Effect of a Persian metabolic diet on the functional dyspepsia symptoms in patients with postprandial distress syndrome: a randomized, double-blind clinical trial.

OBJECTIVES: Postprandial distress syndrome (PDS) is associated with food indigestion. Efficacy of drugs used against PDS is limited whereas dietary modifications were shown to have important beneficial effects. Traditional Persian Medicine (TPM) sages suggested a dietary regimen known as Persian metabolic diet (PMD) for the management of PDS patients. In this study, the efficacy of PMD in alleviating the symptoms of PDS was explored. METHODS: This single-center, parallel-group, randomized clinical trial included 56 patients whom were randomly allocated to PMD group (29 participants) and Optional diet (OD) group (27 participants). They were instructed to follow the protocol for two weeks. Using a standard validated questionnaire, all outcomes were evaluated at baseline, end of the intervention period, and end of follow-up time. RESULTS: At the end of the intervention period, comparing the changes of severity scores between the groups showed a statistically significant difference in week 2 (p-value<0.001) and week 8 (p-value<0.001) follow-up comparing to the baseline. Similarly, at the end of the follow-up period, epigastric fullness, epigastric discomfort, and bloating were significantly improved in the PMD group (p<0.001). CONCLUSIONS: This diet prepared based on Persian medicine seems to be effective in relieving the symptoms of patients with PDS.

Effect of topical marshmallow (Althaea officinalis) on atopic dermatitis in children: A pilot double-blind active-controlled clinical trial of an in-silico-analyzed phytomedicine.

Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease, which primarily affects infants and young children. Due to the side effects of commonly used drugs for its treatment, the development of safer therapeutic strategies is needed. There are many reports on the topical use of marshmallow (Althaea officinalis) for a range of skin diseases in Persian medicine. The main aim of the present investigation was evaluating the efficacy of marshmallow in children with mild-to-moderate atopic dermatitis. Another aim of the study was screening the anti-allergic and anti-inflammatory potential of phytocomponents against target proteins, including TNF-alpha, IL6, and PDEs A, B, and D enzymes with PDB IDs: 2AZ5, 1P9M, 3I8V, 4KP6, and 1Y2K, respectively, along with their respective standard ligands using computational docking analysis. A pilot clinical trial was designed to investigate the safety and efficacy of Althaea officinalis in children with AD. The diagnosis of AD was made according to the criteria of Hanifin and Rajka. Children between 3 months and 12 years old were participated in this trial and randomly allocated into two parallel intervention and control groups. The intervention group used Althaea officinalis 1% ointment while the positive control group used Hydrocortisone 1% ointment twice a day for a week and after that, three times per week for a period of 3 weeks. The severity of AD was measured using the SCORAD score at the end of each assessment visits. A total number of 22 patients completed the study. A significant decrease of the SCORAD score was observed in both groups. At the end of the study, this score change, which indicates the improvement of the patients was significantly higher in the intervention group in comparison to the baseline (p-value = .015) and week 1 (p-value = .018). In the docking analysis of the study, 33 phytochemical compounds were identified, which were docked into the active site of IL6, TNF-alpha, and human PDE4 isoenzymes. Affinity toward the selected enzymes was significantly higher in glycosylated compounds. The results of this pilot study showed that the efficacy of Althaea officinalis 1% ointment in a decrease of disease severity is more than Hydrocortisone 1% in children with AD. However, further studies are needed to confirm this finding. Moreover, the docking analysis revealed that the inhibitory activity of compounds with free hydroxyl groups such as glycosylated compounds was better than others, probably due to the hydrogen bond interaction of hydroxyl groups of the ligands with the enzymes.

A double-blind, randomized pilot study for comparison of Melissa officinalis L. and Lavandula angustifolia Mill. with Fluoxetine for the treatment of depression.

BACKGROUND: Depression has rapidly progressed worldwide, and the need for an efficient treatment with low side effect has risen. Melissa officinalis L and Lavandula angustifolia Mill have been traditionally used in Asia for the treatment of depression. Many textbooks of traditional Persian medicine refer to these herbs for the treatment of depression while there are no adequate clinical trials to support this claim. The present study aimed to evaluate the efficacy of M. officinalis and L. angustifolia compared to fluoxetine for the treatment of mild to moderate depression in an 8-week randomized, double-blind clinical trial. METHODS: Forty-five adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) for major depression, were randomly assigned to 3 groups to daily receive either M. officinalis (2 g) or L. angustifolia (2 g) or fluoxetine (20 mg) and were assessed in weeks 0, 2, 4 and 8 by the Hamilton Rating Scale for Depression (HAM-D) including 17 items. RESULTS: Our study showed that M. officinalis and L. angustifolia effect similar to fluoxetine in mild to moderate depression. (F = 0.131, df = 2,42, p = 0.877). CONCLUSION: Due to some restrictions in this study including absence of placebo group, large-scale trials are needed to investigate the anti-depressant effect of these two herbs with more details. TRIAL REGISTRATION: IRCT2014061718126N1 . Registration date: 2015-06-04-"Retrospectively registered".

