Users Online: 273 | Home Print this page Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
ORIGINAL RESEARCH ARTICLE
Year : 2018  |  Volume : 8  |  Issue : 3  |  Page : 145-150

The effectiveness of Valeriana officinalis on sleep disturbance in patients with chronic heart failure


1 Community-oriented Nursing and Midwifery Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
2 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

Date of Web Publication1-Feb-2019

Correspondence Address:
Prof. Mahmoud Rafieian
Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord
Iran
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jphi.JPHI_43_18

Rights and Permissions
  Abstract 


Background: Sleep disturbances are common problems in patients with chronic heart failure (CHF) and are a significant contributing factor to fatigue and poor quality of life. The aim of the present study was to evaluate the effectiveness of Valeriana officinalis on sleep disturbance in patients with CHF.
Materials and Methods: A randomized, controlled trial design was used for this study. Eighty patients with CHF experiencing insomnia were designated to intervention and control groups. The patients in the intervention group went through conventional treatment while taking 12cc V. officinalis syrup, 1 h before sleeping every night for 4 weeks. The control group received routine medication such as alprazolam. A demographic data form and the Pittsburgh Sleep Quality Index were used to collect data. Questionnaires were completed by all participants before and after the intervention.
Results: The results indicated that regarding the duration of waiting for falling into sleep, there was a significant difference after intervention so that it was less in intervention groups compared to that of the control group (P = 0.001). In view of the hours during which the participants were fully asleep, there was a significant difference after the intervention between control and intervention groups, considerably higher among three intervention groups compared to that in the control group (P < 0.05).
Conclusions: V. officinalis improves the quality of sleep in patients with CHF who experience insomnia. The findings from this study support the reported effectiveness of V. officinalis in the clinical management of insomnia.

Keywords: Chronic heart failure, sleep disturbance, Valeriana officinalis


How to cite this article:
Aliakbari F, Rafieian M. The effectiveness of Valeriana officinalis on sleep disturbance in patients with chronic heart failure. Int J Pharma Investig 2018;8:145-50

How to cite this URL:
Aliakbari F, Rafieian M. The effectiveness of Valeriana officinalis on sleep disturbance in patients with chronic heart failure. Int J Pharma Investig [serial online] 2018 [cited 2019 Jun 19];8:145-50. Available from: http://www.jpionline.org/text.asp?2018/8/3/145/251369




  Introduction Top


Insomnia is the most frequent sleep disorder.[1] It consists of the inability to fall into sleep and stay asleep and/or to obtain the adequate duration and quality of sleep to restore normal states of energy and wakefulness.[2] The prevalence of general sleep disturbance experienced by people over 1 year is estimated at approximately 85%, while the estimation of diagnosed chronic insomnia is considered at around 10%.[3] Other studies have found this to be higher, with the United States National Health Interview Survey in 2002 revealing a 12-month prevalence of 17.4% of adults with self-reported insomnia or having trouble in sleeping.[4] Around 30% of the population worldwide suffers from insomnia.[5]

Sleep disturbance is a common problem in patients with chronic heart failure (CHF) and a significant contributing factor to fatigue and poor quality of life.[6] The pathophysiology of CHF often leads to fatigue, due to nocturnal symptoms causing sleep disruption, including cough, orthopnea, paroxysmal nocturnal dyspnea, and nocturia. Only about 10% of those receive adequate treatment.[1],[7]

Conventional approaches to the treatment of chronic insomnia usually involve either pharmacotherapy or psychological interventions. Pharmaceutical hypnotics are the primary first-line pharmacotherapy used to treat chronic insomnia. Benzodiazepines are the most effective and utilized drugs used to combat insomnia.[7] The use of these drugs has the potential to cause serious adverse effects.[8] The prolonged use of benzodiazepines produces adverse effects such as dependence, rebound insomnia, bad sleep quality, negative repercussions on cognitive functions,[9] and decreased effectiveness[1] which has brought about the search for safe, alternative treatments among herbal products.[10],[11],[12]

Complementary and alternative medical (CAM) therapies may be useful for the management of insomnia in older adults. The 2003 National Sleep Disorders Research Plan recognized as a priority the importance of studies evaluating CAM therapies for sleep disturbances.[13]

Interest in the use of alternative therapies and products for insomnia has grown over the past two decades due to a range of motivational factors.[14]

