For tens of centuries, plants have been highly valued and regularly used as medicine amongst the masses. Insomnia, a loss of sleep, is mostly treated by synthetic sleeping tablets these days. However, questions have been raised about the safety of prolonged use of artificial sedatives due to their deleterious side effects such as physical dependence. In recent years,
there has been an increasing propensity to preclude insomnia by herbal medicines throughout the world. Many herbs have a lengthy background in terms of insomnia treatment in Iran. This paper gives an account of previously published research on sedative and hypnotic effects of medicinal herbs used for treatment of insomnia in Iranian traditional medicine

Andalib, Sasan

Naeini, Azadeh Motavallian

Vaseghi, Ali

Vaseghi, Golnaz

Eldorado - Ressourcen aus und für Lehre, Studium und Forschung

EXCLI Journal 2011;10:192-197 – ISSN 1611-2156 Received: August 31, 2011, accepted: October 03, 2011, published: October 10, 2011  192 Mini review:  SEDATIVE AND HYPNOTIC EFFECTS OF IRANIAN TRADITIONAL MEDICINAL HERBS USED FOR TREATMENT OF INSOMNIA  Sasan Andalib1, Ali Vaseghi2, Golnaz Vaseghi3,*, Azadeh Motavallian Naeini3  1 School of Veterinary Medicine, Islamic Azad University of Tabriz, Tabriz, Iran 2 Department of General Sciences, Capilano University, Vancouver, BC, Canada  3 Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran  * corresponding author: email: golnazvaseghi@yahoo.com; Contact No.: +983117922628; Fax: +983116680011  ABSTRACT For tens of centuries, plants have been highly valued and regularly used as medicine amongst the masses. Insomnia, a loss of sleep, is mostly treated by synthetic sleeping tablets these days. However, questions have been raised about the safety of prolonged use of artificial sedatives due to their deleterious side effects such as physical dependence. In recent years, there has been an increasing propensity to preclude insomnia by herbal medicines throughout the world. Many herbs have a lengthy background in terms of insomnia treatment in Iran. This paper gives an account of previously published research on sedative and hypnotic effects of medicinal herbs used for treatment of insomnia in Iranian traditional medicine.  Keywords: Iranian medicinal herbs, Iranian traditional medicine, insomnia, sedative effect, hypnotic effect   INTRODUCTION Nowadays, insomnia has been a con-spicuous problem or disease in our restless society. It has been reported that 10 to 20 percent of adults across cultures suffer from chronic insomnia (Lamberg, 2005). Insomnia is often defined by sleeping prob-lems. People who suffer from insomnia may encounter difficulty of getting to sleep or staying asleep, or having non-refreshing sleep, to some degree. The poor quality of sleep is naturally followed by functional impairment while awake (Scott et al., 2011). Insomnia is secondary to other con-ditions. Indeed, it may stem from life events, mental disorders, pain, hormone shift and alcohol usage, to name but a few. Insomnia can be treated by synthetic medi-cines. Some insomniacs rely on sleeping tablets such as benzodiazepines and newer nonbenzodiazepines to get rest (Smith and Tett, 2010; Richey and Krystal, 2011). De-spite clinical success, these medicines have a number of problems in use. Apart from daytime fatigue and cognitive impairment as side effects of these sedatives (Zlott and Byrne, 2010; Hendler et al., 1980), they may engender physical dependence (Blais and Petit, 1990). On the other hand, insom-nia can be treated by herbal remedies. Some insomniacs are inclined to take medicinal plants owing to low frequency of side ef-fects. Several medicinal herbs have been used throughout the world (Wing, 2001). Moreover, the usage of herbal medicines has come to Iranian people since ancient times and apparently still serves a key role EXCLI Journal 2011;10:192-197 – ISSN 1611-2156 Received: August 31, 2011, accepted: October 03, 2011, published: October 10, 2011  193 in the arsenal of medicines in modern medicine. In fact, various climates in Iran exert a crucial role in distribution of plants used in traditional medicine. To date, sev-eral reviews have been published with re-spect to hypnotic impacts of herbal reme-dies throughout the world (Kim et al., 2011; LaFrance et al., 2000). We previously pub-lished a review on Persian herbal medicines with anxiolytic properties (Rabbani et al., 2011). Nonetheless, a comprehensive re-view has been absent with regard to hyp-notic effects of herbs used in Iranian tradi-tional medicine. Therefore, this paper re-views the literature pertaining to medicinal herbs used for treatment of insomnia in Iran.  