Effect of Nepeta bracteata Benth. on allergic rhinitis symptoms: A randomized double-blind clinical trial
Mohammad Reza Hajiheydari1, Mohammad Ebrahim Yarmohammadi2, Poopak Izadi2, Farhad Jafari3, Fatemeh Emadi4, Elham Emaratkar1, Sayed Hamid Reza Abtahi5, Arman Zargaran6, Mohsen Naseri7
1 Department of Traditional ian Medicine, Faculty of Medicine, Shahed University, Tehran, Iran
2 Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, Shahed University, Tehran, Iran
3 Department of Health and Social Medicine, Faculty of Medicine, Shahed University, Tehran, Iran
4 Traditional Medicine Clinical Trial Research Center; Department of Traditional ian Medicine, Faculty of Medicine, Shahed University, Tehran, Iran
5 Department of Otolaryngology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
6 Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran
7 Traditional Medicine Clinical Trial Research Center, Shahed University, Tehran, Iran
|Date of Submission||14-May-2017|
|Date of Decision||01-Aug-2017|
|Date of Acceptance||03-Sep-2017|
|Date of Web Publication||28-Nov-2017|
Traditional Medicine Clinical Trial Research Center, Shahed University, Tehran
Source of Support: None, Conflict of Interest: None
Background: Allergic rhinitis (AR) is one of the health problems in the world. It is necessary to develop new treatment procedure for control of this disease. The aim of this study was to assess the effect of Zofa (Nepeta bracteata Benth) on AR patients. Materials and Methods: In this double-blind randomized clinical trial study, 71 patients (37 patients in treatment and 34 in placebo group) participated. In treatment group, N. bracteata syrup (NBS) was used for 4 weeks as three times a day. The efficacy of the drug regarding AR symptoms (rhinorrhea, sneezing, nasal obstruction, itchy nose, and ocular symptoms) were evaluated through a visual analog scale (VAS) by 0–10 before administration and at the end of the whole treatment period. The collected information was entered in the SPSS software (version 18) and was analyzed using the Fisher's exact test, Chi-square test, independent sample t-test, and paired sample test. Results: The improvement of AR symptoms in the group receiving NBS was significantly higher compared to control group (4.73 ± 1.84 vs. 0.38 ± 2.06; P < 0.0001). Furthermore, the mean of total VAS before and after the treatment (in case group) was 7.10 ± 1.92 and 2.37 ± 1.76, respectively (P < 0.001). Conclusion: The results of this study indicate that N. bracteata has significant effects on improving the symptoms of AR. Hence, it can be a good alternative to AR symptoms relief.
Keywords: Allergic rhinitis, Persian medicine, Nepeta bracteata Benth
|How to cite this article:|
Hajiheydari MR, Yarmohammadi ME, Izadi P, Jafari F, Emadi F, Emaratkar E, Reza Abtahi SH, Zargaran A, Naseri M. Effect of Nepeta bracteata Benth. on allergic rhinitis symptoms: A randomized double-blind clinical trial. J Res Med Sci 2017;22:128
|How to cite this URL:|
Hajiheydari MR, Yarmohammadi ME, Izadi P, Jafari F, Emadi F, Emaratkar E, Reza Abtahi SH, Zargaran A, Naseri M. Effect of Nepeta bracteata Benth. on allergic rhinitis symptoms: A randomized double-blind clinical trial. J Res Med Sci [serial online] 2017 [cited 2019 Jan 16];22:128. Available from: http://www.jmsjournal.net/text.asp?2017/22/1/128/219384
| Introduction|| |
Allergic rhinitis (AR) is an inflammatory disease mediated by immune cells in the mucous membranes lining the nose and one of the most prevalent diseases so that the prevalence of the disease in the world and Iran have been reported between 9% and 42% and 7.2% and 23.6%, respectively.,, This is the inflammatory of the nasal mucosa with hypersensitivity symptoms after exposure to allergens such as pollen and dust. The prevalent symptoms are nasal congestion and ocular complications.