Hab-o Shefa, a Persian Medicine Compound for Maintenance Treatment of Opioid Dependence: Randomized Placebo-Controlled Clinical Trial.

Objectives: The major problem in maintenance treatment of opioid use disorder is craving and relapse. The utilization of herbal compounds and complementary therapy for treatment of disease and addiction has been widely expanding. Considering the significant effect of Hab-o Shefa in detoxification phase, this clinical trial has explored the influence of this compound on maintenance treatment of opioid-dependent patients. This product is made of four herbs, including Datura stramonium L., Rheum palmatum L., Zingiber officinale Roscoe, and Acacia senegal L. Design: The authors conducted a two-group parallel randomized double-blind clinical trial on 81 opioid-dependent patients within 12 weeks. After medically assisted detoxification, participants were assigned randomly to Hab-o Shefa (n = 41) and placebo (n = 40). Outcome measures included craving assessed by craving beliefs questionnaire, self-reported opioid use, and lapse (any opioid-positive urine test) according to urinalysis and addiction severity index-lite questionnaire, retention in treatment, and depression and anxiety scores on the Hamilton's anxiety and depression scales. Results: Forty-one participants completed the study for 12 weeks, 21 subjects in the drug group and 20 subjects in the placebo group. The rates of opioid-positive urine tests and self-reported opioid use were significantly lower in Hab-o Shefa group (f = 8.41, p = 0.001). Hab-o Shefa also indicated a significant superiority over placebo in the effect of treatment by time interaction for craving (f = 5.91, p = 0.001), depression (f = 3.40, p = 0.01), and anxiety (f = 2.58, p = 0.035). The retention time was 66.6 days for drug group and 59.6 days for placebo one. Although the causes for dropping out in two groups were different, there was no significant difference (p = 0.623). The side effects of the two groups were not significantly different. Conclusion: Results indicated that Hab-o Shefa could be useful for opioid maintenance treatment, and it can also be considered as a new promising drug for prevention of craving and relapse.

Effects of Viola odorata as an Add-On Therapy on Insomnia in Patients with Obsession or Depression: A Pilot Randomized Double-Blind Placebo-Controlled Trial.

Objective: The present study was conducted to investigate the effect of Viola odorata extracted syrup on the quality and patterns of sleep in patients with depression or obsessive-compulsive disorder (OCD) as add-on therapy. Design: A pilot double-blind randomized placebo-controlled trial. Settings/Location: Psychiatric Clinic of Imam Hossein Hospital, Tehran, Iran. Subjects: Participants were 16-15 years of age with mild and moderate depression or OCD having insomnia. Interventions: This pilot study was conducted on patients with insomnia divided into two groups with depression (40 patients) or OCD (43 patients). Each group randomly assigned into two arms with the same conditions at baseline. The intervention arm daily received 5 mL V. odorata syrup every 12 h for 4 weeks, and the control arm received 5 mL placebo syrup every 12 h for 4 weeks. None of the participants was deprived of their routine treatment for depression or OCD. Outcome measures: The scores of insomnia symptoms were evaluated using total score of the Pittsburgh Sleep Quality Index (PSQI) and the scores of its components, the depression score using the final Beck depression inventory-II (BDI-II) score, and OCD score using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Results: The total PSQI score was found to be improved significantly in the intervention arms with depression or OCD (p < 0.001) compared with the corresponding control arms. Significant improvements were also observed in the final mean difference of BDI-II (p = 0.009) and YBOCS (p = 0.001) scores in the intervention arms. Conclusions: V. odorata syrup significantly improved insomnia symptoms and the scores of depression and OCD.

A Review on the Hypotheses about Arterial Hypertension from the Viewpoint of Traditional Persian Medicine.

