Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Concurrent Use of Crocin During Chemoradiation for Esophageal Squamous Cell Carcinoma.

Crocin is the major active carotenoid of saffron (Crocus sativus L.). Its pluripotent effects have led to a growing body of literature investigating its antitumor properties as well as its diverse potentials for mood stabilization, normal tissue protection, and inflammation reduction; However, there is a gap in clinical trials testing this substance in cancer patients. In this randomized, double-blind, placebo-controlled clinical trial, patients with newly diagnosed esophageal squamous cell carcinoma were randomly assigned to either 30 mg/day of crocin or placebo, prescribed during the neoadjuvant chemo-radiotherapy. The primary endpoints were pathological response and toxicity, and secondary endpoints were depression and anxiety levels and survival analysis.

Aptamer-Based Targeting of Cancer: A Powerful Tool for Diagnostic and Therapeutic Aims.

Cancer is known as one of the most significant causes of death worldwide, and, in spite of novel therapeutic methods, continues to cause a considerable number of deaths. Targeted molecular diagnosis and therapy using aptamers with high affinity have become popular techniques for pathological angiogenesis and cancer therapy scientists. In this paper, several aptamer-based diagnostic and therapeutic techniques such as aptamer-nanomaterial conjugation, aptamer-drug conjugation (physically or covalently), and biosensors, which have been successfully designed for biomarkers, were critically reviewed. The results demonstrated that aptamers can potentially be incorporated with targeted delivery systems and biosensors for the detection of biomarkers expressed by cancer cells. Aptamer-based therapeutic and diagnostic methods, representing the main field of medical sciences, possess high potential for use in cancer therapy, pathological angiogenesis, and improvement of community health. The clinical use of aptamers is limited due to target impurities, inaccuracy in the systematic evolution of ligands via exponential enrichment (SELEX)stage process, and in vitro synthesis, making them unreliable and leading to lower selectivity for in vivo targets. Moreover, size, behavior, probable toxicity, low distribution, and the unpredictable behavior of nanomaterials in in vivo media make their usage in clinical assays critical. This review is helpful for the implementation of aptamer-based therapies which are effective and applicable for clinical use and the design of future studies.

Therapeutic effects of herbal medicines in different types of retinopathies: A systematic review.

Objective: Retinopathy is an ocular manifestation of systemic diseases such as diabetes and vascular diseases. Herbal drugs have been considered as an effective therapeutic option with minimal side effects for the treatment of retinopathy by reducing the symptoms and improving visual acuity. The purpose of this systematic review was to collect studies on the effectiveness of medicinal plants in the treatment or prevention of retinopathy. Materials and Methods: A systematic literature search was performed in PubMed, Scopus, Google Scholar, and other databases in April 2021 using "herbal products" and "Retinopathy" with all their equivalent and similar terms. For this purpose, human clinical trials with the English language were included and articles with subject irrelevancy were excluded from further evaluation. Results: Overall, 30 articles with 2324 patients were studied for possible effects of herbal therapy on retinopathy. From 30 included articles, different herbal products had been evaluated. Out of 30 selected articles, 11 articles were for the treatment of age-related macular degeneration (AMD), 14 articles covered patients with diabetic retinopathy, and the other five studies were for other retinal disorders. The outcomes in majority of the studies include changes in visual acuity (VA), fundus performance, best-corrected visual acuity (BCVA), central macular thickness (CMT), focal electroretinogram (fERG), supplements and adjuvant medications appeared to be more beneficial in patients with AMD and diabetic maculopathy. Conclusion: Herbal therapy can be considered as a potential candidate in the adjuvant and complementary therapies of retinopathy. However, further studies are required to verify such efficiency.

Iranian traditional medicinal plants for management of chronic heart failure: A review.

Chronic heart failure is a public health problem with a high prevalence worldwide and an important topic in clinical cardiology. Despite of advances in the drug treatment strategy for heart failure, the number of deaths from this condition continues to rise. It will be a renewed focus on preventing heart failure using proven and perhaps novel drugs. Management will also focus on comorbid conditions that may influence the progression of the disease. Traditional medicine has a potential to introduce different approaches for treatment of some disorders. We here reviewed top medicinal plants, according to traditional medicine to experimental studies, and their potency for the treatment of chronic heart failure based on the evidence of their functions.

