The Impact of Chrysin on The Folliculogenesis and Ovarian Apoptosis in Ischemia-Reperfusion Injury in The Rat Model.

BACKGROUND: The ovarian Ischemia/reperfusion is one of the gynecological emergency concerns that may lead to the ovary damage and folliculogenesis. The present research aimed to evaluate the impact of the Chrysin (CH) on the ischemia-reperfusion (I/R) injury in the rat model. MATERIALS AND METHODS: In this experimental research, 48 adult female rats, 8 weeks age and 180-200 g weight, have been categorized into 6 equal groups (n=8) including one sham and 5 ovarian torsion groups (OT+CH groups) that received different treatments. Each group has been treated 30 min before detorsion with gavage of CH or normal saline for 1 week and pregnant mare serum gonadotropin (PMSG) has been injected on the day 5 for initiating folliculogenesis. Finally, bio-chemical, molecular, histopathological, apoptotic and hormonal evaluations were performed. RESULTS: The anti-oxidant enzyme, superoxide dismutase and glutathione peroxidase, ameliorated in the ovarian tissues of the OT+CH groups in comparison with the OT group (P<0.001). Moreover, the level of serum Luteinizing hormone considerably declined and estradiol level (P<0.001), partly enhanced in the rats treated with CH in comparison with the ones in the OT group (P<0.05). In addition, histopathological scores of the OT+CH groups ameliorated in comparison with the OT group scores (P<0.05). Furthermore, the expression Caspase-3 and Bax genes were significantly increased while the expression of Bcl-2 was notably decreased in the OT group in comparison with the sham group (P<0.05). CONCLUSION: Here, it seems that CH is possibly beneficial for the protection of ovaries against reperfusion injury and ischemia.

Chitosan-Raloxifene nanoparticle containing doxorubicin as a new double-effect targeting vehicle for breast cancer therapy.

BACKGROUND: treatment of breast cancer as one of the most common cancers in the world remains an important area of drug development based on nanoparticulate systems. Effective targeted therapy of affected cells based on ligand conjugate biocompatible polymeric nanoparticles is an attractive perspective in this context. OBJECTIVE: In this study, a novel double effect nanoparticle based on Chitosan-Raloxifene conjugate was prepared for adjuvant therapy (hormone and chemo therapy) and drug targeting to breast cancer cells via estrogen receptor (ER). METHODS: Chitosan-raloxifene conjugate was synthesized. Related nanoparticles containing doxorubicin (DOX) were prepared and characterized. Experimental design study was performed to determine the optimum levels of variables in the preparation of nanoparticle. Drug loading, release, nanoparticle stability, and the effect of nanoparticles on cell viability were evaluated. Further, inhibition tests were performed to demonstrate that the function of these novel nanoparticles is mediated via ER. RESULTS: Chitosan-raloxifene conjugate was successfully synthesized. The prepared nanoparticles showed sizes within 25-35 nm, more than 95% drug loading, about 60% of drug release and desired stability after 24 h. XTT assay on MCF-7 cell line illustrated that these nanoparticles could inhibit the cellular growth up to 60%. The results from inhibition tests revealed that prepared nanoparticles can inhibit cell growth via ER blocking. CONCLUSION: This study introduced chitosan-raloxifene nanoparticles containing doxorubicin as a novel targeting agent for adjuvant therapy of breast cancer. Graphical abstract.

Supplementation of Culture Media with Lysophosphatidic Acid Improves The Follicular Development of Human Ovarian Tissue after Xenotransplantaion into The Back Muscle of γ-Irradiated Mice.

OBJECTIVE: The aim of the present study was to evaluate the effects of lysophosphatidic acid (LPA) supplementation of human ovarian tissue culture media on tissue survival, follicular development and expression of apoptotic genes following xenotransplantation. MATERIALS AND METHODS: In this experimental study, human ovarian tissue was collected from eight normal female to male transsexual individuals and cut into small fragments. These fragments were vitrified-warmed and cultured for 24 hours in the presence or absence of LPA, then xenografted into back muscles of γ-irradiated mice. Two weeks post-transplantation the morphology of the recovered tissues were evaluated by hematoxylin and eosin staining. The expression of genes related to apoptosis (BAX and BCL2) were analyzed by real time revers transcription polymerase chain reaction (RT-PCR) and detection of BAX protein was done by immunohistochemical staining. RESULTS: The percent of normal and growing follicles were significantly increased in both grafted groups in comparison to the non-grafted groups, however, these rates were higher in the LPA-treated group than the non-treated group (P<0.05). There was a higher expression of the anti-apoptotic gene, BCL2, but a lower expression of the pro-apoptotic gene, BAX, and a significant lower BAX/ BCL2 ratio in the LPA-treated group in comparison with non-treated control group (P<0.05). No immunostaining positive cells for BAX were observed in the follicles and oocytes in both transplanted ovarian groups. CONCLUSION: Supplementation of human ovarian tissue culture medium with LPA improves follicular survival and development by promoting an anti-apoptotic balance in transcription of BCL2 and BAX genes.

