Hypertension medication from guidelines to practice: A cohort study in western Iran.

PURPOSE: Hypertension (HTN) is one of the most common risk factors for non-communicable chronic diseases. The aim of the current study is to evaluate the prescribing patterns of antihypertensive medications in Kermanshah Province, west of Iran. METHODS: The Ravansar Non-Communicable Diseases (RaNCD) cohort study is the first Kurdish community-based study; subjects' age ranged from 35 to 65 years. In order to examine the use of medications to control blood pressure, participants were asked to bring all prescribed medications to the study center. Treatments were compared with 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) Guidelines for the management of arterial HTN. RESULTS: From a total of 10 040 participants in RaNCD cohort, 1575 (15.7%) individuals were hypertensive, of whom, 1271 (80.7%) people were aware of their condition. From 1153 (73.20%) people under treatment, 840 (72.8%) had their HTN properly controlled. The most common medications used to treat HTN were losartan (27.5%), metoprolol (14.3%), and captopril (11.9%). Regardless of type of treatment, 49.3% of all patients have received the medication for l 6 ≥ years. The most commonly used drugs were ß-blockers and angiotension receptor blockers as 620 (31.0%) and 612 (30.6%), respectively. Multivariable analysis showed that female gender, those receive ≥3 antihypertensive agents, and using preferred combinations were associated with a better blood pressure control. In addition, the probability of hypertension control was less likely with increasing duration of treatment (i.e >6 years) and in obese patients with ≥35 kg/m2 . CONCLUSIONS: Even though adherence to the international guidelines was acceptable, improvements can be made for better control of HTN. Therefore, it is imperative to educate healthcare professionals on improving their selection of antihypertensive medications and combination therapy for hypertensive patients.

The role of quercetin in the formation of titanium dioxide nanoparticles for nanomedical applications.

The current work aimed to synthesize and characterize titanium dioxide nanoparticles (TiO2NPs) using quercetin (QE) and evaluate their biological activities, i.e., anti-hemolytic, anti-inflammatory, and cytotoxicity effects. The crystallographic phase and morphology of biosynthesized QE-TiO2NPs were characterized by XRD (X-Ray Diffraction) and TEM/FE-SEM (Transmission/Field-Emission Scanning Electron Microscopy) micrographs. Functional groups involved in the synthesis process were determined by FTIR spectroscopy (Fourier Transform-Infrared Spectroscopy). Based on the characterization results, selected QE-TiO2NPs showed a rutile phase, spherical shape, and a size range of 7.3-39 nm. The QE-TiO2NPs did not show a hemolytic effect. They indicated 95.3% red blood cells (RBCs) membrane stabilization activity and 82.6% inhibition of bovine serum albumin (BSA) denaturation, similar to a standard drug, which proved their anti-inflammatory effects. The attained results from cytotoxicity studies revealed the toxic effects of QE-TiO2NPs with IC50 values below 100 and 50 µg/mL for human breast cancer cells of MCF-7 and melanoma cancer cells of A375, respectively. These NPs did not significantly affect normal skin fibroblast cells up to 50 µg/mL and only showed a 16% inhibition rate on the cell viability at 100 µg/mL. These NPs also induced excessive ROS generation. This work established the blood/biocompatibility and excellent nanomedical applications of biosynthesized QE-TiO2NPs.

Colchicine of Colchicum autumnale, A Traditional Anti-Inflammatory Medicine, Induces Apoptosis by Activation of Apoptotic Genes and Proteins Expression in Human Breast (MCF-7) and Mouse Breast (4T1) Cell Lines.

