The Effect of Astaxanthin and Metformin on Oxidative Stress in Granulosa Cells of BALB C Mouse Model of Polycystic Ovary Syndrome.

Reactive oxygen species (ROS), involved in the pathogenesis of the polycystic ovary syndrome (PCOS), play a key role in the onset of apoptosis in follicles and granulosa cells (GCs). We aimed to investigate the antioxidant effects of AST and metformin separately and in combination on GCs using a PCOS mouse model. Forty-eight prepubertal female BALB C mice aged 25-30 days and weighing 12-14 g were studied. The PCOS model was created by subcutaneous injection of the dehydroepiandrosterone (DHEA) hormone in 8 mice of BALB C for 20 consecutive days. Apoptosis and the amount of ROS were evaluated in GCs of the ovaries via flow cytometry. The activity of AKT protein was measured by western blot, and the viability of GCs was investigated using spectrophotometry. Ovarian tissue sections were prepared, stained with H&E, and the morphology of the sections was examined. Statistical analysis was performed by SPSS v22.0 software using one-way ANOVA. We found that AST administration leads to a significant reduction in oxidative stress (P<0.01) and consequently a significant decrease in the rate of apoptosis (P<0.01). While the expression of AKT in the AST group revealed a significant increase (P<0.05), it decreased in the metformin group. However, it was still significantly higher than the control and PCOS groups. Ovulation was confirmed in both metformin and AST groups. Further studies are warranted to prove the efficacy of AST and to introduce it as a complementary therapeutic agent in PCOS.

Medicinal Plants as Potential Hemostatic Agents.

PURPOSE: Medicinal plants with a variety of phytochemical ingredients remain a potential source for new drug discovery. The use of medicinal herbs in a wide range of diseases and symptoms, such as bleeding, is prevalent in traditional and ethno medicine worldwide. Thus, this work provides a comprehensive review of medicinal plants or their isolated compounds, with respect to their ethno-medicinal use, which have demonstrated the stimulating effect on the hemostasis process. METHODS: The relevant studies were withdrawn from electronic databases including Pubmed, EMBASE and Web of Science with a structured search methodology. RESULTS: The total of 17 medicinal plants with hemostatic activity were extracted. The most frequently studied plant families were Compositae, Lamiaceae, Fabaceae, and Asteraceae. Bioactive compounds exerting hemostatic activity included tannins, iridoid glycosides, glycoconjugate, lignan, saponins and phenolic compounds. The most attributed mechanisms include coagulation stimulation via increasing the factor XII activity and plasma fibrinogen levels, the fibrinolysis inhibition, vascular or smooth muscle constriction and platelet aggregation. The most important adverse effects of high dose extract or isolated compounds administration were hepatotoxicity and nephrotoxicity. CONCLUSION: This review provides a list of medicinal plants with hemostatic activity that could be used as valuable sources of new plant-based hemostatic agents. Furthermore, this could be practical in detecting possible interactions of plants with anticoagulant, antiplatelet, fibrinolytic and antifibrinolytic medications.

Gold nanoparticles promote a multimodal synergistic cancer therapy strategy by co-delivery of thermo-chemo-radio therapy.

Multimodal cancer therapy has become a new trend in clinical oncology due to potential generation of synergistic therapeutic effects. Herein, we propose a multifunctional nanoplatform comprising alginate hydrogel co-loaded with cisplatin and gold nanoparticles (abbreviated as ACA) for triple combination of photothermal therapy, chemotherapy and radiotherapy (thermo-chemo-radio therapy). The therapeutic potential of ACA was assessed in combination with 532 nm laser and 6 MV X-ray against KB human mouth epidermal carcinoma cells. The results demonstrated that tri-modal thermo-chemo-radio therapy using ACA induced a superior anticancer efficacy than mono- or bi-modality treatments. The intracellular reactive oxygen species (ROS) level in KB cells treated with tri-modal therapy was increased by 4.4-fold compared to untreated cells. The gene expression analysis demonstrated the up-regulation of Bax pro-apoptotic factor (by 4.5-fold) and the down-regulation of Bcl-2 anti-apoptotic factor (by 0.3-fold). The massive cell injury and the appearance of morphological characteristics of apoptosis were also evident in the micrograph of KB cells caused by thermo-chemo-radio therapy. Therefore, ACA nanocomplex can be offered as a promising platform to combine photothermal therapy, chemotherapy and radiotherapy, thereby affording an opportunity for combating chemo- and radio-resistant tumors.

Hemostatic activity of aqueous extract of Myrtus communis L. leaf in topical formulation: In vivo and in vitro evaluations.

