Attenuation of cannabis withdrawal symptoms by Prosopis farcta extract, its luteolin and melatonin in mice: Involvement of brain-derived neurotrophic factor and dopamine.

The aim of this study was the identification of luteolin in Prosopis farcta extract (PFE) and melatonin to evaluate its effect on THC withdrawal syndrome in mice. Luteolin was identified by high-performance liquid chromatography (HPCL). Signs of toxicity of mice in PFE and luteolin were monitored for LD50 calculation. The behavioral symptoms of THC withdrawal (stereotypies, ambulation, and inactivity time) induced by the rimonabant challenge were illustrated in THC-dependent mice receiving PFE, luteolin, and melatonin. The expression of mature BDNF (mBDNF) was evaluated by Western blot analysis. The dopamine concentrations were measured using HPLC. PFE and luteolin LD50 were 650 and 220 mg/kg, respectively. PFE (300 mg/kg), all doses of luteolin, and melatonin increased significantly the mBDNF expression and decreased the dopamine concentration. The findings suggest that PFE, luteolin, and melatonin are mighty in reducing the signs of THC withdrawal. It seems these effects were due to a decrease in dopamine concentration level and an increase in mBDNF protein expression in mice brains.

Evaluation of morphine, methadone, digoxin, and dronabinol poisoning during the years 2017 to 2019 in Ilam, Iran.

Background: Every year, drug poisoning is the most prevalent reason for referring patients to medical centers. This study aimed to evaluation of morphine, methadone, digoxin, and dronabinol poisoning in Shahid Mostafa Khomeini Hospital in Ilam. Methods: In this In this Cross-sectional study, patient samples suspected of morphine, methadone, digoxin, and dronabinol poisoning referred to the toxicology laboratory of Ilam University of Medical Sciences were analyzed using the HPLC method, and the results were analysed using SPSS software. Results: Results showed that the percentage of drug use is greater in men than in women. The highest percentage of morphine and methadone poisonings were detected in those under the age of 40, whereas the highest percentage of digoxin poisonings were recorded in those over the age of 80. As a result, the average age of digoxin users was substantially greater in men than in women. Methadone consumers showed significantly greater blood levels than others. In addition, there was a significant difference (P<0.01) in blood levels between men and women who used morphine. Conclusion: In general, it is important to understand the status of drug poisoning with drugs such as morphine, methadone, digoxin, and dronabinol, as well as the prognosis associated with the treatment process of such poisoning.

WITHDRAWN: Evaluation of Morphine, Methadone, Digoxin, and Dronabinol Poisoning in Shahid Mostafa Khomeini Hospital in Ilam, Iran

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Thymol Nanopolymer Synthesis and Its Effects on Morphine Withdrawal Syndrome in Comparison With Clonidine in Rats.

The drug delivery system is valuable in the treatment of the disease. A nanopolymer as a thymol and Thymbra spicata release system was synthesized and its effects on morphine withdrawal syndrome in comparison with clonidine in rats were studied. The nanopolymer was characterized by different methods, namely, IR, HNMR, CNMR, GPC, DLS, and AFM. Thymol in T. spicata extract was assessed. The loading and release rate of thymol and T. spicata extract on the nanopolymer were evaluated by HPLC. The median lethal dose (LD50) of the T. spicata extract, thymol, extract nanopolymer, and thymol nanopolymer was studied. The frequency of jumping, rearing, and teeth chattering in naloxone-induced morphine withdrawal syndrome was studied. Synthesized nanopolymer was desirable as a carrier for the drug. The loaded amount of extract and thymol on nanopolymer was estimated 55 ± 3.2% and 48 ± 2.6% and the drug released was 71 and 68%, respectively. LD50 of the T. spicata extract, thymol, extract nanopolymer, and thymol nanopolymer was 975, 580, 1,250, and 650 mg/kg, respectively. This study showed that thymol nanopolymer was more effective than clonidine to reduce the frequency of morphine withdrawal symptoms. Our results suggest that T. spicata extract, thymol, extract nanopolymer, and thymol nanopolymer are mighty in reducing the narcotic withdrawal signs. The mechanism of action and therapeutic potential is maybe similar to clonidine.

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.

Attenuation of Morphine Withdrawal Syndrome by Prosopis Farcta Extract and Its Bioactive Component Luteolin in Comparison with Clonidine in Rats.

