Nutritional, Antioxidant, Antimicrobial, and Anticholinesterase Properties of Phyllanthus emblica: A Study Supported by Spectroscopic and Computational Investigations.

Dietary fruits and vegetables play a vital role as food and drugs and are the main sources of antioxidant defences against degenerative diseases, such as brain dysfunctions, cardiovascular diseases, immune system deteriorations, and cancers, brought on by oxidative damage. Phyllanthus emblica is a significant herbal remedy used in conventional medicine to recover lost strength and power. In this research, the potential value of Phyllanthus emblica as a food and drug is researched. The total phenolic, total flavonoid, and total tannin contents as well as the nutritional value, vitamin C, vitamin E, and mineral contents of different organs of P. emblica were evaluated. The antioxidant and antimicrobial activities of extracts and fractions of different organs of P. emblica were determined. A total of eleven flavonoids, simple phenolic, tannin-related phenolic, and tannin molecules were isolated from a hydroalcoholic extract of the leaves and fruits. The structures were identified by spectroscopic data and comparison with the literature values as gallic acid (1), naringenin 7-O-(6″-O-galloyl)-ß-D-glucopyranoside (2), 3,3'-di-O-methyl ellagic acid-4'-O-ß-d-glucopyranoside (3), 1-O-galloyl glycerol (4), 1,6-di-O-galloyl-ß-d-glucopyranoside (5), flavogallonic acid bislactone (6), corilagin (7), ethyl gallate (8), urolithin M5 (9), (E)-p-coumaroyl-1-O-ß-d-glucopyranoside (10), and 1,2,4,6-tetra-O-galloyl-ß-d-glucopyranoside (11). Among them, compounds 3 and 10 are first isolated from the plant. Molecular docking was performed to investigate the comparative interactions between positive controls (galantamine and donepezil) and selected compounds utilizing acetylcholinesterase (4EY7) as a target receptor. Results exhibited the potency of these compounds against the target receptor. In summary, P. emblica has a wealth of minerals, vitamins C and E, and polyphenolic phytochemicals that may work together to treat infectious disease, prevent and/or treat oxidative-damage-related illnesses including Alzheimer's disease.

Green Biosynthesis of Silver Nanoparticles Using Annona glabra and Annona squamosa Extracts with Antimicrobial, Anticancer, Apoptosis Potentials, Assisted by In Silico Modeling, and Metabolic Profiling.

Annona glabra L. (AngTE) and Annona squamosa L. (AnsTE) fruits have been widely used in cancer treatment. Accordingly, their extracts were used to synthesize silver nanoparticles via a biogenic route (Ang-AgNPs) and (Ans-AgNPs), respectively. Chemical profiling was established using UPLC-QTOF-MS/MS. All species were tested for anticancer activity against human cervical cancer cells (HeLa), prostate adenocarcinoma metastatic (PC3), and ovary adenocarcinoma (SKOV3) using sulphorhodamine B assay. Apoptosis was determined using Annexin flow cytometry along with cell cycle analysis and supported by a molecular docking. The antibacterial and synergistic effect when combined with gentamicin were evaluated. A total of 114 compounds were tentatively identified, mainly acetogenins and ent-kaurane diterpenes. AnsTE and Ans-AgNPs had the most potent cytotoxicity on HeLa and SKOV3 cells, inducing a significant apoptotic effect against all tumor cells. The AnsTE and Ans-AgNPs significantly arrested PC3, SKOV3, and HeLa cells in the S phase. The nanoparticles demonstrated greater antibacterial and antifungal activities, as well as a synergistic effect with gentamicin against P. aeruginosa and E. coli. Finally, a molecular docking was attempted to investigate the binding mode of the identified compounds in Bcl-2 proteins' receptor, implying that the fruits and their nanoparticles are excellent candidates for treating skin infections in patients with ovarian or prostatic cancer.

