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The agricultural by-products are a significant source of health benefiting bioactive compounds. In this trend, the phenolic and flavonoid contents and functional properties of date palm seeds (DPS) and saw palmetto seeds (SPS) extracts were evaluated in this study. Considerable phenolic and flavonoid contents of 11.8, 7.75 mg GAE/g seed and 3.13, 1.1 mg CE/g seed were detected in DPS ethanol and SPS acetone extracts, respectively. The protocatechuic acid was the major compound in SPS and DPS extracts and represented 1.41 and 1.1 mg/g seed, respectively as well as similar phenolic compounds were detected using HPLC analysis. The DPS and SPS phenolic compounds possessed a strong antioxidant activity with IC50 values of 10.0, 2.2 and 2.0, 0.6 µg GAE/mL, using the DPPH and ABTS assays, respectively. The phenolic compounds of DPS and SPS extracts showed a potent and broad anti-bacterial activity against clinical multiple drug resistance bacterial strains with lower MIC values besides an effective anti-fungal activity against a number of human pathogenic fungal strains. Interestingly, in a model of LPS-induced inflammation in RAW 264.7 cells, DPS and SPS showed efficient anti-inflammatory effects to inhibit the iNOS protein expression and activity (NO release).

Two new E/Z neo-clerodane diterpene isomers, trivially named stachaegyptin D (1) and E (2), together with known compounds, stachysolon monoacetate (3) and stachysolon diacetate (4), were isolated from an organic-solvent extract of the medicinal herb Stachys aegyptiaca. Structures were elucidated by a combination of spectroscopic methods, including HREIMS, 1H, 13C, DEPT, and 2D NMR analysis, as well as, first time X-ray analysis for stachysolone (3). All isolated metabolites showed some activity against the human hepatocellular cell line, HepG2. Compound 4 was the most active with an IC50 of 59.5 μM.

A polysaccharide characterized as galactomannan (GMann) with a molecular weight of 117.76 kDa was isolated from the aqueous extract of Caesalpinia gilliesii (C. gilliesii) seeds then assessed for antiproliferative potential against human hepatocellular carcinoma cell line (HepG2). Further, HCC was induced in Wister albino rats by Diethylnitrosamine (DEN) ip injection (200 mg/kg bw), and CCl4 orally (2 ml/kg bw) for two months then subjected to GMann orally treatment (2 mg/kg bw) for one month. In results, isolated GMann is constituted of sugars (89.99 ± 2.3%), moisture (6.89 ± 0.45%), ash (0.06 ± 0.2%), and protein (2.81%) and composed mainly of mannose and galactose in ratio M/G 3.79. In vitro study, data revealed a concentration-dependent potency of GMann to induce cell death of HepG2 cells with IC50 value of 0.375 µg/ml. Mechanistic studies revealed the potential of GMann to arrest cell cycle at G2/M phase with induction of apoptosis. Biochemical results in vivo showed a significant reduction in serum transaminases (ALT and AST) as well as hepatic malondialdehyde (MDA) and nitric oxide (NOx). Molecular analysis declared a significant down-regulation in mRNA gene expression of both nuclear factor kappa-B (NF-κB) and tumor necrosis factor (TNF-α). Furthermore, a significant down-regulation in the cellular oncogene-fos (C-fos) and marked up-regulation in Glycogen synthase kinase-3 (GSK-3β) level were observed. These results were supported with histopathological investigation. Whereas GMann improved inflammatory and apoptotic markers, it could be a promising new therapeutic agent for HCC suppression and this warrant further development as a possible drug candidate for HCC.

Phytochemical investigation of Stachys aegyptiaca resulted in the characterization of three new diterpenes (1-3) together with eleven known compounds including four neo-clerodane diterpenes and seven flavonoid aglycones. Structure elucidation was performed by spectroscopic analysis by HRFABMS, 1D and 2D NMR and X-ray. Isolated compounds were screened for anti-inflammatory activity using a lipopolysaccharide-induced nitric oxide inhibition assay employing murine macrophage cells. Among the assayed compounds, 13 (calycopterin) showed a concentration-dependent inhibition of LPS-induced nitric oxide release with a IC50 of 62.5 μM.

