Phytoactive Molecules and Nanodelivery Approaches for Breast Cancer Treatment: Current and Future Perspectives.

One of the most common malignancies in women, breast cancer accounts for nearly 25% of all cancer cases. Breast cancer is a diverse cancer form that exhibits variability in both morphology and molecular characteristics, and is linked to numerous risk factors. Although various approaches and research are ongoing in the treatment and prevention of breast cancer, medication resistance in the current breast cancer treatment contributes to the disease's relapse and recurrence. Phytoactive molecules are the subject of growing research in both breast cancer prevention and treatment but currently used conventional medicines and techniques limit their application. Recent years have seen significant advancements in the field of nanotechnology, which has proven to be essential in the fight against drug resistance. The transport of synthetic and natural anticancer molecules via nanocarriers has recently been added to breast cancer therapy, greatly alleviating the constraints of the current approach. In light of these developments, interest in nano-delivery studies of phytoactive molecules has also increased. In this review, research of phytoactive molecules for breast cancers along with their clinical studies and nanoformulations, was presented from current and future perspectives.

Nanodelivery Approaches of Phytoactives for Skin Cancers: Current and Future Perspectives.

In recent years, there has been an increase in skin cancers due to external factors, especially environmental factors, and studies on treatment alternatives have gained importance. Nanomaterials are common, from sunscreen formulas to formulations designed to treat skin cancers at various stages. Using bioactives has multiple effects in treating skin cancers, which provides many advantages. In this regard, many phytochemicals gain importance with their antioxidant, anti-proliferative, anti-inflammatory, antiangiogenic, and analgesic effects. Their delivery with nanocarriers is on the agenda for phytochemicals to gain the targeted stability, effectiveness, and toxicity/safety properties. This review presents types of skin cancers, phytochemicals effective in skin cancers, and their nanocarrier-loaded studies from an up-to-date perspective.

Significance of the Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Preoperative Nutritional Index as Predictors of Morbidity in Patients Who Underwent Liver Resection for Alveolar Echinococcosis.

AIM: We aimed to evaluate the significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and preoperative nutritional index (PNI) as predictors of morbidity in patients who underwent liver resection for alveolar echinococcosis. MATERIAL AND METHODS: This single-center study was designed as a retrospective study after obtaining ethical committee approval. The files of patients hospitalized at Ataturk University Faculty of Medicine, Erzurum, Turkey, between 2010 and 2019 and who underwent resection or liver transplantation for liver alveolar cysts were reviewed. Demographic features, laboratory parameters (complete blood count and biochemical parameters), lesion localizations and characteristics, type of surgery, intraoperative and postoperative complications (morbidity), and mortality status were evaluated by scanning patients' files. Preoperative blood samples were taken the day before the surgery, which is the period farthest from surgical stress, to have more accurate results. By contrast, postoperative blood samples were taken on the first postoperative day when surgical stress was the highest. The differences between the morbidity groups, including NLR, PLR, and PNI, were compared. RESULTS: Of the 172 patients in the study, 96 (55.8%) were female. The mean age of all patients was 48.51±15.57 (18-90). Perioperative complications were seen in 30 (17.4%) patients, while the morbidity and mortality rates of the study were 28.5% and 19.2%, respectively. Age, gender of patients, and preoperative laboratory parameters, including NLR, PLR, and PNI, did not affect morbidity. However, the presence of perioperative vascular injury (P=0.040) and complications (P=0.047), low postoperative lymphocyte rates (P=0.038), and high postoperative NLR were associated with increased morbidity. In addition, the mortality rate was significantly increased in patients with morbidity (P<0.001). CONCLUSION: From the results of the present study, it was found that preoperative parameters did not affect morbidity, while increased postoperative NLR levels and decreased lymphocyte rates increased morbidity.

Can neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, prognostic nutrition index, and albumin be used to predict cholecystectomy morbidity in super-elderly patients?