Garcinia cambogia Phenolics as Potent Anti-COVID-19 Agents: Phytochemical Profiling, Biological Activities, and Molecular Docking.

COVID-19 is a disease caused by the coronavirus SARS-CoV-2 and became a pandemic in a critically short time. Phenolic secondary metabolites attracted much attention from the pharmaceutical industries for their easily accessible natural sources and proven antiviral activity. In our mission, a metabolomics study of the Garcinia cambogia Roxb. fruit rind was performed using LC-HRESIMS to investigate its chemical profile, especially the polar aspects, followed by a detailed phytochemical analysis, which led to the isolation of eight known compounds. Using spectrometric techniques, the isolated compounds were identified as quercetin, amentoflavone, vitexin, rutin, naringin, catechin, p-coumaric, and gallic acids. The antiviral activities of the isolated compounds were investigated using two assays; the 3CL-Mpro enzyme showed that naringin had a potent effect with IC50 16.62 µg/mL, followed by catechin and gallic acid (IC50 26.2, 30.35 µg/mL, respectively), while the direct antiviral inhibition effect of naringin confirmed the potency with an EC50 of 0.0169 µM. To show the molecular interaction, in situ molecular docking was carried out using a COVID-19 protease enzyme. Both biological effects and docking studies showed the hydrophobic interactions with Gln 189 or Glu 166, per the predicated binding pose of the isolated naringin.

Isolation, Structure Elucidation and Antimicrobial Evaluation of Natural Pentacyclic Triterpenoids and Phytochemical Investigation of Different Fractions of Ziziphus spina-christi (L.) Stem Bark Using LCHRMS Analysis.

Ziziphus spina-christi L. (ZSC-L) is a tree with thorny branches, belongs to the family Rhamnaceae and grows in the sub-tropics. The purpose of this research is to isolate and partially purify bioactive components from the crude ethanol extract of the stem bark of ZSC-L. Besides, bioassay-guided fractionation of ZSC-L stem bark was conducted using different solvents. The solvents were reutilized to minimize the production cost and environmental harm. In addition, the antimicrobial activities of the fractions were analyzed, followed by metabolic profiling using LC-HRMS. The n-butanol fraction showed the highest antimicrobial efficacy, so it was subjected to further purification. For the first time, two major compounds were isolated from the stem bark of ZSC-L and identified as lupane-type pentacyclic triterpenoids betulinic acid and betulin. Both compounds were used as antibacterial and anticancer agents and considered as a green product as the extraction procedure reduced the use of hazardous chemicals. Metabolic characterization of ZSC-L and its bioactive fractions were performed using LC-HR-ESI-MS and the results revealed the dereplication of 36 compounds belonging to different chemical classes. Flavonoids and triterpenes were the most prominent metabolite classes in the different fractions. The molecular docking results were obtained by studying the interaction of betulin and betulinic acid with antimicrobial receptors (4UYM, 1IYL, 1AJ2, 6J7L, 1AD4, 2VEG) to support the in vitro results. Our study highlights that Ziziphus spina-christi and its phytoconstituents, especially triterpenoids, act as a promising antimicrobial candidate in pharmaceutical and clinical applications.

Quality Control, Anti-Hyperglycemic, and Anti-Inflammatory Assessment of Colvillea racemosa Leaves Using In Vitro, In Vivo Investigations and Its Correlation with the Phytoconstituents Identified via LC-QTOF-MS and MS/MS.

