DNA damage and genetic aberration induced via different sized silver nanoparticles: Therapeutic approaches of Casimiroa edulis and Glycosmis pentaphylla leaves extracts.

Potential of Casimiroa edulis and Glycosmis pentaphylla leaves extracts were investigated against the effect of two different particle sizes of silver nanoparticles induced toxicity in mice. Mice received silver nanoparticles (AgNPs) (100 mg/kg) with 20 and 100 nm for four weeks followed by daily oral dose of extracts (500 mg/kg) for three weeks. C. edulis leaves identified fourteen phenolic compounds while, G. pentaphylla leaves identified, twelve phenolic compounds. Additionally, biochemical, genotoxicity, mutagenicity, and histopathological investigations were carried out, revealed that liver function activities, lipid profile, hydrogen peroxide, and C-reactive protein were significantly elevate post AgNPs exposure. While, superoxide dismutase, glutathione-S-transferases, and glutathione peroxidase significantly reduce. A marked amelioration in all detected biomarkers, improved histopathological changes and repair DNA damage after treated with C. edulis and G. pentaphylla leaves extracts. These extracts are used for the first time as promising candidate therapeutic agents against toxicity induced by AgNPs. PRACTICAL APPLICATIONS: The potential applications of AgNPs make it necessary to investigate the possible toxicity associated with release of free silver ions in the biological system. AgNPs of varying particle sizes had toxic effects as evidenced by alterations in some cellular biochemical parameters, genotoxicity, mutagenicity, and histopathological indices on mice. Casimiroa edulis and Glycosmis pentaphylla leaves extracts are used for the first time as promising candidate therapeutic, where they are able to ameliorate the toxicity induced via AgNPs and record vacillate percentage of improvement in the selected biomarkers, as a result of the bioactive secondary metabolites especially flavonoids and other polyphenolic compounds.

The potential chemo preventive effect of ursolic acid isolated from Paulownia tomentosa, against N-diethylnitrosamine: initiated and promoted hepatocarcinogenesis.

The present study discusses the isolation of ursolic acid from the chloroform extract of Paulownia tomentosa (Thunb) Steud fruits and its cytotoxic effect has been assessed in-vitro was performed in different cells lines (A-549, MCF-7, HepG2) and in-vivo using N-diethylnitrosamine. The obtained results revealed that ursolic acid showed significant cytotoxic activity on MCF-7 and HepG2 cell lines in comparison to Doxorubicin as a reference drug. Moreover, we have assessed the inhibitory effects of Paulownia tomentosa fruit chloroform extract and the isolated ursolic acid on hepatocarcinogenesis was carried out for the first time using N-diethylnitrosamine, where the group treated with ursolic acid given orally after 8 weeks of cancer induction showed the most significant results in comparison to the chloroform extract. The effect of ursolic acid on intoxicated rats caused significant restoration of most of the normal hepatocytes architecture with regular dark nuclei and the group treated with Paulownia tomentosa fruits showed remarkable results with improvement in biochemical analysis.

Efficiency of the leaves and fruits of Aegle marmelos methanol extract (L.) Correa and their relative hepatotoxicity induced by CCL4 and identification of their active constituents by using LC/MS/MS.

The methanol extracts of both leaves and fruits (MEL & MEF) of A. marmelos (L.) Correa (family Rutaceae) were analyzed by using analytical method based on liquid chromatography-tandem mass spectrometry (LC/MS/MS). The objective of this study was to identify the active constituents of (MEL & MEF) of A. marmelos. Six, alkaloids namely aeglemarmelosine, marmesiline aegelinoside, shahidine, anhydromarmeline and N-2-methoxy-2-(4-methoxyphenyl) ethylcinnamide and two flavonoids, rutin and kaempferol-3-O-rutinoside in leaves were identified. Two alkaloids marmesiline and shahidine in the methanol extracts of fruits, also have been identified. Moreover, the efficiency of extracts was performed for measuring the reducing hepatotoxicity effect induced by carbon tetrachloride (CCl4) in mice. Accordingly, several biochemical parameters were performed such as lipid profile in serum, liver functions enzyme activities, glycolytic enzyme activities. In addition, LDH and SDH were investigated. The results obtained demonstrated, significant increase in lipid profile, liver function biomarkers in addition to glycolytic enzyme activities in CCl4-induced hepatotoxicity. Histopathological examination confirmed the biochemical results. Treatment of intoxicated mice with (MEL & MEF) of A. marmelos showed amelioration signs in biochemical findings as well as at cellular level. It could be concluded that both MEL & MEF can be used clinically for their potential effect as a hepatoprotective that normalized liver function biomarkers, hepatic architecture and restore physiologically status of the body against CCl4 intoxication.

Two new cytotoxic furoquinoline alkaloids isolated from Aegle marmelos (Linn.) Correa.

Two new cytotoxic furoquinoline alkaloids were isolated from the leaves of Aegle marmelos (Linn.) Correa; one from the total alkaloidal fraction (acid/base shake-out method) of the CHCl3 extract and identified as 7,8-dihydroxy-4-hydrofuroquinoline and named trivially as Aegelbine-A. The other new alkaloid isolated from the pet. ether extract and identified as 4-hydro-7-hydroxy-8-prenyloxyfuroquinoline and named trivially as Aegelbine-B, together with a known alkaloid; aegeline and a known phenolic acid; ρ-hydroxybenzoic acid. The structures of all the isolated compounds were established based on 1D and 2D NMR spectroscopy and HR-ESI/MS. The cytotoxic activity of the isolated compounds was evaluated in vitro against HepG-2, PC3, A549 and MCF-7 cell lines. The obtained results revealed promising activity with structure-based relationship which is discussed briefly.