Immunoglobulin E has an essential role in allergic responses so that the initial response was initiated by an IgE-related allergic process. This process leads to release of mediators of inflammation such as histamine, neutral proteases, chemotactic factor, and acid hydrolases from basophils and mast cells. AR has two forms including seasonal and perennial forms. Symptoms of seasonal AR which usually caused by allergic sensitivity to airborne mold spores or pollens from grass, trees, and weeds can occur in spring, summer, and early fall. People with perennial AR experience symptoms year-round. It is generally caused by dust mites, pet hair or dander, cockroaches, or mold. Underlying or hidden food allergies rarely cause perennial nasal symptoms. About 20% of AR cases are seasonal, and 40% are perennial types. Other 40% of patients have a combination of these two types. Due to the high prevalence of AR, it affects community as impaired quality of life and related diseases such as atopy and asthma. In various studies, it is reported that this disease is developing whole around the world; although AR is not a fatal disease, it often leads to change and loss of quality of patients' life. The patients suffer from different problems such as impairment of behavior, learning, and memory. They are susceptible to more serious side effects such as asthma and sinusitis. Annually, the loss of 2 million workdays and 2–5 billion dollars in health costs are the most important complications of the disease in America. There are several available procedures for the treatment of AR. The common treatments include intranasal corticosteroids, oral and topical antihistamines, decongestants, intranasal cromolyn, intranasal anticholinergic, and leukotriene receptor antagonists. These procedures reduce the symptoms of disease temporarily and have low therapeutic effect. On the other hand, long-term use of these agents is associated with side effects. According to this problem and high prevalence of AR as well as tendency to medicinal plants, the development and finding of new herbal drugs for the treatment of this disease are beneficial. There are many successful experiments in the literature about medicinal plants such as the effects of Nigella sativa and Petasites hybridus on AR symptoms in the randomized clinical trial studies. Furthermore, it was investigated that some polyherbal formulations such as Biminne, a Chinese herbal formulation  and Aller-7 a capsule from a standardized extract of seven Indian medicinal plants  improved AR symptoms.
Furthermore traditional, complementary and alternative medicine (TM/CAM) are good sources to find new suggestions, in particular, herbal remedies for evaluating in current medicine.
The use of TM/CAM in Western medicine has highly increased in recent decades. Many treating methods of TM/CAM, such as herbal remedies, are mainstream or traditional in many parts of the world. The World Health Organization (WHO) estimates that most of the world's people regularly using TM, such as traditional Chinese medicine Regarding these issues, despite advances in conventional therapy, a great number of patients with AR are tending to complementary medicine for relief. The lifetime prevalence of TM/CAM use in patients with AR ranges from 27% to 46%, and many of the patients who have not yet used TM/CAM, intend to do so in the future.
Persian Medicine (PM) or Traditional Iranian Medicine (TIM) is one of such traditional systems of medicine. PM has the sum total of all the knowledge and practices administered in prevention, diagnosis, and elimination in Persia in ancient and medieval times.
There are more than thousands of manuscripts in PM; it can be as treasure for researchers in this field as well as good advantage to develop the scientific and universal medicine.
Nepeta bracteata Benth. (Lamiaceae) called as Zofa in PM  is one of the frequently cited medicinal herbs in the case of respiratory problems such as chronic cough (Soale-mozmen), catarrh (Nazleh), asthma (Rabu), and dyspnea (Osral-Nafas) in PM documents. Observed medicinal activities of Nepeta species are probably because of the presence of terpenoids, especially iridoids and diterpenes which are rich in this genus, flavanones, flavonoids, and phenolic acid derivatives, Two clinical studies that were conducted with N. bracteata compound syrup (Sharbat Zoofa Murakkab) on chronic bronchitis and productive cough showed improvement in all of signs and symptoms of above diseases significantly., This plant is one of the endemic species in Iran. Although current investigations support its effects on chronic cough, bronchitis, common cold, and asthma, there is no direct studies about the effect of this plant on AR. Hence, the aim of this study was to assess the effect of N. bracteata on the patients with AR.
| Materials And Methods|| |
This double-blind clinical trial study conducted on all the referred patients with AR symptoms to otolaryngology clinic of Mustafa Khomeini Hospital in Tehran, Iran, from April 2015 to Mars 2016. Among them, 96 individuals were selected as sample size was calculated using sample size formula taking into account the 95% confidence level, 80% statistical power, and the proportion of AR in the mentioned clinic which approximately estimated as 12% and the error level of 0.1.
