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In the current study, we aimed to assess the effect of dried Ziziphus jujube on blood glucose, lipid profiles, anthropometric indices, and inflammatory factors in type 2 diabetic(T2D) patients.In this randomized controlled clinical trial, 48 patients, aged 30-65 years, were randomly assigned to two intervention(n = 24) and control(n = 24) groups. The subjects in the intervention group received 30 g Ziziphus jujube daily for 12 weeks. At baseline and the end of the 12th week, 10 ml of blood was taken from each patient after a 12- to 14-h overnight fasting. Plasma levels of fasting plasma glucose (FPG), triglycerides(TGs), total cholesterol(TC), high-density lipoprotein-cholesterol(HDL-C), low-density lipoprotein-cholesterol(LDL-C), high-sensitivity C-reactive protein(hs-CRP), and interleukin-6(IL-6) were measured. Anthropometric indices were determined.Plasma FPG, TG, TC, and LDL-C decreased significantly up to -11.36%, -13.59%, -7.46%, -7.65% in the Ziziphus jujube group at the end of week 12 compared to baseline, respectively (P 0.05), and this reduction was significant in comparison with the control group (P 0.05). The plasma hs-CRP reduced significantly up to -24.46% in the Ziziphus jujube group at the end of week 12 compared to baseline (P 0.05), however, this reduction was not significant in comparison with the control group (P 0.05). Also, there were no significant differences between the two groups in mean changes of body mass index, plasma HDL-C, and IL-6.The current study showed that daily consumption of Ziziphus jujube may have beneficial effects on the lipid profiles and blood glucose levels in T2D.T his clinical trial was registered at the Iranian registry of clinical trials (IRCT registration number: IRCT20181210041913N1).

Cancer stem cells (CSCs) are a subgroup of cells in malignant cancers, which possess self-renewal capacity, tumor-initiating capability, and pluripotency, as well as being responsible for tumor maintenance, metastasis, relapse, and chemoresistance. The treatment modalities previously established for cancer included surgery, chemotherapy, and radiotherapy. The majority of tumor cells of non-CSCs could be eradicated using conventional chemotherapy and radiotherapy. Therefore, novel and promising therapeutic strategies that selectively target CSCs are of great importance. In this review, we described different therapeutic strategies such as immunotherapy, metabolism-based therapeutic strategies, and additional potential therapeutic approaches (targeting microRNAs [miRNAs], histone deacetylase, and DNA methyl transferase) against CSCs. Taken together, due to the inefficiency of anticancer single therapies, targeting CSCs through their metabolism and using immunotherapy and miRNAs besides classical chemo- and radiotherapy may exert better therapeutic effects.

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder associated with irregular menstrual cycles, hyperandrogenism, obesity, and reduced fertility. Objectives: The present study aimed to formulate herbal syrup based on Iranian traditional medicine (ITM) and evaluate its effect on the letrozole-induced PCOS model in female rats. Methods: The herbal syrup contains anise, fennel, and celery seed extracts. Five different formulations were made with different percentages of additive components. Quality control and stability tests were performed on the selected formulation. During the in vivo step, 6 groups of rats were evaluated: The control group (received carboxymethyl cellulose 1% as a vehicle) and the other 5 groups (received letrozole 1 mg/kg orally for 21 days). During 21 days, daily vaginal smears were examined to detect irregularities of the estrous cycle. After induction of PCOS, rats were orally administered with herbal syrup (1, 2, 4 mL/kg) or metformin (200 mg/kg) for 28 days. Moreover, body and ovarian weights, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and testosterone were measured. Finally, ovarian tissues were isolated for histological examination. Results: The best formulation of the syrup contained the plant extract (totally 10%), sugar (50%), sodium benzoate (0.1%), and potassium sorbate (0.1%). Body weight was significantly increased in all groups compared to the control group, and after treatment, a significant weight reduction was seen in the metformin and 1-mL/kg dose group. Following PCOS induction, ovary weight was significantly increased, while after treatment, it showed a significant decrease. After 21 days of letrozole administration, induction of PCOS was confirmed by the irregularities in estrous cycles and an increase in testosterone and LH levels. After treatments with the syrup, LH levels significantly decreased in all groups (P < 0.05), and serum testosterone and FSH levels significantly decreased in the 2-mL/kg dose group compared to the PCOS group (P < 0.05). Estradiol and progesterone levels significantly increased in the treatment groups in a dose-dependent manner. Histological studies of metformin and herbal syrup groups exhibited normal follicular development with fewer and smaller cystic follicles compared to the PCOS group. Conclusions: The herbal syrup made from anise, fennel, and celery seed extracts improved serum levels of sex hormones, recovered the ovarian morphology in PCOS-induced rats, and can be a good candidate for further clinical trials.

