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      Effect of safranal, a constituent of saffron, on olanzapine (an atypical antipsychotic) induced metabolic disorders in rat

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          Abstract

          Objective(s):

          Olanzapine, an atypical antipsychotic, causes weight gain and metabolic disorders in humans. Safranal, one of the active components of Crocus sativus (saffron), has been shown to have anti-obesity, lipid and blood pressure lowering and anti-diabetes effects. In this investigation, the effect of safranal on metabolic disorders induced by olanzapine was studied.

          Materials and Methods:

          Fourty-two female Wistar rats were divided into 7 groups of 6 animals. The two groups were selected as controls, which received olanzapine and safranal solvents, respectively. The third group treated by olanzapine 5 mg/kg. Groups 4, 5 and 6 treated by olanzapine 5 mg/kg plus safranal (2.5, 5 and 10 mg/kg) and the last group received safranal 10 mg/kg. The injections were performed intraperitoneally for 14 days and on the 15 th day the rats were killed and their serum were collected to measure metabolic factors including glucose, insulin, triglyceride, total cholesterol and HDL cholesterol. Leptin level in plasma was also measured. Mean systolic blood pressure was measured using tail cuff method at the end of study. The rats were weighed every other day and amount of food consumed was measured daily.

          Results:

          Olanzapine significantly elevated body weight, food intake, fasting blood glucose, TG, leptin, and mean systolic blood pressure (MSBP). It also significantly decreased HDL cholesterol blood level. Safranal significantly improved all these complications at three doses.

          Conclusion:

          Based on the results of this study, safranal is thought to be used as an effective combination in controlling metabolic complications caused by olanzapine.

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          Most cited references66

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          Antipsychotic-induced weight gain: a comprehensive research synthesis.

          The purpose of this study was to estimate and compare the effects of antipsychotics-both the newer ones and the conventional ones-on body weight. A comprehensive literature search identified 81 English- and non-English-language articles that included data on weight change in antipsychotic-treated patients. For each agent, a meta-analysis and random effects metaregression estimated the weight change after 10 weeks of treatment at a standard dose. A comprehensive narrative review was also conducted on all articles that did not yield quantitative information but did yield important qualitative information. Placebo was associated with a mean weight reduction of 0.74 kg. Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine. Among newer antipsychotic agents, mean increases were as follows: clozapine, 4.45 kg; olanzapine, 4.15 kg; sertindole, 2.92 kg; risperidone, 2.10 kg; and ziprasidone, 0.04 kg. Insufficient data were available to evaluate quetiapine at 10 weeks. Both conventional and newer antipsychotics are associated with weight gain. Among the newer agents, clozapine appears to have the greatest potential to induce weight gain, and ziprasidone the least. The differences among newer agents may affect compliance with medication and health risk.
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            H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs.

            As a result of superior efficacy and overall tolerability, atypical antipsychotic drugs have become the treatment of choice for schizophrenia and related disorders, despite their side effects. Weight gain is a common and potentially serious complication of some antipsychotic drug therapy, and may be accompanied by hyperlipidemia, hypertension and hyperglycemia and, in some extreme cases, diabetic ketoacidosis. The molecular mechanism(s) responsible for antipsychotic drug-induced weight gain are unknown, but have been hypothesized to be because of interactions of antipsychotic drugs with several neurotransmitter receptors, including 5-HT(2A) and 5-HT(2C) serotonin receptors, H(1)-histamine receptors, alpha(1)- and alpha(2)-adrenergic receptors, and m3-muscarinic receptors. To determine the receptor(s) likely to be responsible for antipsychotic-drug-induced weight gain, we screened 17 typical and atypical antipsychotic drugs for binding to 12 neurotransmitter receptors. H(1)-histamine receptor affinities for this group of typical and atypical antipsychotic drugs were significantly correlated with weight gain (Spearman rho=-0.72; p<0.01), as were affinities for alpha(1A) adrenergic (rho=-0.54; p<0.05), 5-HT(2C) (rho=-0.49; p<0.05) and 5-HT(6) receptors (rho=-0.54; p<0.05), whereas eight other receptors' affinities were not. A principal components analysis showed that affinities at the H(1), alpha(2A), alpha(2B), 5-HT(2A), 5-HT(2C), and 5-HT(6) receptors were most highly correlated with the first principal component, and affinities for the D(2), 5-HT(1A), and 5-HT(7) receptors were most highly correlated with the second principal component. A discriminant functions analysis showed that affinities for the H(1) and alpha(1A) receptors were most highly correlated with the discriminant function axis. The discriminant function analysis, as well as the affinity for the H(1)-histamine receptor alone, correctly classified 15 of the 17 drugs into two groups; those that induce weight gain and those that do not. Because centrally acting H(1)-histamine receptor antagonists are known to induce weight gain with chronic use, and because H(1)-histamine receptor affinities are positively correlated with weight gain among typical and atypical antipsychotic drugs, it is recommended that the next generation of atypical antipsychotic drugs be screened to avoid H(1)-histamine receptors.
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              Review of the protective effects of rutin on the metabolic function as an important dietary flavonoid.

              In recent years, flavonoids have been revealed to be helpful in the treatment of many diseases. Rutin (3,3',4',5,7-pentahydroxyflavone-3-rhamnoglucoside) is an important flavonoid that is consumed in the daily diet. It is also known as vitamin P and quercetin-3-O-rutinoside. In addition, it is found in many food items, vegetables, and beverages. The cytoprotective effects of rutin, including gastroprotective, hepatoprotective, and anti-diabetic effects, have been shown in several studies. Furthermore, rutin has several pharmacological effects such as anti-inflammatory and anti-glycation activities.

                Author and article information

                Journal
                Iran J Basic Med Sci
                Iran J Basic Med Sci
                ijbms
                Iranian Journal of Basic Medical Sciences
                Mashhad University of Medical Sciences (Mashhad, Iran )
                2008-3866
                2008-3874
                December 2019
                : 22
                : 12
                : 1476-1482
                Affiliations
                [1 ]School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
                [2 ]Department of Pharmacodynamics and Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
                [3 ]Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
                [4 ]Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
                [5 ]Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran\
                Author notes
                [* ]Corresponding author: Hossein Hosseinzadeh. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Tel: +98-5138819042; Fax: +98-5138823251; Email: hosseinzadehh@mums.ac.ir
                Article
                10.22038/IJBMS.2019.13992
                7043869
                32133067
                e2cf50dc-70b1-4cf8-befa-5a33279b9b00

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 February 2019
                : 3 July 2019
                Categories
                Original Article

                crocus sativus,metabolic syndrome,obesity,olanzapine,safranal,saffron

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