Comprehensive chemical profiling of Bassia indica Wight. aerial parts extract using UPLC-ESI-MS/MS, and its antiparasitic activity in Trichinella spiralis infected mice: in silico supported in vivo study.

BACKGROUND: Trichinellosis is a public health threat infected both animals and humans as a result of eating undercooked meat. It caused by Trichinella spiralis that has widespread drug resistance and even developed many sophisticated strategies for their survival, this increases the demand in searching for new anthelmintic drugs from natural source. METHODS: Our objectives were to test the in vitro and in vivo anthelmintic activity of Bassia indica BuOH frac., and to characterize its chemical composition using UPLC-ESI-MS/MS. Besides an in silico molecular docking study with the prediction of the PreADMET properties. RESULTS: In vitro investigation of B. indica BuOH frac., showed severe destruction of the adult worm and larvae, marked cuticle swelling, areas with vesicles, blebs and loss of annulations. This was assured via in vivo study, which revealed a significant reduction (P < 0.05) in the mean adult worm count with efficacy of 47.8% along with a significant decrease (P < 0.001) in the mean larval count per gram muscle with efficacy 80.7%. Histopathological examinations of the small intestine and muscular sections showed marked improvement. In addition, immunohistochemical findings demonstrated that B. indica BuOH frac. depressed the proinflammatory cytokines expressions of TNF-α, which was obviously upregulated by T. spiralis. Precise chemical investigation of the BuOH frac. using UPLC-ESI-MS/MS resulted in the identification of 13 oleanolic type triterpenoid saponins; oleanolic acid 3-O-6´-O-methyl-ß-D-glucurono-pyranoside (1), chikusetsusaponin-IVa (2) and its methyl ester (3), chikusetsusaponin IV (4) and its methyl ester (5), momordin-Ic (6) and its methyl ester (7), betavulgaroside-I (8), -II (9) -IV (10), -X (11), licorice-saponin-C2 (12) and -J2 (13). In addition, 6 more phenolics were identified as syringaresinol (14), 3,4-di-O-caffeoylquinic acid (15), 3-O-caffeoyl-4-O-dihydrocaffeoylquinic acid (16), 3,4-di-O-caffeoylquinic acid butyl ester (17), 3,5-di-O-galloyl-4-O-digalloylquinic acid (18) and quercetin 3-O-(6´´-feruloyl)-sophoroside (19). The auspicious anthelmintic activity was further ascertained using in silico molecular docking approach that targeted certain protein receptors (ß-tubulin monomer, tumor necrosis factor alpha (TNF-α), cysteine protease (Ts-CF1), calreticulin protein (Ts-CRT)), all the docked compounds (1-19) fit into the binding site of the active pocket with binding affinities noteworthy than albendazole. In addition, ADMET properties, drug score and drug likeness were predicted for all 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.

Antiviral Activity of Peanut (Arachis hypogaea L.) Skin Extract Against Human Influenza Viruses.

The high propensity of influenza viruses to develop resistance to antiviral drugs necessitates the continuing search for new therapeutics. Peanut skins, which are low-value byproducts of the peanut industry, are known to contain high levels of polyphenols. In this study, we investigated the antiviral activity of ethanol extracts of peanut skins against various influenza viruses using cell-based assays. Extracts with a higher polyphenol content exhibited higher antiviral activities, suggesting that the active components are the polyphenols. An extract prepared from roasted peanut skins effectively inhibited the replication of influenza virus A/WSN/33 with a half maximal inhibitory concentration of 1.3 µg/mL. Plaque assay results suggested that the extract inhibits the early replication stages of the influenza virus. It demonstrated activity against both influenza type A and type B viruses. Notably, the extract exhibited a potent activity against a clinical isolate of the 2009 H1N1 pandemic, which had reduced sensitivity to oseltamivir. Moreover, a combination of peanut skin extract with the anti-influenza drugs, oseltamivir and amantadine, synergistically increased their antiviral activity. These data demonstrate the potential application of peanut skin extract in the development of new therapeutic options for influenza management.

