Effect of hydroalcoholic extract of Berberis integerrima and resveratrol on ovarian morphology and biochemical parameters in Letrozole-induced polycystic ovary syndrome rat model: An experimental study

Background: Resveratrol and Berberis integerrima (B. integerrima) are known to be natural antioxidants and regulators of human metabolism. However, the effects of resveratrol and B. integerrima on the ovarian morphology in polycystic ovary syndrome (PCOS) are not obvious. Objective: This study aimed to determine the effect of the hydroalcoholic extract of B. integerrima in combination with resveratrol on some biochemical parameters and ovarian morphology in the letrozole-induced PCOS rat. Materials and Methods: Seventy adult female Sprague-Dawley rats aged 10-12 weeks weighing 200 ± 20 gr were randomly divided into seven groups (n = 10/each). Group I): normal; Group II): vehicle; Group III): letrozole-induced PCOS 1 mg/kg letrozole orally, rats receiving 1 cc normal saline orally; Group IV): PCOS + receiving 150 mg/kg metformin orally; Group V): PCOS + receiving 20 mg/kg resveratrol orally; Group VI): PCOS + 3 gr/kg barberry orally; and Group VII): PCOS + receiving 3 gr/kg barberry and 20 mg/kg resveratrol orally. All animals were followed-up for 63 days. The biochemical parameters and histological assessments of ovaries were performed. Results: Resveratrol alone and/or in combination with B. integerrima treatment in rats led to a significant decrease in low-density lipoprotein, triglyceride, malondialdehyde , and tumor necrosis factor-alpha concentrations (p = 0.02). The groups IV, V, VI, and VII showed a decrease in insulin resistance and an increase in the superoxide dismutase, total antioxidant capacity, and high-density lipoprotein (p = 0.01). No significant difference was observed between the level of serum glucose in the treatment groups. Number of cystic follicles had a significant decrease in barberry, resveratrol, and their combination groups (p < 0.001). Conclusion: Resveratrol, B. integerrima, and their combination as natural products with fewer side effects might be effective as an alternative medicine in treatment of PCOS. Key words: Barberry, Resveratrol, Polycystic ovary syndrome, Ovary, Rat

The protective effect of Zataria multiflora Boiss. hydroalcoholic extract on TNF-α production, oxidative stress, and insulin level in streptozotocin-induced diabetic rats

Objective: Oxidative stress leads to reactive oxygen species (ROS) overproduction, which causes tissue injury in diabetic patients. The aim of this study was to evaluate the effects of Zataria multiflora extract on TNF-α, oxidative stress products, and insulin levels as well as lipid profile in diabetic rats. Materials and Methods: Rats were randomly divided into 6 groups of 10 animals. Diabetes was induced by a single injection of streptozotocin (STZ). Control and diabetic control rats orally received 1 mL/day of normal saline, whereas the other three groups received 250, 500 and 1000 mg/kg/day of Z. multiflora extract, and one non-diabetic group orally received 1000 mg/kg/day Z. multiflora extract, for 28 days. At the end of the treatment course, rats were anesthetized and their serum samples were analyzed for TNF-α, malondialdehyde (MDA), super oxide dismutase (SOD), total antioxidant capacity (TAC), lipid profile, total plasma protein, blood glucose, insulin, and liver enzymes levels. Results: Our results showed that cholesterol, LDL, TG, MDA and TNF-α levels decreased, but HDL, SOD, TAC, and total protein increased significantly in the diabetic group receiving 1000 mg/kg Z. multiflora compared to the diabetic control group (

Stevia aquatic extract protects the pancreas from streptozocin (STZ) induced damage: A stereological study