OBJECTIVE: Breast cancer is one of the major causes of mortality among women. Due to many side effects of the existing chemotherapeutic agents, the research of anti-cancer drugs, including natural products, is still a big challenge. Here, we investigated the effects of colchicine on apoptosis of two breast cancer cell lines ( human MCF-7 and mouse 4T1). MATERIALS AND METHODS: In this experimental study, we evaluated the apoptotic effects of colchicine on (MCF-7) and (4T1), as well as a human cancer-associated fibroblast cell line as a control group. Extraction and chromatographic techniques were applied to isolate colchicine from Colchicum autumnale L. To compare the isolated colchicine with pure standard colchicine, we used the H-NMR technique. The methyl thiazolyl tetrazolium (MTT) assay, quantitative reverse transcriptase-polymerase chain reaction, Western blotting and annexin V/PI staining were used to evaluate the apoptotic effects of the isolated and standard colchicine. RESULTS: Similar to standard colchicine, the isolated colchicine inhibited cell proliferation significantly in cancer cell lines. Colchine inhibited proliferation and induced apoptosis on a dose-dependent manner. The medicine modified the expression of genes-related to apoptosis by up-regulation of P53 ,BAX, CASPASE-3, -9 and down-regulation of BCL-2 gene, which led to an increase in the BAX/BCL-2 ratio. CONCLUSION: We showed that isolated colchicine from Colchicum autumnale and pure standard colchicines modulate the expression levels of several genes and therefore exerting their anticancer effects on both human (MCF-7) and mouse (4T1) breast cancer cells. Based on these results, we suggest that colchicine can be a potential candidate for prevention and treatment of breast cancer.

Differentiating Cannabis Products: Drugs, Food, and Supplements.

"Hemp" refers to non-intoxicating, low delta-9 tetrahydrocannabinol (Δ9-THC) cultivars of Cannabis sativa L. "Marijuana" refers to cultivars with high levels of Δ9-THC, the primary psychoactive cannabinoid found in the plant and a federally controlled substance used for both recreational and therapeutic purposes. Although marijuana and hemp belong to the same genus and species, they differ in terms of chemical and genetic composition, production practices, product uses, and regulatory status. Hemp seed and hemp seed oil have been shown to have valuable nutritional capacity. Cannabidiol (CBD), a non-intoxicating phytocannabinoid with a wide therapeutic index and acceptable side effect profile, has demonstrated high medicinal potential in some conditions. Several countries and states have facilitated the use of THC-dominant medical cannabis for certain conditions, while other countries continue to ban all forms of cannabis regardless of cannabinoid profile or low psychoactive potential. Today, differentiating between hemp and marijuana in the laboratory is no longer a difficult process. Certain thin layer chromatography (TLC) methods can rapidly screen for cannabinoids, and several gas and liquid chromatography techniques have been developed for precise quantification of phytocannabinoids in plant extracts and biological samples. Geographic regulations and testing guidelines for cannabis continue to evolve. As they are improved and clarified, we can better employ the appropriate applications of this uniquely versatile plant from an informed scientific perspective.

Glucosinolates and their hydrolysis products as potential nutraceuticals to combat cytokine storm in SARS-COV-2.

INTRODUCTION: The high mortality rate in severe cases of COVID-19 is mainly due to the strong upregulation of cytokines, called a cytokine storm. Hyperinflammation and multiple organ failure comprise the main clinical features of a cytokine storm. Nrf2 is a transcription factor which regulates the expression of genes involved in immune and inflammatory processes. Furthermore, Nrf2, as a master regulator, controls the activity of NF-κB which binds to the promoter of many pro-inflammatory genes inducible of various inflammatory factors. Inhibition of Nrf2 response was recently demonstrated in biopsies from patients with COVID-19, and Nrf2 agonists inhibited SARS-CoV-2 replication across cell lines in vitro. Glucosinolates and their hydrolysis products have excellent anti-inflammatory and antioxidant effects via the Nrf2 activation pathway, reduction in the NF-κB activation, and subsequent reduced cytokines levels. CONCLUSION: Accordingly, these compounds can be helpful in combating the cytokine storm associated with COVID-19.

