Amelioration of amyloid beta (Aß1-40) neurotoxicity by administration of silibinin; a behavioral and biochemical assessment.

Objectives: Alzheimer's disease (AD), the most common cause of dementia, is one of the leading causes of morbidity and death in the world. Currently, treatment mostly used to slow down the disease progression. Herbal remedies are considered by many in the community as a natural and safe treatment with fewer side effects. Silibinin, the active ingredient of Silybum marionum, has anti-oxidant, neurotrophic and neuroprotective characteristics. Therefore, here, the effect of different doses of Silibinin extract on oxidative stress and expression of neurotrophic factors was investigated. Materials and Methods: Forty eight male Wistar rats were randomly divided into sham, lesion; Aß1-40 injection, lesion-treatment; Aß1-40 injection followed by different doses of silibinin (50, 100, 200 mg / kg) through gavage and lesion-vehicle group; Aß1-40 injection + vehicle of silibinin. Morris water Maze (MWM) was done 28 days after the last treatment. Hippocampal tissue was removed for biochemical analysis. Production of nitric oxide (NO) and reactive oxygen species (ROS), expression of BDNF/VEGF and cell viability were measured using Griess, fluorimetry, Western blotting and MTT techniques. Results: Different concentrations of silibinin improved behavioral performance in animals. Higher doses of Silibinin could improve memory and learning function through MWM. Also, increasing the concentration of silibinin resulted in decreased ROS and NO production in a dose-dependent manner. Conclusion: Consequently, silibinin may act as a potential candidate for alleviating symptoms of AD.

Evaluating Chondroitin Sulfate and Dermatan Sulfate Expression in Glial Scar to Determine Appropriate Intervention Time in Rats.

INTRODUCTION: The proteoglycans of the extracellular matrix increases in the glial scar during spinal cord injury and significantly affects the inhibition of axonal regeneration. METHODS: The results of injury therapies are limited due to the lack of identifying a timely therapeutic intervention. The present study aimed to investigate the glial scar Chondroitin Sulfate (CS) and Dermatan Sulfate (DS) levels at different post-injury times to determine the appropriate time for therapeutic intervention. RESULTS: By this experimental study, 72 Wistar rats were randomly divided into 12 groups, as follows: control, sham, injured animals at 1, 2, 4, and 8 days, as well as 2, 4, 8, 12, 16, and 20 weeks post-injury. The animals in the injured groups were contused in the T10 segment of the spinal cord. The motor function of animals was assessed using the Basso, Beattie, and Bresnahan (BBB) test. Besides, the histological assessment was performed using Luxol Fast Blue and Bielshovisky Staining. The CS and DS levels of lesions were measured using the Enzyme-Linked Immunosorbent Assay (ELISA) method. CONCLUSION: The motor function assessment indicated a relative recovery over time. Histological results confirmed some regeneration in the injury site at 20 weeks post-injury. The ELISA results demonstrated a much higher level of DS than that of CS in the glial scar. Considering high levels of DS, compared to CS in the glial scar and its reduction from second weeks after SCI onwards, the second week after SCI seems to be the best time for therapeutic interventions in terms of scar permeability.

ChABC-loaded PLGA nanoparticles: A comprehensive study on biocompatibility, functional recovery, and axonal regeneration in animal model of spinal cord injury.

Spinal Cord Injury (SCI) is one of the leading causes of physical disability. In this study, spherical PLGA nanoparticles (NPs) containing ChABC enzyme were manufactured and fully characterized for SCI therapy. The NPs were used in the rat's contused spinal cord to assess the functional improvement and scar digestion. Twenty-three adult male Wistar rats (275 ± 25 g) were assigned into four groups of control, sham, blank-treated particle, and ChABC-treated particle. Throughout the survey, the BBB scores were obtained for all the groups. Finally, the injured sections of animals were dissected, and histological studies were conducted using Luxol fast blue and Bielschowsky. The biocompatibility and non-toxicity effects of the NPs on olfactory ensheathing cells (OECs) were confirmed by the MTT test. The flow-cytometry revealed the purity of cultured OECs with p75+/GFAP+ at around 87.9 ± 2.4%. Animals in the control and the blank-treated groups exhibited significantly lower BBB scores compared with the ChABC-treated particle group. Histological results confirmed the induced contusion models in the injured site. Myelin was observed in the treated groups, especially when the ChABC-loaded nanoparticles were utilized. The immunohistochemistry results indicated the scar glial degradation in animals treated by the ChABC-loaded particles. According to this study, the loaded particles can potentially serve as a suitable candidate for spinal cord repair, functional recovery and axonal regeneration.

Investigating the effect of Crocus sativus L. petal hydroalcoholic extract on inflammatory and enzymatic indices resulting from alcohol use in kidney and liver of male rats.