One new naturally isoflavone compound, 5,7,2′,3′,4′ penta hydroxyl isoflavone-4′- O -β-glucopyranoside (1) was isolated from the aqueous methanol extract (AME) of Pulicaria undulata subsp. undulata , together with seven known compounds: kaempferol (2), kaempferol 3- O -β-glucoside (3), quercetin (4), quercetin 3- O -β-glucoside (5), quercetin 3- O -β-galactoside (6), quercetin 3,7-di OCH 3 (7), and caffeic acid (8). Their structures were established through chemical (acid hydrolysis) and spectral analysis (UV, NMR, and ESIM). The AME and some isolated compounds were evaluated as protective agents. Free radical scavenging using a microscaled 2,2-diphenyl-1-picrylhydrazyl assay was used to assess the direct antioxidant properties that were evaluated by the ability to protect murine Hepa1c1c7 liver cells against damage induced by the organic peroxide tert-butyl hydroperoxide. The neutral red uptake assay (NRU) was used to record the activity. Results of the 2,2-diphenyl-1-picrylhydrazyl assay recorded differential scavenging properties in ascending order: 5,7,2′,3′,4′ penta hydroxyl isoflavone-4′-O-β-glucopyranoside>quercetin>quercetin 3- O -galactoside>caffeic acid>quercetin 3,7-di-OCH 3 >kaempferol with 50% inhibitory concentrations of 3.9 μM, 7.5 μM, 11.4 μM, 12.2 μM, 78.1 μM, and 252.3 μM, respectively. The antioxidative potential reveals the potency of AME, quercetin, and quercetin 3,7-di-OCH 3 . The latter compound showed full protection at 100 μM (33 μg/mL) against the induced toxicant effect where the 50% effective concentration was calculated as 33.6±1.7 μM (11.1 μg/mL). In addition to quercetin, which was extensively shown previously as a cytoprotective agent, AME was less potent; it was capable of protecting 75% at 100 μg/mL with 50% effective concentration of 92.3±4 μg/mL. Moreover, the isolated flavonoids were found to be significantly chemosystematic markers.

The alcoholic extract of Adhatoda vasica showed strong and reversible inhibition of the enzyme acetyl cholinesterase (AChE) with an IC50 = 294 μg/mL. Phytochemical study of the total alcoholic extract of A. vasica yielded four known compounds vasicine, vasicinone, vasicole and anisotine. Vasicine reversibly and competitively inhibited AChE with ki value 11.24 μM. On the other hand, rest of isolated alkaloids showed no/or weak inhibitory effect on AChE. Vasicine showed binding similarity to both galantamine and tacrine in the catalytic site. The obtained results support the multi-pharmacological properties of vasicine, which can be considered as a promising inhibitor for acetyl cholinesterase where it can be used directly or indirectly for the development of efficient anti-Alzheimer drug.

Diterpenoids salvimulticanol (1) and salvimulticaoic acid (2) together with known diterpenoid (3-6) were isolated from Salvia multicaulis. Structures were elucidated by spectroscopic techniques including HRESIMS as well as 1D-, and 2D-NMR. In-vitro cytotoxicity was assayed against human cancer cell lines. As several metabolites exhibited activity against drug-resistance lines, compounds were screened against a panel of human drug-sensitive and multidrug-resistant cancer lines. A proposed biosynthetic pathway for these new diterpenoids (1-2) as well as the cytotoxic structure-activity relationship of all identified compounds were discussed. Compound 1 and 6 showed the most potent cytotoxicity with IC50 11.58 and 4.13 towards leukemia cell lines CCRF-CEM and CEM-ADR5000, respectively.

Background There are increasing interests in natural compounds for cancer chemoprevention. Blocking agents represent an important class of chemopreventive compounds. They prevent carcinogens from undergoing metabolic activation and thereby suppressing their interaction with cellular macromolecular targets. Methods The effect of phenolic compounds isolated from Barleria cristata var. alba as chemopreventive agent was evaluated. The ethyl acetate fraction of B. cristata was subjected to different chromatographic techniques for isolation of its major phenolic compounds. The isolated compounds were evaluated for their potential to induce the cancer chemopreventive enzyme marker NAD(P)H quinonereductase 1 (NQO1) in murine Hepa-1c1c7 cell model. Results The ethyl acetate fraction of B. cristata var. alba yielded five known compounds identified as verbascoside (1), isoverbascoside (2), dimethoxyverbascoside (3), p-hydroxy benzoic acid (4), and apigenin-7-O-glucoside (5). Among the tested compounds, isoverbascoside (2) was shown to potently induce the activity of the enzyme in a dose –dependent manner. As a functional assay for detoxification, compound 2 was the strongest to protect Hepa-1c1c7 against the toxicity of menadione, a quinone substrate for NQO1. Conclusion This effect seemed to be attributed to the compound’s potential to induce both the catalytic activity and protein expression of NQO1 as revealed by enzyme assay and Western blotting, respectively. Electronic supplementary material The online version of this article (10.1186/s12906-018-2214-9) contains supplementary material, which is available to authorized users.