Oral Administration Evaluation of the Hydro-Ethanolic Extract of Ginger (Rhizome of Zingiber officinale) against Postoperative-Induced Peritoneal Adhesion: Investigating the Role of Anti-Inflammatory and Antioxidative Effects.

Peritoneal adhesions (PAs) occur and develop after abdominal surgery. Abdominal adhesions are common and often develop after abdominal surgery. Currently, there are no effective targeted pharmacotherapies for treating adhesive disease. In this regard, ginger is wildly used in traditional medicine because of its anti-inflammatory and antioxidant effects and has been investigated for peritoneal adhesion treatment. This study analyzed ginger ethanolic extraction via HPLC to have a 6-gingerol concentration. Four groups induced peritoneal adhesion to evaluate ginger's effects on peritoneal adhesion. Then, ginger extract (50, 150, and 450 mg/kg) was administered by gavage in various groups of male Wistar rats (220 ± 20 g, 6-8 weeks). After scarifying the animals for biological assessment, macroscopic and microscopic parameters were determined via scoring systems and immunoassays in the peritoneal lavage fluid. Next, the adhesion scores and interleukin IL-6, IL-10, tumor necrosis factor-(TNF-) α, transforming growth factor-(TGF-) ß1, vascular endothelial growth factor (VEGF), and malondialdehyde (MDA) were elevated in the control group. The results showed that ginger extract (450 mg/kg) notably decreased inflammatory (IL-6 and TNF-α), fibrosis (TGF-ß1), anti-inflammatory cytokine (IL-10), angiogenesis (VEGF), and oxidative (MDA) factors, while increased antioxidant factor glutathione (GSH), compared to the control group. These findings suggest that a hydro-alcoholic extract of ginger is a potentially novel therapeutic strategy for inhibiting adhesion formation. Also, it might be considered a beneficial anti-inflammatory or antifibrosis herbal medicine in clinical trials. However, further clinical studies are required to approve the effectiveness of ginger.

Application of green-synthesized carbon dots for imaging of cancerous cell lines and detection of anthraquinone drugs using silica-coated CdTe quantum dots-based ratiometric fluorescence sensor.

Chemotherapy drugs of daunorubicin and doxorubicin treat cancers with many side effects. So, detection of them in the biological system for regulation and controlling of usage is essential. In this study, a ratiometric fluorescent method was introduced for detection of daunorubicin and doxorubicin using bell pepper-based carbon dots, as the variable signal, and silica-coated CdTe quantum dots, as the constant signal. The detection was done based on variations of carbon dots intensity in the presence of drugs in comparison with the constant intensity of silica-coated CdTe quantum dots. The proposed ratiometric fluorescent method was successfully used for detection of daunorubicin and doxorubicin range of 54.37-13594.34 nmolL-1 and 86.2-17242 nmolL-1, with a detection limit of 18.53 nmolL-1 and 29 nmolL-1, respectively. Also, this method was used for detection of drugs in serum samples with recovery ranges of 86.14-99.62 (RSD 3-1.47%) and 86.32-97.53 (3.38-1.48%), respectively. Finally, after evaluation of carbon dots toxicity by MTT test, carbon dots was applied for imaging of prostate cancer cell lines (PC-3) and breast cancer cell lines (MCF7). The results demonstrated that despite improvement of the repeatability and interferences reduction by ratiometric method, also carbon dots were successfully applied for imaging of cell lines.

The effect of crocin versus sertraline in treatment of mild to moderate postpartum depression: a double-blind, randomized clinical trial.

Postpartum depression (PPD) is one of the most common conditions among women. This study aimed to investigate the effect of crocin compared to sertraline in women with mild to moderate PPD. This trial study was performed on women with PPD. Patients in two groups received crocin (15 mg) and sertraline (50 mg) daily for 3 months, respectively. Patients have assessed by Beck's Depression Inventory-II (BDI-II) and Beck's Anxiety Inventory (BAI) at 0-12 weeks. A total of 64 patients were examined. The mean of the BDI-II score in the crocin group decreased after 3 months from 20.75 to 4.93 (P = 0.0001). In the sertraline group, the mean score of BDI-II decreased after 3 months from 21.06 to 2.37 (P = 0.0001). The mean of the BAI score in the crocin group decreased significantly after 3 months from 13.75 to 4.06 (P = 0.0001) and in the sertraline group from 12.9 to 2.71 (P = 0.0001). No significant difference was observed between crocin and sertraline after the clinical trial (P = 0.5). No severe side effects were observed during the study in the two groups. The results of this study showed that crocin (15 mg daily) could be useful in treating PPD. Furthermore, this study showed that crocin, with far fewer side effects than chemical drugs, can be widely used in PPD, but due to the small sample size further studies are necessary to confirm such efficiency.