BACKGROUND: This study aimed to evaluate the usability of neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), prognostic nutritional index (PNI), and serum albumin level in predicting cholecystectomy morbidity in elderly patients (85 years and older) who underwent cholecystectomy for acute cholecystitis. METHODS: This retrospective study included super-elderly patients who underwent cholecystectomy due to acute cholecystitis at a tertiary health centre between January 2010 and January 2021. The patients were divided into two groups according to the presence of postoperative complications (morbidity). The differences between the two groups were evaluated. In addition, the role of NLR, PLR, PNI, and serum albumin level in predicting cholecystectomy morbidity for acute cholecystitis in super-elderly patients was assessed via ROC analysis. RESULTS: Of 30 patients who met the study criteria, 22 (73.3%) were female, and the mean age of all patients was 87.43±2.66 years (range 85-94 years). 7 (23.3%) patients had at least one comorbid disease during the preoperative period. The mean value of NLR, PLR, albumin, and PNI were 8.31, 153.76, 3.45, and 48.37, respectively. The morbidity rate of the study was 23.3%. The area under the curve (AUC) for NLR was 0.466 ([95% confidence interval [CI]: 0.259-0.672]; P=0.787), and the AUC for PLR was 0.429 ([95% CI: 0.201-0.656]; P=0.573). These two factors were not suitable for predicting morbidity. The AUC for PNI was 0.780 ([95% CI: 0.568-0.991]; P=0.027), and the AUC for albumin was 0.894 ([95% CI: 0.770-1.000]; P=0.002). At the cut-off value of 3.05 g/dL, the sensitivity and specificity of albumin were 91.3% and 71.4%, respectively, while the sensitivity and specificity of PNI at the 41.70 cut-off value were 82.6% and 71.4%, respectively. CONCLUSION: This study found that PNI and albumin can be used as predictive factors with high sensitivity and specificity for predicting cholecystectomy morbidity for acute cholecystitis in super-elderly patients. However, NLR and PLR had no significance in predicting cholecystectomy morbidity.

Comments on "Sigmoid volvulus management, only endoscopic devolvulation?"

We read the paper written by Garcia-Calonge et al. presenting a patient with Lewy body dementia and recurrent sigmoid volvulus (SV) treated with emergency surgery due to gangrenous bowel. Our clinic has 1,063-case experience with SV over 56,5-year period between June 1966 and January 2023, which data signifies the largest monocenter SV series over the world. In the light of this experience, our comments relate to neuropsychiatric diseases-SV comorbidity, endoscopic decompression, and recurrence of SV.

How has the COVID-19 pandemic changed the diagnosis of rectus sheath hematoma and its follow-up?

BACKGROUND: There has been an increased incidence of rectus sheath hematoma (RSH) due to chronic cough attacks and anti-coagulant therapy due to the COVID-19 pandemic. The present study aims to determine, in which parameters differ before and during the diagnosis of RSH in COVID-19 patients and what may be expected during diagnosis and follow-up. METHODS: Thirty-five patients diagnosed with RSH were evaluated retrospectively between March 2016 and March 2021. The COVID-19 group comprised 11 patients. Various information including patient history and time of discharge/death were retrieved and compared between the experimental groups. RESULTS: The rates of hypotension on admission (p=0.011) and the rates of defense and rebound (p=0.030) were higher in the patients with COVID-19 than in those without. Although there was no difference in terms of bleeding width, there was a greater decrease in the hemoglobin levels (p=0.009) in the COVID-19 patients and the need for erythrocyte suspension (p=0.040) increased significantly in that group. CONCLUSION: The present study constitutes the first evaluation of RSH in COVID-19 patients. The clinical situation is serious due to high rates of hypotension, defense or rebound, and decreases in hemoglobin levels in COVID-19 patients. This makes the clinical management of RSH more difficult, resulting in longer hospitalization. Despite these difficulties, COVID-19 infection does not increase morbidity or mortality.

Laurus nobilis L. Essential Oil-Loaded PLGA as a Nanoformulation Candidate for Cancer Treatment.