Multidrug resistance (MDR) in various kinds of cancers represents a true obstacle which hinders the successes of most of current available chemotherapies. ATP-binding cassette (ABC) trasporter proteins have been shown to contribute to the majority of MDR in various types of malignancies. c-myc has recently been reported to participate, at least partly, in MDR to some types of cancers. This study aimed to test whether c-myc could play a role, solely or with coordination with other ABCs, in the resistance of HepG2 cells to doxorubicin (Dox). MDR has been induced in wild-type HepG2 and has been verified both on gene and protein levels. Various assays including efflux assays as well as siRNA targeting ABCB1 and c-myc have been employed to explore the role of both candidate molecules in MDR in HepG2. Results obtained, with regard to ABCB1 silencing on HepG2/Dox cells, have shown that ABCB1-deficient cells exhibited a significant reduction in ABCC1 expression as compared to ABCB1-sufficient cells. However, these cells did not show a significant reduction in other tested ABCs (ABCC5 and ABCC10) while c-myc silencing had no significant effect on any of the studied ABCs. Moreover, silencing of ABCB1 on HepG2 significantly increased fluorescent calcein retention in HepG2 cells as compared to the control cells while downregulation of c-myc did not have any effect on fluorescent calcein retention. Altogether, this work clearly demonstrates that c-myc has no role in MDR of HepG2 to Dox which has been shown to be ABCB1-mediated in a mechanism which might involve ABCC1.

Elevation of acetylcholinesterase enzyme (AChE) has been reported to be implicated in the etiology of Alzheimer disease (AD). One of the encouraged strategies to fight AD is the plant-derived inhibitors. Amaryllidaceae species are enriched source of alkaloids. The inhibitory properties of roots and bulbs of Pancratium maritimum L. against AChE have been previously reported. In the present study, the flowers of the wild Egyptian P. maritimum were subjected to screening assays to evaluate its potency as inhibitor to AChE. Besides, its antioxidant and cytotoxic properties were also addressed. The acetylcholinesterase inhibitory properties of P. maritimum ; total extract and its alkaloid mixture were examined using Ellman’s assay. The direct antioxidant examination was carried out using DPPH assay whereas the indirect was monitored by the ability to protect Hepa1c1c7 cells against the induced cytotoxicity produced by tert-butyl hydroperoxide (TBHP). The cytotoxic effect of the total extract and crude alkaloid mixture was evaluated against the human liver hepatoma cell line (HepG2). P. maritimum flowers showed significant inhibitory activity against AChE. The potency of the alkaloid mixture, representing 5.0% of the flowers weight (IC 50 ; 22.02 ± 0.59 μg/ml) was about fourfold of its total extract (IC 50 ; 97.67 ± 4.06 μg/ml). The total extract was able to protect about 33.4% of Hepa1c1c7 against the induced intoxication that carried by TBHP rather than the alkaloid mixture. Weak antioxidant and cytotoxic activities were recorded by both examined samples. Flowers of the Egyptian P. maritimum L. could be an enriched source of AChE inhibitors.

New sesquiterpenes tanacetolide A–C (1–3) were isolated from a Tanacetum sinaicum extract together with known compounds (4–10). The structures were elucidated on the basis of MS and NMR spectroscopic data. All the compounds were evaluated for the inhibition of inducible nitric oxide (NO) production in a mouse peritoneal macrophage system. Iso-seco-tanapartholide-3-O-methyl ether (4) produced potent inhibition of NO production (IC50 = 1.0 μM). At the protein expression level, 4 elicited concentration-dependant down-regulation of inducible nitric oxide synthase.