Coriandrum sativum Coriandrum sativum is an herb which is currently cultivated in Iran. It is popularly referred as Geshniz in Persian. In addition to the extensive use of Coriander leaves in Iranian recipes, various parts of this plant such as seed, leaf, flower and fruit have been used in Iranian traditional medicine (Pathak Nimish et al., 2011). Emamghorei-shi et al. (2005) reported that coriander seeds led to a decrease in spontaneous ac-tivity in mice and therefore exhibited a sedative effect. Thereafter, Emamghoreishi and Heidari-Hamedani (2006) investigated the hypnotic and sedative activities of aqueous or hydro-alcoholic extracts and essential oil of coriander seeds in male al-bino mice by means of pentobarbital-induced sleeping time test and Animex ac-tivity meter. Aqueous extract with doses of 200, 400 and 600 mg/kg, hydro-alcoholic extract with doses of 400 and 600 mg/kg, and essential oil with a dose of 600 mg/kg were found to increase pentobarbital-induced sleeping time. It was also demon-strated that aqueous extract at doses of 50, 100 and 500 mg/kg significantly declined spontaneous locomotor activity. They pointed out that although the extracts and essential oil of coriander seeds exerted sedative and hypnotic influence, aqueous extract was assumed to be mainly responsi-ble for the hypnotic effect.  Rosa damascene Rosa damascene is cultivated in central Iran and known as Gole Sorkh. It is an erect shrub that grows about 1 to 2 meters with colorful and large flowers. In Iranian tradi-tional medicine, flowers, petals and hips are administered to treat insomnia. It was shown that not only did R. damascene in-hibit the reactivity of the hypothalamus and pituitary systems in rats, but also it sup-pressed the activity of the central nervous system (Libster, 2002). Rakhshandah and Hosseini (2006) examined the hypnotic ef-fect of ethanolic, aqueous and chloroformic extracts of R. damascene by means of pento-barbital-induced sleeping time test (30 mg/kg, i.p.) in mice and demonstrated that this herb can relive insomnia. Intraperi-toneal doses of 500 and 1000 mg/kg of ethanolic and aqueous extracts were demon-strated to produce hypnotic effect which was comparable to diazepam. The hypnotic effect of aqueous extract was induced dose dependently, notwithstanding the maximum effect of this extract at the dose of 500 mg/kg. Chloroformic extract-treated mice did not show any hypnotic effect. In another study, hypnotic effect of R. damas-cene extract and fractions (ethanol extract, N-butanol fraction, ethyl acetate fraction, aqueous fraction) was assessed based on prolongation of pentobarbital (diazepam)-induced sleeping time in mice (Rakhshan-dah et al. 2007). They found that ethanol extract and fractions of R. damascena at doses of 250 and 500 mg/kg increased the sleeping time in mice. Aqueous fraction of R. damascene had the minimum hypnotic influence. However, ethyl acetate fraction showed maximum hypnotic influence at a dose of 500 mg/kg. To date, no single study has covered the mechanism in which R. damascene extract or fractions produce their hypnotic effect. Nevertheless, Noguerira and Vassilieff studied the hypnotic effect of the other gen-iuses of Rosaceae family, that is, Rubus EXCLI Journal 2011;10:192-197 – ISSN 1611-2156 Received: August 31, 2011, accepted: October 03, 2011, published: October 10, 2011  194 brasiliensis and suggested that a benzodi-azepine-like principle in hexanic fraction of this herb induced the hypnotic effect through GABAa system (Nogueira and Vassilieff, 2000).  