E. coli DNA gyrase using MOE software. Results revealed that the most active antibacterial compounds 4 and 6 bind with high affinity in the phenylalanine-rich cage and are surrounded with other hydrophobic residues. The antiproliferative activity of all isolated compounds was in vitro evaluated using the human prostatic adenocarcinoma cell lines DU-145, PC-3, PC-3 M, 22Rv1 and CWR-R1ca adopting MTT assay. Compound 4 was the most active against almost all tested cell lines, with IC50 values 28.6, 21.6, 17.1 and 13.3 against PC-3, PC-3 M, 22Rv1 and CWR-R1ca cell lines, respectively.

Pharmacological activity and flavonoids constituents of Artemisia judaica L aerial parts.

ETHNO-PHARMACOLOGICAL RELEVANCE: Artemisia judaica L is an aromatic medicinal plant growing widely in Saint Katherine, Sinai, Egypt, and used in traditional medicine as a herbal remedy for antibacterial, anthelmintic, antidiabetic, analgesic and anti-inflammatory activities. Additionally, other Arabic regions commonly used it in their folk medicines for the treatment of fungal infections, atherosclerosis, cancer, diabetes, arthritis, and inflammatory-related diseases. AIM OF THE STUDY: Based on the traditional medicinal uses of A. judaica, the present study was designed to validate some of the traditional uses as the analgesic, anti-inflammatory, antipyretic, hepatoprotective, antidiabetic, and antioxidant activities of 80% aqueous methanol extract (AME) of A. judaica aerial parts as well as isolation and identification of its flavonoid content. MATERIALS AND METHODS: AME of A. judaica aerial parts was fractionated using column chromatography and the structures of the isolated compounds were established using different spectroscopic data. Analgesic activity was evaluated using acetic acid-induced writhing in mice; antipyretic activity was assessed using yeast suspension-induced hyperthermia in rats; anti-inflammatory activity was evaluated using carrageenan-induced paw edema; the hepatoprotective effect was studied by measuring liver enzymes in carbon tetrachloride(CCl4)-induced hepatotoxicity rats while antidiabetic activity was estimated in alloxan hyperglycemia. RESULTS: Eight flavone compounds namely luteolin 4' methyl ether 7-O-ß-D-4C1-glucopyranoside (1), 8-methoxyapigenin 7-O-ß-D-4C1-galactopyranoside (2), isovitexin (3), 8-methoxyluteolin 7-O-ß-D-4C1-glucopyranoside (4), diosmetin (5), cirsimaritin (6), luteolin (7), and apigenin (8) were identified from AME of A. judaica. The AME was found to be non-toxic to mice up to 5 g/kg b.w. Moreover, it exhibits significant analgesic antipyretic, anti-inflammatory, antidiabetic, hepatoprotective, and antioxidant activities in a dose-dependent manner. CONCLUSION: The AME was nontoxic; it exhibits significant analgesic, antipyretic, anti-inflammatory, antidiabetic, hepatoprotective, and antioxidant activities. Moreover, the isolated flavone was identified from AME for the first time.

Chemical composition and antimicrobial and cytotoxic activities of Antidesm abunius L.

It was deemed of interest to investigate Antidesm bunius aerial parts from phytochemical and biological points of view due to limited previous studies. Isolation and identification of phenolic compounds and evaluation of the potential antimicrobial and cytotoxic effects of A. bunius aerial parts was investigated. The petroleum ether (PEE) and 80% EtOH extracts (EE), as well as, n-hexane (HF), CHCl3 (CF), EtOAc (EAF), n-BuOH (BF) and H2O soluble fractions (WF) of the latter were prepared. Phytochemical study has been performed for isolation and identification of the major polyphenols. Antimicrobial activity, using diffusion agar technique, and potential cytotoxic effect against HepG2, MCF7 and HCT cell lines were evaluated. Malic acid (I), caffeic acid (II), methyl benzoate (III), (+)-catechin (IV), (-)-epicatechin (V), epicatechin-(4ß→8)-catechin (procynidin B1, VI) and epicatechin-(4ß→8)-epicatechin (procyanidin B2, VII) were isolated. Compounds I-VII showed strong to moderate antimicrobial activity, with MIC values in the range of 1.95-125µg/ml except for compounds 1 and IV, which did not show any effect. All tested samples showed dose dependent cytotoxic effect against all three tested cell lines. PEE showed strong cytotoxic activity (IC50=23.7-38.2µg/ml). Furthermore, compound VI showed potent cytotoxicity against HepG2, MCF7 and HCT cell lines (IC50=24.7, 16.5 and 18.0µg/ml) respectively. The strong to moderate antimicrobial activity and cytotoxic effect of the plant could be attributed to its content of phenolic acids, flavan-3-ols and/or proanthocyanidins. These findings were confirmed by results obtained for the isolated compounds.