The Ethics Committee of Shahed University approved the protocol (approval number: 41/215591). Furthermore, this study was registered in the Iranian Registry of Clinical Trials; IRCT ID: IRCT2013122615943N1. All patients were aware of the protocol of the study and fulfilled the informed consent form.
Inclusion and exclusion criteria
As inclusion criteria, all enrolled patients had symptoms of AR, based on the AR and its impact on asthma (ARIA) criteria. The patients were assessed and confirmed by ENT specialist, and also, all the patients were in the age range of 18–65 year old, suffered intermittent or perennial AR, and had not taken any medical treatment of AR at least 2 weeks before the admission. The patients who had a previous history of chronic diseases such as asthma, diabetes and cancer, taking any medication known to affect AR, recent trauma to the nose, recent surgery of the nose, as well as people exposed to irritants such as acid, pregnancy, and breastfeeding, ones with epilepsy, vasomotor rhinitis, alpha-blocker drug users, and acute sinusitis symptoms were excluded from the study.
Dry plant of N. bracteata was purchased from a local spice market (Attari) in Tehran Bazaar, Iran, and identified in the Herbarium center of school of Pharmacy, Tehran University of Medical Sciences, by Professor Dr. Gholamreza Amin, under the voucher number PMP-324.
Preparation of syrup and placebo
NBS was prepared according to “Qarabadin” texts as PM pharmaceutical manuscripts.,
To prepare 160 bottles of syrup for 40 patients, 1.6 kg N. bracteata was weighed and crushed with grinder (Toosshekan T8500, Iran) and engulfed with 48 L boiling water. After half an hour boiling, the extract was filtered and sweetened by adding 3.2 kg of sugar and honey (1:1). The syrup was heated until sugar and honey was completely dissolved. Methylparaben (0.1%) and propylparaben (0.015%) were added as microbial preservatives. Then, it was packed in 250 mL bottles containing either medication or placebo.
Placebo was prepared in the same method. However, N. bracteata extract was replaced by distilled water and approved color additives (B1, Magnolia flavor and fragrance Co., Iran) were added to make the same color of drug.
Standardization of drug based on total phenolic and flavonoid contents
Total phenolic and flavonoid contents of NBS were detected using spectrophotometric method. To determine phenolic concentration in the syrup, ethanol solution of syrup (1 mg/ml) was prepared and the reaction mixture was used by mixing ethanol solution (0.5 ml), 10% Folin-Ciocalteu's reagent (2.5 ml), and 7.5% NaHCO3 (2.5 ml). Blank was prepared the same as reaction solution just using ethanol without syrup. After that, the samples were incubated at 45°C for 45 min. The absorbance was detected using spectrophotometer at λmax = 765 nm. The mentioned samples were prepared in triplicate for analysis. The same procedure was repeated for the gallic acid standard solution. To achieve phenolic concentration, the gallic acid calibration curve based on the detected absorbance was construed.
To determine the flavonoids contents, the samples consisting 1 ml of ethanol solution of syrup (1 mg/ml) and 1 ml of 2% AlCl3 solution dissolved in methanol were prepared. After that, samples were incubated for 1 h at room temperature. The absorbance was determined at λmax = 415 nm. The same procedure was performed for the rutin standard solution, and the calibration line was construed.
In both mentioned methods, based on the measured absorbance, the phenolic and flavonoid contents were read according to the calibration line and then were expressed in terms of gallic acid and rutin equivalent, respectively.
Randomization and blinding
We performed a permuted block randomization with fixed block size of four and one-to-one allocation using a computer-generated random allocation to sequentially numbering. All patients were informed that there was a fifty percent chance of receiving placebo treatment. The physicians and patients were blinded to the medications.
Intervention and main outcome measures
The primary measure was the efficacy in severity and frequency of AR symptoms. The patients in the groups used 10 ml of NBS or placebo, three times a day (30 ml/day) for 4 weeks.
The long of intervention based on similar studies in this field (Herbal medicines on AR) was 4 weeks.
All the patients were evaluated for the efficacy of the drug and placebo on each AR symptoms, by using the AR symptom questionnaire which consists of 5 items according to ARIA criteria  (rhinorrhea, sneezing, nasal obstruction, itchy nose, and ocular symptoms), and the changes of severity of symptoms were measured by VAS (visual analog scale from 0 to 10 cm), scoring by patients, before treatment and at the end of the intervention period.