The aim of this study was to obtain essential oil (LNEO) from the Laurus nobilis L. plant, and to prepare LNEO-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) as an approach in cancer treatment. The components of the obtained LNEO were analyzed using GC-MS. The LNEO-NPs were synthesized by the single-emulsion method. The LNEO-NPs were characterized using UV-Vis spectrometry, Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and a DNA binding assay, which was performed via the UV-Vis titration method. According to the results, the LNEO-NPs had a 211.4 ± 4.031 nm average particle size, 0.068 ± 0.016 PdI, and -7.87 ± 1.15 mV zeta potential. The encapsulation efficiency and loading capacity were calculated as 59.25% and 25.65%, respectively, and the in vitro drug release study showed an LNEO release of 93.97 ± 3.78% over the 72 h period. Moreover, the LNEO was intercalatively bound to CT-DNA. In addition, the mechanism of action of LNEO on a dual PI3K/mTOR inhibitor was predicted, and its antiproliferative activity and mechanism were determined using molecular docking analysis. It was concluded that LNEO-loaded PLGA NPs may be used for cancer treatment as a novel phytotherapeutic agent-based controlled-release system.

Development of Cholesterol-Lowering and Detox Formulations Using Bentonite and Herbal Ingredients.

Detoxification enzymes involved in human metabolism works to minimize the potential xenobiotic-induced damage constantly. Studies have revealed that toxin accumulation plays an important role in the etiology of cardiovascular disease. This study has been designed to provide evidence of medicinal use of bentonite, turmeric (Curcuma longa L.), grape (Vitis vinifera L.) seed, flaxseed (Linum usitatissimum L.), and psyllium (Plantago ovata L.) as detoxification and cholesterol-lowering agents using a hypercholesterolemic model in mice. The potential hypocholesterolemic effects and detoxification ability of these ingredients were evaluated at the same time: Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, glucose, aspartate aminotransferase, alanine aminotransferase, malondialdehyde, plasma total antioxidant activity, nitric acid, leptin levels and glutathione, glutathione peroxidase, lipid peroxidation, superoxide dismutase and catalase values were measured. It was determined that GBTF group (grape seed extract, bentonite, turmeric, and flaxseed), GBTP group (grape seed extract, bentonite, turmeric, and psyllium), and GBT group (grape seed extract, bentonite, and turmeric) of the tested materials decreased the serum total cholesterol concentration by 64.8, 57.5, and 48.9%, respectively, in mice fed a high cholesterol diet. In addition, it was determined that some detoxification parameters such as superoxide dismutase, catalase, glutathione, and glutathione peroxidase were statistically significantly reversed in GBTF, GBTP, and GBT groups. Flaxseed, psyllium, and bentonite clay did not show significant effects in reducing total cholesterol; however, GBTF, GBTP, and GBT groups interventions had a significant effect in reducing total cholesterol levels. Moreover, it was observed that adding flaxseed or psyllium to the GBT group increased the cholesterol-lowering effect. Therefore, it can be thought that this significant effect is due to the synergistic effect of the raw materials. When the results obtained were evaluated, it was seen that the cholesterol-lowering and detoxification effects of the combinations were higher than from the effect of natural material used alone. As a result, combinations of some of these ingredients have a positive effect on reducing the risk of cardiovascular disease.

Determination of Pentraxin-3, Interleukin-8 and Vascular Endothelial Growth Factor Levels in Patients with Gastric Adenocarcinoma.