Many patients prefer “natural remedies” for the treatment of insomnia because they think their adverse effects and interactions are not considerable, they do not require a medical prescription, and do not cause alterations in the sleep state.[8]

Despite evidence on widespread interest, research evidence is lacking on the efficacy of many CAM therapies, especially in older adults. One of the herbal medicines with sedative effect is Valeriana officinalis that has been recognized since the 18th century in Europe and has been used for sleep disorders.[15]

V. officinalis contains a variety of chemical compounds, including valerenic acid and derivatives (hydroxyl-valerenic acid, acetoxy-valerenic acid, and valerenal) that may act synergistically to exert sedative effects.[8] Similar to conventional sedative-hypnotic medications, constituents of V. officinalis are believed to activate gamma-aminobutyric acid (GABA) receptors that are involved in sleep promotion and regulation. Constituents of V. officinalis have also been shown through in vitro and animal studies to affect other receptors, adenosine and glutamine (an amino acid that is metabolized into GABA), involved in the regulation of sleep and waking.[16]

Taibi et al. review[17] concluded that V. officinalis is no more effective than the placebo in the majority of insomnia cases and that this result is deduced above all from the most recent methodologically rigorous clinical trials; however, the meta-analysis by Bent et al.[18] showed a statistically significant greater measure of effect (sleep-quality improvement) in the V. officinalis treated group in comparison to the placebo group. Nevertheless, they recommend further trials with greater methodological rigor to arrive at a more definitive conclusion. Sleep disturbances are a common problem in patients with CHF. The aim of the present study is to evaluate the effectiveness of V. officinalis on sleep disturbance in patients with CHF.


  Materials and Methods Top


A clinical trial was conducted in two groups. Cardiac disease patients of Cardiovascular Clinic of Shahrekord University of Medical Sciences having inclusion criteria comprised the study's sample population.

The study participants were patients who were conscious, communicable, and had agreed to participate, were suffering from CHF confirmed by the patient's physician and older than 40 years old.

Patients were excluded from this study if they were unwilling to continue participating in the study or exhibiting sensitivity or physical problems pertinent to medicines during the study.

The protocol and informed consent document were reviewed and approved by the Ethics Committee of Shahrekord University of Medical Sciences and IRCT201204042289N2 was issued for the study by Iranian Registry of Clinical Trials.

All patients provided written informed consent at study screening before receiving any study medication. First, interviews were held by the researcher to complete questionnaires to select those with scoring at least 6. Then, their disorder (i.e., heart failure) was approved by a physician and finally other criteria for inclusion were ensured. Regarding statistical calculations, the number of population was 40 for each group; totally, 80 cases were selected for pursuing investigation. In the first step, purposeful sampling was adopted. However, the patients were randomly divided into two study groups. At the end of each sampling day, each patient with inclusion criteria was characterized by one and two to be included in groups one and two, respectively. The patients in the first group went through the conventional treatment while taking 12cc V. officinalis syrup (Mina, Pharmaceutical and Cosmetics Laboratory, Tehran, Iran), 1 h before going to bed every night within 1 month. The control received the routine medicine such as alprazolam. Regarding that it was rare to have access to the total sample population within 24 h, we had to do sampling within subsequent days and go to the clinic to complete the sample population. Data were collected through a questionnaire comprised two section of demography and sleep quality questionnaire.

The questions specified for sleep appraised included Petersburg Sleep Quality Investigation (PSQI) questionnaire, with 89.6% sensitivity and 86.5% specification. The questionnaire has been developed for investigating patient's attitude toward sleep quality within 4 weeks and bears seven scales of general description of sleep quality by individual, delay in falling into sleep, useful sleep duration, sleep adequacy (ratio of useful sleep duration to the total time spent in bed), sleep disorders (nightly getting up), the amount of soporific medicine taken, and finally daily performance (i.e., the difficulties due to insomnia experienced by an individual during the day).

The review of the literature indicates an acceptable consistency between the questionnaires results and laboratory sleep investigation by means of polysomnography (PSG). The score for each scale is 0–3, representing the natural condition and moderate to mean and severe difficulties, respectively. The summation of 7-fold scales comprises total score, ranging from 0 to 21. The total score of 6 or more was considered as sleep quality unacceptability.[19] Questionnaires were completed by all participants before and after the intervention.