Effects of Flaxseed on Blood Lipids in Healthy and Dyslipidemic Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

To address hyperlipidemia, flaxseed demonstrates a great impact on experimental and clinical trials. Therefore, the effects of flaxseed on lipid profiles of healthy and dyslipidemic subjects were assayed. The literature search was performed based on English reports of randomized control trials (RCTs) up to April 2021 to seek the effect of flaxseed on lipid profiles of healthy and dyslipidemic subjects. A total of 14 RCTs with 1107 participants were evaluated. Based on results, flaxseed significantly improves the lipid profile in dyslipidemic patients comprising total cholesterol (TC), low-density lipoprotein (LDL-C) and triglyceride (TG) in comparison with the control group. Nevertheless, no significant changes were observed in high-density lipoprotein (HDL-C). Although in healthy individual flaxseed significantly increased HDL-C, LDL-C and TG. Subgroup analysis on healthy subjects showed that flaxseed improved LDL-C on overweight subjects with BMI>25. The evidence suggests that flaxseed significantly improved TC, LDL-C and TG in dyslipidemic subjects and additionally improved the HDL-C on healthy subjects.

Oxypeucedanin and isoimperatorin extracted from Prangos ferulacea (L.) Lindl protect PC12 pheochromocytoma cells from oxidative stress and apoptosis induced by doxorubicin.

BACKGROUND AND PURPOSE: Doxorubicin (DOX) as a chemotherapeutic agent has been widely used in the treatment of various types of cancer. However, DOX exerts a toxic effect on normal tissues such as the brain. Furanocoumarins reduce the risk of cardiovascular and brain diseases because of their antioxidant activities. This study has been designed, for the first time, to evaluate the effect of known furanocoumarins oxypeucedanin and isoimperatorin extracted from Prangos ferulacea (L.) Lindl on oxidative stress and apoptosis induced by DOX toward pheochromocytoma cell line (PC12). EXPERIMENTAL APPROACH: NMR and MASS spectrometers were used to characterize the isolated compounds. The protective effects of isolated compounds on DOX-induced cytotoxicity in PC12 cells were examined by MTT assay. PC12 cells were pretreated with oxypeucedanin and isoimperatorin for 2 and 21 h, respectively, subsequently exposure to DOX at IC50 concentration. Then, mitochondrial membrane potential (MMP), Bax and Bcl2 mRNA expressions, caspase-3 activation, and the generation of intracellular reactive oxygen species (ROS) were measured after 24 h. FINDINGS/RESULTS: Pretreatment with oxypeucedanin and isoimperatorin significantly decreased DOX-induced apoptosis through reduction of caspase-3 activity and ROS generation and an increase in MMP. In addition, our finding showed pretreatment with these compounds leads to regulation of Bcl-2. CONCLUSION AND IMPLICATIONS: Taken together our observation indicated that oxypeucedanin and isoimperatorin have a protective effect against apoptosis induced by DOX in PC12 cells by inhibition of ROS production.

Optimization of Quercetin-Assisted Silver Nanoparticles Synthesis and Evaluation of Their Hemocompatibility, Antioxidant, Anti-Inflammatory, and Antibacterial effects.

In the present study, different effective parameters (temperature, reaction time, and pH) on the synthesis of quercetin-assisted silver nanoparticles (QE-AgNPs) are optimized. These biogenic NPs are characterized by different physico-chemical analyses, including transmission electron microscopy, X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, and UV-visible spectroscopy. In addition, the biological properties of QE-AgNPs are evaluated through antioxidant, antimicrobial, anti-inflammatory, hemolysis, and coagulation time assays. The formation of QE-AgNPs is affected by different parameters. The optimum condition for the synthesis of QE-AgNPs is attained at 70 °C and pH 7. Prepared QE-AgNPs show a spherical shape with a crystalline nature and an average particle size of 20 ± 3.6 nm. The role of QE as a reducing and capping agent in the preparation process of QE-AgNPs is demonstrated using FTIR analysis. These NPs with excellent antioxidant activity (82.3% at a concentration of 400 µg mL-1) and anti-inflammatory properties (82.5% and 100% at concentrations of 37.25 and 500 µg mL-1, respectively), show good antimicrobial effects, particularly against Staphylococcus aureus. Furthermore, the results of the hemolytic and coagulation assay of QE-AgNPs indicate their hemo-compatibility. Therefore, hemo/bio-compatible QE-AgNPs with excellent and unique properties can be employed in different medicinal and pharmacological applications.