Assessment of anti-inflammatory, antinociceptive, immunomodulatory, and antioxidant activities of Cajanus cajan L. seeds cultivated in Egypt and its phytochemical composition.

CONTEXT: Cajanus cajan L. (Fabaceae), a food crop, is widely used in traditional medicine. OBJECTIVES: The phytochemical composition of C. cajan seeds and evaluation of the anti-inflammatory, immunomodulatory, antinociceptive, and antioxidant activities were studied. MATERIALS AND METHODS: Unsaponifiable matter and fatty acids were analyzed by GC and GC/MS. The n-butanol fraction was chromatographed on polyamide column. The anti-inflammatory activity of hexane extract (200 and 400 mg/kg, p.o.) was evaluated using the carrageenan-induced rat paw edema at 1, 2, and 3 h. The serum tumor necrosis factor-α, interleukin-6, and immunoglobulin G levels were detected by ELISA. The hexane extract antinociceptive activity was determined by adopting the writhing test in mice. DPPH radical scavenging, total reduction capability, and inhibition of lipid peroxidation of butanol fraction were evaluated. RESULTS AND CONCLUSION: Twenty-one unsaponifiable compounds (mainly phytol, 2,6-di-(t-butyl)-4-hydroxy-4-methyl-2,5-cyclohexadiene-1-one, ß-sitosterol, stigmasterol, and campesterol), as well as 12 fatty acids (primarily 9,12-octadecadienoic and palmitic acids) were identified in hexane extract of C. cajan seeds. n-BuOH fraction contains quercetin-3-O-ß-d-glucopyranoside, orientin, vitexin, quercetin, luteolin, apigenin, and isorhamnetin. For the first time, quercetin-3-O-ß-d-glucopyranoside is isolated from C. cajan plant. The hexane extract (200 and 400 mg/kg) inhibited carrageenan-induced inflammation by 85 and 95%, respectively, 3 h post-carrageenan challenge. This was accompanied by an 11 and 20%, 8 and 13%, respectively, decrease of TNF-α and IL-6, as well as significant decrease in IgG serum levels. Moreover, hexane extract (200 and 400 mg/kg) decreased the number of writhings by 61 and 83%, respectively. The butanol fraction showed DPPH radical scavenging (inhibitory concentration (IC50) value: 9.07 µg/ml).

Anti-HIV-1 and cytotoxicity of the alkaloids of Erythrina abyssinica Lam. growing in Sudan.

Erythrina abyssinica Lam. is an important medicinal plant growing in Sudan; its seeds were investigated for the first time for their alkaloidal constituents and biological activity. The in vitro cytotoxicity of the crude alkaloidal fraction (CAF) against the cell lines HeLa, Hep-G2, HEP-2, HCT116, MCF-7 and HFB4 showed promising activity, with IC50 values of 13.8, 10.1, 8.16, 13.9, 11.4 and 12.2 µg mL⁻¹, respectively. Doxorubicin (positive control) showed in vitro cytotoxic activity with IC50 values 3.64, 4.57, 4.89, 3.74, 2.97 and 3.96 µg mL⁻¹, respectively. Bioassay-guided fractionation and isolation of the CAF led to the isolation of five Erythrina alkaloids, identified as erythraline, erysodine, erysotrine, 8-oxoerythraline and 11-methoxyerysodine. These were evaluated for their in vitro cytotoxic activity against Hep-G2 which resulted in IC50 values 17.60, 11.80, 15.80, 3.89 and 11.40 µg mL⁻¹, respectively. Furthermore, in vitro cytotoxic activity against HEP-2 was evaluated, which resulted in IC50 values 15.90, 19.90, 21.60, 18.50 and 11.50 µg mL⁻¹, respectively. The CAF caused a reduction in the viability of mock-infected MT-4 cells with a CC50 of 53 µM and a 50% protection of MT-4 cells against HIV-1 induced cytopathogeneticy with a EC50 of >53 µM, compared with EFV as a positive control, which had a CC50 of 45 µM and an EC50 of 0.003 µM. We concluded that the isolated alkaloids were responsible for the anti-carcinogenic [corrected] actions of the plant extract previously reported in the literature.

New acylated flavone and cyanogenic glycosides from Linum grandiflorum.

The first investigation of Linum grandiflorum resulted in the isolation of one new acylated flavone O-diglycoside known as luteolin 7-O-alpha-D-(6'''-E-feruloyl)glucopyranosyl (1 --> 2)-beta-D-glucopyranoside, and one new cyanogenic glycoside known as 2-[(3'-isopropoxy-O-beta-D-glucopyranosyl)oxy]-2-methylbutanenitrile, together with four known flavonoid glycosides, three known cyanogenic glycosides and one alkyl glycoside. The new compounds were structurally elucidated via the extensive 1D, 2D NMR and DIFNOE together with ESI-TOF-CID-MS/MS and HR-MALDI/MS.