Beneficial effects of celery seed extract (Apium graveolens), as a supplement, on anxiety and depression in hypertensive patients: a randomized clinical trial.

BACKGROUND: Anxiety and depression are crucial public health issues, affecting the rising in hospitalizations and death. Anxiety and depression can worsen hypertension and vice versa. OBJECTIVE: The current study has investigated the effects of celery seed extract, as a drug supplement, with the active ingredient of 3-n-butylphthalide, on mental problems primarily anxiety and secondary depression in hypertensive patients. DESIGN: The current study was a randomized, triple-blind, placebo-controlled, cross-over, 4-week clinical trial with a 4-week washout period. Fifty hypertensive patients received 4 placebo or celery seed extract capsules (1.34 g per day) for 4 weeks as a supplement to their usual medication regimen. The blood pressure parameters were assessed using 24-h ambulatory blood pressure monitoring device. Anxiety and depression and their wide range of symptoms were evaluated using Beck anxiety and depression inventories (BAI and BDI). RESULTS: In the celery treatment step, the mean reduction in BAI and BDI scores were 6.78 (P < 0.001) and 3.63 (P < 0.01), respectively. Some symptoms of anxiety including unable to relax, nervousness, numbness, dizziness, flushed face, sweating, and breathing difficulty were significantly improved by celery consumption (P < 0.001). Celery could decrease symptoms of depression such as sadness, crying, loss of energy, insomnia, irritability, fatigue, loss of interest in sex, and punishment feeling (P < 0.01). The mean reduction in blood pressure parameters was also significant during celery therapy (P < 0.001). CONCLUSIONS: The psychometric properties of anxiety and depression were investigated and the results were promising. The results indicated the anti-anxiety and anti-depressive properties of celery seed extract as a supplement in hypertensive patients. CLINICAL TRIAL REGISTRATION: Registry name: Iranian Registry of Clinical Trials (IRCT), Registration number: IRCT20130418013058N8, Registration link: https://www.irct.ir/trial/30021 . The study was carried out between 2018-09-21 and 2020-07-20.

Significant Effect of Crocin on the Gene Expression of MicroRNA-21 and MicroRNA-155 in Patients with Osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis associated with gradual joint destruction. The current treatment aims to alleviate pain and inflammation and improve the quality of life. Crocin is an active ingredient in saffron, with anti-inflammatory properties. MicroRNAs are small, non-coding RNAs that regulate gene expression. We aimed to evaluate the effect of crocin on the gene expression of microRNA-146a, microRNA-155, microRNA-223, and microRNA-21 in OA patients and compare it with a placebo. This study was approved and registered in the Iranian Registry of Clinical Trials (2015021910507N2) and ClinicalTrials.gov identifier: NCT03375814. Forty OA patients were randomly divided into two equal groups, receiving either crocin or placebo. Peripheral blood samples were collected before and four months after the intervention. The pain was assessed using the visual analog scale, and laboratory tests included C-reactive protein and erythrocyte sedimentation rate. The expression levels of microRNA-146a, microRNA-155, microRNA-223, and microRNA-21 genes were evaluated by SYBR Green real-time PCR. The results showed that the gene expression levels of microRNA-21 and microRNA-155 in patients receiving crocin were significantly decreased and increased, respectively. No significant changes were observed in microRNA-146a and microRNA-223 gene expression levels. In conclusion, crocin's anti-inflammatory role might be partly attributed to its effects on the gene expression of microRNA-21 and microRNA-155.

Effect of crocin on diabetic patients: A placebo-controlled, triple-blinded clinical trial.