INTRODUCTION AND AIM: The purpose of this study was to determine the value, in terms of diagnosis, resectability and prognosis of pentraxin-3 (PTX3), interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) in cases of gastric adenocarcinoma, an important condition both worldwide and in Turkey, and to determine their levels in order to contribute to elucidating the pathogenesis of the disease. MATERIALS AND METHODS: Serum was separated from blood specimens collected from 45 patients diagnosed with gastric adenocarcinoma and from a 30-member healthy control group. Serum PTX3, IL-8 and VEGF levels were studied by ELISA method. RESULTS: Serum PTX3 values differed significantly between the patient group and the control group (p <0.05). Serum IL-8 values also differed significantly between the patient group and the control group (p <0.05). A significant difference was also observed between serum VEGF values in the patient group and the control group (p <0.05). Significant correlation was determined between serum PTX3 and VEGF (p <0.01; r=0.833), between serum PTX3 and IL-8 (p <0.01; r=0.818), and between serum VEGF and IL-8 (p <0.01; r=0.803), measurements when the entire study population was evaluated irrespectively of groups. CONCLUSION: Serum PTX3, IL-8 and VEGF levels decreased in cases of gastric adenocarcinoma compared to the control group, and their levels affected one another.
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Effects of Orally Consumed Rosa damascena Mill. Hydrosol on Hematology, Clinical Chemistry, Lens Enzymatic Activity, and Lens Pathology in Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus is a multisystemic metabolic disorder that may affect the eyes, kidneys, vessels, and heart. Chronic hyperglycemia causes non-enzymatic glycation of proteins and elevation of the polyol pathway resulting in oxidative stress that damages organs. The current study aimed to investigate the dose-dependent effects of orally consumed Rosa damascena Mill. hydrosol on hematology, clinical biochemistry, lens enzymatic activity, and lens pathology in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced into male Sprague-Dawley rats by intraperitoneal administration of STZ (40 mg/kg body weight). Rose hydrosols containing 1515 mg/L and 500 mg/L total volatiles (expressed as citronellol) were introduced to rats orally for 45 days. Consumption of 1515 mg/L volatile containing rose hydrosol successfully ameliorated hematologic, hepatic, and renal functions. Hydrosols also attenuated hyperglycemia and decreased the advanced glycation end-product formation in a dose-dependent manner. Rose hydrosol components significantly increased the lens enzymatic activities of glutathione peroxidase and decreased the activity of aldose reductase to prevent cataractogenesis. Histopathological examinations of rat lenses also indicated that increasing the dose of rose hydrosol had a protective effect on lenses in diabetic conditions. Additionally, in silico modeling of aldose reductase inhibition with rose hydrosol volatiles was carried out for extrapolating the current study to humans. The present results suggest that rose hydrosol exerts significant protective properties in diabetes mellitus and has no toxic effect on all studied systems in healthy test groups.

Sage tea-thyme-peppermint hydrosol oral rinse reduces chemotherapy-induced oral mucositis: A randomized controlled pilot study.

OBJECTIVE: This pilot study aimed to investigate the preventive effect of sage tea-thyme-peppermint hydrosol oral rinse used in conjunction with basic oral care on chemotherapy-induced oral mucositis. DESIGN: An open-label randomized controlled study. SETTING: Two oncology hospitals in Ankara, Turkey. INTERVENTIONS: Patients receiving 5-fluorouracil-based chemotherapy regimens were divided into the intervention group (N=30) and control group (N=30). Basic oral care was prescribed to the control group, while the intervention group was prescribed sage tea-thyme-peppermint hydrosol in addition to basic oral care. All patients were called to assess their compliance with the study instructions on day 5 and 14. MAIN OUTCOME MEASURES: Oral mucositis was evaluated using an inspection method or by assessing oral cavity photos based on the World Health Organization oral toxicity scale on day 5 and 14. RESULTS: Most of the patients in the intervention group did not develop oral mucositis on day 5. In addition, the incidence of grade 1 oral mucositis was statistically lower in the intervention group (10%) than the control group (53.3%) on day 5. By day 14, the majority of patients in both the groups had grade 0 oral mucositis. CONCLUSIONS: Sage tea-thyme-peppermint hydrosol oral rinse has promising results in alleviating oral mucositis. This hydrosol can be recommended for clinical use as it is well tolerated and cost-effective. However, further randomized controlled trials are needed to support the study.