299-307In recent years, among antidiabetic medicinal herbs, Stevia received a lot of attention due to its diverse therapeutic applications. Despite extensive reports on the effects of Stevia on the pancreas, its molecular mechanism is not clear yet. In this study, we investigated the protective and preventive effects of oral extracts of Stevia on the pancreas through the stereological methods in streptozocin (STZ) induced diabetic rats. Thus, 66 adult male rats were assigned to six groups (n = 11) viz., healthy control, healthy Stevia (400 mg /kg), diabetic-control, diabetic-metformin (500 mg/kg), diabetic-Stevia and pre-Stevia-diabetic group. Treatment with Stevia significantly reduced fasting blood sugar (FBS) and MDA compared to the diabetic control group (P <0.05). The results indicated that the weight and the volume of the pancreas increased significantly in all our treated groups compared to the diabetic one (P <0.05). The volume density of the pancreatic islands and the number of beta cells increased in healthy and diabetic groups treated with Stevia (P <0.05). However, the pre-treated diabetic rats with Stevia did not show significant preventive effects on the volume and number of beta cells as well as the volume of islets against destructive effects of STZ. More specifically, our results confirmed the protective effects of Stevia through restoring pancreatic cells and repairing the stereological damage induced by STZ

Effects of the Hydroalcoholic Extract of the Psidium guajava Fruit on Osteoporosis Prevention in Ovariectomized Rats

Background: Several plants have been shown to possess antioxidant and estrogenic properties that can be useful in postmenopausal bone-loss prevention. The present study aimed to investigate the anti-osteoporotic effects of the hydroalcoholic extract of the Psidium guajava (PG) fruit in ovariectomized (OVX) rats. Methods: Sixty female Sprague–Dawley rats were randomly divided into 6 groups: a control positive group, a sham-operated group, an OVX group given normal saline (OVX-only group), and 3 treatment groups comprising 2 OVX groups treated orally with 500 and 1000 mg/kg/d of the hydroalcoholic extract of the PG fruit respectively and an OVX group treated with an injection of 0.15 mg/kg of estradiol. The study was conducted over a 12-week period. Samples from the animals’ blood, femoral bones, and uteri were collected for stereological and biochemical analyses. The data were analyzed using SPSS, version 19. A P value equal to or less than 0.05 was considered statistically significant. Results: The results revealed a significant decrease in the levels of calcium, total antioxidant capacity, and phosphorus as well as uterus weight, femoral ash density, femoral volume and weight, and numbers of osteocytes and osteoblasts. Moreover, there was an increase in the levels of alkaline phosphatase and urine deoxypyridinoline together with a rise in the number of osteoclasts in the OVX-only group compared to the control and treatment groups (P≤0.05). The hydroalcoholic extract of the PG fruit increased femoral weight and volume, femoral ash density, numbers of osteocytes and osteoblasts, and trabecular volume of the bones in comparison with the OVX-only group in a dose-dependent manner. No significant difference was observed between the groups in the levels of malondialdehyde and interleukin-6. Conclusion: The hydroalcoholic extract of the PG fruit prevented OVX-induced bone loss in the rats, with no proliferative effect on atrophic uteri; it should, therefore, be considered for treatment purposes

Protective effect of loboob (a Persian traditional remedy) on sexual hormones, antioxidant activities and stereological changes of testis tissue on busulfan induced oligospermia in rats

Loboob as a traditional drug in Iranis known for its beneficial effects on busulfan-induced oligospermia. In this experimental study, protective effects of loboob (a Persian traditional remedy) on sexual hormones, antioxidant levels and stereological changes of testis tissue were evaluated in an oligospermia rat model induced by busulfan. Fifty male rats were randomly divided into five different groups: control, received no treatments; and the other groups administrated with a single dose of busulfan (10 mg/kg body weight). After 30 days, these groups were treated with 0, 35, 70 or 140 mg/kg/day of loboob for 60 days. Blood samples were collected for hormone and antioxidant enzyme assays. Unbiased stereology was performed on testis tissues to evaluate the volume of different parts of the testis and the number of various testis cells. Data indicated that FSH, LH and MDA were increased, and testosterone, catalase, SOD were decreased in the busulfan group, while treatment with loboob at 70 and 140 mg/kg significantly improved these parameters (P &lt;0.05). Treatment with 70 and 140 mg/kg of loboob ameliorated the germinal epithelium volume, types A and B spermatogonia, spermatocytes, elongated and round spermatids, and Sertoli cells in the seminiferous tubules (P &lt;0.05). High concentration of loboob also improved testis weight and volume, and leydig cell number (P &lt;0.05). Thus, loboob is more effective for the recovery of seminiferous tubules and their cells than for the interstitial tissue. Loboob with various antioxidants, minerals and vitamins could overcome the side effects of busulfan