OBJECTIVE: The purpose of this study was to evaluate the effect of Saffron and its active ingredient, crocin, as a natural antioxidant in the treatment of type II diabetes. METHODS: A total of 150 uncontrolled type 2 (non-insulin-dependent) diabetic patients were selected based on inclusion criteria, randomly divided into three groups (crocin, saffron and placebo) for three months' clinical trial. Fasting blood glucose (FBS), insulin level, glycosylated hemoglobin (HbA1c), lipid profile, kidney and liver function tests were performed before and three months after the study. The patients were followed every two weeks for possible clinical side effects. RESULTS: Our results showed that after three months of treatment with crocin and saffron, FBS reduction was significant in all groups (P-value < 0.05). In addition, reduction of HbA1c was significant in the crocin and saffron groups compared to placebo group. Comparison between groups showed that treatment with crocin and saffron led to a significant reduction in HbA1c than placebo, and FBS level significantly reduced only in crocin compared to saffron and placebo groups. In addition, changes in lipid profile were not significant in any of the three groups. Also, there was no significant difference in liver and liver parameters in all three groups. Inter-group comparison of insulin levels showed significant difference only between the saffron and placebo groups. CONCLUSION: Crocin can be effective in controlling the level of FBS and HbA1c in patients with type 2 diabetes.

Effect of celery (Apium graveolens) seed extract on hypertension: A randomized, triple-blind, placebo-controlled, cross-over, clinical trial.

In the present work, the antihypertensive effects of celery seed extract (Apium graveolens) with active ingredients, such as 3-n-butylphthalide, were studied as a drug supplement in the treatment of hypertension. This study was a randomized, triple-blind, placebo-controlled, cross-over clinical trial. Fifty-two patients were divided into two groups (celery and placebo) and completed the two-step clinical trial. Four celery seed extract capsules (totally 1.34 g per day) or 4 placebo capsules per day were administered to the patients during a 4-week clinical trial. The blood pressure was assessed using a 24-hr ambulatory blood pressure monitoring method. In celery group, systolic blood pressure changed from 141.2 ± 5.91 to 130.0 ± 4.38 mmHg (p < .001) while diastolic blood pressure changed from 92.2 ± 5.74 to 84.2 ± 4.87 mmHg (p < .001). Moreover, the mean arterial blood pressure changed from 108.5 ± 5.76 to 99.5 ± 4.66 mmHg (p < .001), and pulse pressure decreased from 49.0 ± 6.21 to 45.8 ± 6.01 mmHg (p < .01). However, no significant changes were observed in placebo group in terms of the above-mentioned parameters (p > .05). Furthermore, no significant side effect was reported in the celery group, compared to the placebo group (p > .05). The results were promising and indicated the therapeutic effects of celery seed extract as a supplement in the management of hypertension.

Safety evaluation and biochemical efficacy of celery seed extract (Apium Graveolens) capsules in hypertensive patients: a randomized, triple-blind, placebo-controlled, cross-over, clinical trial.

The present study was conducted to evaluate the safety of celery seed extract (Apium graveolens), as a medicinal herb with active ingredients such as 3-n-butylphthalide (NBP), in hypertensive patients. This study was a randomized, triple-blind, placebo-controlled, cross-over clinical trial. Hypertensive patients (51 participants) received 4 celery seed capsules (a total of 1.34 g extract per day) or 4 placebo capsules per day for 4 weeks as a supplement to their usual medication regimen. The results indicated that the celery seed capsule not only was safe for hypertensive patients but also caused a reduction in BP, FBS, and lipid profile values. Also, it had beneficial effects on kidney and liver functions. No significant change was observed in blood cells and serum electrolytes (p > 0.05). The mean reduction in BUN and SCr were 3.43 and 0.075 mg/dL, and in SGPT and SGOT were 4.08 and 3.03 U/L, respectively (p < 0.05). FBS reduced from 108.53 to 97.96 mg/dL after 4 weeks of celery administration (p < 0.01). The decrease in TC, TG, LDL, and increase in HDL were 16.37, 16.22, 11.84, and 2.52 mg/dL, respectively (p < 0.001). According to the promising results of this clinical trial, celery seed extract can be considered a safe supplement for hypertensive patients. The study is limited by the small sample size; therefore, larger randomized trials are required.

