Effect of a medicinal plant (Passiflora incarnata L) on sleep
Fructuoso Ayala Guerrero and Graciela Mexicano Medina
Additional article information
Abstract
Introduction
Extracts of the plant Passiflora incarnata L. (Passifloraceae) were administered intraperitoneally in order to test its effects on sleep.
Methods
Experiments were carried out on chronically implanted male adult wistar rats to obtain cerebral (EEG), ocular (EOG) and muscular (EMG) activities throughout their states of vigilance. Polygraphic recordings were taken during 9 continuous hours before and after the extract administration (500 mg/kg).
Results
Passiflora incarnata induced a significant increment in the total sleep time (p<0.05). This increment was due to an increase in the time spent by animals in slow wave sleep (SWS). Concomitantly, a significant decrement in wakefulness (W) was observed (p<0.05). In contrast, time spent in rapid eye movement (REM) sleep showed a decreasing tendency, since both its frequency and mean duration were reduced.
Conclusion
The extracts obtained from Passiflora incarnata can be considered as appropriated sleep inducers.
Keywords: Passifloraceae, Sleep Aids, Pharmaceutical, Insomnia, Sleep, Sleep, REM
Introduction
Sleep is a complex phenomenon constituted by two electrophysiologically and behaviorally different stages: Non-REM or Slow wave sleep (SWS) and paradoxical or rapid eye movement (REM) sleep. SWS is characterized by presenting a high voltage slow wave electroencephalographic pattern, while REM sleep exhibits a low voltage fast wave electroencephalographic pattern and ocular movements. Both sleep phases may be disturbed both by external and internal factors; therefore, the normal sleep patterns may be frequently affected.
Insomnia is a sleep disturbance that is increasing in the general population inducing serious troubles of public health; this situation has led many researchers to seek alternative therapies and test sleep inducing substances of diverse chemical nature to cope with this problem1.
Substances regarded as appropriated hypnotics are those which prevent continuous awakenings, shorten the period of latency for sleep initiation and increase sleep duration, besides displaying low toxicity.
The chemical structure of hypnotic drugs is diverse. Barbiturates, introduced more than 50 years ago, are considered to be the prototype for these drugs. However, since they exhibit serious undesired side effects their use has declined2.
Benzodiazepines are currently the most well-known and most frequently prescribed hypnotic medications, although their use in recent years is being replaced by newer non-benzodiazepine hypnotic drugs3, and the hormone melatonin4.
The most recently discovered class of hypnotics are the non-benzodiazepine drugs which were introduced in the 1980s with the development of the so-called "Z-drugs" such as Zopiclone, Zolpidem, Zaleplon and Ezopiclone5. The non-benzodiazepine drugs have similar properties to the benzodiazepines, but different chemical make-ups. They are considered relatively safer than benzodiazepines because they are less likely to cause addiction or fatal overdose.
However, they have been known to cause amnesia, hallucinations, sleepwalking problems and an increased risk of depression.These substances are usually prescribed for reducing sleep latency and increasing the total sleeping time. Among benzodiazepines, the most commonly utilized are flurazepam, triazolam, temazepam and nitrazepam. AIl these drugs increase the total sleeping period, but their effect on the sleep latency differs and some of them show undesired side effects, such as oversedation, excessive somnolence and different degrees of ataxia6.
Variations in the specific effects caused by hypnotic drugs basically depend on their physico-chemical characteristics, especially their liposolubility as well as their intensity and duration7. It is also frequent for intermediate metabolites to be pharmacologically active, which implies a longer duration of the effects. Therefore, when considering the pharmacokinetics of a hypnotic substance it is necessary to contemplate the original compound and its active metabolites, since the effect of a given substance depends on both factors8.
As mentioned previously, treatment of insomnia by means of synthesized substances originates different types of undesirable side effects. This has motivated the searching of alternative approaches such as the employment of phythotherapeutic agents9. In this context, there is ethnomedical information concerning medicinal plants which possess sedative and hypnotic properties. Among these plants are Valeriana officinalis L. (Valerianaceae)10 and Galphimia glauca Cav (Malpighiaceae)11 which have shown important sedative effects.
Hypnotic effects have also been reported for Passiflora incarnata L.12, a medicinal plant native from tropical areas of America. However, this assumption has been originated from no quantifiable subjective information13 and consequently it may lead to imprecise interpretations. Therefore the aim of this work was to analyze by means of electrophysiological methods, the effect of administration of an extract of P. incarnata L. on sleep.