Standardization of the drug

To standardize the syrup, total flavonoid and phenolic compounds as well as antioxidant activity of the syrup were determined as follows:

The amount of total flavonoid compounds in the syrup was determined using the colorimetric method as previously described by Asadi et al.[20] One mL of the extract or routine (standard flavonoid compound) was added to 1.5 mL of methanol (60%), 1 mL of 2% aluminum chloride, and 6 mL of 5% potassium acetate and the mixture was left at room temperature for 35 min. Then, the absorbance of the mixture was measured at 415 nm with a double beam spectrophotometer (Unico UV-2100, USA). Standard solutions (Rutin) were prepared at concentrations of 25, 50, 100, 250, and 500 ppm in methanol and the calibration curve was prepared. The experiments were repeated three times. Total flavonoids were expressed regarding routine equivalent (mg/g), which is a common reference compound.[21]

Total phenolic compounds in the syrup were determined colorimetrically using Folin–Ciocalteu reagent.[22],[23] Half mL of the extract or standard phenolic compound (gallic acid) was mixed with the Folin–Ciocalteu reagent (1:10 dilution with distilled water) and aqueous Na2 CO (0.4 ml, 7.5%). The mixture was left at room temperature for 30 min, and the amount of total phenolic compounds was determined by spectrophotometer (Unico UV-2100, USA) at 765 nm. The standard curve was prepared using gallic acid at concentrations of 12.5, 25, 50, 62.5, 100, and 125 mg/L in methanol and water (60:40, v/v). The experiment was repeated three times and the amount of total phenols were expressed regarding gallic acid equivalent (mg/g), which is a common reference compound.[24]

Total antioxidant activity of the syrup was evaluated using the previously described method of Shirzad et al.[25] A stock solution of β-carotene (0.5 mg) in one mL of chloroform, linoleic acid (25 μl), and tween-40 (200 mg) was prepared. The chloroform was evaporated using a vacuum evaporator at 50°C. Then, 100 mL of oxygenated water (30 min 100 ml/min) were added and 2500 μl aliquots were added to test tubes and 350 μl of the extracts (prepared at 2 g/L concentration) or butylated hydroxy toluene (BHT) (as a positive control) were added and incubated for 48 h at room temperature. The absorbance of the solutions was measured at 490 nm. Antioxidant capacities of the extracts were compared with those of BHT and blank.[26]

Statistical analysis

Data were analyzed using SPSS software 17 (SPSS Inc., Chicago, IL, USA) software. In all analyses, P - 0.05 was considered as statistically significant. We used independent and paired t-tests to compare mean scores between the experimental and control groups at pre- and post-tests.


  Results Top


Total phenol and flavonoid compounds were measured to be 60.04 and 27.7 mg/ml syrup, respectively. The antioxidant activity of the syrup was 40% of routine equivalent.

In this study, 85 participants were initially included in the study. However, five people were subsequently set aside, two because of death and three due to unwillingness to take medicine, finally leaving 80 people divided into two groups of 40 each. The mean age was 58.1 ± 10 years. About 37.5% were male while the rest 62.5% were female (P > 0.05). Before the intervention, the mean time to fall into sleep was 1.47 ± 1.06 and after intervention 0.74 ± 0.61 h. Besides, the time duration in which an individual was fully asleep during the night was 0–10 h, with mean 4.54 ± 1.74, and 2–8 h, with mean 5.38 ± 1.05 before and after intervention, respectively (P < 0.05). The results obtained by statistical analysis before intervention indicated that there was no significant difference regarding the time of falling into sleep, time duration of waiting for falling into sleep, and the number of hours during which the participants were fully asleep as well as sex and age distribution (P > 0.05). Besides, the samples were normally distributed among the two groups.

Regarding the time duration of waiting for falling into sleep, there was a significant difference after intervention so that it was less among intervention groups compared to that of the control group (P = 0.001). Given hours during which the participants were fully asleep, there was a significant difference after intervention between control and intervention groups, and this score was significantly higher in the intervention group (P < 0.05).

In addition, before intervention, there was no significant difference between two groups regarding total score (P = 0.239). However, after intervention, control group had lower quality of sleep in comparison to intervention group (P = 0.001).

Finally, the intervention group showed a better sleep quality compared to the control group.