Polycystic ovary syndrome (PCOS) is an endocrine disorder that disrupts the menstrual cycle and causes infertility. Considering the increasing use of medicinal plants, the present study aimed to evaluate the effects of Teucrium polium L. on letrozole-induced PCOS in female rats.Six groups of rats (n=7 each) were evaluated. The control group received 1% carboxy methyl cellulose as vehicle, while the five other groups received letrozole 1 mg/kg orally for 21 days. After PCOS induction, the rats were orally administered T. polium extract (50, 100, 200 mg/kg) or metformin (200 mg/kg) for 28 days. Subsequently, body and ovarian weights and serum levels of follicle stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, and testosterone were measured. Finally, the ovarian tissues were isolated for histological examination.There were no significant changes in weekly body weight in any group. After 21 days of letrozole administration, PCOS induction was confirmed by estrous cycle irregularities and increased LH and testosterone levels. After treatment with the hydroalcoholic extract of T. polium, testosterone and LH levels were significantly reduced in all groups (P0.05). Histological studies of ovaries in the metformin and T. polium groups exhibited normal follicular development with fewer and smaller cystic follicles than those in the PCOS group.The hydroalcoholic extract of T. polium improves serum levels of sex hormones, restores ovarian morphology in PCOS-induced rats, and is a good candidate for further clinical trials.

Peripheral neuropathy is one of the most common adverse effects of cancer chemotherapy. Vincristine is prescribed to treat a variety of carcinomas, including lymphoma and leukemia, and may cause progressive peripheral neuropathy due to the damage of microtubules and mitochondria of neurons and affects inflammatory processes. This study was designed to evaluate the effects ofNeuropathy was induced in rats by daily intraperitoneal administration of vincristine (0.1 mg/kg for 2 weeks). Following the induction of neuropathy, animals were treated with the LHE (100, 200, and 400 mg/kg, p.o.) or pregabalin (20 mg/kg, IP) for 2 weeks, and their responses to vincristine-induced hyperalgesia and locomotor impairment were measured.LHE, at the dose of 400 mg/kg, showed analgesic effects in response to thermal hyperalgesia, tactile allodynia, and gait impairment. Also, pregabalin (20 mg/kg, IP) improved the symptoms of vincristine-induced peripheral neuropathy.According to the results, we can conclude that LHE alleviates neuropathic symptoms of vincristine and the effect is probably related to the presence of phenols and flavonoids in the extract.

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BACKGROUND: Sexual dysfunction in women is a common disorder. Yet, there is no consensus on its treatment. Few studies have shown that Vitex agnus-castus improves sexual dysfunction in postmenopausal women; the present study was conducted to evaluate the effect of V. agnus-castus on the female sexual function in the reproductive age. MATERIALS AND METHODS: This was a double-blinded randomized control clinical trial on the women of reproductive age referred to the gynecology clinic of Al-Zahra Medical Center in Rasht, Iran, from February 2018 to December 2019. The intervention group received Agnugol tablet containing 3.2–4.8 mg dried extract V. agnus-castus (51 participants) and the control group received a placebo tablet (51 participants). All participants received one tablet daily for 16 weeks. The participants were asked to complete the Female Sexual Function Index questionnaire at the beginning of the study and after 4, 8, 12, and 16 weeks. Data were analyzed in SPSS statistics (version 21) using Chi-square test, t-test, Mann–Whitney U-test, analysis of variance, and mixed model to examine the differences between the groups. RESULTS: The results showed that the difference between the two groups was not significant in each domain, but there was a significant difference in the overall sexual function mean score so that the intervention group had a higher score than the placebo group after 16 weeks (P < 0.05). CONCLUSION: In the present study, it was observed that the consumption of V. agnus-castus during 16 weeks was more effective than the placebo in improving sexual dysfunction. Further studies with larger sample sizes are needed to be able to decide on the prescription of this drug in the clinics.