While select eudesmane sesquiterpenes exhibit anti-neoplastic activity, tumor-inhibition for costic-acids has not been established. Here biological activity of 3-oxo-γ-costic acid (1), previously isolated from Chiliadenus montanus, as well as new sesquiterpenes (2–5) and the known derivative, 3-oxoeudesma-1,4,11(13)-trien-7-1061αH-l2-oic acid (6), all produced from 1 by the fungus Athelia rolfsii, are reported. Structures were elucidated using MS and NMR spectroscopy with activity-screening utilizing human colon- and lung-tumor lines, Caco-2 and A549 respectively. Compound 1 exhibited anti-proliferative activity against Caco-2 (IC50 39 µM) and 2 was active against A549 (IC50 74 µM) suggesting therapeutic potential for the original substrate and a bio-transformed product.

Multidrug resistance (MDR) is a critical hindrance to the success of cancer chemotherapy. The main thing responsible for MDR phenotypes are plasma-membranes associated with adenosine triphosphate (ATP) Binding Cassette (ABC) drug efflux transporters, such as the P-glycoprotein (Pgp) transporter that has the broadest spectrum of substrates. Curcumin (CURC) is a Pgp inhibitor, but it is poorly soluble and bioavailable. To overcome these limitations, we validated the efficacy and safety of CURC, loaded in biocompatible solid lipid nanoparticles (SLNs), with or without chitosan coating, with the goal of increasing the stability, homogeneous water dispersibility, and cellular uptake. Both CURC-loaded SLNs were 5&ndash, 10-fold more effective than free CURC in increasing the intracellular retention and toxicity of doxorubicin in Pgp-expressing triple negative breast cancer (TNBC). The effect was due to the decrease of intracellular reactive oxygen species, consequent inhibition of the Akt/IKK&alpha, &beta, /NF-kB axis, and reduced transcriptional activation of the Pgp promoter by p65/p50 NF-kB. CURC-loaded SLNs also effectively rescued the sensitivity to doxorubicin against drug-resistant TNBC tumors, without signs of systemic toxicity. These results suggest that the combination therapy, based on CURC-loaded SLNs and doxorubicin, is an effective and safe approach to overcome the Pgp-mediated chemoresistance in TNBC.

Background and objectives Quinoa (Chenopodium quinoa Willd) is a plant species that belongs to Chenopodiaceae family. It has a high nutritional value as it is rich in proteins, lipids, and fiber, and has an extraordinary balance of essential amino acids, vitamins, and minerals, in addition to a high number of health-beneficial phytochemicals, including saponins and phytosterols. The present study aims to investigate the lipoidal components of C. quinoa and assessment of C. quinoa lipoidal components and different fractions (methanol, chloroform, ethylacetate, and butanol) cytotoxicity potential against three human cancer cell lines using MTT reduction assay. Materials and methods The seeds of C. quinoa were extracted by different solvents and the extracts prepared were tested for their lipiodial constituents and cytotoxic activities in three cancer cell lines. Results and conclusion The results obtained from Gas Liquid Chromatography (GLC) analysis of nonsaponifiable fraction of C. quinoa seeds indicated that it consists mainly of a mixture of a series of n-alkanes and sterols (79.96 and 7.91%. respectively). The oil was also found to be rich in linoleic acid (52.7%) and oleic acid (25.33%). The investigation of the cytotoxic potential of the plant’s low polarity fractions, including CHCl3, and nonsaponifiable fraction against the studied cell lines revealed the sensitivity of A549 human lung cancer cells. Further studies are needed to uncover the mechanism and chemical constituents of the obtained activity of C. quinoa.

An efficient, expeditious catalytic route for the synthesis of ethyl 6-amino-5-cyano-2-methyl-4-aryl-4H-pyran-3-carboxylates 2 was achieved via a three-component, one-pot reaction of malononitrile, ethyl acetoacetate, and various aromatic aldehydes in water as a solvent at room temperature. The key advantages are excellent yield, reaction time, and inexpensive catalyst. Also, cyclization of 4H-pyrans 2 to the corresponding 4H-pyrano[2,3-d]pyrimidines 3 using silica sulfuric acid in the presence of acetic anhydride was described. Some synthesized compounds exhibited promising antioxidant activities.