Crocus sativus Saffron stigma (Crocus sativus), is the world’s most expensive herb. It is cultivated in north east of Iran and called as Zafaran in Persian. Saffron, a spice derived from the flower of the saffron crocus, is found almost in every kitchen in Iran. Additionally, Saf-fron stigma has traditionally been adminis-tered in order to prevent insomnia. Sedative and hypnotic effects of Saffron aqueous ex-tract and its constituents, crocin and safranal formed the central focus of a study by Hosseinzadeh and Noraei (2009) in which the authors found that Saffron aqueous ex-tract and Safranal showed sedative and hyp-notic effects. They administered agents in-traperitoneally to mice before tests of sodium pentobarbital-induced sleeping time (30 mg/kg) and locomotor activity (open field test). It was then mentioned that the decline in locomotor activity caused by aqueous extract was dose dependent, and Saffron only with a dose of 0.56 g/kg pro-longed the total sleeping time in the hyp-notic test. Crocin was identified to have no anxiolytic, hypnotic or myorelaxation ef-fects. Safranal was shown to increase the total sleeping time dose dependently. How-ever, at lower doses (0.05 and 0.15 mL/kg), it decreased some parameters of locomotion activity. It was also demonstrated that Safranal had no effects on motor coordina-tion.  Salvia leriifolia Salvia leriifolia, which is known as Noruzak, is endemic to Khorasan province of Iran. It has traditionally been used for its various health benefits. It is generally thought that it can relive pain, decrease blood sugar and treat inflammation and in-somnia. Hosseinzadeh and Hassan Zadeh (2001) investigated sedative and hypnotic effects of extract of S. leriifolia on mice by means of thiopental-hypnosis test. Aqueous decoction extract at intraperitoneal doses of 1.15 and 1.57 g/kg was shown to slightly increase the total sleeping time up to 20.58 minutes versus 63.67 minutes in di-azepam (3 mg/kg). Relaxation of skeletal muscles was also assessed by traction test. An intraperitoneal treatment of the extract (0.29-2.87 mg/kg) caused relaxation in muscles; even so, muscle relaxation in-duced by the extract with a low dose of 0.29 mg/kg was found to be as effective as relaxation produced by diazepam (1 mg/kg). In another study, preliminary phytochemical test showed that the extract was composed of low amount of flavonoid, but enriched with tannin and saponin (Hosseinzadeh and Hassan Zadeh, 2001). Nevertheless, the mechanism in which they produce effect has not been well character-ized.  Salvia reuterana Salvia reuterana, which is commonly known as Mariam Goli Esfahani in Iran, has been mostly found in highlands of center of Iran. The aerial parts of this herb have been used in Iranian traditional medicine ow-ing to its sedative and anxiolytic effects. Perry et al. (2003) reported that the mecha-nism of inhibition of acetylcholinesterase by constituents of S. reuterana was respon-sible for its sedative effects. In addition, it was reported that Miltirone inhibited the binding of [3H]flunitrazepam to central benzodiazepine receptor; and elucidated a major role for GABA receptor in its mechanism (Lee et al., 1991). Another study investigated volatile constituents of S. reuterana and showed that there are 21 components in the oil of plant (Mirza and Sefidkon, 1999). The authors found that (E)-β-Ocimene (32.3 %), α-gurjunene (14.1 %), germacrene-d (11.2 %) and hexyl acetate (7.6 %) were the major constituents in the oil of S. reuterana (Mirza and Sefid-kon, 1999). In our previous study, we as-sessed sedative effect of hydroalcoholic ex-tract of S. reuterana in mice by means of spontaneous locomotor activity test at a EXCLI Journal 2011;10:192-197 – ISSN 1611-2156 Received: August 31, 2011, accepted: October 03, 2011, published: October 10, 2011  195 dose of 100 mg/kg (Rabbani et al., 2005). The total locomotor activity count meas-ured in 15 minutes of the test was found to be significantly decreased in animals which received diazepam pretreatment and S. reuterana extract treatment. It is interesting to note that a decline in locomotor activity was also evident in 5 minutes. We also ob-served that an increase in the dose of the plant extract leaded to higher sedative properties.  