Furthermore, total VAS scores were registered in the beginning and the end of treatment according to ARIA criteria. The frequency was measured according to the ARIA questionnaire (a WHO confirmed questionnaire) by patients and practitioner.
Finally, the collected data were entered into Statistical Package for the Social Sciences (version 18.0; SPSS Inc., Chicago, Ill., USA) and were represented by frequency (percent) or Mean ± standard deviation (SD). According to the results of the Kolmogorov-Smirnov test indicating the normality of data distribution, independent sample t-test was used for comparing the mean of ARIA score between two groups, and paired sample test was used for comparing the mean of ARIA score in each of the two groups; also, Fisher's exact test was used to compare the frequency distribution of qualitative data among the two groups. In all analyses, the significance level was considered <0.05.
| Results|| |
Standardization of drug
Total phenols and flavonoid contents were determined, as follows: 293 ± 7 mg gallic acid equivalent/100 ml and 258 ± 5 mg rutin equivalent/100 ml of syrup, respectively.
In total, 96 volunteer patients of AR, after obtaining informed consent participated in this study, and some of 86 eligible patients who met inclusion criteria were divided into two groups, randomly. Finally, 71 patients completed the trial, 37 patients in treatment, and 34 ones in placebo groups [Figure 1].
|Figure 1: Consort chart study of clinical trial Nepeta bracteata and placebo on allergic rhinitis patients|
Click here to view
The demographic data of two groups were summarized in [Table 1]. As shown in this table, no significant differences were identified between patients in the groups with regard to basic demographic data including sex, age, and smoking.
A comparative examination of these two groups in mean AR symptoms proved that the severity of symptoms in both groups was the same at baseline (P > 0.05). Afterward (treatment), this mean in the group of treatment with NBS was significantly less compared to control group (P < 0.001). Thus, overall improvement in symptoms in treatment group (mean ± SD = 1.84 ± 4.73) was significantly more than control group (mean ± SD = 2.06 ± 0.38) (P < 0.0001) [Table 2]. On the other hand, NBS improved all symptoms of AR, significantly in the treatment group (P < 0.001). In the control group, observed difference before and after treatment with placebo was not significant (P = 0.065). Furthermore, the mean of severity of symptoms was 7.10 ± 1.92 and 2.37 ± 1.76 before and after treatment by NBS, respectively (P < 0.001), but the mean of severity of symptoms was 6.38 ± 2.18 and 6.00 ± 1.95 before and after treatment by placebo, respectively (P = 0.096), showed in [Table 2].
|Table 2: Comparison mean of severity of allergic rhinitis symptoms before and after treatment in two groups|
Click here to view
| Discussion|| |
Four-week treatment of AR with N. bracteata showed that these syrups could significantly reduce the symptoms of AR without side effects while the placebo group had no significant effect. Our study is the first experiment on the effect of N. bracteata on AR on humans, and interesting results were acquired. We indicated that NBS improved all symptoms of AR (P < 0.001). The symptom relief was from 78% to 87% in drug group, while in comparison with similar previous studies such as the effect of N. sativa (from 66.4% to 70%) and a Chinese nine herbal compound, 60.7% improvement rate of drug  had better affect.
Some clinical studies on N. bracteata confirmed its anti-inflammatory mechanisms of action such as reducing basophil and neutrophil infiltration in the experimental study on asthma. Another clinical study on productive cough showed that N. bracteata compound syrup (Sharbat Zoofa Murakkab) had high significant reduction in erythrocyte sedimentation rate, eosinophil, and anti-allergic properties.
Investigations considered flavonoids and related compounds as possible natural inhibitors of IgE; these agents have anti-allergic activities such as prevention of the expression of CD40 receptor ligand by basophiles and inhibition of the release of histamine by interleukin (IL-4) and IL-3.
Furthermore, flavonoids have anti-inflammatory effects by inhibiting of both cyclooxygenase and 5-lipoxygenase pathways, degranulation of neutrophils, other known and unknown mechanisms. Furthermore, luteolin and its derivatives were clinically effective to relieve AR nasal symptoms in rat.