Methods
Animals
Six male adult wistar rats were used to perform this study according to human criteria and institutional approval (Bioethical Committee and the Mexican Standard for the production care and use of laboratory animals NOM-062-Z00-1999). Under general anesthesia (Sodium pentobarbital, 50 mg/kg ip) two pairs of stainless steel electrodes were epidurally implanted to obtain the electrical activity of the frontal (2 mm anterior to bregma) and occipital (5 mm posterior to bregma) regions of the brain (EEG). Ocular activity (EOG) was also obtained by means of similar electrodes placed on the supraorbital bone of each eye. Another pair of electrodes was placed on the nape muscles to obtain the electromyogram (EMG).
Animals were left to recover from surgery during a minimal period of one week. Subsequently, they were placed for their habituation to experimental conditions during 7 days in a sound attenuated chamber under a 12-hr light (7 AM-7 PM), 12-hr dark cycle (7 PM-7AM). Temperature inside the chamber oscillated between 23 and 25º C. Food and water were continuously available.
Instrumentation
Under saline injection, control polygraphic recordings were made with a Model 7 Grass electroencephalograph during 9 continuous hours from 09:00 to 18:00 hr. On the next day, an extract from Passiflora incarnata was injected intraperitoneally (500 mg/kg) at 09:00 hr and polygraphic recordings were immediately taken during another period of 9 continuous hours, as for control conditions.
Preparation of the extract
Shade-dried powdered aerials parts (3.5 kg), fruits being included, were macerated. Afterwards, the plant material was extracted exhaustively by percolation with an ethanol-water (6:4) mixture. The resulting hydro-ethanol extract was evaporated and concentrated under reduced pressure at a temperature of 40ºC in order to eliminate the ethanol. Water was then added to reach the original volume of the fluid extract. The resulting solution was considered as the aqueous extract used for pharmacological tests
Data Analysis
Recordings were visually analyzed. Quantification of states of vigilance was carried out second by second and the total time spent by animals in each state of vigilance per 9 hour periods was measured. Average duration, frequency and latency of the REM sleep phase were obtained, as well as the latency of SWS. A statistical analysis by means paired sample t-tests followed by power analysis was used to determine significant differences among the variables induced by the studied substance.
Results
Effect of a medicinal plant (Passiflora incarnata L) on sleep
Fructuoso Ayala Guerrero and Graciela Mexicano Medina
Additional article information
Abstract
INTRODUCTION
Extracts of the plant Passiflora incarnata L. (Passifloraceae) were administered intraperitoneally in order to test its effects on sleep.
METHOD
Experiments were carried out on chronically implanted male adult wistar rats to obtain cerebral (EEG), ocular (EOG) and muscular (EMG) activities throughout their states of vigilance. Polygraphic recordings were taken during 9 continuous hours before and after the extract administration (500 mg/kg).
RESULTS
Passiflora incarnata induced a significant increment in the total sleep time (p<0.05). This increment was due to an increase in the time spent by animals in slow wave sleep (SWS). Concomitantly, a significant decrement in wakefulness (W) was observed (p<0.05). In contrast, time spent in rapid eye movement (REM) sleep showed a decreasing tendency, since both its frequency and mean duration were reduced.
CONCLUSIONS
The extracts obtained from Passiflora incarnata can be considered as appropriated sleep inducers.
Keywords: Passifloraceae, Sleep Aids, Pharmaceutical, Insomnia, Sleep, Sleep, REM
INTRODUCTION
Sleep is a complex phenomenon constituted by two electrophysiologically and behaviorally different stages: Non-REM or Slow wave sleep (SWS) and paradoxical or rapid eye movement (REM) sleep. SWS is characterized by presenting a high voltage slow wave electroencephalographic pattern, while REM sleep exhibits a low voltage fast wave electroencephalographic pattern and ocular movements. Both sleep phases may be disturbed both by external and internal factors; therefore, the normal sleep patterns may be frequently affected.
Insomnia is a sleep disturbance that is increasing in the general population inducing serious troubles of public health; this situation has led many researchers to seek alternative therapies and test sleep inducing substances of diverse chemical nature to cope with this problem1.
Substances regarded as appropriated hypnotics are those which prevent continuous awakenings, shorten the period of latency for sleep initiation and increase sleep duration, besides displaying low toxicity.
The chemical structure of hypnotic drugs is diverse. Barbiturates, introduced more than 50 years ago, are considered to be the prototype for these drugs. However, since they exhibit serious undesired side effects their use has declined2.
Benzodiazepines are currently the most well-known and most frequently prescribed hypnotic medications, although their use in recent years is being replaced by newer non-benzodiazepine hypnotic drugs3, and the hormone melatonin4.