  Discussion Top


This study tested the effects of V. officinalis on sleep quality in patients with CHF. Findings showed improvement of sleep quality in intervention group compared to control group. Scientific evidence relative to the efficacy of V. officinalis is inconclusive. The current study is one of the few randomized placebo-controlled trials evaluating herbal treatment of insomnia among CHF patients. Some systematic reviews on the efficacy of V. officinalis on insomnia have been performed; however, they reach different conclusions.[1]

In a previous study, Wheatley found that stress decreased significantly after the daily taking of 600 mg V. officinalis for 6 months. Besides, the patient's insomnia was considerably improved.[27] In another study, Donath et al. found that the patient's sleep improved significantly after V. officinalis taking for several days.[28] Moreover, there was a significant decrease in sleep latency time in the intervention group in the recent study. The same result was achieved by Leathwood and Chauffard that demonstrated the group taking V. officinalis achieved an improvement in sleep quality compared to the placebo group. In addition, the sleep latency time, as well as nightly getting up frequency was decreased.[29]

The use of 450 mg V. officinalis, at bedtime in improving sleep in patients who were undergoing treatment for cancer in a study of Barton, could not improve sleep as measured by the PSQI.[30]

Morin in a clinical trial study assessed V. officinalis-hops combination and diphenhydramine for treating insomnia. The result showed that V. officinalis produced a nonsignificant reduction in sleep latency relative to placebo and diphenhydramine at the end of 14 days of treatment and a significant reduction in comparison to the placebo group at the end of 28 days of treatment.[31]

Although some studies have reported improvement in sleep quality with V. officinalis administration over time, there are few studies mentioning significant improvement in any of the sleep outcomes when V. officinalis is compared with a placebo.[32] Despite evidence from in vitro studies of V. officinalis effect on neuropeptide systems involved in sleep mechanisms,[33] Vitiello et al. reported moderately disrupted sleep on PSG recordings in older healthy women who had no complaint of sleep problems; however, this pattern was not observed in healthy older men.[34]

Recently, Shinomiya et al. reported that a significant shortening in sleep latency without any significant effects on the total times of wakefulness was observed with V. officinalis extract.[35] Although GABA is present in V. officinalis extracts, its brain bioavailability through oral administration is uncertain. The action of V. officinalis on the central nervous system might be due in part to GABA involvement through a number of mechanisms, including an inhibition of GABA uptake into synaptosomes.[36]V. officinalis constituents inhibit the enzymatic breakdown of GABA and enhance benzodiazepine binding.[37] The other potential mechanisms for the pharmacological activity of V. officinalis have been proposed, including partial agonistic activities on 5-HT5a receptor.[38]

The results of this study support the hypothesis that V. officinalis can improve sleep quality in patients with CHF. Due to less side effect of herbal medicines,[39] these products could be taken as a safe substitute for synthetic medicines.[10]


  Conclusions Top


V. officinalis has been demonstrated to have antioxidant activity, and therefore, its beneficial effect on insomnia might be, at least in part, due to its antioxidant activity.

Acknowledgments

We are grateful to the patients who participated in this study for their cooperation.

Financial support and sponsorship

This study was funded by the Research and Technology Deputy of Shahrekord University of Medical Sciences, Shahrekord, Iran.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Fernández-San-Martín MI, Masa-Font R, Palacios-Soler L, Sancho-Gómez P, Calbó-Caldentey C, Flores-Mateo G, et al. Effectiveness of valerian on insomnia: A meta-analysis of randomized placebo-controlled trials. Sleep Med 2010;11:505-11.  Back to cited text no. 1
    
2.
Sarrais F, de Castro Manglano P. The insomnia. An Sist Sanit Navar 2007;30 Suppl 1:121-34.  Back to cited text no. 2
    
3.
Roth T, Roehrs T. Insomnia: Epidemiology, characteristics, and consequences. Clin Cornerstone 2003;5:5-15.  Back to cited text no. 3
    
4.
Pearson NJ, Johnson LL, Nahin RL. Insomnia, trouble sleeping, and complementary and alternative medicine: Analysis of the 2002 national health interview survey data. Arch Intern Med 2006;166:1775-82.  Back to cited text no. 4
    
5.
Reeder CE, Franklin M, Bramley TJ. Current landscape of insomnia in managed care. Am J Manag Care 2007;13:S112-6.  Back to cited text no. 5
    