Tyrosinase and Cholinesterase Inhibitory Potential and Flavonoid Characterization of Viola odorata L. (Sweet Violet).

Inhibitory potential of the dichloromethane, ethyl acetate, ethanol, and aqueous extracts of Viola odorata L. (VO) was investigated against tyrosinase (TYR) and cholinesterases by microplate assays. The antioxidant activity was tested using six in vitro assays. Only the ethanol extract inhibited TYR (80.23 ± 0.87% at 100 µg mL-1 ), whereas none of them were able to inhibit cholinesterases. The extracts were more able to scavenge NO radical (31.98 ± 0.53-56.68 ± 1.10%) than other radicals tested, and displayed low to moderate activity in the rest of the assays. HPLC analysis revealed that the aqueous extract of VO contained a substantial amount of vitexin (18.81 ± 0.047 mg g-1 extract), while the ethanol extract also possessed rutin (1.31 ± 0.013 mg g-1 extract) and vitexin (4.65 ± 0.103 mg g-1 extract). Furthermore, three flavonoids (rutin, isovitexin, and kaempferol-6-glucoside) were isolated from the ethanol extract. This is the first report on TYR inhibitory activity of VO as well as presence of vitexin and isovitexin in this species. Copyright © 2015 John Wiley & Sons, Ltd.

Triterpene saponins from Eryngium kotschyi.

Four new oleanane-type saponins 3-O-α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucuronopyranosyl-22-O-ß,ß-dimethylacryloylA1-barrigenol (1), 3-O-α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucuronopyranosyl-22-O-angeloylA1-barrigenol (2), 3-O-ß-D-glucopyranosyl-(1 → 2)-[ß-D-glucopyranosyl-(1 → 6)]-ß-D-glucopyranosyl-21,22,28-O-triacetyl-(3ß,21ß,22α)-olean-12-en-16-one (3), and 3-O-ß-D-glucopyranosyl-(1 → 2)-glucopyranosyl-22-O-ß-D-glucopyranosylsteganogenin (4), along with the known 3-O-ß-D-galactopyranosyl-(1 → 2)-[α-L-arabinopyranosyl-(1 → 3)]-ß-D-glucuronopyranosyl-22-O-angeloylA1-barrigenol and 3-O-α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucuronopyranosyloleanolic acid, were isolated from a methanol extract of the roots of Eryngium kotschyi by multiple chromatographic steps. Saponins 3 and 4 are unusual by the original structure of their aglycon. Compound 3 possessed an oleanane-type skeleton with a 21,22,28-triacetylation and a ketone function at the C-16 position. For compound 4, the 17,22-seco-oleanolic acid skeleton is rarely found in natural saponins.

Inhibitory effect of St. John׳s Wort oil macerates on TNFα-induced NF-κB activation and their fatty acid composition.

ETHNOPHARMACOLOGICAL RELEVANCE: The oil macerates of Hypericum perforatum L. (St. John׳s Wort=SJW) have a long history of medicinal use and SJW has been used in traditional medicine both orally and topically for centuries worldwide mainly for wound healing, ulcer and inflammation. MATERIALS AND METHODS: We analyzed the fatty acid composition of 10 traditionally (home-made) and 13 commercially (ready-made) prepared SJW oil macerates by GC-MS. The acid, peroxide, iodine, saponification values, and the unsaponifiable matters of the samples were determined according to the European Pharmacopoeia. We also explored potential mechanism of wound healing effect of the samples, i.e. TNFα-induced NF-κB activation. RESULTS: The most home-made oil samples contained oleic acid predominantly and complied with the requirements set for olive oil by European Pharmacopoeia. However, majority of the ready-made samples appeared to have adulteration with some other oils. Moderate NF-κB inhibitory effects have been observed with some of the oil samples. CONCLUSION: This study sheds light on the fact that application of the proper traditional method to prepare olive oil macerates from Hypericum perforatum is able to get bioactive constituents in the oil. Besides, inhibition of TNFα-induced NF-κB activation appears to be a potential mechanism for topical wound healing activity of SJW oil macerates.

