Application of pistachio (Pistacia sp.) extract in Morphine Withdrawal Syndrome improvement: A review Saeedeh Akhavan1 5, Bahareh Kashefi 2, Samira Rezaei Mojdehi 3 5, Kobra Shabanzadeh Delcheh4 5, Reza Mohammadhassan4 5 * M.Sc. student, Department of Cellular and Molecular biology, faculty of Science, Tehran East branch , Islamic Azad university, Tehran ,Iran 2- Assistant professor , Department of Horticulture Science , College of Agriculture, Damghan Branch, Islamic Azad University, Damghan, Iran 3- BSc. Graduated, Department of Cellular and Molecular Biology , College of Basic Science ,Gilan University, Gilan, Iran 4- M.Sc. student, Department of Agricultural Biotechnology, College of Agriculture, Damghan Branch, Islamic Azad University, Damghan, Iran 5- Bioresearcher , Amino Techno Gene Research Institute, Tehran ,Iran *Corresponding Author:
[email protected] 1-
Abstract Opioids are compounds which influence on the central nervous system similar to morphine. Morphine is an opioid and analgesic drug. It reduces chronic and acute pain by direct impact on the central nervous system. It can be addictive. Morphine withdrawal syndrome occurs when the dose is reduced after long-term use. Because of intolerance withdrawal symptoms, addicts' treatment is difficult and clinical use of morphine has decreased. Pistachio species grow in the Zagros Mountains, in Iran. Traditionally, pistachio plant has been consumed in headache. Research has revealed the several pharmacological effects in pistachio species, like analgesic, anti-cholinergic activity, reduce symptoms of withdrawal. In the article, we try to introduce potential pistachio extract in reduce symptoms of morphine withdrawal syndrome. Keywords: Morphine, Pistachio, Opioids, Morphine Withdrawal Syndrome. Introduction Opioids are substances which influence on the nervous system similar to morphine and codeine (9).
They are one of the oldest known drugs in the world. Medical application of opium (Opium poppy) has been recorded in history (1). Today in medicine, synthetic pharmaceutical compounds are called opioids. They are used to treat pain in medicine (9). Opioids act by binding to their receptors in the central and peripheral nervous system and gastrointestinal tract. Opioids receptors mediate mental and physical effects (1). The use of opioids is associated with side effects, including drowsiness, constipation, euphoria and respiratory depression. Respiratory depression induced by overdose can lead to death. Naturally, the human body produces substances for pain relief; the substances are classified as opioids. Also there are opioids-like compounds in Opium sap. These compounds are classified as opiates (9). Although these two terms are synonymous, the alkaloids in opium resin are called opiate, while opioids are synthetic (1). Morphine is an opioid and analgesic drug. It reduces chronic and acute pain by direct impact on the central nervous system (13). The first time, Friedrich Sertürner isolated morphine in 18031805 (3). The main source of morphine is straw of opium. After the invention of the injection syringe, morphine was used widely (2). Morphine is prescribed in different ways including intravenously, intramuscularly, subcutaneously, orally and rectally. Maximum effect has been reported between 20 minutes (intravenously) and 60 minutes (orally) (13). Potentially it has side effects, including respiratory depression, hypotension and vomiting. The use of morphine can affect the baby during pregnancy and breastfeeding. Also morphine can be addictive (2). Morphine production quantity morphine is 532 tones in 2013. About 45 tones (8.6) are used for analgesic purposes and about 366.1 tones (70%) for the manufacture of other opioids such as Oxycodone, Hydromorphone, Methadone and Heroin (2). Morphine consumption causes incidence of addiction in neural and molecular common ground (6). Tolerance and dependence problems occur in consumer morphine (16). Body and central nervous system react to sudden discontinuation of morphine. A set of symptoms which occur in this case, called withdrawal syndrome. Rodents indicate withdrawal symptoms including Jumping, writhing, wet dog shake diarrhea, teeth chattering, hyperactivity (6), weight reduction, ejaculation, shake a paw, tenderness and sensitivity to displacement. Nuerochemical and neurophysiologic studies has approved involvement of several neurotransmitter systems in incidence and severity of morphine withdrawal syndrome such as noradrenergic, cholinergic and glutaminergic (5). Observation of three of the symptoms is incidence of the syndrome (6). Today, dependence on morphine is a social problem (7). Due to the intolerance of withdrawal syndrome symptoms, Addicts treatment is difficult (6). Despite the analgesic effects of