Potential role of green tea extract and epigallocatechin gallate in preventing bisphenol A-induced metabolic disorders in rats: Biochemical and molecular evidence.

BACKGROUND: Bisphenol A (BPA) is an artificial chemical widely used in the production of polycarbonate plastics and epoxy resins. Accumulating evidence indicates that BPA exposure is associated with metabolic disorders. The beneficial effects of green tea and epigallocatechin gallate (EGCG), major catechin present in green tea, on alleviating BPA-induced metabolic disorders have been shown in various studies. PURPOSE: Protective effects of green tea extract and EGCG on BPA-induced metabolic disorders and possible underlying mechanisms were investigated. METHODS: Rats were randomly divided into control, green tea extract (50 and 100 mg/kg, IP), EGCG (20 and 40 mg/kg, IP), BPA (10 mg/kg, gavage), BPA plus green tea extract (25, 50, and 100 mg/kg, IP), BPA plus EGCG (10, 20, and 40 mg/kg, IP), and BPA plus vitamin E (200 IU/kg, IP). After two months, body weight, blood pressure, biochemical blood tests, hepatic malondialdehyde (MDA), and glutathione (GSH) were assessed. By enzyme-linked immunosorbent assay, serum levels of insulin, leptin, adiponectin, TNFα, and IL-6, and by western blotting, hepatic insulin signaling (IRS-1, PI3K, Akt) were measured. RESULTS: BPA increased body weight, blood pressure, and MDA, decreased GSH, elevated serum levels of low-density lipoprotein cholesterol, total cholesterol, triglyceride, glucose, insulin, leptin, TNFα, IL-6, and liver enzymes including alanine aminotransferase and alkaline phosphatase, and lowered high-density lipoprotein cholesterol and adiponectin levels. In western blot, decreased phosphorylation of IRS-1, PI3K, and Akt was obtained. Administration of green tea extract, EGCG, or vitamin E with BPA reduced the detrimental effects of BPA. CONCLUSION: These findings indicate that green tea extract and EGCG can be effective in preventing or reducing metabolic disorders induced by BPA linked to their antioxidant and anti-inflammatory activity, regulating the metabolism of lipids, and improving insulin signaling pathways.

Promising effects of gingerol against toxins: A review article.

Ginger is a medicinal and valuable culinary plant. Gingerols, as an active constituent in the fresh ginger rhizomes of Zingiber officinale, exhibit several promising pharmacological properties. This comprehensive literature review was performed to assess gingerol's protective and therapeutic efficacy against the various chemical, natural, and radiational stimuli. Another objective of this study was to investigate the mechanism of anti-inflammatory, antioxidant, and antiapoptotic properties of gingerol. It should be noted that the data were gathered from in vivo and in vitro experimental studies. Gingerols can exert their protective activity through different mechanisms and cell signaling pathways. For example, these are mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-kB), Wnt/ß-catenin, nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE), transforming growth factor beta1/Smad3 (TGF-ß1/Smad3), and extracellular signal-related kinase/cAMP-response element-binding protein (ERK/CREB). We hope that more researchers can benefit from this review to conduct preclinical and clinical studies, treat cancer, inflammation, and attenuate the side effects of drugs and industrial pollutants.

Surface-decorated graphene oxide sheets with nanoparticles of chitosan-Arabic gum for the separation of bioactive compounds: A case study for adsorption of crocin from saffron extract.

This work provides a new perception toward the application of the graphenic-biopolymeric composites as a solid-bed for separation and purification of bioactive compounds. Graphene oxide nanocomposites with functionalized sheets by soluble and insoluble nanocomplexes of chitosan and Arabic gum, were successfully synthesized and employed for the adsorption and purification of crocin, a nutraceutical from saffron. The composites exhibited a nanostructured scaffold with a particle size of 10 nm and experienced an unprecedented increase in the surface area by about 300% and improved d-spacing sheets by 17%. The optimum conditions for crocin separation were temperature = 318 K, stirring rate = 300 rpm, initial concentration = 100 mg L-1 and pH = 6. Under these conditions, the nanocomposites separated 99.1% of crocin in an equilibrium time of 30 min. The adsorption data were best represented by Freundlich isotherm and pseudo-second-order kinetic models. The thermodynamic studies indicated that the crocin adsorption on nanocomposites was an endothermic, spontaneous and physisorption process. The high-performance liquid chromatography (HPLC) analysis revealed that produced nanocomposites adsorbed crocin efficiently from saffron extract with a purity similar to the standard sample. The possible interaction mechanisms between crocin and nanocomposites were electrostatic interactions and hydrogen bonding.