Assessment of antimicrobial and antiprotozoal activity of the olive oil macerate samples of Hypericum perforatum and their LC-DAD-MS analyses.

Twenty-one samples of traditionally-prepared (home-made) and ready-made (commercial) St. John's Wort olive oil macerates were profiled for their in vitro antimicrobial and antiprotozoal activity. Their cytotoxic potential was evaluated on MRC-5 fibroblasts. In the antiprotozoal assays, ten of the oils inhibited Trypanosoma brucei rhodesiense (IC(50) 15.9-64.5 µg/mL), while only one oil exerted antimicrobial activity towards Staphylococcus aureus (IC(50)=88.7 µg/mL). LC-DAD-MS data revealed the presence of pseudohypericin (0.135-3.280 µg/g) and hypericin (0.277-6.634 µg/g) in all the oils, whereas chlorogenic acid (1.063 µg/g) was detected only in one oil sample. Hyperforin was detected in four (0.977-2.399 µg/g) and adhyperforin in six samples (0.005-3.165 µg/g). Hypericin and pseudohypericin were common in the active oils, whereas hyperforin, adhyperforin, and chlorogenic acid were absent in these samples. Our results indicated that if the correct plant material is used, the infused oils from Hypericum perforatum may contain active components.

In vitro isoflavonoid production and analysis in natural tetraploid Trifolium pratense (red clover) calluses

Isoflavones are polyphenolic phytoestrogens, predominantly found in leguminous plants. Trifolium pratense L., Fabaceae (red clover), is rich in isoflavones that possess estrogenic activity due to their similar molecular structure and effectiveness in preventing health conditions such as menopause, osteoporosis, cardiovascular disease, hypertension and hormone-dependent cancers. In this study, presence and amount of various phytoestrogens in the tetraploid plant and in the calluses derived from the plants were investigated. Calluses were generated from explants obtained from natural tetraploid T. pratense seedlings. The best callus formation was obtained from hypocotyl explants cultured in Phillips Collins and Gamborg B5 media containing different plant growth regulators. Flowers of plants and calluses were analysed for formononetin, biochanin A, genistein and daidzein contents using HPLC. In HPLC analysis, high levels of formononetin (0.249 µg/mg) were determined in natural tetraploid T. pratense flowers in addition to genistein and biochanin A. In calluses, highest isoflavone content (1.15 µg/mg formononetin) was observed in modified Gamborg B5 medium. Biochanin A content of calluses and the plant were found to be nearly the same. But formononetin and genistein contents of the calluses in this medium were found to be respectively 4.62 and 21.39 folds higher than the tetraploid plant.

Indole alkaloids from Vinca major and V. minor growing in Turkey.

A new indole alkaloid, 11-hydroxypolyneuridine, was isolated from Vinca major subsp. major L. and the known indole alkaloids vallesiachotamine and isovallesiachotamine from Vinca minor L. This is the first report on the alkaloids of both Vinca species growing in Turkey; vallesiachotamine and isovallesiachotamine were isolated from a Vinca species for the first time. V. minor may be considered as a new source for these two alkaloids due to their occurrence in high amount in the aerial parts of the plant. The alkaloid extracts of the two Vinca species were found to have high lipid peroxidation inhibitory and DPPH radical scavenging activities. Anticholinesterase activity of the extracts was also very strong.

Aldose reductase inhibitory activity and antioxidant capacity of pomegranate extracts.