Background: Nitric oxide and reactive nitrogen species play an important role in various pathological conditions like cancer, inflammation and neurodegeneration. As plants and natural compounds have a great potency of discovering lead compounds which might affect NO production during inflammation and various pathologies, we examined the effects of three medicinal plants native to Iran, on NO production during oxidative stress in PC12 cells. Methods: In this study, cell death and NO levels were measured by MTT and by Griess assay, respectively. Oxidative stress was induced by hydrogen peroxide and extracts of Astragalus jolderensis, Convolvulus commutatus and Salvia multicaulis were used as pretreatment in oxidative stressed PC12 cells. Results: A. jolderensis extract significantly suppressed NO production in 150 and 200 μg/ml concentrations and C. commutatus extract in all concentration inhibited NO production in stressed PC12 cells. In addition, the extract of S. multicaulis inhibited NO production during stress at all concentrations above 50 μg/ml. Besides, the extract of S. multicaulis showed protective effect at lower doses in stressed cells. Conclusion: According to the results, S. multicaulis inhibited NO production and protected cells from oxidative stress. Hence, S. multicaulis is a good candidate for further in vitro and in vivo investigations. A. jolderensis and C. commutatus also suppressed NO production during stress. Therefore, they could be noticed in experiments that centralize on the inhibition of NO production and drug discovery studies in the field of neurodegenerative and chronic inflammatory diseases.

Background and objectives NF-kB, SIRT1 and systemic inflammation factors including hs-CRP, IL-6 and TNF-α accelerate atherosclerosis pathogenesis. Our purpose was to evaluate the effect of daily supplementation of three-gram cinnamon on plasma levels of NF-kB, SIRT, hs-CRP, IL-6 and TNF-α among type 2 diabetes patients. Subjects and methods A randomized, double blind, and controlled clinical trial was performed with 44 adult patients who were 25 to 70 years old with type 2 diabetes, randomized to two intervention (n = 22) and control (n = 22) groups differing by daily three grams cinnamon supplementation and placebo for 8 weeks, respectively. The plasma levels of NF-kB, SIRT, hs-CRP, IL-6 and TNF-α were measured by ELISA assay at the beginning and end of the study. Results After 8-week intervention, 39 subjects (n = 20 in the cinnamon and n = 19 in the placebo groups) ended up the trial. It was not observed significant difference in levels of hs-CRP (P = 0.29), TNF-α (P = 0.27), IL-6 (P = 0.52), and Sirtuin-1 (P = 0.51) in between group comparison. While, the result showed significant difference in levels of NF-kB (P = 0.02) between groups. As well as, in among group comparison, there was not observed significant differences except in hs-CRP (P = 0.008) in placebo group. Conclusions This study elucidated that cinnamon supplementation has no beneficial effects in reduction of NF-kB, SIRT1, hs-CRP, IL-6 and TNF-α levels in type 2 diabetes patients which have a considerable role in development of atherogenesis.

Introduction The current study was designed to examine the effect of the herbal medicine purslane on heavy menstrual bleeding (HMB). Methodology This randomized double-blinded placebo-controlled clinical trial was performed on women who suffered from HMB with their regular menstrual cycles. Both groups (48 in purslane-using group and 47 in control group) received mefenamic acid every 8 h from the first day to the third day of their periods in two menstrual cycles. In the intervention group, in addition to mefenamic acid, a capsule of purslane seeds, and in the control group, a similar capsule containing corn starch with the same protocol were administered. A pictorial blood loss assessment chart (PBLAC) was used to determine bleeding. Findings A significant difference was observed between the purslane and control groups (p Conclusions Purslane appears to boost the effect of mefenamic acid and reduces symptoms in women with HMB.