Protective effect of loboob (a Persian traditional remedy) on sexual hormones, antioxidant activities and stereological changes of testis tissue on busulfan induced oligospermia in rats

175-184Loboob as a traditional drug in Iranis known for its beneficial effects on busulfan-induced oligospermia. In this experimental study, protective effects of loboob (a Persian traditional remedy) on sexual hormones, antioxidant levels and stereological changes of testis tissue were evaluated in an oligospermia rat model induced by busulfan. Fifty male rats were randomly divided into five different groups: control, received no treatments; and the other groups administrated with a single dose of busulfan (10 mg/kg body weight). After 30 days, these groups were treated with 0, 35, 70 or 140 mg/kg/day of loboob for 60 days. Blood samples were collected for hormone and antioxidant enzyme assays. Unbiased stereology was performed on testis tissues to evaluate the volume of different parts of the testis and the number of various testis cells. Data indicated that FSH, LH and MDA were increased, and testosterone, catalase, SOD were decreased in the busulfan group, while treatment with loboob at 70 and 140 mg/kg significantly improved these parameters (P <0.05). Treatment with 70 and 140 mg/kg of loboob ameliorated the germinal epithelium volume, types A and B spermatogonia, spermatocytes, elongated and round spermatids, and Sertoli cells in the seminiferous tubules (P <0.05). High concentration of loboob also improved testis weight and volume, and leydig cell number (P <0.05). Thus, loboob is more effective for the recovery of seminiferous tubules and their cells than for the interstitial tissue. Loboob with various antioxidants, minerals and vitamins could overcome the side effects of busulfan

Thymoquinone improves folliculogenesis, sexual hormones, gene expression of apoptotic markers and antioxidant enzymes in polycystic ovary syndrome rat model

Abstract Background Nowadays, polycystic ovary syndrome (PCOS) is a prevalent cause of infertility affecting women of reproductive age around the world. Thymoquinone is a natural antioxidant, derived from Nigella sativa. Objectives The current study aimed to evaluate the protective effects of thymoquinone on the detrimental effects of PCOS rats induced with letrozole. Methods Thirty‐two female rats were randomly divided into four groups: (1) Control, (2) PCOS, (3) PCOS+5 mg/kg thymoquinone and (4) PCOS+10 mg/kg thymoquinone. Thymoquinone was administered every 3 days for 30 days. Ovaries were histopathologically and stereologically examined, and antioxidant and apoptotic enzymes gene expression in ovaries and sex hormones in serum were measured. Results The number of unilaminar, multilaminar, antral, and graffian follicles, volume density of corpus luteum (p < 0.01), and GPx1 gene expression in ovaries and level of FSH in the blood increased in both thymoquinone groups when compared to untreated PCOS (p < 0.05). Ovaries in thymoquinone groups showed a significant reduction in the number of atretic follicles, ovary weight and volume, volume density of cortex and ovarian cysts, Bax gene expression (p < 0.01) and Bax/Bcl2 ratio as well as levels of luteinizing hormone (LH), LH/FSH ratio and testosterone (p < 0.05) in the blood of female rats when compared to PCOS group. Administration of thymoquinone restored the most detrimental effects of PCOS on ovaries (p < 0.01) and sexual hormones (p < 0.05) in rats. Conclusions These data suggest that thymoquinone has improved effects on ovarian function in the PCOS rat model. Therefore, thymoquinone might be useful as a protective agent and adjunct treatment in PCOS patients

Recombinant GPEHT Fusion Protein Derived from HTLV-1 Proteins with Alum Adjuvant Induces a High Immune Response in Mice