Salvigenin, a Trimethoxylated Flavone from Achillea Wilhelmsii C. Koch, Exerts Combined Lipid-Lowering and Mitochondrial Stimulatory Effects.

Phytochemical analysis of the Iranian plant Achillea wilhelmsii led to the isolation of 17 pure secondary metabolites belonging to the classes of sesquiterpenoids and phenolics. Two of these compounds, named wilhemsin (7) and wilhelmsolide (9), are new sesquiterpenoids, and the first shows undescribed structural features. Their structures were elucidated through extensive spectroscopic analysis, mainly based on 1D and 2D NMR, and chemical derivatization. Starting from plant traditional use and previous reports on the activity of the plant extracts, all the pure compounds were evaluated on endpoints related to the treatment of metabolic syndrome. The sesquiterpene hanphyllin (8) showed a selective cholesterol-lowering activity (-12.7% at 30 µM), santoflavone (13) stimulated glucose uptake via the GLUT transporter (+16.2% at 30 µM), while the trimethoxylated flavone salvigenin (14) showed a dual activity in decreasing lipid levels (-22.5% palmitic acid biosynthesis at 30 µM) and stimulating mitochondrial functionality (+15.4% at 30 µM). This study further confirms that, in addition to the antioxidants vitexin, isovitexin, and isoschaftoside, A. wilhelmsii extracts contain molecules that can act at different levels on the metabolic syndrome symptoms.

Biological and Catalytic Activities of Green Synthesized Silver Nanoparticles from the Leaf Infusion of Dracocephalum kotschyi Boiss.

The discovery and development of active compounds to eliminate drug resistance and side effects is a crucial process. In this study, the leaf infusion of Dracocephalum kotschyi Boiss as a novel green alternative is used to synthesize silver nanoparticles (Drac-AgNPs). Antibacterial, cytotoxicity effects, hemocompatibility, and the catalytic properties of these nanoparticles are evaluated. The synthesis of Drac-AgNPs is confirmed by UV-vis spectroscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and transmission electron microscopy, where Drac-AgNPs are spherical, with a size range of 5-63 nm. Their IC50 values against H1299 and MCF-7 cell lines are above 50 and 100 µg mL-1, respectively. Drac-AgNPs are effective against an inclusive range of the gram-positive and gram-negative bacteria, that is, Staphylococcus epidermidis, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Serratia marcescens, and Pseudomonas aeruginosa, and a low hemolytic effect makes them an exceptional AgNP with a great hemocompatibility. They show a moderate catalytic-effect in terms of removing methylene blue, with 67% degradation. Altogether, Drac-AgNP, as a multi-tasker material, shows potential for the prevention and treatment of infections and photothermal/chemotherapy of cancers.

Comparison of the cytotoxic effects of different fractions of Artemisia ciniformis and Artemisia biennis on B16/F10, PC3 and MCF7 Cells.