Amelioration of anxiety, depression, and chemotherapy related toxicity after crocin administration during chemotherapy of breast cancer: A double blind, randomized clinical trial.

The effects of saffron (Crocus sativus L.) on mood disorders have already been established. More recently, its anti-neoplastic effects have provoked a great attention. This study aims to assess the effects of crocin administration during doxorubicin-based chemotherapy of breast cancer on anxiety, depression, and chemotherapy toxicity profile. Seventy-two patients with non-metastatic Her2/neu positive or triple negative breast cancer were enrolled and randomly assigned to receive either 30 mg/day of crocin or placebo during chemotherapy [2:2]. Beck's Depression and Anxiety Inventories were used at baseline and end of the trial. In addition, the ECOG Common Toxicity Criteria were applied to assess chemotherapy side-effects. After the intervention, the degree of anxiety and depression decreased significantly in the crocin group (p = .001 for both) and increased significantly in the placebo-group (p = .006 and p = .036, respectively). There were significantly higher grade II-IV leukopenia (47.2% vs. 19.4%, p = .012) in the crocin group, and grade II-IV hypersensitivity-reaction (30.6% vs. 5.6%, p = .006) in addition to neurological disorders (66.7% vs. 41.7%, p = .03) in the placebo-group. The results indicate that using crocin during chemotherapy in patients with breast cancer has ameliorated anxiety and depression. Moreover, leucopenia increased whereas hypersensitivity reaction and neurological disorders decreased in the crocin group. In addition, a trend toward survival improvement was observed, which is going to be investigated on longer follow up.

Effect of crocin versus fluoxetine in treatment of mild to moderate obsessive-compulsive disorder: A double blind randomized clinical trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common disabling disorder. Crocin, the active component of the saffron plant (Crocus Sativus L.) has various pharmacological activities. The present study compared the efficacy and safety of crocin and fluoxetine in treatment of mild to moderate OCD. METHODS & MATERIALS: Fifty patients with OCD, aged 18 to 60 years, were randomized to receive either crocin (15 mg) or fluoxetine (20 mg) capsules for 8 weeks. Eligible participants received one capsule/day in the first month, which followed by two capsules daily in the second month. The patients were evaluated using Yale-Brown Obsessive-compulsive scale (Y-BOCS) and Hamilton Anxiety Rating scale (HARS). RESULTS: The mean Y-BOCS score in both groups decreased significantly during 2 months (p-value = 0.0001). Also, HARS score in the crocin group was changed from 17.16 to 13.04 whereas, in the fluoxetine group was decreased from 18.28 to 12.34. The results indicated no difference between the two groups in Y-BOCS and HARS score changes after 2-month trial (p-value >0.5). Also, fewer adverse effects were reported in the crocin group compared to the fluoxetine group. CONCLUSION: According to our study, it seems that crocin is effective in treatment of patients with mild to moderate OCD with possibly fewer adverse effects compared to fluoxetine.

Design and synthesis of new carbamates as inhibitors for fatty acid amide hydrolase and cholinesterases: Molecular dynamic, in vitro and in vivo studies.