Stachys lavandulifolia Stachys lavandulifolia is widely distrib-uted in Iran and known as Chaye Kuhi. As well as being administered for several me-dicinal purposes, the traditional use of S. lavandulifolia for its hypnotic and sedative effects has been of great importance. Rab-bani et al. (2003) studied the impacts of S. lavandulifolia extracts upon ketamine-induced sleeping time and locomotor activ-ity tests in mice and demonstrated that the extract produced hypnotic and sedative ac-tivities. It was shown that intraperitoneal doses of 100 and 300 mg/kg of S. lavan-dulifolia extract significantly prolonged the duration of sleep by 28 and 42 percent, re-spectively. It was also reported that a treat-ment with plant extract at doses of 100 or 300 mg/kg (30 minutes prior to ketamine treatment), significantly shortened the ini-tiation of induced sleep (latency time) by 24 and 25 %, respectively. Moreover, they mentioned that the locomotor activity sig-nificantly diminished in S. lavandulifolia-treated mice at a dose of 100 mg/kg. The authors then demonstrated that at all three time intervals (5, 10 and 15 minutes), the decline in locomotor activity was evident; even so, greatest decline in locomotor activ-ity was found to be during the initial 5 min-utes.  Moreover, the mechanism of action of constituents of S. lavandulifolia has not yet been completely worked out, and only a few studies have been carried out on its ac-tive constituents. It was demonstrated that S. lavandulifolia contained volatile oil and a phenyl propanoid glycoside (Basaran et al., 1988; Sezik and Basaran, 1985).  CONCLUSION Insomnia is a major health concern throughout the world and a highly prevalent sleep disorder in Iran. To elude deleterious side effects of artificial medicines abating insomnia, there has been a propensity for herbal remedies. Despite the fact that plants have been used in Iranian traditional medi-cine in order to preclude insomnia for cen-turies, special attention has recently been devoted to them as alternatives for synthetic medicines in Iran. In fact, plausible justifi-cation provided by previously mentioned Iranian studies has made it difficult to trivi-alize the role of these medicinal herbs in treatment of insomnia. Various herbs have been used for reliving insomnia in Iranian traditional medicine, Valeriana officinalis, Blue   violte, Salix aegyptiaca, lotus flower, lettuce, and Echium amoenum, to name but a few. It is interesting to note that in our previous study, we investigated the sedative and hypnotic effects of E. amoenum by means of locomotor activity and ketamin-induced sleeping tests. The ethanolic ex-tract of this plant increased the latency time and excreted no effect on total sleeping time. This extract also did not produce a significant effect in locomotor activity test. As a result, we suggested that this herb did not exhibit sedative and hypnotic effects (Rabbani et al., 2004).  Considering the fact that reviewed stud-ies have been carried out on animals, fur-ther research on human provides a better insight concerning hypnotic and sedative effects of herbal medicines and approves their efficacy. Nonetheless, many pharma-cological and toxicological studies are needed to be conducted prior to clinical tri-als. In fact, more work should be done to establish active constituents of these herbal medicines used for insomnia treatment. What has to be finally considered is that these medicinal herbs have not yet been ap-proved. Therefore, they should undergo several approval processes. Indeed, there is EXCLI Journal 2011;10:192-197 – ISSN 1611-2156 Received: August 31, 2011, accepted: October 03, 2011, published: October 10, 2011  196 a long way from laboratory to market for these herbal medicines.  REFERENCES Basaran AA, Calis I, Anklin C, Nishibe S, Sticher O. Lavandulifolioside: a new phe-nylpropanoid glycoside from Stachys la-vandulifolia. Helv Chim Acta 1988;71: 1483-90.   Blais D, Petit L. Benzodiazepines: depend-ence and a therapeutic approach to gradual withdrawal. Can Fam Physician 1990;36: 1779-82.  Emamghoreishi M, Heidari-Hamedani G. Sedative-hypnotic activity of extracts and essential oil of Coriander seeds. Iran J Med Sci 2006;31(1):22-7.  Emamghoreishi M, Khasaki M, MaFath Aazam M. Coriandrum sativum: evaluation of its anxiolytic effect in the elevated plus-maze. J Ethnopharmacol 2005;96:365-70.  