BACKGROUND AND PURPOSE: Artemisia is one of the well-known herbal medicinal plants for antimicrobial, insecticidal, antioxidant, and antimalarial activities. The antiproliferative effects of dichloromethane extracts of Artemisia biennis (A. biennis) and A. ciniformis and the petroleum ether extract of A. ciniformis have been demonstrated previously on human cancerous cell lines. In the current study, further fractionation was carried out on the aforementioned extracts and their cytotoxic effects were evaluated on three human cancer cell lines; B16/F10, PC3, and MCF7. F1 to F16, F1' to F11', and F1" to F10" were resulted from the fractionation of dichloromethane extracts of A. biennis, A. ciniformis, and petroleum ether extract of A. ciniformis, respectively. EXPERIMENTAL APPROACH: The cytotoxic effects of 16 (F1-F16), 11 (F1'-F11') and 10 (F1"-F10") fractions, on B16/F10, PC3, and MCF7 cell lines were assessed using resazurin to measure viability and propidium iodide staining (sub G1) and flow cytometry to detect apoptosis. FINDINGS / RESULTS: The results showed that, some fractions at 100 µg/mL decreased cell viability. F2" in B16/F10 cells, F2, F4-F6, F10', F11', and F2" in PC3 cells, and F10', F11', and F2" in MCF7 significantly decreased cell viability in a concentration-dependent manner (12.5-50 µg/mL). Among different fractions, F2" demonstrated the most potent cytotoxic effects on cancer cell lines (P < 0.001). All of the mentioned fractions (except F11' on PC3 cells) increased the number of apoptotic cells and showed the cytotoxic effects on cancer cells compared with the control group. CONCLUSION AND IMPLICATIONS: A. biennis and A. ciniformis are suggested as the potential sources of cytotoxic phytochemicals. The probable presence of terpenoids, steroids, and alkaloids in the selected fractions is proposed based on the preliminary phytochemical study.

Isofraxidin: Synthesis, Biosynthesis, Isolation, Pharmacokinetic and Pharmacological Properties.

Isofraxidin (7-hydroxy-6, 8-dimethoxy coumarin) (IF) is a hydroxy coumarin with several biological and pharmacological activities. The plant kingdom is of the most prominent sources of IF, which, among them, Eleutherococcus and Fraxinus are the well-known genera in which IF could be isolated/extracted from their species. Considering the complex pathophysiological mechanisms behind some diseases (e.g., cancer, neurodegenerative diseases, and heart diseases), introducing IF as a potent multi-target agent, which possesses several herbal sources and the multiple methods for isolation/purification/synthesis, along with the unique pharmacokinetic profile and low levels of side effects, could be of great importance. Accordingly, a comprehensive review was done without time limitations until February 2020. IF extraction methods include microwave, mechanochemical, and ultrasound, along with other conventional methods in the presence of semi-polar solvents such as ethyl acetate (EtOAc). In addition to the isolation methods, related synthesis protocols of IF is also of great importance. From the synthesis point of view, benzaldehyde derivatives are widely used as precursors for IF synthesis. Along with the methods of isolation and biosynthesis, IF pharmacokinetic studies showed hopeful in vivo results of its rapid absorption after oral uses, leading to different pharmacological effects. In this regard, IF targets varieties of inflammatory mediators including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α (TNF-α), and matrix metalloproteinases (MMPs). thereby indicating anticancer, cardioprotective, and neuroprotective effects. This is the first review on the synthesis, biosynthesis, isolation, and pharmacokinetic and pharmacological properties of IF in combating different diseases.

Antidiabetic Potential of Prosopis farcta Roots: In Vitro Pancreatic Beta Cell Protection, Enhancement of Glucose Consumption, and Bioassay-Guided Fractionation.

By using the streptozotocin- (STZ-) induced cytotoxicity in ß-TC3 cells as an assay model, a bioassay-guided fractionation study was employed to isolate and characterize the potential antidiabetic principles of roots of Prosopis farcta. A combination of open column chromatography on reverse-phase silica gel using a water-ethanol gradient (10 : 90 to 100 : 0) followed by HPLC-based fractionation led to an active compound that appears to be composed of carbohydrate/sugar. When cell viability under STZ was reduced to 49.8 ± 4% (mean ± SD), treatment with the active compound at the concentration of 0.5 mg/mL either as a coadministration or a pretreatment improved the viability to 93 ± 1.9% and 91.5 ± 7%, respectively. The reduction in the mitochondrial membrane potential by STZ (47.34 ± 8.9% of control) was similarly recovered to 84.5 ± 4.3 (coadministration) and 88 ± 5.5% (pretreatment) by the active fraction. The bioassay-guided fractionation, ß-cell protective effect, and increased glucose consumption (up to 1.49-fold increase) in hepatocytes by the extracts and active fraction are also discussed.

