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      Safety Assessment of Mentha mozaffarianii Essential Oil: Acute and Repeated Toxicity Studies

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          Abstract

          Background:

          Mentha mozaffarianii, an endemic species from the Labiatae family, is used in Iranian traditional medicine. This study evaluated the acute and repeated oral toxicity of the Mentha mozaffarianii essential oil (MMEO) in rats and mice.

          Methods:

          To assess the toxicity profile of the MMEO, we administered the essential oil to 48 rats and mice of both sexes by gavage in acute and repeated models. In acute toxicity, the animals were administered the MMEO (2000 mg/kg) and were monitored for 14 days. In the repeated toxicity, the MMEO was administered (100 mg/kg) daily for 4 weeks. On the 28th day, all the animals were scarified and blood and tissue samples were prepared. All the clinical, biochemical, and histopathological changes were assessed and compared with those in the controls.

          Statistical significance was determined by one- and two-way analyses of variance, followed by the Tukey test using GraphPad Prism 6.

          Results:

          In the acute test, there was no mortality; therefore, the oral LD 50 value determined in the mice and rats of both sexes was greater than 2000 mg/kg. In the repeated test, the animals received the MMEO and there was no mortality. In the biochemical analysis, there were significant increases in blood glucose, cholesterol, ALT, AST, ALP, and TSH in the female rats and also in BUN in the male rats. The histopathological studies revealed evidence of microscopic lesions in the liver, kidney, stomach, and small intestine tissues of the MMEO group.

          Conclusion:

          The results indicated that the acute toxicity of the MMEO in the mice and rats was of a low order and it revealed slight tissue damage to several organs when given subchronically at a dose of 100 mg/kg.

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          Most cited references19

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          Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents)

          This review highlights the current advances in knowledge about the safety, efficacy, quality control, marketing and regulatory aspects of botanical medicines. Phytotherapeutic agents are standardized herbal preparations consisting of complex mixtures of one or more plants which contain as active ingredients plant parts or plant material in the crude or processed state. A marked growth in the worldwide phytotherapeutic market has occurred over the last 15 years. For the European and USA markets alone, this will reach about $7 billion and $5 billion per annum, respectively, in 1999, and has thus attracted the interest of most large pharmaceutical companies. Insufficient data exist for most plants to guarantee their quality, efficacy and safety. The idea that herbal drugs are safe and free from side effects is false. Plants contain hundreds of constituents and some of them are very toxic, such as the most cytotoxic anti-cancer plant-derived drugs, digitalis and the pyrrolizidine alkaloids, etc. However, the adverse effects of phytotherapeutic agents are less frequent compared with synthetic drugs, but well-controlled clinical trials have now confirmed that such effects really exist. Several regulatory models for herbal medicines are currently available including prescription drugs, over-the-counter substances, traditional medicines and dietary supplements. Harmonization and improvement in the processes of regulation is needed, and the general tendency is to perpetuate the German Commission E experience, which combines scientific studies and traditional knowledge (monographs). Finally, the trend in the domestication, production and biotechnological studies and genetic improvement of medicinal plants, instead of the use of plants harvested in the wild, will offer great advantages, since it will be possible to obtain uniform and high quality raw materials which are fundamental to the efficacy and safety of herbal drugs.
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            Effects of inhaled Linalool in anxiety, social interaction and aggressive behavior in mice.

            Aromatherapy uses essential oils (EOs) for several medical purposes, including relaxation. The association between the use of aromas and a decrease in anxiety could be a valuable instrument in managing anxiety in an ever increasing anxiogenic daily life style. Linalool is a monoterpene commonly found as the major volatile component of EOs in several aromatic plant species. Adding to previously reported sedative effects of inhaled linalool, the aim of this study was to investigate the effects of inhaled linalool on anxiety, aggressiveness and social interaction in mice. Additionally, we investigated the effects of inhaled linalool on the acquisition phase of a step-down memory task in mice. Inhaled linalool showed anxiolytic properties in the light/dark test, increased social interaction and decreased aggressive behavior; impaired memory was only seen the higher dose of linalool. These results strengthen the suggestion that inhaling linalool rich essential oils can be useful as a mean to attain relaxation and counteract anxiety.
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              Effects of Linalool on glutamatergic system in the rat cerebral cortex.

              Linalool is a monoterpene compound reported to be a major component of essential oils in various aromatic species. Several Linalool-producing species are used in traditional medical systems, including Aeolanthus suaveolens G. Dom (Labiatae) used as anticonvulsant in the Brazilian Amazon. Psychopharmacological in vivo evaluation of Linalool showed that this compound have dose-dependent marked sedative effects at the Central Nervous System, including hypnotic, anticonvulsant and hypothermic properties. The present study reports an inhibitory effect of Linalool on Glutamate binding in rat cortex. It is suggested that this neurochemical effect might be underlining Linalool psychopharmacological effects. These findings provide a rational basis for many of the traditional medical use of Linalool producing plant species.
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                Author and article information

                Journal
                Iran J Med Sci
                Iran J Med Sci
                Iranian Journal of Medical Sciences
                Iranian Journal of Medical Sciences (Iran )
                0253-0716
                1735-3688
                September 2018
                : 43
                : 5
                : 479-486
                Affiliations
                [1 ]Herbal Medicines Research Center, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran;
                [2 ]Department of Pharmacognosy, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran;
                [3 ]Department of Pharmacology, Iran University of Medical Sciences, Tehran, Iran;
                [4 ]Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran;
                [5 ]Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
                Author notes
                Correspondence:Zahra Mousavi, PhD; Department of Toxicology and Pharmacology, Pharmaceutical Sciences Branch, Islamic Azad University, No. 99, Yakhchal, Gholhak, Shariati St., P. O. Box: 19419-33111, Tehran, Iran. Tel:+98 21 22640051-5, Fax:+98 21 22602059
                Article
                IJMS-43-5
                6123553
                30214100
                da7fbd43-5dc5-4d0d-8729-a5c4faacd0cd
                Copyright: © Iranian Journal of Medical Sciences

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 April 2017
                : 30 April 2017
                : 21 February 2017
                Categories
                Original Article

                Medicine
                mentha , mentha mozaffarianii , essential oil , toxicity , rat , mice
                Medicine
                mentha , mentha mozaffarianii , essential oil , toxicity , rat , mice

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