Sleep disorder is considered as a common problem throughout the world. Aromatherapy is a kind of treatment performed by using essential oils of plants for improving disease. There is much evidence in the literature, including Iranian traditional medicine, which confirms its positive effects on improving sleep disorder. Related keywords searched some Iranian traditional medicine texts and some new valid databases. In Iranian traditional medicine, aromatherapy is one of the methods of treatment for improving sleep disorders and its done by the temperamental approach. Aroma temperament, brain mal-temperament and specific performance of aroma are three factors for selection of the plants. Fourteen aromatic plants are introduced that can be effective by hypnotic in insomnia and reducing sleep in oversleeping. Aromatherapy is an effective method to improve sleep disorders, and it can be used through various plants in the more specified way with fewer side effects using temperamental approach. [GMJ.2017;6(1):3-11]

Soluble forms of vascular adhesion molecules, ICAM-1 and VCAM-1, accelerate atherosclerosis pathogenesis. The present study was conducted to evaluate the effect of daily supplementation of 3 g cinnamon on the plasma levels of ICAM-1 and VCAM-1 among patients with type 2 diabetes. This randomized double-blind placebo-controlled trial was performed on 44 adult patients with type 2 diabetes aged 25-70 years. The patients were randomized to two groups of intervention (n = 22) and control (n = 22), differing by daily cinnamon supplementation or placebo (3 g) for 8 weeks. Plasma levels of ICAM-1 and VCAM-1 were measured at the beginning and end of the study. After 8 weeks, 39 subjects (n = 20 in the cinnamon and n = 19 in the placebo groups) completed the trial. There was a significant reduction in the mean levels of ICAM-1 and VCAM-1 within cinnamon and placebo groups (P

Corylus avellana L. (hazelnut) is known to be a delicious and nutritious food. This study was carried out to evaluate the use of hazelnut as a therapy for memory impairment because in Iranian traditional medicine, it is recommended for those suffering from a particular type of dementia, with symptoms of Alzheimer's disease.In this study, rats were fed with hazelnut kernel [(without skin) 800 mg/kg/day] during 1 week before stereotaxic surgery to 24 hours before behavioral testing (in general, for 16 consecutive days) and the effect of hazelnut eating on memory, anxiety, neuroinflammation and apoptosis was assessed in the amyloid beta-injected rat.The results of this study showed that feeding with hazelnut improved memory, (which was examined by using Y-maze test and shuttle box apparatus), and reduced anxiety-related behavior, that was evaluated using elevated plus maze. Also, western blotting analysis of cyclooxygenase-2, interleukin-1β, tumor necrosis factor-α, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, and caspase-3 showed that hazelnut has an ameliorating effect on the neuroinflammation and apoptosis caused by Aβ.These findings suggest that hazelnut, as a dietary supplement, improves healthy aging and could be a beneficial diet for the treatment of AD.

Allium hirtifolium Boiss and Astragalus hamosus L. are mentioned in Iranian traditional medicine documentation as therapy for a kind of dementia with the features and symptoms similar to those of Alzheimer’s disease (AD). In the present study, the effects of these herbs on neuro-inflammation and memory have been evaluated as new therapies in amyloid beta (Aβ)-induced memory impairment model. Separate groups of rats were fed with A. hirtifolium or A. hamosus extract (both 100 mg/(kg·day)−1) started 1 week before stereotaxic surgery to 24 h before behavioral testing (totally, for 16 successive days). The effects of oral administration of mentioned extracts on the memory and neuro-inflammation were assessed in the Aβ-injected rats. The results of this study showed that oral administration of both A. hirtifolium and A. hamosus improved the memory, examined by using Y-maze test and shuttle box apparatus. Also, Western blotting analysis of cyclooxygenase-2, interleukin-1β, and tumor necrosis factor-α showed that these herbs have ameliorating effects against the neuro-inflammation caused by Aβ. These findings suggest that the use of A. hirtifolium and A. hamosus as herbal therapy may be suitable for decreasing AD-related symptoms and treatment of other neurodegenerative disorders.