One-step Synthesized Silver Nanoparticles Using Isoimperatorin: Evaluation of Photocatalytic, and Electrochemical Activities.

In the current study, isoimperatorin, a natural furanocoumarin, is used as a reducing reagent to synthesize isoimperatorin mediated silver nanoparticles (Iso-AgNPs), and photocatalytic and electrocatalytic activities of Iso-AgNPs are evaluated. Iso-AgNPs consisted of spherically shaped particles with a size range of 79-200 nm and showed catalytic activity for the degradation (in high yields) of New Fuchsine (NF), Methylene Blue (MB), Erythrosine B (ER) and 4-chlorophenol (4-CP) under sunlight irradiation. Based on obtained results, Iso-AgNPs exhibited 96.5%, 96.0%, 92%, and 95% degradation rates for MB, NF, ER, and 4-CP, respectively. The electrochemical performance showed that the as-prepared Iso-AgNPs exhibited excellent electrocatalytic activity toward hydrogen peroxide (H2O2) reduction. It is worth noticing that the Iso-AgNPs were used as electrode materials without any binder. The sensor-based on binder-free Iso-AgNPs showed linearity from 0.1 µM to 4 mM with a detection limit of 0.036 µM for H2O2. This binder-free and straightforward strategy for electrode preparation by silver nanoparticles may provide an alternative technique for the development of other nanomaterials based on isoimperatorin under green conditions. Altogether, the application of isoimpratorin in the synthesis of nano-metallic electro and photocatalysts, especially silver nanoparticles, is a simple, cost-effective and efficient approach.

Phytochemicals: Potential Therapeutic Interventions Against Coronavirus-Associated Lung Injury.

Since the outbreak of coronavirus disease 2019 (COVID-19) in December 2019, millions of people have been infected and died worldwide. However, no drug has been approved for the treatment of this disease and its complications, which urges the need for finding novel therapeutic agents to combat. Among the complications due to COVID-19, lung injury has attained special attention. Besides, phytochemicals have shown prominent anti-inflammatory effects and thus possess significant effects in reducing lung injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also, the prevailing evidence reveales the antiviral effects of those phytochemicals, including anti-SARS-CoV activity, which could pave the road in providing suitable lead compounds in the treatment of COVID-19. In the present study, candidate phytochemicals and related mechanisms of action have been shown in the treatment/protection of lung injuries induced by various methods. In terms of pharmacological mechanism, phytochemicals have shown potential inhibitory effects on inflammatory and oxidative pathways/mediators, involved in the pathogenesis of lung injury during COVID-19 infection. Also, a brief overview of phytochemicals with anti-SARS-CoV-2 compounds has been presented.

Preparation and Characterization of Silk Fibroin Nanoparticles as a Potential Drug Delivery System for 5-Fluorouracil.