Hypertension is one of the most common chronic diseases in recent decades worldwide. It has been distinguished as the main risk factor of coronary artery disease, aortic dissection, heart failure, renal failure, cerebrovascular diseases, and death. In recent years, the global attention has been paid to complementary medicine to preventive, diagnostic and treatment strategies for hypertension, in previous studies, the history of hypertension from the viewpoint of traditional Persian medicine have been reviewed and several hypotheses raised. In this article, we present the concept of an Iranian physician namely Ali ibn Sahl Rabban al-Tabari on hypertension, which has not been considered properly until now. He defined a state called "Hayajan al-dam" that has clinical manifestations similar to hypertension, although these are not the same, also, we reviewed the viewpoint of other Persian medicine scholars namely Rhazes, Haly Abbas, Akhawayni and Avicenna for this topic.

ALOX12 gene polymorphisms and serum selenium status in elderly osteoporotic patients.

BACKGROUND: Osteoporosis is a systemic bone disease which leads to a reduction in bone mass. Many studies have shown that up to 80% of bone mineral density (BMD) variations are attributed to genetic factors. Arachidonate 12-lipoxygenase enzyme, encoded by the ALOX12 gene, produces lipid peroxides as reactive oxygen species (ROS), leading to oxidative stress and the development of osteoporosis. Selenium (Se) is incorporated into selenoproteins, which may reduce the risk of osteoporosis. OBJECTIVES: We aimed to investigate the association of 2 ALOX12 single nucleotide polymorphisms (SNPs) and serum Se level with lumbar spine and femoral neck BMD among elderly individuals living in Amirkola, Iran. MATERIAL AND METHODS: The study consisted of 180 individuals aged ≥60 years (90 healthy and 90 osteoporotic patients). We examined the effect of 2 ALOX12 SNPs (rs2292350 and rs9897850), using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) on both BMD regions measured by dual energy X-ray absorptiometry (DXA). Serum Se level was measured using an atomic absorption spectrophotometer PGG990 AAS (PG Instruments Ltd., Luterworth, USA). RESULTS: The rs2292350 SNP showed a significant association with femoral neck BMD (p = 0.04). Moreover, in terms of serum Se level, a significant difference was found between the patient group (57.58 ±25.54 µg/L) and the control group (81.09 ±25.58 µg/L) (p < 0.001). In addition, individuals with higher serum Se levels also had higher BMD of the lumbar spine (r2 = 0.392; p < 0.001) and the femoral neck (r2 = 0.478; p < 0.001). CONCLUSIONS: The results suggested that genetic variation in ALOX12 might influence BMD variations in our recruited participants. As for the patients with lower serum Se levels, it was observed that serum Se deficiency was accompanied by some ALOX12 variation, contributing to the development of osteoporosis.

The medieval Persian manuscript of Afyunieh: the first individual treatise on the opium and addiction in history.

According to historical evidence, the abuse of opium has been reported all over the globe-specifically throughout Eastern nations-since the sixteenth century. Before that, opium had mostly been applied as medication. Reference has been made in traditional Persian medical literature to the method of cultivation, properties, side effects and toxicity. In sixteenth century Iran, during the reign of the Safavids, opium abuse began. It was from then that prominent Persian scholars started to think of solutions to this societal problem. One of the most famous scholars was Imad al-Din Mahmud ibn Mas'ud Shirazi, who composed a book concerning addiction-Afyunieh, a comprehensive book on the topic of opium and all issues of opium. Furthermore, he recommended methods for reducing opium dose as well as substitution with other medications that had a narrower range of side effects, in order to eradicate dependency upon opium and opium-derived materials. This is most likely the first book that comprehensively addressed opium and discussed drug rehabilitation methodology, in traditional Persian medical literature. In this historical review, the authors have introduced the book Afyunieh, which presents methods for treating addiction to and giving up opium; the text comprises a synthesis of the author's opinions, professional experience and references to the work of other famous physicians.

Heart palpitation relief with Melissa officinalis leaf extract: double blind, randomized, placebo controlled trial of efficacy and safety.

ETHNOPHARMACOLOGICAL RELEVANCE: In Traditional Iranian Medicine (TIM), Melissa officinalis L. is commonly regarded as an effective therapy for heart palpitations. OBJECTIVE: Heart palpitation is a common complaint that is often benign and associated with a marked distress that makes the condition difficult to treat. Herbal medicines provide an alternative to conventional drugs for treating various kinds of diseases. This study was done as a double blind randomized placebo-controlled clinical trial to evaluate the efficacy and safety of the dried extract of M. officinalis on adults suffering from benign palpitations. MATERIALS AND METHODS: Eligible volunteers were randomly assigned as outpatients to a 14 day treatment with 500 mg twice a day of lyophilized aqueous extract of M. officinalis leaves (or placebo). Participants in the tests, physicians and researchers were blind to group assignments. Both primary and secondary outcomes were patient-reported. Primary outcomes were obtained from two measures: mean frequency of palpitation episodes per week, derived from patients׳ diaries, and mean intensity of palpitation estimated through Visual Analogue Scale (VAS) in a self-report questionnaire. Psychiatric symptoms (somatization, anxiety and insomnia, social dysfunction and severe depression) were evaluated as secondary outcomes by General Health Questionnaire-28 (GHQ-28), before and after intervention. RESULTS: Fifty-five volunteers out of 71 recruited study subjects completed the trial. Results showed that 14-day of treatment with lyophilized aqueous extract of M. officinalis leaves reduced frequency of palpitation episodes and significantly reduced the number of anxious patients in comparison to the placebo (P=0.0001, P=0.004 resp.). Also, M. officinalis extract showed no indication of any serious side effects. CONCLUSION: Lyophilized aqueous extract of M. officinalis leaves may be a proper and safe herbal drug for the treatment of benign palpitations.