Recent findings showed that flavonoids, phenolic compounds, and terpenes act with the mechanisms of reduction of eosinophils and basophils, neutrophil infiltration, and inhibition of inflammation pathways and IgE as well as anti-allergic activity.,, Therefore, improvement of the symptoms such as congestion, runny nose, and irritation in this study can cause due to these compounds.
On the other hand, based on PM beliefs, the effect of N. bracteata on AR can be due to its molifying (Molattef) and laxative (Moshel) effects on phlegm (Balgham).
It seems that traditional beliefs and current concepts meet together in this case and our investigation approved the efficacy of this plant on AR.
| Conclusion|| |
According to obtained results, N. bracteata has significant effects on the AR symptoms. Therefore, it can be a good alternative remedy for relieving the symptoms of AR.
Limitations of the study
The sample size and short duration of intervention may be not enough to mention definitely about “Adverse Reactions” and safety of this treatment option.
This manuscript is resulted from a PhD student thesis (number, 19/89) of TIM in Department of TM, School of Medicine, Shahed University, Tehran, Iran.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al.
Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2) LEN and allerGen). Allergy 2008;63 Suppl 86:8-160.
Nikakhlagh S, Rahim F, Aryani FH, Syahpoush A, Brougerdnya MG, Saki N, et al.
Herbal treatment of allergic rhinitis: The use of Nigella sativa
. Am J Otolaryngol 2011;32:402-7.
Settipane RA, Charnock DR. Epidemiology of rhinitis: Allergic and nonallergic. Clin Allergy Immunol 2007;19:23-34.
Tran NP, Vickery J, Blaiss MS. Management of rhinitis: Allergic and non-allergic. Allergy Asthma Immunol Res 2011;3:148-56.
Sinha, B., Vibha, R. S., and Chowdhury, R. Allergic rhinitis: a neglected disease—a community based assessment among adults in Delhi. Journal of postgraduate medicine, 2015, 61:169.
Farhoudi A, Razavi A, Chavoshzadeh Z, Heidarzadeh M, Bemanian MH, Nabavi M, et al.
Descriptive study of 226 patients with allergic rhinitis and asthma in Karaj City. Iran J Allergy Asthma Immunol 2005;4:99-101.
Reed SD, Lee TA, McCrory DC. The economic burden of allergic rhinitis: A critical evaluation of the literature. Pharmacoeconomics 2004;22:345-61.
Guo R, Pittler MH, Ernst E. Herbal medicines for the treatment of allergic rhinitis: A systematic review. Ann Allergy Asthma Immunol 2007;99:483-95.
Thomet OA, Schapowal A, Heinisch IV, Wiesmann UN, Simon HU. Anti-inflammatory activity of an extract of Petasites hybridus in allergic rhinitis. Int Immunopharmacol 2002;2:997-1006.
Hu G, Walls RS, Bass D, Ramon B, Grayson D, Jones M, et al.
The Chinese herbal formulation biminne in management of perennial allergic rhinitis: A randomized, double-blind, placebo-controlled, 12-week clinical trial. Ann Allergy Asthma Immunol 2002;88:478-87.
Soltanian AR, Mehdibarzi D, Faghihzadeh S, Naseri M, Gerami A. Mixture of Arnebia euchroma and Matricaria chamomilla (Marhame-Mafasel) for pain relief of osteoarthritis of the knee–a two-treatment, two-period crossover trial. Archives of medical science: AMS. 2010;6:950.
Mozaffarpur SA, Naseri M, Esmaeilidooki MR, Kamalinejad M, Bijani A. The effect of cassia fistula emulsion on pediatric functional constipation in comparison with mineral oil: a randomized, clinical trial. DARU Journal of Pharmaceutical Sciences. 2012;20:83.
Witt CM, Brinkhaus B. Efficacy, effectiveness and cost-effectiveness of acupuncture for allergic rhinitis – An overview about previous and ongoing studies. Auton Neurosci 2010;157:42-5.
Rezaeizadeh H, Alizadeh M, Naseri M, Ardakani MS. The Traditional Iranian medicine point of view on health and disease. Iran J Public Health 2009;38:169-72.