Purpose: The aim of this study is to prepare 5-fluorouracil (5-FU) loaded silk fibroin nanoparticles (SFNPs) and to achieve a controlled release delivery system with the high loading capacity. Methods: SFNPs with 1:1, 1:3, and 1:10 ratios of 5-FU to silk fibroin were prepared. SFNPs were characterized by Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) analysis, Scanning electron microscope (SEM), and Transmission electron microscope (TEM). Loading efficiency, in vitro release, and cell viability were studied for optimal SFNPs. Results: The ratio of 1:1 was optimal formulation with the size and polydispersity index (PDI) of 221.03 nm and 0.093 before freeze drying, and 286.7 nm and 0.154 after freeze drying by lactose, respectively. The loading efficiency and loading content of this ratio were 52.32% and 34.35%, respectively. FT-IR and XRD analysis indicated the conformational change (from random coil to ß-sheet) in the structure of nanoparticles by increasing amount of the drug, which caused the smaller size, the higher loading efficiency, and the slower release pattern. The drugloaded nanoparticles reached to the half maximal inhibitory concentration (IC50) that were comparable with free drug on MCF7 (human breast cancer) cell line. Conclusion: This study was planned to achieve a promising controlled release drug delivery system for carrying 5-FU, as a potent anticancer drug. SFNPs were found proper candidates for delivery of a hydrophilic drug such as 5-FU.

Efficacy and safety of Achillea wilhelmsii C. Koch capsules on symptom severity and quality of life in patients with irritable bowel syndrome: a randomized, placebo-controlled clinical trial.

Background Irritable bowel syndrome (IBS) is one of the most common digestive diseases. The aim of this clinical trial was to determine the effectiveness of Achillea wilhelmsii C. Koch on the symptom severity and quality of life (QOL) in patients with IBS. Methods The patients were randomized into two groups of 45 each. The QOL and symptom severity of the patients were evaluated at baseline and at completion of the treatments by means of IBS-QOL and IBS severity index. Results The mean severity of clinical symptoms in the Achillea wilhelmsii C. Koch receiving groups before and after the treatment was 282.56 ± 103.57 and 178.06 ± 88.40, and in the placebo group was 265.93 ± 93.56 and 197.74 ± 106.26, respectively. The mean QOL in the Achillea wilhelmsii C. Koch receiving group before and after treatment was 51.49 ± 11.98 and 50.44 ± 13.39 and in the placebo group was 60.71 ± 11.97 and 58.39 ± 11.67, respectively. In both groups, there was a significant difference in the recovery rate in each group (p<0.05). However, the mean difference between the two groups before and after intervention was not significantly different (p>0.05). Also, no patient reported any adverse events during the trial. Although the symptom severity and QOL in both groups were improved compared to those before intervention, there was no significant difference between the two groups. Conclusion It is recommended to conduct future studies with larger sample size and longer treatment periods, and also investigate the efficacy on the IBS subtypes, separately.

Ugi efficient synthesis, biological evaluation and molecular docking of coumarin-quinoline hybrids as apoptotic agents through mitochondria-related pathways.

Ugi reaction was a reliable procedure for the synthesis of new coumarin-quinoline frameworks. Excellent yields, mild reaction conditions and easily available and inexpensive starting materials are advantages of this protocol. Cytotoxic effects of fourteen products were investigated in A2780 human ovarian cancer cells. Two synthesized compounds (L11 and L12) exhibited more anti-cancer activity than other derivatives with IC50 values of 0.042 mmol/L and 0.102 mmol/L, respectively and were thus selected for further studies. Apoptosis was induced through the intrinsic pathway by activating caspase 9 and ended at the executioner pathway of caspase 3. Measurement of intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were also carried out for both of them. Further studies on a mechanism by Real Time-PCR and Western blot analysis were performed for anti-apoptotic proteins Bcl-2 and survivin both in mRNA and protein level relating to the untreated A2780 cells. The treatment of A2780 cells with compound L11 significantly (P-value ≤ 0.05) induced apoptosis by down-regulation of Bcl-2 and survivin both in mRNA and protein level via a single dose (0.042 mmol/L), as well as activation of caspase 9 and 3, loss of MMP, and high ROS. Accordingly, findings supported the first report under which the pro-apoptotic activity of compound L11 as an apoptosis-inducing agent was related to mitochondrial-mediated dysfunction signaling pathways. Molecular docking supports experimental outcomes. Evidently, coumarin-quinoline scaffolds are potentially favorable options for further assessment as influential chemotherapeutic agents for the future.

