Safety and hemostatic effect of Achillea millefolium L. in localized bleeding.

Background and Aim: This study aims to demonstrate the hemostatic effect of the hydroalcoholic extract of Achillea millefolium L. in localized bleeding and to assess the safety of its topical application on rat liver. Materials and Methods: The aerial parts of A. millefolium were macerated in methanol for two days. Twelve female Wistar rats, weighing 120-220 g, underwent anesthesia and laparotomy. The liver was exposed, and two incisions were made to induce bleeding. One incision was treated with a sponge soaked in A. millefolium extract, while the other served as a control. The animals were divided into two groups: in one, A. millefolium (150 mg/kg) was applied to the first incision, and in the other, to the second incision. Liver biopsies were collected after 4, 6, and 8 weeks. Results: Application of A. millefolium to liver incisions, whether first or second, significantly reduced bleeding time (by 36.1% and 31.9%, respectively). Histopathological analysis showed no signs of toxicity or hepatic damage after 4, 6, and 8 weeks in the female rats. Conclusion: The study confirms the hemostatic effect of the hydroalcoholic extract of A. millefolium in localized bleeding and establishes its safety for topical use.

A randomized, double-blind placebo-controlled phase I clinical study on safety and efficacy of the G-Rup® syrup (a mixture of ginger extract and honey) in symptomatic treatment of knee osteoarthritis.

WHAT IS KNOWN AND OBJECTIVES: Present study evaluated the safety profile and efficacy of G-Rup® syrup (100 mg/ml ginger extract plus 150 mg/ml honey) in symptomatic treatment of knee osteoarthritis (OA). METHODS: Patients diagnosed with knee OA were randomly assigned (1:1) to receive either of a 30 ml twice daily regimen of G-Rup® syrup or placebo over a 12-week period. Primary endpoints of the study comprised of an improvement in the joint's stiffness, physical functioning and pain score, assessed by WOMAC questionnaire and the visual analog scale (VAS). Secondary objectives comprised of safety and tolerability of the syrup by patients. RESULTS AND DISCUSSION: The 30 ml twice-daily regimen of G-Rup® syrup was safe and well tolerated by patients. Moreover, in whole studied time points, treatment with G-Rup® syrup could significantly Power the VAS score (p < 0.001) whereas improving WOMAC total score (p < 0.001) and pain (p < 0.001), physical functioning (p < 0.001), and stiffness sub-scores (p = 0.006) compared to the placebo receiving group. WHAT IS NEW AND CONCLUSION: Based on obtained results, the G-Rup® syrup, composed of a combination of honey and ginger, may be a proper supplementary choice, along with routine therapeutic regimens, for improvement of symptomatic treatment of OA.

Endocannabinoids and related compounds as modulators of angiogenesis: Concepts and clinical significance.

Vasculogenesis (the process of differentiation of angioblasts toward endothelial cells and de novo formation of crude vascular networks) and angiogenesis (the process of harmonized sprouting and dispersal of new capillaries from previously existing ones) are two fundamentally complementary processes, obligatory for maintaining physiological functioning of vascular system. In clinical practice, however, the later one is of more importance as it guarantees correct embryonic nourishment, accelerates wound healing processes, prevents uncontrolled cell growth and tumorigenesis, contributes in supplying nutritional demand following occlusion of coronary vessels and is in direct relation with development of diabetic retinopathy. Hence, discovery of novel molecules capable of modulating angiogenic events are of great clinical importance. Recent studies have demonstrated multiple angio-regulatory activities for endocannabinoid system modulators and endocannabinoid-like molecules, as well as their metabolizing enzymes. Hence, in present article, we reviewed the regulatory roles of these molecules on angiogenesis and described molecular mechanisms underlying them.

The Novel Role of Crocus sativus L. in Enhancing Skin Flap Survival by Affecting Apoptosis Independent of mTOR: A Data-Virtualized Study.

