Acylated flavonol diglucosides from Ammania auriculata.

Chemical investigation of the extract of the whole Ammania auriculata plant resulted in the identification of 13 polyphenols, including the hitherto unknown flavonoids, kaempferol 3-O-ß-(6″-galloylglucopyranoside)-7-O-ß-glucopyranoside, and its quercetin analogue. The structures of all isolates were elucidated by conventional methods, spectroscopic analysis, including 1D and 2D NMR, and by HRESI-MS as well.

Three new di-O-glycosyl-C-glucosyl flavones from the leaves of Caesalpinia ferrea Mart..

Three hitherto unknown di-O-xylosyl-C-glycosyl flavones were isolated from the leaves of Caesalpinia ferrea. The structures of all isolated compounds were elucidated by conventional methods and spectroscopic analysis, including 1D and 2D NMR, as well as by HRESIMS.

Antidiabetic Activity and In Silico Molecular Docking of Polyphenols from Ammannia baccifera L. subsp. Aegyptiaca (Willd.) Koehne Waste: Structure Elucidation of Undescribed Acylated Flavonol Diglucoside.

Chemical investigation of the aerial parts of Ammania aegyptiaca ethanol extract (AEEE) showed high concentrations of polyphenol and flavonoid content, with notable antioxidant activity. Undescribed acylated diglucoside flavonol myricetin 3-O-ß-4C1-(6″-O-galloyl glucopyranoside) 7-O-ß-4C1-glucopyranoside (MGGG) was isolated from the aerial parts of AEEE, along with four known polyphenols that had not been characterized previously from AEEE. The inhibitory effects of MGGG, AEEE, and all compounds against α-amylase, pancreatic lipase and ß-glucosidase were assessed. In addition, molecular docking was used to determine the inhibition of digestive enzymes, and this confirmed that the MGGG interacted strongly with the active site residues of these enzymes, with the highest binding free energy against α-amylase (-8.99 kcal/mol), as compared to the commercial drug acarbose (-5.04 kcal/mol), thus justifying its use in the potential management of diabetes. In streptozotocin (STZ)-induced diabetic rats, AEEE significantly decreased high serum glucose, α-amylase activity and serum liver and kidney function markers, as well as increasing insulin blood level. Moreover, AEEE improved the lipid profile of diabetic animals, increased superoxide dismutase (SOD) activity, and inhibited lipid peroxidation. Histopathological studies proved the decrease in pancreas damage and supported the biochemical findings. These results provide evidence that AEEE and MGGG possess potent antidiabetic activity, which warrants additional investigation.

A Unique Acylated Flavonol Glycoside from Prunus persica (L.) var. Florida Prince: A New Solid Lipid Nanoparticle Cosmeceutical Formulation for Skincare.

Polyphenols are known dietary antioxidants. They have recently attracted considerable interest in uses to prevent skin aging and hyperpigmentation resulting from solar UV-irradiation. Prunus persica (L.) leaves are considered by-products and were reported to have a remarkable antioxidant activity due to their high content of polyphenols. This study aimed at the development of a cosmeceutical anti-aging and skin whitening cream preparation using ethanol leaves extract of Prunus persica (L.) (PPEE) loaded in solid lipid nanoparticles (SLNs) to enhance the skin delivery. Chemical investigation of PPEE showed significantly high total phenolic and flavonoids content with notable antioxidant activities (DPPH, ABTS, and ß-carotene assays). A unique acylated kaempferol glycoside with a rare structure, kaempferol 3-O-ß-4C1-(6″-O-3,4-dihydroxyphenylacetyl glucopyranoside) (KDPAG) was isolated for the first time and its structure fully elucidated. It represents the first example of acylation with 3,4-dihydroxyphenyl acetic acid in flavonoid chemistry. The in-vitro cytotoxicity studies against a human keratinocytes cell line revealed the non-toxicity of PPEE and PPEE-SLNs. Moreover, PPEE, PPEE-SLNs, and KDPAG showed good anti-elastase activity, comparable to that of N-(Methoxysuccinyl)-Ala-Ala-Pro-Val-chloromethyl ketone. Besides, PPEE-SLNs and KDPAG showed significantly (p < 0.001) higher anti-collagenase and anti-tyrosinase activities in comparison to EDTA and kojic acid, respectively. Different PPEE-SLNs cream formulae (2% and 5%) were evaluated for possible anti-wrinkle activity against UV-induced photoaging in a mouse model using a wrinkle scoring method and were shown to offer a highly significant protective effect against UV, as evidenced by tissue biomarkers (SOD) and histopathological studies. Thus, the current study demonstrates that Prunus persica leaf by-products provide an interesting, valuable resource for natural cosmetic ingredients. This provides related data for further studying the potential safe use of PPEE-SLNs in topical anti-aging cosmetic formulations with enhanced skin permeation properties.

Lagerstroemia speciosa (L.) Pers Leaf Extract Attenuates Lung Tumorigenesis via Alleviating Oxidative Stress, Inflammation and Apoptosis.