Objective: Headache is a common cause of visits to health care centers. According to World Health Organization Forum, migraine alone is the seventh cause of disability among all diseases. This article attempts to highlight the importance of normal bowel movement in management of headache symptoms. Methods: This study was carried out with searching through traditional books using keywords ‘Sodaa’ (headache) and ‘Yobusat’ (constipation) in Noor software, while search in modern medicine literature was performed using Medline(PubMed) and Scopus da tabases and Persian medical databases such as SID, with keywords “headache”, “migraine”, “constipation”, “gastrointestinal” and “autonomic”. Insufficient attention to underlining factor of headache was limitation in mentioned studies. Finally, studies evaluating the comorbidity of these two disorders were selected. Results: According to Persian medicine texts, constipation is considered one of the important factors for onset or exacerbation of headache. As well, the results obtained from studies in modern medicine, relatively confirmed this relationship and demonstrated a close association between constipation and headache (especially non migraine headache). Conclusion: In Persian medicine, constipation is one of the most important predisposing factors for headaches and the results achieved from modern literature in this study, suggested that constipation might be considered as a contributing factor; however, more researches are needed to clarify the relationship between headache and constipation. Therefore, considering the importance of treating constipation, use of medicines with no constipation as a side effect or use of traditional medicine laxatives along with the conventional treatment might be suggested. Keywords: Headache, Constipation, Persian Medicine, Modern Medicine.

Background Many plants have been introduced in Iranian traditional medicine for treatment of different joint problems including knee pain. Topical application of the mixture of Lawsonia inermis L. leaves (Henna) with aqueous extract of Ricinus communis L. leaves have been mentioned to have significant effects on reducing knee pain. The present study was designed to evaluate the analgesic and anti-inflammatory effects of the mixture of these two herbs in male rats. Methods We induced knee osteoarthritis as a model of chronic pain by intra-articular injection of mono sodium iodoacetate (MIA). Mechanical allodynia, hotplate latency test, spontaneous movements and gait analysis were used for the evaluation of analgesic activity. Anti-inflammatory activity was evaluated by measuring the diameter and the volume of the injected paw compared to contralateral paw. These tests were monitored at days 1, 3, 7, 14 and 21 of MIA administration. Histopathological evaluations were also used to assess the efficacy of the treatment on inflammation and lesions in knee tissue. In all tests, diclofenac topical gel was used as a positive control. The herbal extracts, their mixture, and vehicle or diclofenac gel were administered daily for 14 days by topical route. Results The mixture of these two extracts significantly reduced the knee joint width and volume of the injected paws and also improved foot prints in gait analysis after 3 days of MIA injection. Analysis of mechanical allodynia (after 21 days), hotplate latency test (after 10 days), spontaneous movements (after 7 days) and in positive control group (after 3 days in all tests and in mechanical allodynia after 14 days) compared to the vehicle group, showed significant effects. Topical usage of the selected formulation made significant histopathological changes on the knee of the rats. Compared to the vehicle group, the tests and diclofenac groups showed less reactions characterized by negligible edema and a few scattered inflammatory lymphoid cells. Conclusion The present findings showed that the present formulation not only was able to mitigate pain and inflammation in the paws but also made significant histopathological changes on the knee of the rats. Further studies are necessary to confirm the effect of the formulation.

Phytochemical investigation of the chloroform extract of BRYONIA ASPERA roots resulted in the isolation and structure elucidation of two new cucurbitacins ( 1, 2) together with eight known cucurbitane derivatives ( 6 - 13), the pentacyclic triterpene bryonolic acid ( 5) and two hydroxybenzoic acid amides ( 3, 4). Their structures were elucidated by spectroscopic analysis, including 2D NMR techniques.

Ethnopharmacological relevance An investigation of plants was undertaken through interviews and literature surveys on plants used to treat malaria or cancer or microbial diseases in Iran. Aim of study In vitro and in vivo antiplasmodial tests were carried out on selected plants traditionally used in Iran. Materials and methods Thirty-two plants were extracted with methanol and tested for their in vitro (pLDH assay) activity against Plasmodium falciparum, in vivo activity against Plasmodium berghei and assessed for any cytotoxicity against the human cancer cell line MCF7 and the normal cell MDBK. Results Extracts from four plants, Buxus hyrcana Pojark. (Buxaceae), Erodium oxyrrhnchum M. Bieb. (Geraniaceae), Glycyrrhiza glabra L. (Fabaceae) and Ferula oopoda (Boiss and Bushe) Boiss. (Apiaceae) were found to have significant antiplasmodial activity (IC50 ranging from 4.7 to 26.6 μg/ml). These findings lend support to the use of Buxus hyrcana and Glycyrrhiza glabra in traditional medicine. The chloroformic fraction also was active against K1 and 3D7 strains. The chloroformic fraction was studied at 10 mg per kg body weight mouse per day. This fraction reduced parasitaemia by 86.1% compared to untreated control mice. Conclusion Glycyrrhiza glabra showed antiplasmodial activity and has selectivity for Plasmodium falciparum and Plasmodium berghei when tested on mammalian cells. This is the first report that mentioned in vitro and in vivo antiplasmodial activity of Glycyrrhiza glabra.