Alpha-Amylase and Alpha-Glucosidase Enzyme Inhibition and Antioxidant Potential of 3-Oxolupenal and Katononic Acid Isolated from Nuxia oppositifolia.

Nuxia oppositifolia is traditionally used in diabetes treatment in many Arabian countries; however, scientific evidence is lacking. Hence, the present study explored the antidiabetic and antioxidant activities of the plant extracts and their purified compounds. The methanolic crude extract of N. oppositifolia was partitioned using a two-solvent system. The n-hexane fraction was purified by silica gel column chromatography to yield several compounds including katononic acid and 3-oxolupenal. Antidiabetic activities were assessed by α-amylase and α-glucosidase enzyme inhibition. Antioxidant capacities were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) scavenging assays. Further, the interaction between enzymes (α-amylase and α-glucosidase) and ligands (3-oxolupenal and katononic acid) was followed by fluorescence quenching and molecular docking studies. 3-oxolupenal and katononic acid showed IC50 values of 46.2 µg/mL (101.6 µM) and 52.4 µg/mL (119.3 µM), respectively against the amylase inhibition. 3-oxolupenal (62.3 µg/mL or 141.9 µM) exhibited more potent inhibition against α-glucosidases compared to katononic acid (88.6 µg/mL or 194.8 µM). In terms of antioxidant activity, the relatively polar crude extract and n-butanol fraction showed the greatest DPPH and ABTS scavenging activity. However, the antioxidant activities of the purified compounds were in the low to moderate range. Molecular docking studies confirmed that 3-oxolupenal and katononic acid interacted strongly with the active site residues of both α-amylase and α-glucosidase. Fluorescence quenching results also suggest that 3-oxolupenal and katononic acid have a good affinity towards both α-amylase and α-glucosidase enzymes. This study provides preliminary data for the plant's use in the treatment of type 2 diabetes mellitus.

In vitro evaluation of new 2-phenoxy-benzo[g][1,2,4]triazolo[1,5-a]quinazoline derivatives as antimicrobial agents.

Previously, seventeen 2-phenoxy-benzo[g][1,2,4]triazolo[1,5-a]quinazoline derivatives were prepared and characterized by physicochemical and spectral means. This study was conducted to evaluate their activities in vitro against five Gram-negative and five Gram-positive of clinically pathogenic bacterial strains and ten fungal strains. The antimicrobial activity was assessed, and the minimum inhibitory concentration values of the tested compounds were determined in µg ml-1, using the diffusion agar technique. The bacterial strains used were Escherichia coli (ATCC 25922), Proteus mirabilis (ATCC 7002), Klebsiella oxytoca (ATCC 700324), Pseudomonas aeruginosa (ATCC 10145), Enterobacter cloacae (ATCC 13047D-5), Bacillus subtilis (NRRL B-543), Enterococcus faecalis (RCMB 0100154-2), Staphylococcus aureus (ATCC 29213), Staphylococcus epidermidis (ATCC 12228), and Streptococcus pyogenes (RCMB 0100174-2). Aspergillus fumigatus (RCMB 02568), Syncephalastrum racemosum (IMI 21178), Geotricum candidum (IMI 329542), Candida albicans (ATCC 10231), Aspergillus niger (IMI 130783), Cryptococcus neoformans (NRRL Y-1518), Candida tropicalis (RCMB 05239), Penicillium expansum (IMI 146655), Microsporum canis (RCMB 0834), and Trichophyton mentagrophytes (RCMB 0925) were used as the fungal strains. Ampicillin and gentamicin were used as reference antibacterial drugs and amphotericin B was used as the reference antifungal drug. The antimicrobial studies revealed that the tested compounds 6-8, 11, 12, and 14-16 showed the highest activities against the bacterial and fungal strains. The current study showed that some benzo[g]traizoloquinazolines displayed remarkable antimicrobial activity and could be used as template for further design of potent antimicrobial agent.

Antimicrobial Activity of Synthesized 2-Methylthiobenzo[g][1,2,4]- triazolo[1,5-a]quinazoline Derivatives.