Ghaffari F, Naseri M, Khodadoost M. Traditional medicine and necessary reasons due to rehabilitation and developement. Teb Va Tazkiey 1389 2011;3:63-71.
Latif A, Mahmood Z, Siddiqui N, Rauf A. Physiochemical standardization of market sample of Gul-e-Zofa (Nepeta bracteata Benth). Int J Drug Formul Res 2013;4:76-86.
Khorasani MA. al Advieh M. Research Institute for Islamic and Complementary Medicine. Tehran, Iran: Iran University of Medical Sciences Bavardaran Press; 2001.
Naghibi F, Mosaddegh M, Motamed MM, Ghorbani A. Labiatae family in folk medicine in Iran: From ethnobotany to pharmacology. Iranian J Pharm Res 2005:2;63-79.
Sehar N, Alam I, Arfin TA, Ahmad MW, Goswami A. Clinical study of unani formulation 'Sharbat Zoofa Murakkab' in the management of sual ratab (productive cough). Hippocratic J Unani Med 2015;2015:1-8.
Quddus, A., Siddiqui, M. M. H., Siddiqui, M. Y., Aleem, S. Clinical evaluation of the efficacy of Qurs Sartan Kafoori and Sharbat Zoofa Murakkab in Chronic Bronchitis; 2009.
Aghili, M.H, Kabir Garabadin. Tehran, Iran: Islamic Medicine and Complementary Medicine Institute Press; 2004. p. 571-6.
Ghayeni, M.S, Qarabadin-e-Salehi, Tehran, Iran: Islamic Medicine and Complementary Medicine Institute Press; 2004. p. 156.
Marinova D, Ribarova F, Atanassova M. Total phenolics and total flavonoids in Bulgarian fruits and vegetables. J Univ Chem Technol Metall 2005;40:255-60.
Beketov E, Pakhomov V, Nesterova O. Improved method of flavonoid extraction from bird cherry fruits. Pharm Chem J 2005;39:316-8.
Bousquet PJ, Combescure C, Neukirch F, Klossek JM, Méchin H, Daures JP, et al.
Visual analog scales can assess the severity of rhinitis graded according to ARIA guidelines. Allergy 2007;62:367-72.
Xue CC, Thien FC, Zhang JJ, Da Costa C, Li CG. Treatment for seasonal allergic rhinitis by Chinese herbal medicine: A randomized placebo controlled trial. Altern Ther Health Med 2003;9:80-7.
Wang J, Li FS, Pang NN, Tian G, Jiang M, Zhang HP, et al.
Inhibition of asthma in OVA sensitized mice model by a traditional Uygur Herb Nepeta bracteata
Benth. Evid Based Complement Alternat Med 2016;2016:5769897.
Kawai M, Hirano T, Higa S, Arimitsu J, Maruta M, Kuwahara Y, et al.
Flavonoids and related compounds as anti-allergic substances. Allergol Int 2007;56:113-23.
Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA, et al.
Flavonoids: A review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001;74:418-25.
Inoue T, Sugimoto Y, Masuda H, Kamei C. Antiallergic effect of flavonoid glycosides obtained from mentha piperita L. Biol Pharm Bull 2002;25:256-9.
[Table 1], [Table 2]
|This article has been cited by|
||Nepeta species: From farm to food applications and phytotherapy
| ||Bahare Salehi,Marco Valussi,Arun Kumar Jugran,Miquel Martorell,Karina Ramírez-Alarcón,Zorica Z. Stojanovic-Radic,Hubert Antolak,Dorota Kregiel,Ksenija S. Mileski,Mehdi Sharifi-Rad,William N. Setzer,María de la Luz Cádiz-Gurrea,Antonio Segura-Carretero,Bilge Sener,Javad Sharifi-Rad |
| ||Trends in Food Science & Technology. 2018; 80: 104 |
|[Pubmed] | [DOI]|
||Effect of Nepeta bracteata Benth. on Chronic Obstructive Pulmonary Disease: A Triple-Blinded, Randomized Clinical Trial
| ||Ali Abdolahinia,Mohsen Naseri,Alireza Eslaminejad,Farzaneh Ghaffari,Aliakbar Velayati |
| ||Iranian Red Crescent Medical Journal. 2018; 20(12) |
|[Pubmed] | [DOI]|