BACKGROUND: Despite the improvements to enhance skin flap viability, the effects of ischemia-reperfusion (IR), oxidative stress, necrosis, and apoptosis are still challenging. Crocus sativus L. (Saffron) is highly noticeable due to its tissue-protective and antioxidant properties. So, we aimed to investigate its effects on skin flap viability, oxidative stress, apoptosis markers, histopathological changes, and mTOR/p-mTOR expression. MATERIALS AND METHODS: 40 Sprauge-Dawley rats, weighting 200-240 g, were divided into four groups including: (1) Sham (8 × 3 cm skin cut, without elevation); (2) Flap Surgery (8 × 3 cm skin flap with elevation from its bed); (3) Saffron 40 mg/kg + Flap Surgery; and (4) Saffron 80 mg/kg + Flap Surgery. Saffron was administrated orally for 7 days. At day 7, flap necrosis percentage, histopathological changes, malondialdehyde level, Myeloperoxidase and superoxide dismutase activity, Bax, Bcl-2, mTOR, and p-mTOR expression were measured. Protein expressions were controlled by ß-Actin. RESULTS: Saffron administration decreased flap necrosis percentage (p < 0.01), which was not dose-dependent. Treatment groups showed significant histological healing signs (Neovascularization, Fibroblast migration, Epithelialization, and Epithelialization thickness), decreased MDA content (p < 0.01), increased SOD (p < 0.01) and decreased MPO activity (p < 0.01). Bax and Bcl-2 expression, decreased and increased respectively in treated groups (p < 0.0001). mTOR and p-mTOR expression were not changed significantly in Saffron treated groups. CONCLUSION: Saffron could increase skin flap viability, alleviate necrosis, decrease oxidative stress and decrease apoptotic cell death, after skin flap surgery, but it acts independent of the mTOR pathway. So, Saffron could potentially be used clinically to enhance skin flap viability. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. https://www.springer.com/00266.

A Phase I Randomized, Double-blind, Placebo-controlled Study on Efficacy and Safety Profile of a Sublingually Administered Cannabidiol /Delta 9-tetrahydrocannabidiol (10: 1) Regimen in Diabetes Type 2 Patients.

The current study aimed to evaluate the safety profile and efficacy of a cannabis-based sublingual spray, CBDEX10® (containing 100 µg cannabidiol and 10 µg Δ9-tetrahydrocannabinol per puff; CBD/Δ9-THC 10:1), in improving lipid profile and glycemic state of the diabetic patients. Fifty diabetic patients were randomly allocated to the treatment (n = 25; receiving two puffs of CBDEX10® twice daily) or the control groups (n = 25; receiving two puffs of placebo). The primary endpoint of the study was to evaluate the efficacy of the CBDEX10® adjunctive therapy in improving the lipid profile and glycemic state of diabetic patients; the secondary endpoint was to assess the safety profile and tolerability of the spray. A statistically significant decline in total cholesterol [estimated treatment difference (ETD) = -19.73 mg/dL; P < 0.05], triglyceride (ETD = -27.84 mg/dL; P < 0.01), LDL-C (ETD = -5.37 mg/dL; P < 0.01), FBS (ETD = -12 mg/dL; P < 0.01), Hb A1C (ETD = -0.21 mg/dL; P < 0.01) and insulin secretion (ETD = -5.21 mIU/L; P < 0.01) was observable in the patients treated with CBDEX10® at the end of the 8-week treatment period. Regarding safety, the mentioned adjunctive regimen was well, and there were no serious or severe adverse effects. Overall, CBDEX1® sublingual spray could be a new therapeutic agent for lipid and glycemic control in diabetic patients.

Effectiveness of Echium amoenum on premenstrual syndrome: a randomized, double-blind, controlled trial.