BACKGROUND: Studies have shown that consumption of high levels of alcohol causes many negative effects on the liver and kidneys where antioxidant ingredients can be a proper solution to reducing the resulting damages. So, the present study investigated the effect of hydroalcoholic extract of Crocus sativus L. (saffron) petal with antioxidant properties on the changes in inflammatory and enzymatic indices resulting from alcohol use in the male rats' kidney and liver. MATERIALS AND METHODS: After preparing the extract, LD50 was determined and high-performance liquid chromatography (HPLC) was employed to specify the type and the rate of the active ingredients of the extract. Then, 36 male Wistar rats were randomly assigned into six groups (n=6). The first group was only administered with normal saline and the second group only received ethyl alcohol 6 mL/kg/day·BW. The third and the fourth groups received ethyl alcohol 6 mL/kg/day·BW plus 167.5 and 335 mg/kg/day·BW saffron petal extract for 8 weeks. The fifth and the sixth groups received ethyl alcohol 6 mL/kg/day·BW for the first 8 weeks and were subsequently gavage fed on saffron extract for 167.5 and 335 mg/kg/day·BW, respectively, during the next 8 weeks. In the beginning and after the termination of the treatment, blood samples were collected from all rats. RESULTS: The LD50 of the extract was about 670 mg/kg. The HPLC results indicated that the extract contains important antioxidant ingredients. At the end of the study, the serum concentration of the inflammatory indices, renal enzymes, and hepatic enzymes experienced a significant reduction in all of the intervened groups compared to the negative control group (minimum significant difference: P<0.05) except for the treatment group 1. CONCLUSION: Based on the current results, the extract has a protective effect in a dosage-dependent way and greater protective roles were documented for higher dosages.

The effects of mumie extract on cell proliferation and enzyme expression of human osteoblast-like cells (MG63).

Background: Mumie, as an inorganic and semi-solid herbal substance, could be obtained from crevice caves and is used for bone diseases in traditional medicine. This study investigated the effects of this substance on the expression of bone alkaline phosphatase (BALP) enzyme as well as proliferation and mortality rates of MG63 human osteoblast-like cells. Materials and methods: The MG63 cells were cultured and the effect of 100, 200 and 300 µg/ml of mumie extract on cell viability were compared with zoledronic acid and estradiol valerate as positive controls, as well as with MG63 cells alone as the negative control group. The activity rate of the BALP enzyme was also assessed. Results: During 48 hours of the study period, the concentrations of 100 and 200µg/ml of mumie extract increased the proliferation rate and decreased the mortality rate of MG63 cells significantly; however, the concentration of 300µg/ml decreased the proliferation rate and increased the mortality rate of the cells. Also, BALP enzyme expression was slightly affected by 100 and 200 µg/ml of mumie extract whilst it was significantly decreased by the concentration of 300 µg/ml. Conclusion: This study showed that mumie extract has an increasing effect on proliferation rate and a decreasing effect on the mortality rate of osteoblast cells in low concentrations; however, the higher concentrations of this substance could be toxic and effect inversely.

Histopathological study of liver tissue due to methadone consumption and its effect on liver enzymes and inflammatory indices in rat.

BACKGROUND: Methadone (MET)-based treatment is currently one of the best known approaches in the treatment of opioid dependence. It is claimed that MET use exerts adverse effects on the performance of some organs, especially liver. Thus, the present study aims to investigate MET effects on the hepatic tissue as well as its effect on the hepatic enzyme levels and inflammatory markers in rats. MATERIALS AND METHODS: Twenty-eight mature male Wistar rats underwent an 8-week treatment in four equal groups including the control group (an ordinary daily dietary regime) as well as the experimental groups 1, 2, and 3 (an ordinary daily dietary regime and gavage-fed on MET syrup for 5, 20, and 40 mg/kg body weight per day). Blood samples were collected from all rats in the beginning and end of the study to measure their hepatic enzyme levels and inflammatory markers. In the end, their livers were subjected to histological examinations. RESULTS: The mean serum levels of hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) increased considerably across all the three groups that had received various dosages of MET (5, 20, and 40 mg/kg) in the end of the study as compared to the beginning of the study (P<0.001). It was also found that the inflammatory indicators (interleukin-6, tumor necrosis factor-alpha, and C-reactive protein) rose significantly in the groups that had received various dosages of MET in contrast to the control group (P<0.01, P<0.001, and P<0.001, respectively). The histopathological images of the liver cross-sections revealed dosage-dependent tissue changes in the groups that had received various dosages of MET. CONCLUSION: The present study tried to prove the adverse effects of MET in the development of liver damage. Since MET-based treatment is frequently prescribed by physicians for curing the addiction to narcotics, better strategies are required for its correct usage.

Stereologic study of the effects of prostaglandin E2 on the induction of angiogenesis in full-thickness skin autografts.

OBJECTIVE: To determine whether prostaglandin E2 improves angiogenesis in full-thickness skin grafts. DESIGN: Randomized study SUBJECTS: 20 male rabbits, divided into 2 experimental and 2 control groups. METHODOLOGY: Prostaglandin E2 (experimental groups) or prostaglandin E2 vehicle (control groups) was injected locally into experimental skin autografts once a day for up to 5 days. Five and 10 days after the surgery, the grafts were harvested and after processing, fractional and absolute volumes of the vessels were estimated in the grafted skin using stereologic methods. MAIN RESULTS: Gross appearance of the control and experimental grafts were the same. Qualitative histologic examination of successful grafts in experimental and control groups showed areas of viable epidermis with a negligible inflammatory infiltrate and moderate fibrosis. Blood cells were frequently seen in the vessels under investigation. Histologic slides showed significantly higher mean fractional volume (percent) and absolute volume of the vessels (mm3) per unit volume (mm3) of the grafted skin in the experimental groups than in the control groups. CONCLUSION: Fractional and absolute volume of the vessels were greater in prostaglandin E2-treated grafts than in the control grafts. Prostaglandin E2 appears to increase the volume of vessels in full-thickness skin grafts and can be explored as an agent to improve angiogenesis of the grafts.