The aim of the current study was to determine the effect of a daily intake of three grams of cinnamon over eight weeks on glycemic indicators, advanced glycation end products, and antioxidant status in patients with type 2 diabetes. In a double-blind, randomized, placebo controlled clinical trial study, 44 patients with type 2 diabetes, aged 57 ± 8 years, were randomly assigned to take either a three g/day cinnamon supplement (n = 22) or a placebo (n = 22) for eight weeks. We measured the fasting blood glucose, insulin, hemoglobinbA1c, homeostasis model assessment for insulin resistance (HOMA-IR), carboxymethyl lysine, total antioxidant capacity, and malondialdehyde levels at the beginning and the end of the study. Thirty-nine patients (20 in the intervention group and 19 in the control group) completed the study. After an eight-week intervention, changes in the level of fasting blood glucose, insulin, hemoglobinbA1c, HOMA-IR, carboxymethyl lysine, total antioxidant capacity, and malondialdehyde were not significant in either group, nor were any significant differences between groups observed in these glycemic and inflammatory indicators at the end of the intervention. Our study revealed that cinnamon supplementation had no significant effects on glycemic and inflammatory indicators in patients with type 2 diabetes.

Methanolic extract of 15 Iranian medicinal plants were prepared and tested for their cytotoxic activities against three cancer cell lines (MCF7, HepG2, WEHI164) and one normal cell line (MDBK). Some plants showed cytotoxic activities. The extract of Ferula szowitsiana root, which proved to be the most active, was chosen for further phytochemical studies. The major compounds of the most potent acetone extract were isolated. They were identified as chimgin and chimganin, two known monoterpenoids, by spectroscopic means. Their cytotoxic activity was evaluated in three cell lines. The results show that these compounds are responsible, at least in part, for the cytotoxic activity of this plant.

Botanicals are used traditionally for treatment and prevention of the liver diseases. In the past decades, the use of herbal remedies for non-alcoholic fatty liver disease (NAFLD) has become more popular. This study was conducted to determine the efficacy of herbal medicines used for the treatment of NAFLD in clinical trials. This research was carried out by searching through the studies done on human beings, which have been reported from 1966 to Feb. 2016 and recorded in Cochrane library, Google Scholar, Pub Med, and Scopus. A number of medicinal herbs have been evaluated in human trials. A scientific evaluation of these manuscripts can give an insight into the ideas of the past: it might well be valuable in finding new data on clinical use of the herbal medicines for the treatment of NAFLD and should lead to future opportunities to investigate their potential medicinal use.

Fruits of Olea europaea L. have been used for centuries in folk medicine to treat many inflammatory diseases. In order to evaluate the anti-nociceptive activities of the methanolic and aqueous extracts of defatted fruits of O. europaea, formalin test was used and for evaluation of anti-inflammatory effects of the extract, the volume of paw edema was measured. The results revealed that both extracts did not exhibit significant analgesic activity in the first phase of formalin test, whereas methanolic extract at the 600 mg/Kg dose and aqueous extract at the 450 and 600 mg/Kg doses could inhibit induced pain in the second phase of formalin test. Furthermore, the results of paw edema volume measurement indicated that the aqueous extract has anti-inflammatory effects at dose of 600 mg/Kg. Induced anti-nociception by aqueous olive extract was not reversed by naloxone, which indicates that the opioid receptors are not involved in the analgesic effects of the extracts. The present data pointed out that the extracts of olive defatted fruit have anti-nociceptive and anti-inflammatory effects in rats but further studies are needed to elucidate the mechanism(s) of action and active components which are involved in analgesic and anti-inflammatory effects.