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.

Cytotoxic new furoquinoline alkaloid isolated from Ammi majus L. growing in Egypt.

Two alkaloids of the furoquinoline-type were isolated from Ammi majus L.; a new one and was identified as 4-hydro-7-hydroxy-8-methoxyfuroquinoline (1), and the other was isolated for the second time from nature and was identified as 4-hydro-7-hydroxy-8-prenyloxyfuroquinoline (2). The structures of the isolated compounds were established and confirmed by 1D and 2D NMR spectroscopy including 1H, 13C NMR, COSY, HSQC and HMBC, while the exact masses were confirmed by HRESI/MS. The cytotoxic activity of the isolated compounds (1 and 2) was evaluated against HepG-2, PC-3, A-549 and MCF-7 and the obtained results suggested selective antiproliferative and cytotoxic effects, with IC50 = 230.2 and 326.5 µM against HepG-2 and MCF-7, respectively, for compound (1). While, compound (2) recorded IC50 = 234.2 µM against MCF-7.

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.

Anti-influenza A virus activity of a new dihydrochalcone diglycoside isolated from the Egyptian seagrass Thalassodendron ciliatum (Forsk.) den Hartog.

One new dihydrochalcone diglycoside has been isolated from the EtOAc fraction of the Egyptian seagrass Thalassodendrin ciliatum (Forsk.) den Hartog, and was identified as 6'-O-rhamnosyl-(1‴ → 6″)-glucopyranosyl asebogenin for which a trivial name Thalassodendrone was established. Furthermore, five known phenolics were isolated and identified as asebotin, quercetin 3,7-diglucoside, protocatechuic acid, ferulic acid and p-hydroxybenzoic acid. The structures of all the isolated compounds were established based on 1D and 2D NMR spectroscopy and high-resolution-mass spectrometer. High-resolution electrospray ionization mass spectra (HR-ESI-MS) were obtained using a JEOL JMS-T100TD spectrometer (JEOL Ltd., Tokyo, Japan). The anti-influenza A virus activity of the isolated new compound and asebotin was evaluated, and the obtained results revealed that the inhibition dose concentration of asebotin was more than that of Thalassodendrone with IC50 = 2.00 and 1.96 µg/mL, respectively, and with cytotoxic concentration (CC50) of 3.36 and 3.14 µg/mL, respectively.

Isolation and anti-HIV-1 activity of a new sesquiterpene lactone from Calocephalus brownii F. Muell.

As part of our ongoing collaborative effort to discover potential anti-HIV-1 agents from plants, the CH2Cl2 extract of Calocephalus brownii F. Muell. was phytochemically investigated, which resulted in the isolation of two sesquiterpene lactones of the cis-fused guaianolides type, one new identified as 1α-hydroxy-3ßH-3α,4α-epoxy-4,10-dimethyl-5αH,7αH,8ßH,10αH-guai-11(13)-ene-7,8-olide (1) and one known identified 1αH-4α-hydroxy-4,10-dimethyl-5αH,7αH,8ßH,10αH-guai-11(13)-ene-7,8-olide (2). Their structures were elucidated on the bases of IR, UV, 1D-NMR, 2D-NMR, DIFNOE and high-resolution ESI-TOF-MS. The anti-HIV-1 activity was evaluated and revealed that STLs (1 and 2) caused a reduction for the viability of mock-infected MT-4 cells by CC50 = 29.1 and 0.5 µg/mL, respectively, and caused 50% protection of MT-4 cells against HIV-1 induced cytopathogeneticy by EC50 = 29.1 and 0.5 µg/mL, respectively, as compared with Efavirenz (EFV) as positive control that showed a CC50 = 11.6 and EC50 = 0.0006 µg/mL, using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide method.

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.