Colvillea racemosa is a cultivated ornamental plant that is a monotypic genus of Fabaceae. It is native to Madagascar, with limited studies. For the first time, the leaf quality control parameters, the anti-hyperglycemic and anti-inflammatory in vitro activity of Colvillea racemosa ethanol extract (CRE) and its fractions of petroleum ether (CRP), methylene chloride (CRMC), ethyl acetate (CREA), n-butanol (CRB), and methanol (CRME) were evaluated. It exhibited significant inhibition against α-amylase, α-glucosidase and membrane stabilization. CRB was the most active fraction, and in vivo studies revealed that oral treatment with CRB of STZ-induced diabetic rats efficiently lowered blood glucose by 67.78%, reduced serum nitric oxide and lipid peroxide levels by 41.23% and 38.45%, respectively, and increased the GSH level by 90.48%. In addition, compared with the diabetic group, there was a 52.2% decrease in serum VCAM, a 55.5% increase in paraoxonase, an improved lipid profile, and improved liver and kidney functions for a treated diabetic group with CRB. Metabolite profiling of CRB was determined by UPLC-ESI-QTOF-MS and tandem MS/MS. Twenty-three chromatographic peaks were identified, which were classified into phenolic compounds and amino acids. The characterized flavonoids were apigenin and luteolin derivatives.

Four new phenolics and antiparasitic secondary metabolites from Flacourtia rukam Zoll. & Mortizi.

Phytochemical investigation of Flacourtia rukam Zoll. & Mortizi (F. rukam) leaves and bark led to the isolation and characterization of seventeen compounds of which four phenolics were not previously described; 2-[(benzoyloxy)methyl]-phenyl-O-ß-xylosyl-(1→2)-ß-glucopyranoside (1), 2-[(benzoyloxy)methyl]-4-hydroxyphenyl-O-ß-xylosyl-(1→2)-ß-D-glucopyranoside (2), 2-hydroxy-5-(2-hydroxyphenoxy)phenoxy-ß-glucopyranoside (3) and biphenyl-1,1',2,2'-tetraol (5). Interestingly, the later compound is known as a synthetic but this is the first report for its isolation from nature. Chemical structures were established using extensive analysis of spectroscopic data (1 D and 2 D NMR and HRESIMS). Biphenyl-1,1,2,2'-tetrol (5) exhibited a good activity against Trypanosoma brucei trypomastigotes with IC50= 6.66 ug/mL. Compounds 2, 5, 9, 10, 11 and 12 showed a good in-vitro anti-inflammatory activity using proteinase inhibitory assay. On the contrary, all tested compounds were inactive as antileishmanial or antimalarial.

Wound Healing Metabolites from Peters' Elephant-Nose Fish Oil: An In Vivo Investigation Supported by In Vitro and In Silico Studies.

Gnathonemuspetersii (F. Mormyridae) commonly known as Peters' elephant-nose fish is a freshwater elephant fish native to West and Central African rivers. The present research aimed at metabolic profiling of its derived crude oil via GC-MS analysis. In addition, wound healing aptitude in adult male New Zealand Dutch strain albino rabbits along with isolated bioactive compounds in comparison with a commercial product (Mebo®). The molecular mechanism was studied through a number of in vitro investigations, i.e., radical scavenging and inhibition of COX enzymes, in addition to in silico molecular docking study. The results revealed a total of 35 identified (71.11%) compounds in the fish oil, belonging to fatty acids (59.57%), sterols (6.11%), and alkanes (5.43%). Phytochemical investigation of the crude oil afforded isolation of six compounds 1-6. Moreover, the crude oil showed significant in vitro hydrogen peroxide and superoxide radical scavenging activities. Furthermore, the crude oil along with one of its major components (compound 4) exhibited selective inhibitory activity towards COX-2 with IC50 values of 15.27 and 2.41 µM, respectively. Topical application of the crude oil on excision wounds showed a significant (p < 0.05) increase in the wound healing rate in comparison to the untreated and Mebo®-treated groups, where fish oil increased the TGF-ß1 expression, down-regulated TNF-α, and IL-1ß. Accordingly, Peters' elephant-nose fish oil may be a potential alternative medication helping wound healing owing to its antioxidant and anti-inflammatory activities.

Correction: Triple-negative breast cancer suppressive activities, antioxidants and pharmacophore model of new acylated rhamnopyranoses from Premna odorata.

[This corrects the article DOI: 10.1039/D0RA01697G.].