BACKGROUND: The present study was carried out to evaluate the antimicrobial activity of a synthesized 2-methylthio-benzo[g][1,2,4]triazolo[1,5- a]quinazoline series. The compounds (1-21) were tested against a variety of Gram-positive bacterial species including Bacillus subtilis (RCMB 01001 69-3), Enterococcus faecalis (RCMB 0100154-2), Staphylococcus aureus (RCMB 0100183-9), Staphylococcus epidermidis (RCMB 0100183-9) and Streptococcus pyogenes (RCMB 0100172-5). In addition, Gram-negative bacteria were also tested including Pseudomonas aeruginosa (RCMB 0100243-5), Escherichia coli (RCMB 010052-6), Proteus mirabilis (RCMB 01002 54-2), Klebsiella oxytoca (RCMB 01002 83-4) and Enterobacter cloacae (RCMB 01002 64-5). Furthermore, their activities were screened against ten types of fungi i.e. Aspergillus fumigatus (RCMB 02568), Syncephalastrum racemosum (RCMB 05922), Geotricum candidum (RCMB 05097), Candida albicans (RCMB 05036), Aspergillus niger (RCMB 02724), Cryptococcus neoformans (RCMB 05642), Candida tropicalis (RCMBA 05239), Penicillium expansum (RCMB 01924), Microsporum canis (RCMB 0834) and Trichophyton mentagrophytes (RCMB 0925). METHODS: Evaluation of antimicrobial activity was performed using agar well diffusion method in comparison with ampicillin and gentamycin as antibacterial reference drugs, and amphotericin B as antifungal reference drug. The minimum inhibitory concentration (MIC) was determined using the broth double dilution technique. RESULTS: The MIC values of the tested compounds were reported in .g/mL in which ampicillin, gentamicin and amphotericin B were used as standard reference drugs. The obtained results revealed that compounds 3, 4, 7, 8, 9, 10, 11, 14, 17, 18, 19, 20 and 21 showed significant antimicrobial activity against six bacterial and six fungal strains. CONCLUSION: The promising compounds could be employed as useful scaffolds for building of new derivatives with more potent antimicrobial effects.

Two new triterpenoid estersaponins and biological activities of Pittosporum tobira 'Variegata' (Thunb.) W. T. Aiton leaves.

Two new triterpenoid estersaponins (1, 2) were isolated from the leaves of Pittosporum tobira 'Variegata' (Thunb.) W. T. Aiton, along with one known saponin (3) and one known flavonoid glycoside (4). Their structures were established by different spectroscopic methods including 1D and 2D NMR, UV, as well as ESI-MS analysis. The investigated 80% aqueous methanol extract showed significant dose dependent inhibition of acetic acid induced abdominal writhing in mice. The n-butanol fraction exerted moderate antimicrobial activity against Staphylococcus aureus and Escherichia coli. In addition, it showed in vitro antioxidant activity with IC50 value (7.3 µg/ml) lower than that of the positive control ascorbic acid (11.2 µg/ml), using DPPH free radical scavenging activity method. Evaluation of its in vitro cytotoxicity showed strong activity against breast carcinoma (MCF-7), hepatocellular carcinoma (HepG2), and colon carcinoma (HCT) cell lines.

New triterpene saponins from Duranta repens Linn. and their cytotoxic activity.

From the leaves of Duranta repens (Verbenaceae) two new triterpene saponins, named durantanin IV (1) and V (2)were isolated.In addition, ten known compounds were isolated, namely a bidesmosidic saponin, oleanolic acid, three phenylethanoids and five flavonoids. All metabolites were isolated for the first time from this genus except for 3 (oleanolic acid) and 7 (E/Z acteoside). The structures were determined mainly by spectroscopic methods (UV, IR, HRESI-MS, (1)H-, (13)C-NMR, (1)H-(1)H COSY, HSQC and HMBC). Cytotoxic screening of the chloroform, ethyl acetate and methanol extracts was carried out on brine shrimps. In addition, the investigated methanol extract and compounds 1, 2 and 7 showed significant cytotoxic activity against a HepG2 cell line.

Polyphenolic profile and bioactivity study of Oenothera speciosa Nutt. aerial parts.

Two new flavonol glycosides, myricetin 4'-O-alpha-L-rhamnopyranoside (1) and quercetin 3'-O-alpha-L-rhamnopyranoside (2), together with a novel biflavonol compound, speciin (3), as well as eleven phenolic metabolites, namely myricitrin (4), europetin 3-O-alpha-L-(1)C(4)-rhamnopyranoside (5), quercitrin (6), hyperin (7), rhamnetin 3-O-beta-galacto-pyranoside (8), caffeic acid (9), caffeic acid methyl ester (10), chlorogenic acid (11), chlorogenic acid methyl ester (12), gallic acid (13) and gallic acid methyl ester (14), were identified from the 80 % methanol extract of the aerial parts (leaves and stems) of Oenothera speciosa Nutt. (Onagraceae). In addition myricetin (15), quercetin (16) and ellagic acid (17) were identified from the chloroform extract. The structures were established depending on their chemical and physical analyses (UV, HR-ESIMS, 1D and 2D NMR). It was found that 80 % aqueous methanol extract of O. speciosa is non-toxic to mice up to 5 g kg(-1)b wt. The investigated extract exhibited significant antihyperglycaemic and anti-inflammatory activities in a dose dependant manner. Also, the 80 % methanol extract, myricitrin(4) and hyperin(7) showed potent antioxidant activity in vitro using 1,1-diphenyl 2-picryl hydrazyl (DPPH) radical assay.