In continuation of our chemical investigation on some medicinal plants of the genus Achillea, chromatographic investigation of the methylene chloride/methanol (1:1) extract of the air-dried aerial part of Achillea biebersteinii Afan. (family Asteraceae) afforded a new natural monoterpene (2), in addition to two known sesquiterpenes (3 and 4). Compound 1 was isolated as light needle crystals. Structures were established on the basis of MS and NMR spectroscopic (1H, 13C, 1H-1H correlation spectroscopy, heteronuclear multiple-quantum coherence and heteronuclear multiple-bond correlation) data and in case of compound 1 were confirmed by X-ray analysis. All isolated compounds were examined for their anti-inflammatory activity to inhibit lipopolysaccharide-induced NO production in RAW264.7 macrophage cells. Compounds 3 and 4 produced a promising anti-inflammatory effect (76% and 80% inhibition, respectively). However, compounds 1 and 2 produced moderate inhibition of NO release recording a 41% and 36% inhibition of NO production, respectively.

An efficient, expeditious catalytic route for the synthesis of ethyl 6-amino-5-cyano-2-methyl-4-aryl-4H-pyran-3-carboxylates 2 was achieved via a three-component, one-pot reaction of malononitrile, ethyl acetoacetate, and various aromatic aldehydes in water as a solvent at room temperature. The key advantages are excellent yield, reaction time, and inexpensive catalyst. Also, cyclization of 4H-pyrans 2 to the corresponding 4H-pyrano[2,3-d]pyrimidines 3 using silica sulfuric acid in the presence of acetic anhydride was described. Some synthesized compounds exhibited promising antioxidant activities.

Background Egyptians recognized the healing power of herbs and used them in their medicinal formulations. Nowadays, “Attarin” drug shops and the public use mainly the Unani medicinal system for treatment of their health problems including improvement of memory and old age related diseases. Numerous medicinal plants have been described in old literature of Arabic traditional medicine for treatment of Alzheimer’s disease (AD) (or to strengthen memory). Methods In this study, some of these plants were evaluated against three different preliminary bioassays related to AD to explore the possible way of their bio-interaction. Twenty three selected plants were extracted with methanol and screened in vitro against acetylcholinesterase (AChE) and cycloxygenase-1 (COX-1) enzymes. In addition, anti-oxidant activity using DPPH was determined. Results Of the tested plant extracts; Adhatoda vasica and Peganum harmala showed inhibitory effect on AChE at IC50 294 μg/ml and 68 μg/ml respectively. Moreover, A. vasica interacted reversibly with the enzyme while P. harmala showed irreversible inhibition. Ferula assafoetida (IC50 3.2 μg/ml), Syzygium aromaticum (34.9 μg/ml) and Zingiber officinalis (33.6 μg/ml) showed activity against COX-1 enzyme. Potent radical scavenging activity was demonstrated by three plant extracts Terminalia chebula (EC50 2.2 μg/ml), T. arjuna (3.1 μg/ml) and Emblica officinalis (6.3 μg/ml). Conclusion Interestingly, differential results have been obtained which indicate the variability of the mode of actions for the selected plants. Additionally, the reversible interaction of A. vasica against AChE and the potent activity of F. assafoetida against COX-1 make them effective, new and promising agents for treatment of AD in the future, either as total extracts or their single bioactive constituents.

Capparis cartilagineaandC. desertigrowing in Egypt were investigated for their glucosiolates and rutin content. FromCapparis cartilagineafour isothiocynates were isolated and identified using GC and EI/MS techniques. These compounds were butyl isothiocyanate (1), 6-methylsulphonylhexyl isothiocyanate (2), 7-methylsulphonylheptyl isothiocyanate (3) and 5-benzylsulphonyl-4-pentenyl isothiocyanate (4). In addition to compounds (1) and (2), two other compounds were isolated and identified fromCapparis deserti. These compounds are 3-methylthiopropyl isothiocyanate (5) and [11-(2-butenylthio)6-undecenyl isothiocyanate] (6). Compounds (1), (2), (5) and (6) are reported in this study for the first time fromCapparis deserti. The main flavonoid component in the studied species was isolated and identified as rutin by comparing the data with those reported. Also, quantitative evaluation of rutin in the two species was carried out by TLC-densitometric analysis. The antioxidant activity was done using diphenylpicrylhydrazyl (DPPH) radical scavenging method. The butanol fraction fromC. cartilagineaandC. desertishowed the highest antioxidant properties.