One of the major etiological factors that account for lung cancer is tobacco use. Benzo(a)pyrene [B(a)P], one of the main constituents of tobacco smoke, has a key role in lung carcinogenesis. The present study was conducted to investigate the cytotoxicity of an aqueous ethanolic extract of Lagerstroemia speciosa (L.) Pers leaves (LLE) on human lung adenocarcinoma cells (A549), as well as its in vivo antitumor effect on a lung tumorigenesis mice model. Our results revealed that LLE possesses cytotoxic activity against the A549 cell line. Mice orally administered B(a)P (50 mg/kg body weight) showed an increase in relative lung weight with subsequent decrease in final body weight. Serum levels of tumor marker enzymes AHH, ADA and LDH and the inflammatory mediator NF-κB increased, while total antioxidant capacity (TAC) decreased. In addition, we observed the increased activity of metalloproteinases (MMP-2 and MMP-12) and levels of the tumor angiogenesis marker VEFG and the lipid peroxidation marker MDA, as well as decreased levels of the non-enzymatic antioxidant GSH and enzymatic antioxidants CAT and GSH-Px in lung tissues. Moreover, B(a)P administration up-regulated the expression of the COX-2 gene, pro-inflammatory cytokines TNF-α and IL-6, and an anti-apoptotic gene Bcl-2, and at the same time down-regulated expression of pro-apoptotic genes BAX and caspase-3 and the p53 gene. Pre- and post-treatment with LLE (250 mg/kg body weight) attenuated all these abnormalities. Histopathological observations verified the protective effect of LLE. Overall, the present data positively confirm the potent antitumor effect of L. speciosa leaves against lung tumorigenesis.

Antitumor activity of Cuphea ignea extract against benzo(a)pyrene-induced lung tumorigenesis in Swiss Albino mice.

Lung cancer has one of the highest mortality rates among various types of cancer and is the most frequent cancer in the world. The incidence of lung cancer is increasing rapidly, in parallel with an increased incidence of smoking. Effective chemoprevention may be an alternative strategy to control the incidence of lung cancer. Thus, the objective of current work was to ascertain the possible preventive and therapeutic efficacies of Cuphea ignea extract in a mouse model of lung tumorigenesis and its cytotoxicity toward the A549 human lung cancer cell line. Lung tumorigenesis was induced by the oral administration of benzo(a)pyrene (50 mg/kg b.w.) twice per week to Swiss albino mice for 4 weeks. Benzo(a)pyrene-treated mice were orally administered C. ignea (300 mg/kg body weight, 5 days/week) for 2 weeks before or 9 weeks after the first benzo(a)pyrene dose, for a total of 21 weeks. At the end of the administration period, various parameters were measured in the serum and lung tissues. The results revealed that the oral administration of benzo(a)pyrene resulted in increases in relative lung weight, serum levels of tumor markers (ADA, AHH, and LDH), and the inflammatory marker NF-κB, and a decreased total antioxidant capacity compared with the control. In addition, decreased levels of enzymatic and non-enzymatic antioxidants, with a concomitant increase in lipid peroxidation, metalloproteinases (MMP-2 and MMP-12), and the angiogenic marker VEGF were detected in lung tissues. Moreover, benzo(a)pyrene administration induced the upregulation of PKCα, COX-2, and Bcl-2 expression, with the downregulation of BAX and caspase-3 expression. C. ignea treatment alleviated all alterations in these parameters, which was further confirmed by the histopathological analysis of lung tissues. The findings of the current work provide the first verification of the preventive and therapeutic potentials of C. ignea extract against benzo(a)pyrene-induced lung tumorigenesis in mice.

Caffeoyl sugar esters and an ellagitannin from Rubus sanctus.

The new natural caffeoyl esters, 3,6-di-O-caffeoyl-(alpha/beta)-glucose and 1-O-caffeoyl-beta-xylose, together with the hitherto unknown natural tannin, 2,3-O-hexahydroxydiphenoyl-4,6-O-sanguisorboyl-(alpha/beta)-glucose, have been isolated from the aqueous alcohol aerial part extract of Rubus sanctus. Establishment of all structures was based on the chemical and spectral evidence, including ESI-MS and 2D NMR.

Polyoxygenated flavonoids from Eugenia edulis.

Leaves of Eugenia edulis contain the new polyoxygenated flavonoid derivatives, gossypetin-3,8-dimethyl ether-5-O-beta-glucoside; gossypetin-3,5-dimethyl ether, and myricetin-3,5,3'-trimethyl ether. In addition, ten known polyphenolics were also isolated and identified. All structures were established on the basis of chemical and spectral evidence, including ESI-MS and 13C NMR.

Cytotoxic isoferulic acidamide from Myricaria germanica (Tamaricaceae).