Brainstem response to speech and non-speech stimuli in children with learning problems.

Neuronal firing synchronization is critical for recording auditory responses from the brainstem. Recent studies have shown that both click and/da/synthetic syllable (speech) stimuli perform well in evoking neuronal synchronization at the brainstem level. In the present study, brainstem responses to click and speech stimuli were compared between children with learning problems (LP) and those with normal learning (NL) abilities. The study included 49 children with LP and 34 children with NL. Auditory brainstem response (ABR) to 100-µs click stimulus and speech ABR (sABR) to/da/40-ms stimulus were tested in these children. Wave latencies III, V, and Vn and inter-peak latency (IPL) V-Vn in click ABR and wave latencies I, V, and A and IPL V-A in sABR were significantly longer in children with LP than children with NL. Except IPL of I-III, a significant positive correlation was observed between click ABR and sABR wave latencies and IPLs in children with NL; this correlation was weaker or not observed in children with LP. In this regard, the difference between correlation coefficients of wave latencies I, III, and V and IPLs I-V and V-Vn/V-A was significant in the two groups. Deficits in auditory processing timing in children with LP may have probably affected ABR for both click and speech stimuli. This finding emphasizes the possibility of shared connections between processing timing for speech and non-speech stimuli in auditory brainstem pathways. Weak or no correlation between click and speech ABR parameters in children with LP may have a clinical relevance and may be effectively used for objective diagnoses after confirming its sufficient sensitivity and specificity and demonstrating its acceptable validity with more scientific evidence.

Crocin improved locomotor function and mechanical behavior in the rat model of contused spinal cord injury through decreasing calcitonin gene related peptide (CGRP).

Various approaches have been offered to alleviate chronic pain resulting from spinal cord injuries (SCIs). Application of herbs and natural products, with potentially lower adverse effects, to cure diseases has been recommended in both traditional and modern medicines. Here, the effect of crocin on chronic pain induced by spinal cord contusion was investigated in an animal model. Female Wistar rats were randomly divided into five groups (5 rats in each); three groups were contused at the L1 level. One group was treated with crocin (150mg/kg) two weeks after spinal cord injury; the second group, control, was treated with vehicle only; and the third group was treated with ketoprofen. Two normal groups were also considered with or without crocin treatment. The mechanical behavioral test, the locomotor recovery test and the thermal behavioral test were applied weekly to evaluate the injury and recovery of rats. Significant improvements (p<0.05) in mechanical behavioral and locomotor recovery tests were seen in the rats treated with crocin. Thermal behavioral test did not show any significant changes due to crocin treatment. Plasma concentration of calcitonin-gene related peptide (CGRP) changed from 780.2±2.3 to 1140.3±4.5pg/ml due to SCI and reached 789.1±2.7pg/ml after crocin treatment. These changes were significant at the level of p<0.05. The present study shows the beneficial effects of crocin treatment on chronic pain induced by SCI, through decreasing CGRP as an important mediator of inflammation and pain.

Effects of diabetes mellitus type Ι with or without neuropathy on vestibular evoked myogenic potentials.

Diabetes mellitus type Ι is a metabolic disorder that affects multiple systems including the inner ear. Patients with diabetes mellitus commonly complain about dizziness, floating sensation, tinnitus and sweating. The aim of this study was to compare vestibular evoked myogenic potentials (VEMPs) between diabetic patients with or without neuropathy. Subjects included 14 patients with diabetes mellitus type Ι with polyneuropathy, 10 patients with diabetes mellitus type Ι without polyneuropathy and 24 healthy volunteers. Range of age in participants was 15-40 years old. The VEMPs were recorded with 500 Hz tone bursts with intensity at 95 dB. There was statistically significant difference between the groups in P13 and N23 latencies (P<0.05). There was no statistically significant difference between groups in absolute and relative amplitudes. Prolonged latencies of the VEMP suggest lesions in the retrolabyrinthine, especially in the vestibulospinal tract.