BACKGROUND Today, the plant Prosopis farcta is frequently used for traditional medicinal purposes. The aim of this study was the identification of luteolin in P. farcta extract (PFE) and to evaluate its effect on morphine discontinuation syndrome in rats. MATERIAL AND METHODS Using high-performance liquid chromatography (HPCL), luteolin was evaluated in PFE. The frequency of behavioral symptoms of morphine withdrawal (jumping, rearing, and teeth chattering) induced by naloxone challenge were illustrated in morphine-dependent rats receiving PFE, luteolin, saline, or clonidine. LD50 of PFE and luteolin was 540 mg/kg and 150 mg/kg, respectively. Signs of behavioral morphine withdrawal in rats were significantly inhibited by chronic co-administration of PFE, luteolin, or clonidine with morphine. RESULTS This study showed that PFE was less effective than clonidine at a dose of 100 mg/kg, and at doses of 200 mg/kg and 300 mg/kg it was comparable to clonidine, and did not show a significant difference in the reduction of morphine withdrawal symptoms. Luteolin was comparable in 30 mg/kg, 60 mg/kg, and 90 mg/kg with clonidine to reduce the frequency of morphine withdrawal symptoms. PFE can be used as a source of luteolin. CONCLUSIONS The study findings suggest that PFE and luteolin might reduce the signs of narcotic withdrawal. Due to a similar effect to clonidine, its mechanism of action might be through the protein kinase A pathway and might have human therapeutic potential.

Association between GSTM1, GSTT1, and GSTP1 variants and the risk of end stage renal disease.

INTRODUCTION: There are some evidences indicating DNA damage by oxidant and mutant agents has an essential role in the chronic renal failure and end stage renal disease (ESRD). To investigate the possible association of GSTs variants with ESRD, we investigated the frequency of GST- T1, M1, and P1 genotypes, and the level of malondialdehyde (MDA) in patients with ESRD. MATERIALS AND METHODS: The present case-control study consisted of 136 ESRD patients treated with maintenance hemodialysis and 137 gender- and age-matched, unrelated healthy controls from the population of west of Iran. The GST- T1, M1, and P1 genotypes were determined in all individuals using multiplex-PCR and PCR-RFLP. The level of MDA was measured by high-performance liquid chromatography (HPLC). RESULTS: We found that GSTM1 and GSTT1 null genotypes (GSTT1-/GSTM1-) increased the risk of ESRD by 1.8 times (p < 0.001) and the increased risk of ESRD for GSTM-null (T1+-M1-) genotype was 3.04 times (p = 0.002). ESRD patients carriers the GST (GSTM1-null + GSTT1-null + GST-null) genotypes compared to GST normal genotype increased the risk of ESRD by 3.3 (p < 0.001) times. ESRD patients carriers of GST-null, GSTM1-null, and GSTT1-null genotypes had greater MDA concentration compared with the same genotypes of control subjects. Our results indicated that the GST-null allele (GSTT1-null/GSTM1-null) is a risk factor for ESRD and carriers of this allele have high levels of MDA. CONCLUSION: Our findings indicate that oxidative stress, impairment of the antioxidant system and abnormal lipid metabolism may play a role in the pathogenesis and progression of ESRD and its related complications. These data suggest that patients with ESRD are more susceptible to vascular diseases.

Biphasic Response to Luteolin in MG-63 Osteoblast-Like Cells under High Glucose-Induced Oxidative Stress.

BACKGROUND: Clinical evidence indicates the diabetes-induced impairment of osteogenesis caused by a decrease in osteoblast activity. Flavonoids can increase the differentiation and mineralization of osteoblasts in a high-glucose state. However, some flavonoids such as luteolin may have the potential to induce cytotoxicity in osteoblast-like cells. This study was performed to investigate whether a cytoprotective concentration range of luteolin could be separated from a cytotoxic concentration range in human MG-63 osteoblast-like cells in high-glucose condition. METHODS: Cells were cultured in a normal- or high-glucose medium. Cell viability was determined with the MTT assay. The formation of intracellular reactive oxygen species (ROS) was measured using probe 2',7' -dichlorofluorescein diacetate, and osteogenic differentiation was evaluated with an alkaline phosphatase bioassay. RESULTS: ROS generation, reduction in alkaline phosphatase activity, and cell death induced by high glucose were inhibited by lower concentrations of luteolin (EC50, 1.29±0.23 µM). Oxidative stress mediated by high glucose was also overcome by N-acetyl-L-cysteine. At high concentrations, luteolin caused osteoblast cell death in normal- and high-glucose states (IC50, 34±2.33 and 27±2.42 µM, respectively), as represented by increased ROS and decreased alkaline phosphatase activity. CONCLUSION: Our results indicated that the cytoprotective action of luteolin in glucotoxic condition was manifested in much lower concentrations, by a factor of approximately 26 and 20, than was its cytotoxic activity, which occurred under normal or glucotoxic condition, respectively.