TRPA1 Modulating C14 Polyacetylenes from the Iranian Endemic Plant Echinophora platyloba.

Phytochemical investigation of the apolar extract obtained from aerial parts of the Iranian endemic plant Echinophora platyloba DC (Apiaceae) resulted in the characterization of the polyacetylene fraction of this plant. This resulted to be composed of the known echinophorins A and B, embedding the very rare α-pyrone terminal, and of the new echinophorin D (3), including also three conjugated triple bonds. The chemical structures of these compounds were secured by detailed inspection of MS and 1D/2D NMR spectra. The isolated polyacteylenes were evaluated for their modulation of six thermo-TRP channels and they revealed a selective activity on TRPA1, an ion channel involved in the mediation of neuropathic and inflammatory pain. This is the first report on the activity of plant polyacetylenes on transient receptor potential (TRP) channels.

Potential Anticancer Properties of Osthol: A Comprehensive Mechanistic Review.

Cancer is caused by uncontrolled cell proliferation which has the potential to occur in different tissues and spread into surrounding and distant tissues. Despite the current advances in the field of anticancer agents, rapidly developing resistance against different chemotherapeutic drugs and significantly higher off-target effects cause millions of deaths every year. Osthol is a natural coumarin isolated from Apiaceaous plants which has demonstrated several pharmacological effects, such as antineoplastic, anti-inflammatory and antioxidant properties. We have attempted to summarize up-to-date information related to pharmacological effects and molecular mechanisms of osthol as a lead compound in managing malignancies. Electronic databases, including PubMed, Cochrane library, ScienceDirect and Scopus were searched for in vitro, in vivo and clinical studies on anticancer effects of osthol. Osthol exerts remarkable anticancer properties by suppressing cancer cell growth and induction of apoptosis. Osthol's protective and therapeutic effects have been observed in different cancers, including ovarian, cervical, colon and prostate cancers as well as chronic myeloid leukemia, lung adenocarcinoma, glioma, hepatocellular, glioblastoma, renal and invasive mammary carcinoma. A large body of evidence demonstrates that osthol regulates apoptosis, proliferation and invasion in different types of malignant cells which are mediated by multiple signal transduction cascades. In this review, we set spotlights on various pathways which are targeted by osthol in different cancers to inhibit cancer development and progression.

The effect of cinnamon extract and long-term aerobic training on heart function, biochemical alterations and lipid profile following exhaustive exercise in male rats.

PURPOSE: Regular training is suggested to offer a host of benefits especially on cardiovascular system. In addition, medicinal plants can attenuate oxidative stress-mediated damages induced by stressor insults. In this study, we investigated the concomitant effect of cinnamon extract and long-term aerobic training on cardiac function, biochemical alterations and lipid profile following exhaustive exercise. METHODS: Male Wistar rats (250-300 g) were divided into five groups depending on receiving regular training, cinnamon bark extraction, none or both of them, and then encountered with an exhausted exercise in last session. An 8-week endurance training program was designed with a progressive increase in training speed and time. Myocardial hemodynamics was monitored using a balloon-tipped catheter inserted into left ventricles. Blood samples were collected for analyzing biochemical markers, lipid profiles and lipid-peroxidation marker, malondealdehyde (MDA). RESULTS: Trained animals showed an enhanced cardiac force and contractility similar to cinnamon-treated rats. Co-application of regular training and cinnamon had additive effect in cardiac hemodynamic (P<0.05). Both regular training and supplementation with cinnamon significantly decreased serum levels of total cholesterol, low-density lipoprotein (LDL), and increased high-density lipoprotein (HDL) level and HDL/LDL ratio as compared to control group (P<0.01). Furthermore, pre-treatment with cinnamon extract and/or regular training significantly reduced MDA level elevation induced by exhausted exercise (P<0.01). CONCLUSION: Long-term treatment of rats with cinnamon and regular training improved cardiac hemodynamic through an additive effect. The positive effects of cinnamon and regular training on cardiac function were associated with a reduced serum MDA level and an improved blood lipid profile.

Histological changes in the liver of fetuses of pregnant rats following citalopram administration.

OBJECTIVE: Depression is a dilapidating disorder, which may occur during pregnancy. Citalopram is an antidepressant drug often prescribed to pregnant women. The purpose of the present study is to determine whether maternal administration of citalopram affects fetal liver histology. MATERIALS AND METHODS: Pregnant Wistar albino rats were treated with citalopram (10 or 20 mg/kg/day). A control group received no treatment. Rat fetal liver samples were obtained on day 18 of gestation and evaluated morphologically and histologically. RESULTS: Statistical evaluation of data showed that there were no differences in liver weight and relative liver weight between control and citalopram treatment groups. Liver histology changes (such as increases in the number of Kupffer cells and lymphocytes) were seen in the fetuses of the group receiving a high dose of citalopram during gestation. Degeneration of hepatocytes was not seen and the megakaryocyte number did not change significantly in the citalopram treated groups. CONCLUSION: This study showed that citalopram administration during gestation may have some adverse effects on the phagocytic cell population in the fetal liver of rats.