The most recently discovered class of hypnotics are the non-benzodiazepine drugs which were introduced in the 1980s with the development of the so-called "Z-drugs" such as Zopiclone, Zolpidem, Zaleplon and Ezopiclone5. The non-benzodiazepine drugs have similar properties to the benzodiazepines, but different chemical make-ups. They are considered relatively safer than benzodiazepines because they are less likely to cause addiction or fatal overdose.
However, they have been known to cause amnesia, hallucinations, sleepwalking problems and an increased risk of depression.These substances are usually prescribed for reducing sleep latency and increasing the total sleeping time. Among benzodiazepines, the most commonly utilized are flurazepam, triazolam, temazepam and nitrazepam. AIl these drugs increase the total sleeping period, but their effect on the sleep latency differs and some of them show undesired side effects, such as oversedation, excessive somnolence and different degrees of ataxia6.
Variations in the specific effects caused by hypnotic drugs basically depend on their physico-chemical characteristics, especially their liposolubility as well as their intensity and duration7. It is also frequent for intermediate metabolites to be pharmacologically active, which implies a longer duration of the effects. Therefore, when considering the pharmacokinetics of a hypnotic substance it is necessary to contemplate the original compound and its active metabolites, since the effect of a given substance depends on both factors8.
As mentioned previously, treatment of insomnia by means of synthesized substances originates different types of undesirable side effects. This has motivated the searching of alternative approaches such as the employment of phythotherapeutic agents9. In this context, there is ethnomedical information concerning medicinal plants which possess sedative and hypnotic properties. Among these plants are Valeriana officinalis L. (Valerianaceae)10 and Galphimia glauca Cav (Malpighiaceae)11 which have shown important sedative effects.
Hypnotic effects have also been reported for Passiflora incarnata L.12, a medicinal plant native from tropical areas of America. However, this assumption has been originated from no quantifiable subjective information13 and consequently it may lead to imprecise interpretations. Therefore the aim of this work was to analyze by means of electrophysiological methods, the effect of administration of an extract of P. incarnata L. on sleep.
METHODS
Animals
Six male adult wistar rats were used to perform this study according to human criteria and institutional approval (Bioethical Committee and the Mexican Standard for the production care and use of laboratory animals NOM-062-Z00-1999). Under general anesthesia (Sodium pentobarbital, 50 mg/kg ip) two pairs of stainless steel electrodes were epidurally implanted to obtain the electrical activity of the frontal (2 mm anterior to bregma) and occipital (5 mm posterior to bregma) regions of the brain (EEG). Ocular activity (EOG) was also obtained by means of similar electrodes placed on the supraorbital bone of each eye. Another pair of electrodes was placed on the nape muscles to obtain the electromyogram (EMG).
Animals were left to recover from surgery during a minimal period of one week. Subsequently, they were placed for their habituation to experimental conditions during 7 days in a sound attenuated chamber under a 12-hr light (7 AM-7 PM), 12-hr dark cycle (7 PM-7AM). Temperature inside the chamber oscillated between 23 and 25º C. Food and water were continuously available.
Instrumentation
Under saline injection, control polygraphic recordings were made with a Model 7 Grass electroencephalograph during 9 continuous hours from 09:00 to 18:00 hr. On the next day, an extract from Passiflora incarnata was injected intraperitoneally (500 mg/kg) at 09:00 hr and polygraphic recordings were immediately taken during another period of 9 continuous hours, as for control conditions.
Preparation of the extract
Shade-dried powdered aerials parts (3.5 kg), fruits being included, were macerated. Afterwards, the plant material was extracted exhaustively by percolation with an ethanol-water (6:4) mixture. The resulting hydro-ethanol extract was evaporated and concentrated under reduced pressure at a temperature of 40ºC in order to eliminate the ethanol. Water was then added to reach the original volume of the fluid extract. The resulting solution was considered as the aqueous extract used for pharmacological tests.
Data analysis
Recordings were visually analyzed. Quantification of states of vigilance was carried out second by second and the total time spent by animals in each state of vigilance per 9 hour periods was measured. Average duration, frequency and latency of the REM sleep phase were obtained, as well as the latency of SWS. A statistical analysis by means paired sample t-tests followed by power analysis was used to determine significant differences among the variables induced by the studied substance.
RESULTS
Animals displayed three different states of vigilance: Wakefulness (W), slow wave sleep (SWS) and rapid eye movement (REM) sleep
By: ArsalRajpot