Anti-Inflammatory and Antioxidant Activities of Terpene- and Polyphenol-Rich Premna odorata Leaves on Alcohol-Inflamed Female Wistar Albino Rat Liver.

Premna odorata Blanco (Lamiaceae) is an ethnomedicinal plant native to different tropical regions. Although some reports addressed their anti-inflammatory, cytotoxic, and antituberculotic effects, their hepatoprotective potential is yet to be discovered. Accordingly, this study investigated the crude extract and different fractions of the plant leaves; metabolic profiling using liquid chromatography/high-resolution electrospray ionization mass spectroscopy (LC-HRESIMS) analysis, in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties for the dereplicated metabolite via online PreADMET program, ROS scavenger activity on the Hep G2 human liver cancer cell line, and the possible hepatic cellular treatment effects in alcohol-inflamed liver female Wistar albino rats. Metabolic profiling dereplicated a total of 28 metabolites from the crude extract and its various fractions. In silico ADMET and ROS scavenger activity screening suggested plant metabolites are of potential bioactivity. In vivo hepatic treatment with crude, defatted crude, and n-hexane leave extracts suggested all extracts significantly improved liver damage, which was indicated by the reduction of elevated serum levels of bilirubin, AST, ALT, ALP, CRP, TNF-α, ICAM-1, VCAM-1, and MDA. The reduced levels of GSH and TAC were normalized during the study. Histological examinations of liver tissue showed collagen fiber distribution nearly back to its normal pattern. The anti-inflammatory and antioxidant potentials of Premna odorata extracts could be partly related to the combined effects of these phytochemicals or their synergistic interactions.

Bioassay-Guided Isolation, Metabolic Profiling, and Docking Studies of Hyaluronidase Inhibitors from Ravenala madagascariensis.

Hyaluronidase enzyme (HAase) has a role in the dissolution or disintegration of hyaluronic acid (HA) and in maintaining the heathy state of skin. Bioassay-guided fractionation of Ravenala madagascariensis (Sonn.) organ extracts (leaf, flower, stem, and root) testing for hyaluronidase inhibition was performed followed by metabolic profiling using LC-HRMS. Additionally, a hyaluronidase docking study was achieved using Molecular Operating Environment (MOE). Results showed that the crude hydroalcoholic (70% EtOH) extract of the leaves as well as its n-butanol (n-BuOH) partition showed higher HAase activity with 64.3% inhibition. Metabolic analysis of R. madagascariensis resulted in the identification of 19 phenolic compounds ranging from different chemical classes (flavone glycosides, flavonol glycosides, and flavanol aglycones). Bioassay-guided purification of the leaf n-BuOH partition led to the isolation of seven compounds that were identified as narcissin, rutin, epiafzelechin, epicatechin, isorhamnetin 7-O-glucoside, kaempferol, and isorhamnetin-7-O-rutinoside. The docking study showed that narcissin, rutin, and quercetin 3-O-glucoside all interact with HAase through hydrogen bonding with the Asp111, Gln271, and/or Glu113 residues. Our results highlight Ravenala madagascariensis and its flavonoids as promising hyaluronidase inhibitors in natural cosmetology preparations for skin care.

Triple-negative breast cancer suppressive activities, antioxidants and pharmacophore model of new acylated rhamnopyranoses from Premna odorata.