6.
Steptoe A, Mohabir A, Mahon NG, McKenna WJ. Health related quality of life and psychological wellbeing in patients with dilated cardiomyopathy. Heart 2000;83:645-50.  Back to cited text no. 6
    
7.
Tariq SH, Pulisetty S. Pharmacotherapy for insomnia. Clin Geriatr Med 2008;24:93-105, vii.  Back to cited text no. 7
    
8.
Rafieian-Kopaei M. Medicinal plants and the human needs. J Herbmed Plarmacol 2012;1:1-2.  Back to cited text no. 8
    
9.
Stewart SA. The effects of benzodiazepines on cognition. J Clin Psychiatry 2005;66 Suppl 2:9-13.  Back to cited text no. 9
    
10.
Nasri H, Shirzad H. Toxicity and safety of medicinal plants. J Herbmed Plarmacol 2013;2:21-2.  Back to cited text no. 10
    
11.
Akhlaghi M, Shabanian G, Rafieian-Kopaei M, Parvin N, Saadat M, Akhlaghi M, et al. Citrus aurantium blossom and preoperative anxiety. Rev Bras Anestesiol 2011;61:702-12.  Back to cited text no. 11
    
12.
Roohafza H, Sarrafzadegan N, Sadeghi M, Rafieian-Kopaei M, Sajjadi F, Khosravi-Boroujeni H, et al. The association between stress levels and food consumption among Iranian population. Arch Iran Med 2013;16:145-8.  Back to cited text no. 12
    
13.
2003 national sleep disorders research plan. Sleep 2003;26:253-7.  Back to cited text no. 13
    
14.
Sewell RD, Rafieian-Kopaei M. The history and ups and downs of herbal medicine usage. J Herbmed Pharmacol 2014;3:1-3.  Back to cited text no. 14
    
15.
Morris CA, Avorn J. Internet marketing of herbal products. JAMA 2003;290:1505-9.  Back to cited text no. 15
    
16.
Khom S, Baburin I, Timin E, Hohaus A, Trauner G, Kopp B, et al. Valerenic acid potentiates and inhibits GABA(A) receptors: Molecular mechanism and subunit specificity. Neuropharmacology 2007;53:178-87.  Back to cited text no. 16
    
17.
Taibi DM, Landis CA, Petry H, Vitiello MV. A systematic review of valerian as a sleep aid: Safe but not effective. Sleep Med Rev 2007;11:209-30.  Back to cited text no. 17
    
18.
Bent S, Padula A, Moore D, Patterson M, Mehling W. Valerian for sleep: A systematic review and meta-analysis. Am J Med 2006;119:1005-12.  Back to cited text no. 18
    
19.
Soleimany M, Masoodi R, Sadeghi T, Bahrami N, Ghorban M, Hassanpoor A. General health and its association with sleep quality in two groups of nurses with and without shift working in educational centers of Iran University of Medical Sciences (IUMS). J Shahrekord Univ Med Sci 2008;10:70-5.  Back to cited text no. 19
    
20.
Asadi SY, Parsaei P, Karimi M, Ezzati S, Zamiri A, Mohammadizadeh F, et al. Effect of green tea (Camellia sinensis) extract on healing process of surgical wounds in rat. Int J Surg 2013;11:332-7.  Back to cited text no. 20
    
21.
Parsaei P, Karimi M, Asadi SY, Rafieian-Kopaei M. Bioactive components and preventive effect of green tea (Camellia sinensis) extract on post-laparotomy intra-abdominal adhesion in rats. Int J Surg 2013;11:811-5.  Back to cited text no. 21
    
22.
Sharafati R, Sharafati F, Rafieian-Kopaei M. Biological characterization of Iranian walnut (Juglans regia) leaves. Turk J Biol 2011;35:635-9.  Back to cited text no. 22
    
23.
Karimi M, Parsaei P, Asadi Y, Ezzati S, Khadivi Boroujeni R, Zamiri A, et al. Effects of Camellia sinensis ethanolic extract on histometric and histopathological healing process of burn wound in rat. Middle East J Sci Res 2013;13:14-9.  Back to cited text no. 23
    
24.
Rabiei Z, Rafieian-Kopaei M, Heidarian E, Saghaei E, Mokhtari S. Effects of Zizyphus jujube extract on memory and learning impairment induced by bilateral electric lesions of the nucleus basalis of meynert in rat. Neurochem Res 2014;39:353-60.  Back to cited text no. 24
    