As anandamide (N-arachidonoylethanolamine, AEA) shows neuroprotective effects, the inhibition of its degradative enzyme, fatty acid amide hydrolase (FAAH) has been considered as a hopeful avenue for the treatment of neurodegenerative diseases, like Alzheimer's disease (AD). Memory loss, cognitive impairment and diminution of the cholinergic tone, due to the dying cholinergic neurons in the basal forebrain, are common hallmarks in patients with AD. By taking advantage of cholinesterase inhibitors (ChEIs), the degradation of acetylcholine (ACh) is decreased leading to enhanced cholinergic neurotransmission in the aforementioned region and ultimately improves the clinical condition of AD patients. In this work, new carbamates were designed as inhibitors of FAAH and cholinestrases (ChEs) (acetylcholinestrase (AChE), butyrylcholinestrase (BuChE)) inspired by the structure of the native substrates, structure of active sites and the SARs of the well-known inhibitors of these enzymes. All the designed compounds were synthesized using different reactions. All the target compounds were tested for their inhibitory activity against FAAH and ChEs by employing the Cayman assay kit and Elman method respectively. Generally, compounds possessing aminomethyl phenyl linker was more potent compared to their corresponding compounds possessing piperazinyl ethyl linker. The inhibitory potential of the compounds 3a-q extended from 0.83 ± 0.03 µM (3i) to ˃100 µM (3a) for FAAH, 0.39 ± 0.02 µM (3i) to 24% inhibition in 113 ± 4.8 µM (3b) for AChE, and 1.8 ± 3.2 µM (3i) to 23.2 ± 0.2 µM (3b) for BuChE. Compound 3i a heptyl carbamate analog possessing 2-oxo-1,2-dihydroquinolin ring and aminomethyl phenyl linker showed the most inhibitory activity against three enzymes. Also, compound 3i was investigated for memory improvement using the Morris water maze test in which the compound showed better memory improvement at 10 mg/kg compared to reference drug rivastigmine at 2.5 mg/kg. Molecular docking and molecular dynamic studies of compound 3i into the enzymes displayed the possible interactions of key residues of the active sites with compound 3i. Finally, kinetic study indicated that 3i inhibits AChE through the mixed- mode mechanism and non-competitive inhibition mechanism was revealed for BuChE.

Preparation, evaluation, and application of dummy molecularly imprinted polymer for analysis of hesperidin in lime juice.

Lime juice as the most commonly used natural source production can be characterized using determination of flavonoids contents such as hesperidin. So, development of analyzing methods for checking the quality and healthiness of lime juices is necessary. In this study, we aimed to set up a selective solid phase extraction method using dummy molecularly imprinting approach for extraction and separation of hesperidin in lime juice to check the quality of commercial lime juice products of Mashhad city market. The imprinted polymers were synthesized by hesperitin as dummy template due to the hesperitin solubility in the wide range of porogenic solvents. The specificity extent of synthesized polymers toward hesperidin was tested and optimum one was used as adsorbent in solid-phase extraction cartridge. The dummy molecularly imprinted polymer with high adsorption capacity for hesperidin (dissociation constant 0.12 µM) was successfully used for extraction and clean-up of hesperidin in the lime juice matrix prior to analysis by high-performance liquid chromatography. The analysis of hesperidin was done in the range of 0.312-50 µg/mL with detection limit of 0.05 µg/mL. This technique was successfully set up to remove the interfering compounds for analysis of hesperidin in commercial lime juice products.

Therapeutic effects of medicinal plants on isoproterenol-induced heart failure in rats.

AIMS: Natural products still serves as a hope for some illnesses which modern medicine fails to cure. Many people, either knowing their effects or not, are using these herbal products. Treatment of chronic heart failure (CHF) is yet a complicated clinical challenge and there is need to improve or make new therapeutic targets. Finding new agents for CHF is an important subject in cardiovascular drug research. In this study, we evaluated the effects of ten herbals on treatment of CHF on isoproterenol-induced model. METHODS AND RESULTS: Ninety-six male Wistar rats (16 weeks old) were used in 12 groups. Transthoracic echocardiography was performed on the rats for confirmation of CHF model by decreasing ejection fraction. After 4 weeks' treatment, hearts were removed and blood samples were collected in tubes to measure plasma levels of laboratory findings. Our results showed that the mean of ejection fraction in model rats was 51.82 ± 3.49 percent and all of our used natural products could significantly increase the ejection fraction (P < 0.01). The most effective herbals in improving the ejection fraction were Allium sativum (30.69 %), Peganum harmala (26.08 %) and Apium graveolens (24.09 %). The best results in decreasing NT-ProBNP, was obtained from Allium sativum, Peganum harmala and Berberis vulgaris respectively. Our results showed that none of natural products had toxic effect on renal and liver tissues. CONCLUSION: Our results showed that Allium sativum, Peganum harmala and Berberis vulgaris could significantly improve cardiac function by improvement of left ventricular remodeling, lowering hs-CRP and NT-ProBNP and echocardiographic indexes without liver or renal side effects.