Phytochemical investigation of Premna odorata Blanco "Lamiaceae" young stems afforded four new acylated rhamnopyranoses 1-4, along with fourteen known compounds 5-19. The structures of the new compounds were confirmed using extensive 1D, 2D NMR, and HRESIMS analysis. The isolated compounds were tested for their cell proliferation and migration inhibition activities against the invasive human triple-negative breast cancer cells MDA-MB-231 and MCF-7, and the normal human breast cell line MCF-10A. In addition, free radical scavenging activities using 2,2'-diphenyl-1-picrylhydrazyl (DPPH) were studied. Compound 1 was the most active as an antiproliferative agent, showing a high to moderate antiproliferative effect with an IC50 value of 4.95 and 17.7 µM against MCF-7 and MDA-MB-231, respectively. The antiproliferative activities of compounds 1-5 against the normal breast cell line MCF-10A were moderate to low with IC50 values of 13.91 to 27.70 µM. On the other hand, compounds 1 and 10 suppressed MDA-MB-231 cell migration in the wound-healing assay at 10 µM concentration. Meanwhile, compounds 1-5 exhibited the highest value of DPPH radical scavenging activities with an IC50 value range of 17.5-20.43 ± 0.5 µg mL-1. The pharmacophore model generated using Molecular Operating Environment (MOE) for compounds 1-5 showed three hydrogen bond acceptors (HBAs), one hydrogen bond donor (HBD), one aromatic ring (Aro), and one hydrophobic (Hyd.) group. The central HBA feature lies at a distance of 4.36 Å and 6.38 Å from the remaining two HBA features. Also, the HBD feature maintains a distance of 2.74 Å from the aromatic feature. Acylated rhamnopyranoses can be considered good scaffolds for developing new anti-breast cancer and antioxidant compounds.

Zingiber officinale extract and omega-3 fatty acids ameliorate endoplasmic reticulum stress in a nonalcoholic fatty liver rat model.

Endoplasmic reticulum (ER) stress was reported to play a major role in non-alcoholic fatty liver disease (NAFLD) induction and progression. Here, we study the effect of Zingiber officinale and omega-3 fatty acids on ER stress for treating NAFLD. Male Wistar rats were fed on a normal diet (control group) or high-fat diet (HFD) for 8 weeks. The HFD rats were later treated with vehicle, omega-3 or with Z. officinale extract. HFD group demonstrated significantly more body weight gain and higher plasma lipid profile, glucose, and hepatic enzymes. The expressions of lipogenic ChREBP and ER stress genes CHOP, XBP1, and GRP78 were increased. This was accompanied by intrahepatic fat accumulation visualized by hepatic morphology and H&E-stained sections. Treatment with Z. officinale and omega-3 fatty acids reverted these changes into a normal healthy state. From these results, we prove that both therapeutic approaches can be potential drugs for treating NAFLD besides other ER stress-associated diseases. PRACTICAL APPLICATIONS: The effect of Zingiber officinale extract and omega-3 fatty acid on ER stress associated with NAFLD was investigated. The results revealed that Z. officinale extract and omega-3 fatty acids significantly inhibited ER stress and intrahepatic fat accumulation with the upper hand for Z. officinale extract. Both can be used as future promising therapies for the treatment of NAFLD patients and also treating different diseases that involve ER stress as a pathological modulator like diabetes mellitus, Alzheimer's disease, Parkinson's disease, and cancer.

Acylated Iridoids and Rhamnopyranoses from Premna odorata (Lamiaceae) as Novel Mesenchymal-Epithelial Transition Factor Receptor Inhibitors for the Control of Breast Cancer.

Phytochemical investigation of Premna odorata Blanco, Lamiaceae, leaves afforded three new acylated iridoid glycosides 1-3 and two new acylated rhamnopyranoses 9 and 10, in addition to ten known compounds. The structures of the new compounds were confirmed using extensive 1D and 2D NMR analysis. Molecular modeling study suggested the potential of the acylated rhamnopyranoses to bind at the c-Met kinase domain. Cell-free Z'-LYTE™ assay testing revealed the good c-Met phosphorylation inhibitory activity of 9, followed by 8, and 10, with IC50 values of 2.5, 6.9, and 12.7 µM, respectively. The (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay testing against the human c-Met expressing highly invasive MDA-MB-231 suggested compound 9 as the most active with IC50 value of 13.3 µM. Testing of compound 9 against multiple phenotypic breast cancer cell lines including MCF-7, BT-474 cells, and MDA-MB-468 proved enhanced activity against the highly c-Met expressing triple-negative breast cancer cell lines. Acylated rhamnopyranoses are potential novel c-Met inhibitors appropriate for future optimizations to control c-Met-dependent breast malignancies. Copyright © 2017 John Wiley & Sons, Ltd.