BACKGROUND: The present study aimed to evaluate the effect of Echium amoenum (EA) on the severity of premenstrual syndrome (PMS) in comparison with placebo. METHODS: The present study was a randomized double-blind controlled clinical trial. A checklist questionnaire was completed by 120, 18 to 35-year-old, college students. And then, 84 eligible women (20 to 35 years old) were enrolled in the trial; they were randomly assigned to two groups of intervention (EA) and control (placebo), with 42 participants in each group. Participants in the intervention group received 450 mg capsules of EA per day (three times a day) from the 21st day of their menstrual cycle until the 3rd day of their next cycle for two consecutive cycles. The severity of PMS was measured and ranked using the premenstrual symptoms screening tool (PSST). The generalized estimating equation was used to compare the total score of the severity of PMS between the two groups. RESULTS: Sixty-nine women with regular menstrual cycles suffering from PMS completed the study. The mean scores of the symptoms in the EA group were 35.3 and 16.1 (P ≤ 0.001) at baseline and after 2 months, respectively, while the mean scores of the symptoms in the placebo group were 31.0 and 28.3 (P = 0.09) at baseline and after 2 months, respectively. The evaluation of the first and the second follow-ups in the intervention group showed that, after being adjusted for age and body mass index (P ≤ 0.001), the mean scores of the premenstrual syndrome, using GEE analysis, have decreased to 6.2 and 11.6, respectively. CONCLUSION: Based on the results, in comparison with the placebo group, EA was found to be more effective in improving the symptoms of PMS, and is highly recommended for treatment of this syndrome. TRIAL REGISTRATION: IRCT2015110822779N3 ; Registration date: 2015-11-27.

Could Anise decrease the intensity of premenstrual syndrome symptoms in comparison to placebo? A double-blind randomized clinical trial.

Background Premenstrual syndrome (PMS) has a high prevalence among women of reproductive ages but despite its high prevalence, it has no determined and absolute treatment, so far. So, the aim of the present study was to compare the effect Pimpinella Anisum (Anise) with placebo on the intensity of the symptoms of PMS. Methods The present study was a randomized double-blind controlled clinical trial. College students who were suffering from PMS and had the inclusion criteria were selected and randomly assigned into two groups of intervention (Anise) and control (placebo). Participants in the intervention group, received 110 mg capsules of Anise three times day (a total dose of 330 mg per day); the control group received similar capsules with the same dosing that contained starch. Consumption of the capsules was started 7 days before the start of the menstruation and continued until 3 days after, which was a total of 10 days during two consecutive menstruation cycles. The intensity of the symptoms of premenstrual syndrome was measured using Premenstrual Symptoms Screening Tool (PSST). To compare the intensity of the symptoms between the two study groups, generalized estimating equation statistical method was used. Results Eventually, sixty-seven 18-35 year old college students who were suffering from premenstrual syndrome were enrolled in the study. Comparing the mean score of the intensity of the syndrome between the two groups after the first and the second menstruation cycles showed a decrease in the intervention group to 13.9 (p-value<0.001; 95% CI: 16.5,-11.4) and 9.8 (p-value<0.001; 95% CI: 12.4,-7.3), respectively. Conclusion Results of the study showed that, in general, Anise was effective in decreasing the symptoms of premenstrual syndrome in comparison to placebo.

Histone deacetylase inhibitory and cytotoxic activities of the constituents from the roots of three species of Ferula.