The pomegranate, Punica granatum L., has been the subject of current interest as a medicinal agent with wide-ranging therapeutic indications. In the present study, pomegranate ethanolic seed and hull extracts were tested, in comparison with a commercial sample, for the inhibition of aldose reductase, an enzyme involved in the etiology of diabetic complications. In vitro inhibition of rat lens aldose reductase was determined by a conventional method. Pomegranate ethanolic hull extract and commercial pomegranate hull extract exhibited similar aldose reductase inhibitory activity characterized by IC(50) values ranging from 3 to 33.3 µg/ml. They were more effective than pomegranate ethanolic seed extract with IC(50) ranging from 33.3 to 333 µg/ml. Antioxidant action of the novel compounds was documented in a DPPH test and in a liposomal membrane model, oxidatively stressed by peroxyl radicals. All the plant extracts showed considerable antioxidant potential in the DPPH assay. Pomegranate ethanolic hull extract and commercial pomegranate hull extract executed similar protective effects on peroxidatively damaged liposomal membranes characterized by 10

Selective cholinesterase inhibitors from Buxus sempervirens L. and their molecular docking studies.

In this work, two alkaloids namely (+)-buxabenzamidienine (1) and (+)-buxamidine (2) were isolated from Buxus sempervirens, using bioassay-guided fractionation and isolation method. Their acetyl- (AChE) and butyrylcholinesterase (BChE) inhibitory activities were studied and the compounds were found to be quite selective inhibitors of AChE. IC50 values of compound 1 for electric eel AChE and horse BChE were 0.787 and 7.68 mM, respectively; while the corresponding IC50 of compound 2 were 1.70 and 549.98 mM, respectively. Theoretical (quantum mechanical, homology modelling and docking) calculations were performed in order to explain their interactions with different AChE (electric eel and human) and BChE (horse and human). The x-ray crystal structures of electric eel AChE, human AChE, human BChE and a model of horse BChE constructed by homology with human BChE were used for docking of compounds 1 and 2. Density functional theory (DFT) calculations of the compounds were performed at the B3LYP/6- 31G** level using the program Spartan™, and their HOMO and LUMO energy levels were calculated. Docking studies exhibited that compound 1 interacts with the acyl-binding pocket of the active site gorge of huAChE, and including several other hydrophobic interactions.

Polyphenolic extracts from Olea europea L. protect against cytokine-induced ß-cell damage through maintenance of redox homeostasis.

Various pancreatic ß-cell stressors, including cytokines, are known to induce oxidative stress, resulting in apoptotic/necrotic cell death and inhibition of insulin secretion. Traditionally, olive leaves or fruits are used for treating diabetes, but the cellular mechanism(s) of their effects are not known. We examined the effects of Olea europea L. (olive) leaf and fruit extracts and their component oleuropein on cytokine-induced ß-cell toxicity. INS-1, an insulin-producing ß-cell line, was preincubated with or without increasing concentrations of olive leaf or fruit extract or oleuropein for 24 hr followed by exposure to a cytokine cocktail containing 0.15 ng/mL interleukin-1ß (IL-1ß), 1 ng/mL interferon-γ (IFN-γ), and 1 ng/mL tumor necrosis factor-α (TNF-α) for 6 hr. The cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) testing. Apoptosis was quantified by detecting acridine orange/ethidium bromide-stained condensed nuclei under a fluorescent microscope. The cells exposed to cytokines had a higher apoptotic rate, a decreased viability (MTT), and an increased caspase 3/7 activity. Both extracts and oleuropein partially increased the proportion of living cells and improved the viability of cells after cytokines. The protective effects of extracts on live cell viability were mediated through the suppression of caspase 3/7 activity. Oleuropein did not decrease the amount of both apoptotic and necrotic cells, whereas extracts significantly protected cells against cytokine-induced death. Cytokines led to an increase in reactive oxygen species (ROS) generation and inhibited glutathione level, superoxide dismutase activity, and insulin secretion in INS-1. Insulin secretion was almost completely protected by leaf extract, but was partially affected by fruit extract or oleuropein. Neither cytokines nor olive derivatives had a significant effect on cellular cytochrome c release and catalase activity. Moreover, the cells incubated with each extract or oleuropein showed a significant reduction in cytokine-induced ROS production and ameliorated abnormal antioxidant defense. The molecular mechanism by which olive polyphenols inhibit cytokine-mediated ß-cell toxicity appears to be involving the maintenance of redox homeostasis.