The fatty acid-rich fraction of Eruca sativa (rocket salad) leaf extract exerts antidiabetic effects in cultured skeletal muscle, adipocytes and liver cells.

CONTEXT: Eruca sativa Mill. (Brassicaceae), commonly known as rocket salad, is a popular leafy-green vegetable with many health benefits. OBJECTIVE: To evaluate the antidiabetic activities of this plant in major insulin-responsive tissues. MATERIALS AND METHODS: Five E. sativa leaf extracts of varying polarity were prepared (aqueous extract, 70% and 95% ethanol extracts, the n-hexane-soluble fraction of the 95% ethanol extract (ES3) and the defatted 95% ethanol extract). Eruca sativa extracts were investigated through a variety of cell-based in vitro bioassays for antidiabetic activities in C2C12 skeletal muscle cells, H4IIE hepatocytes and 3T3-L1 adipocytes. Guided by the results of these bioassays, ES3 was fractionated into the saponifiable (SM) and the unspaonifiable (USM) fractions. Glucose uptake was measured using [3H]-deoxy-glucose, while the effects on hepatic glucose-6-phosphatase (G6Pase) and adipogenesis were assessed using Wako AutoKit Glucose and AdipoRed assays, respectively. RESULTS: ES3 and its SM fraction significantly stimulated glucose uptake with EC50 values of 8.0 and 5.8 µg/mL, respectively. Both extracts significantly inhibited G6Pase activity (IC50 values of 4.8 and 9.3 µg/mL, respectively). Moreover, ES3 and SM showed significant adipogenic activities with EC50 of 4.3 and 6.1 µg/mL, respectively. Fatty acid content of SM was identified by GC-MS. trans-Vaccenic and palmitoleic acids were the major unsaturated fatty acids, while palmitic and azelaic acids were the main saturated fatty acids. DISCUSSION AND CONCLUSION: These findings indicate that ES3 and its fatty acid-rich fraction exhibit antidiabetic activities in insulin-responsive cell lines and may hence prove useful for the treatment of type 2 diabetes.

Effect of 6-gingerol on AMPK- NF-κB axis in high fat diet fed rats.

OBJECTIVES: Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in metabolic homeostasis and regulation of inflammatory responses through attenuation of nuclear factor kappa-B (NF-κB), Thus AMPK may be a promising pharmacologic target for the treatment of various chronic inflammatory diseases. We examined the effect of 6-gingerol, an active ingredient of ginger on AMPK-NF-κB pathway in high fat diet (HFD) rats in comparison to fish oil. METHODS: Protein levels of AMPK-α1 and phosphorylated AMPK-α1 were measured by western blot while Sirtuin 6 (Sirt-6), resistin and P65 were estimated by RT-PCR, TNF-α was determined by ELISA, FFAs were estimated chemically as well as the enzymatic determination of the metabolic parameters. RESULTS: 6-Gingerol substantially enhanced phosphorylated AMPK-α1 more than fish oil and reduced the P65 via upregulation of Sirt-6 and downregulation of resistin, and resulted in attenuation of the inflammatory molecules P65, FFAs and TNF-α more than fish oil treated groups but in an insignificant statistical manner, those effects were accompanied by a substantial hypoglycemic effect. CONCLUSION: Gingerol treatment effectively modulated the state of inflammatory privilege in HFD group and the metabolic disorders via targeting the AMPK-NF-κB pathway, through an increment in the SIRT-6 and substantial decrement in resistin levels.

INVESTIGATION OF AMOEBICIDAL POTENTIAL OF ARACHIS HYPOGAEA L. PERICARP ON CYSTS OF ACANTHAMOEBA ASTRONYXIS T7 GENOTYPE.