Hendler N, Cimini C, Ma T, Long D. A comparison of cognitive impairment due to benzodiazepines and to narcotics. Am J Psychiatry 1980;137:828-30.  Hosseinzadeh H, Hassan Zadeh A. Muscle relaxant and hypnotic effects of Salvia Leri-ifolia Benth leaves extract in mice. Iran J Basic Med Sci 2001;4(3(11)):130-8.  Hosseinzadeh H, Noraei NB. Anxiolytic and hypnotic effect of Crocus sativus aque-ous extract and its constituents, crocin and safranal, in mice. Phytother Res 2009;23: 768-74.  Kim CS, Han JY, Kim S, Jin Tae Hong JT, Oh KW. Herbs for the treatment of insom-nia. Biomol Ther 2011;19:274-81.  LaFrance WC, Lauterbach EC, Coffey CE, Salloway SP, Kaufer DI, Reeve A et al. The use of herbal alternative medicines in neu-ropsychiatry. J Neuropsychiatr Clin Neuro-sci 2000;12:177-92. Lamberg L. Insomnia shows strong link to psychiatric disorders. Psychiatr News 2005;40(12):21.  Lee CM, Wong HN, Chui KY, Choang TF, Hon PM, Chang HM. Miltirone, a central benzodiazepine receptor partial agonist from a Chinese medicinal herb Salvia miltiorrhiza. Neurosci Lett 1991;127:237-41.  Libster M. Delmar,s integrative herb guide for nurses. 1st ed. Albany: Delmar Thomson Learning, 2002.  Mirza M, Sefidkon F. Essential oil compo-sition of two Salvia species from Iran, Sal-via nemorosa L. and Salvia reuterana Boiss. Flavour Frag J 1999;14:230-2.  Nogueira E, Vassilieff VS. Hypnotic, anti-convulsant and muscle relaxant effect of Rubus brasiliensis. Involvment of GABA (A)-system. J Ethnopharmacol 2000;70: 275-80.  Pathak Nimish L, Kasture Sanjay B, Bhatt Nayna M, Rathod Jaimik D. Phytopharma-cological properties of Coriander Sativum as a potential medicinal tree: an Overview. J Appl Pharm Sci 2011;1(4):20-5.  Perry NSL, Bollen C, Perry EK, Ballard C. Salvia for dementia therapy: review of pharmacological activity and pilot tolerabil-ity clinical trial. Pharmacol Biochem Behav 2003;75: 651–9.  Rabbani M, Sajjadi SE, Zarei HR. Anxio-lytic effects of Stachys lavandulifolia Vahl on the elevated plus-maze model of anxiety in mice. J Ethnopharmacol 2003;89:271-6.  Rabbani M, Sajjadi SE, Vaseghi G, Jafarian A. Anxiolytic effects of Echium amoenum on the elevated plus-maze model of anxiety in mice. Fitoterapia 2004;75:457-64.  EXCLI Journal 2011;10:192-197 – ISSN 1611-2156 Received: August 31, 2011, accepted: October 03, 2011, published: October 10, 2011  197 Rabbani M, Sajjadi SE, Jafarian A, Vaseghi G. Anxiolytic effects of Salvia reuterana Boiss. on the elevated plus-maze model of anxiety in mice. J Ethnopharmacol 2005; 101:100-3.  Rabbani M, Vaseghi G, Sajjadi SE, Amin B. Persian herbal medicines with anxiolytic properties. J Med Plants 2011;39(10):7-11.  Rakhshandah H, Hosseini M. Potentiatian of pentobarbital hypnosis by Rosa damascene. Indian J Exp Biol 2006;44:910-2.  Rakhshandah H, Shakeri MT, Ghasem-zadeh MR. Comparative hypnotic effect of Rosa damascena fractions and diazepam in mice. Iran J Pharm Res 2007;6: 193-7.  Richey SM, Krystal AD. Pharmacological advances in the treatment of insomnia. Curr Pharm Des 2011;17:1471-5.  Scott GW, Scott HM, O'Keeffe KM, Gan-der PH. Insomnia-treatment pathways, costs and quality of life. Cost Eff Resour Alloc 2011;9(1):10.  Sezik E, Basaran A. Phytochemical investi-gations on the plants used as folk medicine and herbal tea in Turkey: II. Essential oil of Stachys lavandulifolia Vahl. J Fac Pharm Ankara 1985;21:98–107.  Smith AJ, Tett SE. Improving the use of benzodiazepines – is it possible? A nonsys-tematic review of interventions tried in the last 20 years. BMC Health Serv Res 2010;10:321.  Wing YK. Herbal treatment of insomnia. Hong Kong Med J 2001;7:392-402.  Zlott DA, Byrne M. Mechanisms by which pharmacologic agents may contribute to fatigue. PM&R 2010;2:451-5.  

Sedative and hypnotic effects of Iranian traditional medicinal herbs used for treatment of insomnia

https://eldorado.tu-dortmund.de/bitstream/2003/29213/1/Andalib_insomnia_10102011_proof.pdf

Sedative and hypnotic effects of Iranian traditional medicinal herbs used for treatment of insomnia

Abstract

Similar works

Full text

Available Versions

Eldorado - Ressourcen aus und für Lehre, Studium und Forschung