Efficacy and safety of a standardized extract from Achillea wilhelmsii C. Koch in patients with ulcerative colitis: A randomized double blind placebo-controlled clinical trial.

BACKGROUND: Using Achillea wilhelmsii as a dietary supplement for gastrointestinal disorders is common in Persian traditional medicine. Its anti-inflammatory, anti-spasmodic and antibacterial properties have been proven by different in vitro and in vivo studies, yet it has not been evaluated in a controlled clinical trial. AIM: This study intended to evaluate the efficacy and safety of A. wilhelmsii in patients with mild to moderate active ulcerative colitis in a randomized, double-blinded, placebo-controlled clinical trial. The hydroalcoholic extract of A. wilhelmsii was standardized based on caffeic acid. METHODS: Forty-nine patients were randomly received A. wilhelmsii capsules or placebo, twice daily for 4 weeks in a 1:1 ratio. The disease activity index (DAI) (Partial Mayo Score), haemoglobin, platelet count, erythrocyte sedimentation rate (ESR) and serum level of C-reactive protein (CRP) were measured at the entry and the end of the treatment. To standardize the extract, caffeic acid was detected and measured in the plant extract using high performance liquid chromatography (HPLC). RESULTS: Of 49 patients who entered the trial, 40 patients completed the study. In both treatment and placebo groups, significant reductions were observed in stool frequency, rectal bleeding, physician global assessment and partial mayo score. There was no significant difference in stool frequency (P = 0.176), rectal bleeding (P = 0.523), physician global assessment (P = 0.341) and partial mayo score (P = 1) in the treatment versus the placebo groups. Laboratory variables including hemoglobin, platelet count, ESR and CRP showed no significant difference between the treatment and the placebo group. Of all participants, only one patient in the treatment group complained about skin rash (grade 1 based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0). CONCLUSION: Oral administration of A. wilhelmsii powder for 4 weeks did not create a clinical response more than placebo. It seemed to be safe in UC patients. Further studies are obligatory to evaluate the therapeutic potential of A. wilhelmsii in the form of extract in UC patients.

Cytotoxic and Apoptogenic Sesquiterpenoids from the Petroleum Ether Extract of Artemisia aucheri Aerial Parts.

Different types of Artemisia aucheri extracts were reported to have various biological activities including a cytotoxic effect on some cancer cell lines. We investigated the antiproliferative activity of isolated sesquiterpenoids from petroleum ether extract of Artemisia aucheri (A. aucheri) aerial parts on SK-N-MC, MCF-7, and A2780 cell lines. Phytochemicals from the petroleum ether cold macerated extract were isolated using normal phase vacuum liquid chromatography and high pressure liquid chromatography (VLC and HPLC) and the structures of the components were determined by spectroscopic means. Cell viability was determined by 3-(4,5- dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. Activation of caspases-3 and -9 was evaluated using a spectrophotometer. Mitochondrial membrane potential (MMP) was measured using rhodamine 123 fluorescent dye. Two tetrahydrofuran- type sesquiterpenoids, hydroperoxide of davanone (1) and hydroxydavanone (2) were isolated and characterized. Between these compounds, compound 1 exhibited more potent activity against the MCF-7, SK-N-MC and A2780 cell lines with IC50 values of 8.45 ± 0.81 µg/mL, 9.60 ± 1.32 µg/mL and 10.9 ± 2.03 µg/mL in A2780, MCF-7 and SK-N-MC cells, respectively. Compound 1 inhibited the growth of human cancer cells by induction of apoptosis. To the best of our knowledge, this is the first comprehensive study on cytotoxic and apoptotic mechanism of two davanone derivatives isolated from A. aucheri in human cancer cells. Overall, our data suggest that hydroperoxide of davanone (1) should be further studied in-vivo as a potential antitumor agent.