Acanthamoeba is an opportunistic pathogen cauAing keratitis and fatal encephalitis. Early diagnosis, followed by intense treatment using a drugs mixture is a necessity for effective therapy. Many natural compounds have proved lethal effects, yet the search for original natural amebicidal agents is still of current concern. This study investigated the acanthamoebicidal effect of A. hypogaea L. pericarp; total ethanol extract and its successive fractions, n-hexane, dichloro-methane, ethyl acetate, and methanol as well as resveratrol. Acanthamoebae were isolated and cultivated on E. coli seeded non-nutrient agar, genotyped, and the in vitro acanthamoebicidal potentials of different concentrations of A. hypogaea L. pericarp; total extract ethanol and its successive fractions and resveratrol compound was investgated on cysts of A. astronyxis T7 genotype. The results showed variable degrees of lethal potentials were obtained by all examined A. hypogaea L. pericarp ethanol extract and its successive fractions, with the highest mean of non-viable cysts on the first and the second days. bf the study by total ethanol extract followed by the methanol fraction . On the third day of the study n-hexane and ethyl acetate gave the highest mean of non-viable cysts. Resveratrol showed the lowest mean of non-viable cysts count all through the study duration. Significantly higher difference was observed between all examined A. hypogaea L. pericarp extract and fractions and chlorohexidine, except for resveratrol compound the difference was found to be noinsignificant.

Bioactive Formylated Flavonoids from Eugenia rigida: Isolation, Synthesis, and X-ray Crystallography.

Two new flavonoids, rac-6-formyl-5,7-dihydroxyflavanone (1) and 2',6'-dihydroxy-4'-methoxy-3'-methylchalcone (2), together with five known derivatives, rac-8-formyl-5,7-dihydroxyflavanone (3), 4',6'-dihydroxy-2'-methoxy-3'-methyldihydrochalcone (4), rac-7-hydroxy-5-methoxy-6-methylflavanone (5), 3'-formyl-2',4',6'-trihydroxy-5'-methyldihydrochalcone (6), and 3'-formyl-2',4',6'-trihydroxydihydrochalcone (7), were isolated from the leaves of Eugenia rigida. The individual (S)- and (R)-enantiomers of 1 and 3, together with the corresponding formylated flavones 8 (6-formyl-5,7-dihydroxyflavone) and 9 (8-formyl-5,7-dihydroxyflavone), as well as 2',4',6'-trihydroxychalcone (10), 3'-formyl-2',4',6'-trihydroxychalcone (11), and the corresponding 3'-formyl-2',4',6'-trihydroxydihydrochalcone (7) and 2',4',6'-trihydroxydihydrochalcone (12), were synthesized. The structures of the isolated and synthetic compounds were established via NMR, HRESIMS, and electronic circular dichroism data. In addition, the structures of 3, 5, and 8 were confirmed by single-crystal X-ray diffraction crystallography. The isolated and synthetic flavonoids were evaluated for their antimicrobial and cytotoxic activities against a panel of microorganisms and solid tumor cell lines.

Comparative DNA profiling, phytochemical investigation, and biological evaluation of two Ficus species growing in Egypt.