OBJECTIVES: Histone deacetylase inhibitory and cytotoxic activities of 18 naturally occuring terpenoids (ferutinin, stylosin, tschimgine and guaiol), coumarins (umbelliprenin, farnesiferone B, conferone, feselol, ligupersin A, conferdione, conferoside) and sulfur-containing derivatives (latisulfies A-E, persicasulphides A and C) from the roots of three species of Ferula (Ferula latisecta, Ferula ovina and Ferula flabelliloba) were evaluated. MATERIALS AND METHODS: The cytotoxic activity of compounds was evaluated against human cancer cell lines (HeLa, HCT116, A2780 and A549) by AlamarBlue® assay using vorinostat as the positive control. On the other hand, we aimed to evaluate their inhibitory activities against pan-HDAC. RESULTS: The methanolic extract of the roots of F. flabelliloba was subjected to silica gel column chromatography. Further purification by preparative thin-layer chromatography (PTLC) and semipreparative RP-HPLC yielded twelve known compounds (1-12). This is the first report on the isolation of guaiol (1), persicasulphide C (3) and conferoside (10) from the roots of F. flabelliloba. Six compounds including persicasulfide A, conferone, feselol, latisufide C, conferoside and ferutinin showed cytotoxic activity with IC50 values in the range of 11.61-49.40 µM against cancer cells and pan-HDAC inhibitory activity with IC50 values in the range of 1.06-35.27 µM. CONCLUSION: Results indicated that persicasulfide A (2), conferone (6) and feselol (7) showed moderate cytotoxicity with IC50 values in the range of 11.76-39.24 µM against cancer cells and potent pan-HDAC inhibitory activity with IC50 values in the range of 1.06-10.73 µM. Conferone was more active than others with a higher potency for HDAC inhibition (1.06- 1.17 µM).

Effects of a combination of Nigella sativa and Vitex agnus-castus with citalopram on healthy menopausal women with hot flashes: results from a subpopulation analysis.

The goal of the current study was to evaluate the efficiency of a phytotherapeutic intervention consisting of a combination of Nigella sativa and Vitex agnus-castus with citalopram in the control of hot flashes in healthy menopausal women. An 8 week, double-blind, randomized, placebo-controlled study was performed among 46 women aged between 40 and 60 years experiencing an average of more than four hot flashes per day recruited during July 2016 to June 2017. Data on severity of vasomotor symptoms were collected at the end of the eighth week. Herbal medication or placebo capsules were administered once daily in morning. At the end of the 8-week treatment period, analyses of covariance demonstrated the superiority of herbal combination with citalopram over placebo and citalopram for three MENQOL domain scores including vasomotor (p < .001), physical (p = .036), psychosocial (p = .001) but no significant differences were observed in terms of sexual function (p = .231). Based on the results, the addition of a combination of N. sativa and V. agnus-castus to the citalopram may be a potential clinical application for improving therapeutic outcomes. Larger randomized, controlled trials are also warranted for further investigations of these symptoms.

Effect of Cuscuta epithymum Acquainted with Risperidone on the Improvement of Clinical Symptoms and Cognitive Impairment in Patients with Schizophrenia: A Triple-Blind Randomized Placebo-Controlled Trial.

BACKGROUND: Cuscuta epithymum (CE) is an established medicinal herb utilized for treating psychosis in Persian medicine. The aim of this study was to investigate the effect of CE combined with risperidone on the clinical symptoms and the cognitive impairment in patients diagnosed with schizophrenia. MATERIALS AND METHODS: In this triple-blind randomized placebo-controlled trial, the intervention group received a dose of 500 mg of CE in the form of a capsule to be taken twice a day accompanied by an appropriate dose of risperidone. The control group was presented with a placebo identical to that of the CE capsule plus the allocated dose of risperidone. The PANSS and SCoRS questionnaires were used to assess the status of subjects prior to the initiation of the intervention as well as being put to use at the end of the second, fourth, and eighth week post-intervention. Registering and recording intel concerning positive and negative symptoms felt by participants (PANNS), and a test to assess the cognitive impairment of the individuals. RESULTS: After eight weeks of treatment, all negative and positive symptoms besides hostility and somatic concern exhibited a significant improvement in the CE group (P <0.05). In contrast, the CE placebo group displayed no substantial improvement in the cases of the positive, negative and general symptoms (P>0.05) regarding cognitive impairment, after eight weeks of treatment, all symptoms were greatly improved in the CE group (P<0.05), while the effect of the placebo on the patients cognitive impairment remained mostly stationary (P>0.05). Consequently, after eight weeks after the intervention, we can determine that the CE treatment has been noticeably more effective at improving positive, negative and cognitive symptoms of patients with schizophrenia. CONCLUSION: The results of this study demonstrated that CE, possessing possible antioxidant and neuroprotective properties, safely improved the positive and negative symptoms, and cognitive impairment of patients with schizophrenia.