Tamgermanitin, a unique N-trans-Isoferuloyltyramine, together with the hitherto unknown polyphenolics, 2,4-di-O-galloyl-(α/ß)-glucopyranose and kaempferide 3,7-disulphate have been isolated from the leaf aqueous ethanol extract of the false tamarisk, Myricaria germanica DESV. In addition, 18 known phenolics were also separated and characterized. All structures were elucidated on the basis of detailed analysis of 1D- (1)H and (13)C NMR, COSY, HSQC, HMBC and HRFTESIMS spectral data. The extract, its chromatographic column fractions and the isolated isoferuloyltyramine, tamgermanetin demonstrated potential cytotoxic effect against three different tumor cell lines, namely liver (Huh-7), breast (MCF-7) and prostate (PC-3). The IC 50''s were found to be substantially low with low-resistance possibility. DNA flow-cytometic analysis indicated that column fractions and tamgermanetin enhanced pre-G apoptotic fraction. Both materials showed inhibiting activity against PARP enzyme activity. In conclusion, we report the isolation and identification of a novel compound, tamgermanitin, from the aqueous ethanol extract of Myricaria germanica leaves. Further, different fractions of the extract and tamgermanitin exhibit potent cytotoxic activities which warrant further investigations.

A flavonol triglycoside and investigation of the antioxidant and cell stimulating activities of Annona muricata Linn.

Chemical investigation on leaves of Annona muricata resulted in the isolation of the flavonol triglycoside, quercetin 3-O-α-rhamnosyl-(1″″ → 6″)-ß-sophoroside, together with twelve known phenolics. The structures of these compounds were established by 1D- and 2D-nuclear magnetic resonance spectroscopic techniques and mass spectrometry data. The in vitro antioxidant studies of the investigated aqueous ethanol extract and its column fractions were accomplished using the oxygen radical absorbance capacity (ORAC) method. A stimulating effect on HaCaT human keratinocytes by the leaf extract was also assessed. Il-6 production after UV irradiation was not influenced by A. muricata leaf extract.

Cytotoxic ellagitannins from Reaumuria vermiculata.

Three ellagitannins and one disulfated flavonol were isolated from the aerial parts of Reaumuria vermiculata L. Besides that, 16 known compounds were characterized as well. The structures of all compounds were elucidated on the basis of spectroscopic data including 1D and 2D NMR and ESI HR-FTMS. The in vivo antioxidant activity using the oxygen radical absorbance capacity (ORAC) method, of the extract, its column fractions and two of the isolated ellagitannins was accomplished. In addition, a possible cytotoxicity of the extract and two of the new ellagitannins on HaCaT human keratinocytes and the activity of both compounds against the prostate cancer cell line (PC-3) were also assessed, whereby a potent cytotoxicity with IC50 less than 1 µg/ml was determined for both compounds. Besides, the extract exhibited a potential cytotoxic effect against four different solid tumor cell lines, namely liver (Huh-7), colorectal (HCT-116), breast (MCF-7) and prostate (PC-3). The IC50s were found to be substantially low (ranged from 1.3±0.15 to 2.4±0.22 µg/ml) with relatively low resistance possibility reaching to 0% in the case of Huh-7 cell.

Constitutive phenolics of Harpephyllum caffrum (Anacardiaceae) and their biological effects on human keratinocytes.

Assessment of the UV protecting potential of an aqueous methanol leaf extract of Harpephyllum caffrum proved that it possesses a distinct radical scavenging effect and inhibits the production of the proinflammatory cytokine IL-6 by human keratinocytes (HaCaT cells) following UV radiation. Phytochemical investigation of this extract led to isolation and structural determination of the hitherto unknown phenolics, kaempferol 3-O-(2″-sulphatogalactopyranoside), its quercetin analogue and 3-methoxyellagic acid 4-O-galactopyranoside in addition to 18 known phenolic compounds. The structures were determined by spectroscopic and conventional methods of analysis. Flavonoid sulphatoglycosides which have been rarely found in nature were major phenolic constituents of this plant, and this is the first report of the isolation of any of them from Anacardiaceae. The extract was found to diminish UV phototoxic reaction of keratinocytes. However, the isolated kaempferol sulphatogalactopyranoside did not interact with UVB triggered IL-6 production of HaCaT keratinocytes.

Deuteromycols A and B, two benzofuranoids from a Red Sea marine-derived Deuteromycete sp.

Two benzofuranoids, deuteromycol A, 6,7-dihydroxy-2-[1'-hydroxy-(1'→5″)-2″,3″,4″-trihydroxy-2″,3″-dihydropyran]benzofuran and deuteromycol B, 1-(6,7-dihydroxy benzofuran-2-yl)methyl acetate have been isolated from the ethanol extract of the marine-derived fungal strain MF 003 (Deuteromycete) obtained from Red Sea mangrove drift wood. Deuteromycols A and B contain a catecholic nucleus that to the best of our knowledge is unusual in association with marine fungi secondary metabolites. Structures were established on the basis of extensive 1D-and 2D-NMR spectroscopic studies as well as on mass spectrometric analysis. Besides, the extracts exhibited in vitro antibacterial activity.