The human T-cell leukemia virus type 1 (HTLV-1) is a positive single-stranded RNA virus that belongs to the delta retrovirus family. As a result, a vaccine candidate that can be recognized by B cells and T cells is a good candidate for generating a durable immune response. Further, the GPEHT protein is a multi-epitope protein designed based on the Gag, Pol, Env, Hbz, and Tax proteins of HTLV-1. In developing a suitable and effective vaccine against HTLV-1, the selection of a designed protein (GPEHT) with the formulation of an alum adjuvant was conducted. In this study, we assessed the potential of a multi-epitope vaccine candidate for stimulating the immune response against HTLV-1. In assessing the type of stimulated immune reaction, total IgG, IgG1, and IgG2a isotypes, as well as the cytokines associated with Th1 (IFN-γ), Th2 (IL-4), and Th17 (IL-17), were analyzed. The outcomes showed that the particular antisera (total IgG) were more elevated in mice that received the GPEHT protein with the alum adjuvant than those in the PBS+Alum control. A subcutaneous vaccination with our chimera protein promoted high levels of IgG1 and IgG2a isotypes. Additionally, IFN-γ, IL-4, and IL-17 levels were significantly increased after spleen cell stimulation in mice that received the GPEHT protein. The immunogenic analyses revealed that the GPEHT vaccine candidate could generate humoral and cell-mediated immune reactions. Ultimately, this study suggests that GPEHT proteins developed with an alum adjuvant can soon be considered as a prospective vaccine to more accurately evaluate their protective efficacy against HTLV-1

Stevia aquatic extract protects the pancreas from streptozocin (STZ) induced damage: A stereological study

In recent years, among antidiabetic medicinal herbs, Stevia received a lot of attention due to its diverse therapeutic applications. Despite extensive reports on the effects of Stevia on the pancreas, its molecular mechanism is not clear yet. In this study, we investigated the protective and preventive effects of oral extracts of Stevia on the pancreas through the stereological methods in streptozocin (STZ) induced diabetic rats. Thus, 66 adult male rats were assigned to six groups (n = 11) viz., healthy control, healthy Stevia (400 mg /kg), diabetic-control, diabetic-metformin (500 mg/kg), diabetic-Stevia and pre-Stevia-diabetic group. Treatment with Stevia significantly reduced fasting blood sugar (FBS) and MDA compared to the diabetic control group (P &lt;0.05). The results indicated that the weight and the volume of the pancreas increased significantly in all our treated groups compared to the diabetic one (P &lt;0.05). The volume density of the pancreatic islands and the number of beta cells increased in healthy and diabetic groups treated with Stevia (P &lt;0.05). However, the pre-treated diabetic rats with Stevia did not show significant preventive effects on the volume and number of beta cells as well as the volume of islets against destructive effects of STZ. More specifically, our results confirmed the protective effects of Stevia through restoring pancreatic cells and repairing the stereological damage induced by STZ

Evaluation of morphology and angiogenesis of breast cancer in BALB/c mice using trypsin inhibitor from Cucumis melo seeds. In vitro and in vivo study

INTRODUCTION: Melon seeds, as an excellent source of protease inhibitors, may have a protective role against tumor progression and angiogenesis. However, their effects on angiogenesis and the mechanism of their action against cancer progression remain elusive. This study aimed to investigate the effect of bioactive compounds of melon seed on the expression of angiogenesis genes in BALB/c mice with breast cancer. MATERIAL AND METHODS: Trypsin inhibitor (TI) was purified from the seed powder of Cucumis melo. Half- maximal inhibitory concentration was determined for TI, extract of melon seed powder (EXT), and tamoxifen (TAM) by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Also, breast tumor was induced by subcutaneous injection of MC4–L2 cells in BALB/c inbred mice breast tissue. After tumor growth, mice were treated with TI, EXT, and TAM to examine their effects on the tumor characteristics and expression of angiogenesis-related genes including MMP-2, MMP-9, and vascular endothelial growth factor (VEGF) using the reverse transcription polymerase chain reaction method. RESULTS: Trypsin inhibitor, EXT, TAM, and adjuvant treatment of TI + TAM resulted a reduction in expression of MMP-2, MMP-9, and VEGF. All treatments improved the breast tumor characteristics and the necrosis. The real-time polymerase chain reaction method verified the positive effects of the treatments on the breast cancer cell line and tumors. CONCLUSIONS: The results indicated that treatments with TI purified from Cucumis melo seeds and also combination therapy of TI and TAM can be considered as an alternative therapy in breast cancer patients. Further studies are warranted