morphine, its clinical use has decreased due to the intolerance syndrome traits too (7). If the symptoms decline, it will be possible to achieve public health (7). Pistachio belongs to Anacardiaceae family and Pistacia genus. This classification has been done by Carl Linnaeus in 1737 (10). There are several species, including P. terebinthus, P. weinmanifolia, P. lentiscus, P. chines and P. vera (17). Various species of the plants are generally wild and self-propelled trees (12). In large quantities, pistachios are grown in warm and dry areas. It is resistant to water scarcity and drought and resistant to salinity tree after the date (10). Pistachios are distributed over wide areas of the Mediterranean and the Middle East (17). In Iran pistachio species grow in the Zagros Mountains (10). There are very different varieties pistachio in terms of shape, color, size and composition of nut (12). Pistachio is rich source of oil (50-60 percent) (15). Pistachio oil contains high protein, high amounts vitamins A, B, C and D, low fat and low cholesterol, minerals such as iron, phosphorus, copper, zinc and magnesium (11), high fiber (8) and fatty acids such as linolenic and linoleic and oleic acid (15). Different varieties pistachio have compounds including Neoflavin, Procyanidin, Triterpenes, and Flavonoids (7) and high Phenolic compounds. The amount of phenolic compounds is a substantial compared to other sources (4). Thus pistachio is considered as a source of inexpensive and accessible biological compounds (12). Traditionally, pistachio plant has been consumed in digestive diseases, dysentery, headache, influenza (17), Reduce blood fat, refreshing; strengthen of spleen, liver and gender force (14). In traditional medicine, pistachio is used in the treatment of liver congestion. Resin or water of P.lentiscus is effective in treatment of liver and stomach tumors (10). Research has revealed the several pharmacological effects in pistachio species. Including reducing blood pressure, anti-inflammatory (10), antibacterial, antifungal, Treatment of duodenal and gastritic ulcers, anti-hepatotoxic, reduce symptoms of withdrawal, anti-cholinergic activity, analgesic and estrogen-like effect (7). Effect of pistachio extract on symptoms of morphine withdrawal syndrome Researchers have shown that pistachio contains compounds including Flavonoids and Pepines derivatives like α-Pepine and β-Pepine. These compounds can reduce symptoms of withdrawal syndrome. In a research, effect of infusion extract of pistachio red nutshell on morphine withdrawal syndrome was evaluated in rats. In order to make a dependence on morphine, different concentrations of morphine was resolved in drinking water for 14 days. Naloxone (2 mg/kg) was injected subcutaneously in the control group. In 4 test group infusion extract of pistachio red nutshell was injected at doses 25, 50, 100 and 200 intraperitoneally, 30 minute before Naloxone injection. Incidence and severity of the syndrome symptoms and weight loss was evaluated in all groups after 20 minutes and 24 hours, respectively. There are three
symptoms writhing, diarrhea and weight loss in all dependent on morphine rats. The writhing numbers are declined significantly by doses 25 and 50 mg/kg (P< 0.05) and 100 (P< 0.01).While incidence of diarrhea was reduced in all treatments, significantly. Weight loss was less in doses 50 and 100 mg/kg (P< 0.05 and P< 0.01, respectively). There are most reducing symptoms in 100 mg/kg (5). In another research, effect of aqueous extract of pistachio red nutshell on morphine withdrawal syndrome was evaluated in male rats. Concentration of morphine was 0.1, 0.2 and 0.3 mg/ml in the first, second and third 48 hours, respectively. Morphine concentration was 0.4 mg/ml from seventh day to fourteenth day. Naloxone (2 mg/kg) was injected and the syndrome symptoms were evaluated in 15th day. Treatments and aqueous extract concentration of pistachio are expressed in the following table: Table 1; Treatment and aqueous extract concentration of pistachio red nutshell Treatment
Control
aqueous extract concentration of pistachio red nutshell (mg/kg)
Saline Injection*
6
12.5
25
50
100
200
400
50
100
200
400
800
1600
-----
Injection Acute Gavage** Chronic Gavage***
Saline Gavage 30 minutes before Naloxone injection ** 60 minutes before Naloxone injection *** Once a day (9:00 AM), during dependence on morphine
Injection caused reducing symptoms. Doses 50 and 100 mg/kg of the extract could prevent weight loss (P< 0.05 and P