25.
Shirzad H, Shahrani M, Rafieian-Kopaei M. Comparison of morphine and tramadol effects on phagocytic activity of mice peritoneal phagocytes in vivo. Int Immunopharmacol 2009;9:968-70.  Back to cited text no. 25
    
26.
Shirzad H, Taji F, Rafieian-Kopaei M. Correlation between antioxidant activity of garlic extracts and WEHI-164 fibrosarcoma tumor growth in BALB/c mice. J Med Food 2011;14:969-74.  Back to cited text no. 26
    
27.
Wheatley D. Stress-induced insomnia treated with kava and valerian: Singly and in combination. Hum Psychopharmacol 2001;16:353-6.  Back to cited text no. 27
    
28.
Donath F, Quispe S, Diefenbach K, Maurer A, Fietze I, Roots I, et al. Critical evaluation of the effect of valerian extract on sleep structure and sleep quality. Pharmacopsychiatry 2000;33:47-53.  Back to cited text no. 28
    
29.
Leathwood PD, Chauffard F. Aqueous extract of valerian reduces latency to fall asleep in man. Planta Med 1985;2:144-8.  Back to cited text no. 29
    
30.
Barton DL, Atherton PJ, Bauer BA, Moore DF Jr., Mattar BI, Lavasseur BI, et al. The use of Valeriana officinalis (Valerian) in improving sleep in patients who are undergoing treatment for cancer: A phase III randomized, placebo-controlled, double-blind study (NCCTG trial, N01C5). J Support Oncol 2011;9:24-31.  Back to cited text no. 30
    
31.
Morin CM, Koetter U, Bastien C, Ware JC, Wooten V. Valerian-hops combination and diphenhydramine for treating insomnia: A randomized placebo-controlled clinical trial. Sleep 2005;28:1465-71.  Back to cited text no. 31
    
32.
Kuhlmann J, Berger W, Podzuweit H, Schmidt U. The influence of valerian treatment on “reaction time, alertness and concentration” in volunteers. Pharmacopsychiatry 1999;32:235-41.  Back to cited text no. 32
    
33.
Schumacher B, Scholle S, Hölzl J, Khudeir N, Hess S, Müller CE, et al. Lignans isolated from valerian: Identification and characterization of a new olivil derivative with partial agonistic activity at A(1) adenosine receptors. J Nat Prod 2002;65:1479-85.  Back to cited text no. 33
    
34.
Vitiello MV, Larsen LH, Moe KE. Age-related sleep change: Gender and estrogen effects on the subjective-objective sleep quality relationships of healthy, noncomplaining older men and women. J Psychosom Res 2004;56:503-10.  Back to cited text no. 34
    
35.
Shinomiya K, Fujimura K, Kim Y, Kamei C. Effects of valerian extract on the sleep-wake cycle in sleep-disturbed rats. Acta Med Okayama 2005;59:89-92.  Back to cited text no. 35
    
36.
Santos MS, Ferreira F, Faro C, Pires E, Carvalho AP, Cunha AP, et al. The amount of GABA present in aqueous extracts of valerian is sufficient to account for [3H]GABA release in synaptosomes. Planta Med 1994;60:475-6.  Back to cited text no. 36
    
37.
Ortiz JG, Nieves-Natal J, Chavez P. Effects of valeriana officinalis extracts on [3H]flunitrazepam binding, synaptosomal [3H] GABA uptake, and hippocampal [3H]GABA release. Neurochem Res 1999;24:1373-8.  Back to cited text no. 37
    
38.
Dietz BM, Mahady GB, Pauli GF, Farnsworth NR. Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro. Brain Res Mol Brain Res 2005;138:191-7.  Back to cited text no. 38
    
39.
Tamadon MR, Baradaran A, Rafieian-Kopaei M. Antioxidant and kidney protection; differential impacts of single and whole natural antioxidants. J Renal Inj Prev 2014;3:41-2.  Back to cited text no. 39
    




 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Materials and Me...
Results
Discussion
Conclusions
References

 Article Access Statistics
    Viewed399    
    Printed22    
    Emailed0    
    PDF Downloaded86    
    Comments [Add]    

Recommend this journal