AIM AND BACKGROUND: A comparison between two Ficus species, cultivated in Egypt, was carried out in this study. Their DNA analysis revealed that they are not closely related. MATERIALS AND METHODS: The pharmacopoeial constants of the leaves showed higher total ash and acid insoluble ash in F. lyrata than in F. platypoda. The other parameters were close in both species. Preliminary phytochemical screening revealed the presence of carbohydrate and/or glycosides, tannins, flavonoids, sterols, and triterpenes in their leaves and was detected in traces in their stems. RESULTS: Saponification of n-hexane extract of the leaves yielded 46% and 74.8% for the unsaponifiable matters and 20% and 15% for the fatty acids for F. platypoda and F. lyrata, respectively. n-Docosane (21.69%) and n-heptacosane (33.77%) were the major hydrocarbons in F. platypoda and F. lyrata, respectively. b-Sitosterol was the main sterol, palmitic (22.07%) and carboceric (35.72%) acids were the major identified saturated fatty acids in both species, while linoleic acid was the main unsaturated fatty acid (18.66% and 16.7%) in both species, respectively. The acute toxicity study revealed that the two species were safe up to 2 g/kg. The antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and pyrogallol as the standard was more significant for F. platypoda (232.6 µg/ml) than for F. lyrata, (790.9 µg/ml). The oral antihyperglycemic activity in diabetic rats using alloxan revealed that the 80% ethanolic extract of the leaves of F. platypoda was more active than that of the leaves of F. lyrata in decreasing the blood glucose level at 200 mg/kg/day (107.9 ± 5.817, 127.2 ± 4.359) and 400 mg/kg/day (64.11 ± 4.358, 127.7 ± 6.889), respectively, when compared with the diabetic control gliclazide (172.3 ± 2.089). CONCLUSION: The results of this study provide evidence that the two Ficus species have antioxidant and antihyperglycemic activity, in the order F. platypoda and then F. lyrata.

Preparation and application of reversed phase Chromatorotor for the isolation of natural products by centrifugal preparative chromatography.

A method of preparation of rotors with a reversed phase (RP) solid silica gel sorbent layer has been developed for centrifugal preparative chromatography (CPC), also known as rotational planar chromatography (RPC). The rotors consist of binder free RP solid SiO2 layers of different thicknesses packed between two supported circular glass discs and can be used in any appropriate device for centrifugal chromatography, like Chromatotron and CycloGraph. Polar and /or semi-polar compounds with close R(f) values, as well as extracts and column fractions were separated and/or purified in a preparative and/or semi-preparative scale using the RP rotors, eluted with mixtures of aqueous-based solvents. We herein report three examples of its application, using RP Chromatorotors, for the isolation of the diastereoisomeric alkaloids banistenosides I and II from Banisteriopsis caapi, saponins III and IV from Fagonia cretica, and the sesquiterpenes artemisinin (V) and artemisinic acid (VI) from Artemisia annua.

Cytotoxicity and modulation of cancer-related signaling by (Z)- and (E)-3,4,3',5'-tetramethoxystilbene isolated from Eugenia rigida.

Bioassay-guided fractionation of the leaves of Eugenia rigida yielded three stilbenes, (Z)-3,4,3',5'-tetramethoxystilbene (1), (E)-3,4,3',5'-tetramethoxystilbene (2), and (E)-3,5,4'-trimethoxystilbene (3). Their structures were determined using 1D- and 2D-NMR spectroscopy and HRESIMS. The sterically hindered Z-stereoisomer 1, a new natural product, was prepared by time-dependent photoisomerization of the E-isomer (2) under UV irradiation at λ254 nm, while 2,3,5,7-tetramethoxyphenanthrene (5) was identified at λ365 nm by UHPLC/APCI-MS and NMR spectroscopy. Compounds 1-3 were tested against a panel of luciferase reporter gene assays that assess the activity of many cancer-related signaling pathways, and the Z-isomer (1) was found to be more potent than the E-isomer (2) in inhibiting the activation of Stat3, Smad3/4, myc, Ets, Notch, and Wnt signaling, with IC50 values between 40 and 80 µM. However, both compounds showed similar inhibition against Ap-1 and NF-κB signaling. In addition, 1 demonstrated cytotoxic activity toward human leukemia cells, solid tumor cells of epidermal, breast, and cervical carcinomas, and skin melanoma, with IC50 values between 3.6 and 4.3 µM, while 2 was weakly active against leukemia, cervical carcinoma, and skin melanoma cells. Interestingly, 2 showed antioxidant activity by inhibition of ROS generation to 50% at 33.3 µM in PMA-induced HL-60 cells, while 1 was inactive at 100 µM (vs Trolox 1.4 µM).