Topical application of Cassia fistula L. fruit gel in management of cutaneous lesions of pemphigus vulgaris: A double-blind, placebo-controlled clinical trial.

OBJECTIVE: Cassia fistula L. fruit extract has been traditionally used in the treatment of pemphigus vulgaris (PV) lesions in Iran. The aim of this study was to determine the efficacy of C. fistula fruit gel on healing time of PV lesions in a clinical setting. MATERIALS AND METHODS: This was a randomized, double-blind placebo-controlled clinical trial that was performed in dermatology ward at Saadi hospital, affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. Right- or left- sided lesions of PV patients on standard systemic treatment were randomized for treatment with either C. fistula fruit gel or placebo prescribed twice daily. The largest diameter of each lesion was measured at the baseline (day 0) and on days 10 and 20. Epithelialization Index (EI), as outcome measure was calculated and compared between the two groups. RESULTS: The present study comprised 20 patients, with overall 82 cutaneous lesions including 41 lesions in the C. fistula fruit gel group and 41 lesions in the placebo group. The EI in the C. fistula fruit gel group was significantly higher than that of the placebo group both on day 10 (65±28vs 30±34; p=0.001) and at the end of the study (91±22 vs 69±49; p=0.003). CONCLUSION: Topical application of C. fistula fruit gel can be considered as an effective adjuvant therapy in treatment of PV.

Investigation of phenolic compounds and antioxidant activity of leaves extracts from seventeen cultivars of Iranian olive (Olea europaea L.).

The leaves of seventeen cultivars of olive growing in the north of Iran were investigated for total phenol content and antioxidant activity. The identification and quantification of main phenolic compounds were performed by reverse phase high performance liquid chromatography with diode array detector. The cultivars Kalamon, Gordal, and Coratina contained the highest concentration of phenolic compounds (190.65 ± 0.03, 184.72 ± 0.001, and 155.91 ± 0.06 mg GAE/g extract, respectively). The maximum radical scavenging activities were found in Gordal, Coratina, and Kalamon extracts (IC50 20.66, 22.95, and 26.74 µg ml-1, respectively). The extracts of Mishen, Fishomi, and Arbequina (1971.37 ± 0.007, 1794.57 ± 0.001, and 1760.57 ± 0.005 µmol Fe II/g dried extract, respectively) showed highest antioxidant activity in FRAP assay. The identification analysis demonstrated the present of vanillin, rutin, luteolin 7-O-glucoside, oleuropein, and quercetin. The highest oleuropein concentrations were detected in cultivars Mishen, Beleidi, Kalamon, and Roghani while it was not detected in cultivars Conservolea, Amigdalolia, Leccino, and Fishomi.

Antioxidant and Larvicidal Activity of Areal Parts of Scrophularia striata against Malaria Vector Anopheles stephensi.