Therapeutic effects of HESA-A in patients with end-stage metastatic cancers.

BACKGROUND: After cardiovascular disease, cancer is the most common cause of death. HESA-A is a natural product of herbal and marine origin. The aim of this study was to investigate the beneficial effects of HESA-A in patients with end-stage metastatic cancers. METHODS: In this clinical trial, 30 consecutive patients (18 men, 12 women) with end-stage cancers and liver metastasis at the Cancer Research Center of Tehran University of Medical Sciences were studied. Patients received HESA-A 50 mg/kg/d orally in 2 to 3 divided doses for 3 months. At the start and end of the 1st, 4th, 8th, and 12th weeks of the study, the patients were assessed and hematological and hepatic biochemical indices were measured. Also, the Karnofsky Performance Scale questionnaire was completed for each patient. RESULTS: The mean age of patients was 56.23 +/- 12.10 years. Mean Karnofsky Performance Scale scores of the patients increased from 48 +/- 14.36 to 78.42 +/- 15.37 after 12 weeks of treatment. A total of 90.4% of the patients who remained in the study were alive for 12 weeks. No significant hepatic or hematologic adverse effect was seen during the study. CONCLUSION: HESA-A appears to be an effective and safe anticancer compound that may increase survival of end-stage patients and can be used in selected cases. Further prospective controlled clinical trials with large sample size and longer follow-up period are warranted to understand the mechanisms of action of HESA-A and evaluate its long-term effects on the survival and quality of life of patients with cancer and as well as its unfavorable side effects.

Mixture of Arnebia euchroma and Matricaria chamomilla (Marhame-Mafasel) for pain relief of osteoarthritis of the knee - a two-treatment, two-period crossover trial.

INTRODUCTION: Osteoarthritis is the most prevalent chronic non-infective joint arthritis. Because of its chronic disease nature, local drugs are preferred due to lower complications. In the present study, the new herbal pomade Marhame-Mafasel for knee osteoarthritis was used in a double-blind crossover trial. The aim of the study was to assess the efficacy and safety of Marhame-Mafasel pomade, which consists of several medical herbs including Arnebia euchroma and Matricaria chamomilla, in osteoarthritis of the knee. MATERIAL AND METHODS: This study was a placebo-controlled double-blind crossover trial. Forty-two patients with pain associated with osteoarthritis of the knee (diagnosed by criteria of the European League against Rheumatism and physical examination) were drawn from patients attending the Clinic of Mostafa-Khomeini Hospital. In this study we assessed efficacy (analgesic effect and improved function) of herbal pomade Marhame-Mafasel, which was used locally in patients with primary osteoarthritis of the knee over three weeks. The instrument of the study was the Western Ontario and McMaster Universities (WOMAC) LK3.1 standard questionnaires. RESULTS: The participants in each group were 21 patients; 30 (71.4%) were women and 12 (28.6%) of them were men. The participants were between 40 and 76 years old. Six patients had mild arthritis, 15 had moderate arthritis and 21 had severe arthritis. The positive analgesic effect of the herbal pomade Marhame-Mafasel in primary knee osteoarthritis was proven. The herbal joint pomade Marhame-Mafasel had a significantly greater mean change in score compared to the placebo group for osteoarthritis severity (p < 0.05). CONCLUSIONS: Herbal pomade Marhame-Mafasel in comparison to placebo has more effect on reduction of pain of primary knee osteoarthritis.

An Iranian herbal-marine medicine, MS14, ameliorates experimental allergic encephalomyelitis.

Multiple sclerosis is an inflammatory and demyelinating disease of the central nervous system which mainly affects young adults. To overcome wide spectrum troublesome symptoms of multiple sclerosis which affects the quality of life both in patients and their families, new drugs and remedies have been examined and offered. The preclinical beneficial effects of different medicines have mostly been examined in an animal model of multiple sclerosis called experimental allergic encephalomyelitis (EAE). In this study we have tested a traditionally used natural (herbal-marine) product called MS(14) in EAE mice. EAE mice were fed with MS(14) containing diet (30%) on the immunization day and monitored for 20 days. The results show that while clinical scores and therefore severity of the disease was progressive in normal-fed EAE mice, the disease was slowed down in MS(14)-fed EAE mice. Moreover, while there were moderate to severe neuropathological changes in normal fed mice, milder changes were seen in MS(14) fed mice.