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      Evaluation of analgesic activity and toxicity of alkaloids in Myristica fragrans seeds in mice

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          Abstract

          Aim

          To examine the analgesic effect of alkaloids in Myristica fragrans seed in a mouse model of acetic acid-induced visceral pain.

          Methods

          Alkaloids were extracted from ground nutmeg seed kernels with 10% acetic acid in 95% ethyl alcohol. Visceral pain was induced in male and female BALB/c mice by intraperitoneal injection of 0.6% acetic acid. Analgesic effect of alkaloids (0.5 gram or 1 gram per kilogram [g/kg], by mouth) was assessed by evaluating writhing response. Acute toxicity was tested in response to 2, 3, 4, 5, or 6 g/kg of alkaloid extract; the median lethal dose (LD 50) was determined by probit analysis.

          Results

          Alkaloid extract at a dose of 1 g/kg significantly reduced the number of writhing responses in female, but not male mice; 0.5 g/kg of alkaloid extract had no effect in either sex. The LD 50 was 5.1 g/kg. Signs of abnormal behavior, including hypoactivity, unstable gait, and dizziness were seen in animals given a dose of 4 g/kg or higher; abnormal behavior lasted for several hours after administration of the alkaloids.

          Conclusion

          According to the classification of Loomis and Hayes, M. fragrans seed alkaloids have analgesic activity and are slightly toxic.

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          Most cited references 35

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          Ethical guidelines for investigations of experimental pain in conscious animals.

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            Phytochemical Methods

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              Involvement of resident macrophages and mast cells in the writhing nociceptive response induced by zymosan and acetic acid in mice.

              Intraperitoneal administration of zymosan and acetic acid induced a dose-dependent nociceptive writhing response in mice. Lavage of the peritoneal cavities with saline reduced the number of total resident peritoneal cells and caused a proportional decrease in the nociceptive responses induced by these stimuli. Furthermore, the specific reduction of the peritoneal mast cell population by intraperitoneal administration of compound 48/80 also reduced the nociceptive responses induced by zymosan and acetic acid. In contrast, enhancement of the peritoneal macrophage population by pretreatment of the cavities with thioglycollate caused an increase in the number of writhes induced by both stimuli. These data suggest that the nociceptive responses induced by zymosan and acetic acid are dependent upon the peritoneal resident macrophages and mast cells. These cells modulate the nociceptive response induced by zymosan and acetic acid via release of tumour necrosis factor alpha (TNF-alpha), interleukin 1beta and interleukin 8. This suggestion is supported by the following observations: (a) pretreatment of the peritoneal cavities with antisera against these cytokines reduced the nociceptive responses induced by these stimuli; (b) peritoneal cells harvested from cavities injected with zymosan or acetic acid released both interleukin 1beta and TNF-alpha; (c) although individual injection of TNF-alpha, interleukin 1beta or interleukin 8 did not induce the nociceptive effect, intraperitoneal injection of a mixture of these three recombinant cytokines caused a significant nociceptive writhing response. In conclusion, our results suggest that the nociceptive activity of zymosan and acetic acid in the writhing model is due to the release of TNF-alpha, interleukin 1beta and interleukin 8 by resident peritoneal macrophages and mast cells.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2013
                31 July 2013
                : 6
                : 611-615
                Affiliations
                [1 ]College of Science, Department of Medical Analysis, Thi-Qar University, Thi-Qar, Iraq
                [2 ]College of Science, Biology Department, University of Basrah, Basrah, Iraq
                [3 ]College of Science, Biology Department, Thi-Qar University, Thi-Qar, Iraq
                Author notes
                Correspondence: A Al-Shammary Hayfaa College of Science, Department of Medical Analysis, Thi-Qar University, Al-mtanzah Street, Nassriya, Thi-Qar, Iraq Email hayfaashamer@ 123456yahoo.com
                Article
                jpr-6-611
                10.2147/JPR.S45591
                3738253
                23946667
                © 2013 Hayfaa et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Categories
                Original Research

                Anesthesiology & Pain management

                nutmeg, analgesic, mice, ld50, acetic acid, visceral pain

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