ETHNOPHARMACOLOGICAL RELEVANCE: Myrtus communis L. (MC) is a well-known medicinal plant in traditional Persian medicine, which contains a large amount of phenolic compounds (mainly hydrolyzable tannins). As mentioned in ancient literature, MC was widely used to control bleeding in every part of the body. Nevertheless, there is no pharmacological study on the anti-hemorrhagic activity of this plant till now. AIM OF THE STUDY: The current in vivo and in vitro study aimed at evaluating the hemostatic activity of M. communis aqueous leaf extract (MCE) in topical formulation. MATERIALS AND METHODS: Two parameters of bleeding time and amount in tail bleeding model were measured in vivo in rats treated with MCE (1%, 2.5%, 5%, 7.5%, 10%, 15%, and 20% w/v), 5% M. communis aqueous leaf extract gel (G), tannic acid (TA) (1%, 2.5%, 5%, 7.5%, and 10%), normal saline (NS), and the Monsel's solution (MS), a commercial hemostatic agent. Also, the effect of 5% MCE and 5% TA on PT (prothrombin time) and aPTT (activated partial thromboplastin time) as well as protein precipitation and platelet aggregation were assessed in vitro. RESULTS: In the rat-tail bleeding model, bleeding time and amount significantly (P < 0.001) reduced by the application of 5% MCE solution on the cut tail compared with the NS group. The bleeding time and amount in the MS group were not significantly different from those of the 5% MCE group. Platelet microaggregates were detected by fluorescent microscope. PT and aPTT values increased >120 s and >180 s by 5% MCE, respectively. Also, protein precipitation and significant reduction in serum proteins were observed in the 5% MCE group. CONCLUSION: The current study provided new insights into the hemostatic effect of MCE, which may be partially mediated by platelet aggregation activity. Hence, it could be evaluated as the resource of new plant origin hemostatic agent.

Effects Of Saffron Supplementation On Inflammation And Metabolic Responses In Type 2 Diabetic Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Type 2 diabetes (T2D) is accompanied by elevated inflammation, oxidative stress, hyperlipidemia and hyperglycemia which all contribute to cardiovascular disease pathogenesis. Saffron as a complementary medicine and source of antioxidants could play a role in alleviating diabetes and its complications. The aim of this study was to determine the effects of saffron supplementation as an adjunct therapy in T2D. PATIENTS AND METHODS: This randomized controlled trial included 80 T2D patients with a mean age of 54.1 years. Participants were randomly assigned into two groups to take either saffron tablets (100 mg/day; n=40) or placebo (n=40) for 12 weeks. Fasting blood samples were obtained at the beginning and after the intervention period to quantify glycemic factors, lipid profile, and biomarkers of inflammation and oxidative stress. Anthropometric indices and dietary intakes were also measured at baseline and at study end. RESULTS: Compared with placebo, saffron supplementation resulted in significant decreases in waist circumference (p<0.001) and malondialdehyde (MDA) (p=0.001). There was no statistically significant difference in other indices, including anthropometric parameters, serum insulin, fasting blood glucose, HbA1c, insulin sensitivity indices, lipid profile, high-sensitivity C-reactive protein, total antioxidant capacity, and tumor necrosis factor-α between the study groups (p>0.05). CONCLUSION: Overall, 12 weeks of saffron supplementation in diabetic patients had beneficial effects on waist circumference and serum MDA levels. However, saffron did not influence other evaluated cardio metabolic risk markers in diabetic patients.

The effect of saffron (Crocus sativus L.) supplementation on blood pressure, and renal and liver function in patients with type 2 diabetes mellitus: A double-blinded, randomized clinical trial.

OBJECTIVE: Microalbuminuria and hypertension are the risk factors for diabetic nephropathy, and increased levels of liver enzymes are prevalent among diabetic patients. The aim of this research was to examine the effects of Crocus sativus supplementation on nephropathy indices, liver enzymes, and blood pressure in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: This placebo-controlled, randomized clinical trial was performed among 80 T2D patients. Subjects were randomly assigned to either Crocus sativus (n = 40) or placebo (n = 40) groups and treated with C. sativus and or placebo for 12 weeks, respectively. Alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum urea, creatinine, 24-hr urine albumin, systolic blood pressure (SBP), diastolic blood pressure (DBP), physical activity, and dietary intakes were measured and blood samples were taken at baseline and after the 12­week intervention to assess the differences between the two groups. RESULTS: C. sativus supplementation compared with the placebo resulted in a significant reduction of SBP (P<0.005). However, changes in other indices including liver enzymes, serum creatinine, serum urea, and 24-hr urine albumin, and DBP were not significantly different between the two groups (p>0.05). Also, no significant changes in dietary intakes and physical activity were seen between the two groups. CONCLUSION: This report shows that daily supplementation with 100 mg C. sativus powder improved SBP. However, it did not considerably improve DBP, nephropathy indices and liver functions in T2D patients after 12 weeks of administration.

Sesquiterpene lactones from Ferula oopoda and their cytotoxic properties.

Two new sesquiterpene lactones, namely feruhodin A and feruhodin B, together with six known compounds, daucoeudesmanolactone, dehydrooopodin, oopodin, badkhysin, 7-demethylplastochromenol, and scoparone, were isolated from the roots of Ferula oopoda. The structures of these compounds were elucidated by 1D and 2D NMR techniques as well as high-resolution mass spectrometry. Cytotoxic effects of these compounds were evaluated against two human cancer cell lines including MCF7and K562 using the Alamar blue assay. The results showed that dehydrooopodin possessed significant cytotoxic effects with IC50 values of 15 and 5 µM against MCF7 and K562, respectively.