BACKGROUND: Scrophularia striata is a perennial plant which is native in all parts of Iran, Turkey, and Azerbaijan. In this study, the total phenol content, antioxidant and larvicidal activities of total extract and different fractions of this plant were evaluated. METHODS: The aerial parts of S. striata were collected from Boli village, Illam Province, western Iran in Apr 2013. The total phenol content of total extract and different fractions were evaluated by Folin-Ciocalteu method. Moreover, antioxidant activity was tested by DPPH and FRAPS assays. Larvicidal activity was investigated according to standard method described by WHO. RESULTS: Ethyl acetate fraction (EF) had the highest content of total phenol (75.9±0.06mg Gallic acid equivalent/g dry extract). Furthermore, among the tested extract, methanol-water fraction (MWF), total methanol extract (TME) and water fraction (WF) showed the highest antioxidant activity in the DPPH assay (IC50= 226.8, 283.66 and 299.4 µg.ml-1, respectively). In FRAP assay MWF and WF and TME had the highest antioxidant activities (664.4±0.002, 565.3±0.003, 519.5±0.003mmol FeII/g dry extract, respectively). Ethyl acetate fraction had maximum larvicidal activity (LC50 49.1ppm) followed by TME (LC50 64.26ppm) and hexane fraction (HF) (LC50 89.69). CONCLUSION: Scrophularia striata collected from west of Iran illustrated considerable antioxidant and larvicidal effects and further in vitro and in vivo experimental models for investigation would be required.

Effect of vaginal suppository on bacterial vaginitis based on Persian medicine (Iranian traditional medicine): a randomised double blind clinical study.

This trial was conducted on 127 women aged 18-50 years with bacterial vaginosis to compare the vaginal suppository of metronidazole with Forzejeh, a vaginal suppository of herbal Persian medicine combination of Tribulus terrestris, Myrtus commuis, Foeniculum vulgare and Tamarindus indica. The patients (63 in metronidazole group and 64 in Forzejeh group) received the medications for 1 week. Their symptoms including the amount and odour of discharge and cervical pain were assessed using a questionnaire. Cervical inflammation and Amsel criteria (pH of vaginal discharge, whiff test, presence of clue cells and Gram staining) were investigated at the beginning of the study and 14 days after treatment. The amount and odour of discharge, Amsel criteria, pelvic pain and cervical inflammation significantly decreased in Forzejeh and metronidazole groups (p = <.001). There was no statistically significant difference between the metronidazole and Fozejeh groups with respect to any of the clinical symptoms or the laboratory assessments. This study showed that Forzejeh, which is an herbal Persian medicine preparation, has a therapeutic effect the same as metronidazole in bacterial vaginosis. Impact statement What is already known on this subject? Bacterial vaginosis (BV) is a common problem in women. Common antibiotics for the treatment of BV include: metronidazole, tinidazole and clindamycin. Unfortunately, treatments often occur with a recurrence and failure. Therefore, alternative treatments are necessary. Many natural treatments are recommended for this condition in Persian Traditional Medicine sources. One of them is the vaginal suppository "Forzejeh" which is the combination of Tribulus terrestris, Myrtus commuis, Foeniculum vulgare and Tamarindus indica. These plants have antimicrobial activities. Forzejeh has been used for the treatment of BV in folk medicine for many years and has been formulated and standardised recently. What do the results of this study add? This study showed that the therapeutic effect of Forzejeh on bacterial vaginosis is similar to metronidazole. What are the implications of these findings for clinical practice and/or further research? A clinical study with a longer follow-up time is suggested for assessing the recurrence of BV after treatment with Forzejeh metronidazole.

Effect of Onopordon acanthium L. as Add on Antihypertensive Therapy in Patients with Primary Hypertension Taking Losartan: a Pilot Study.

Purpose: Onopordon acanthium L. is known for its medicinal properties. Our recent study showed that its seed extract is a novel natura angiotensin-converting-enzyme inhibitor (ACEI). This study was carried out to investigate its possible antihypertensive effects in patients receiving losartan. Methods: This uncontrolled clinical trial was carried out among 20 patients (30-60y) with uncontrolled hypertension despite receiving 50 mg losartan (stage I & II) in two hospitals in Iran. After completing informed consent, patients were treated by 2 capsules [each 1g of Onopordon acanthium seed extract (OSE)] as add-on therapy, two times per day. Results: 18 patients completed the study (50.94 ±8.37y). Mean systolic blood pressure (SBP) at the baseline was 151.9 ± 13.74mmHg and at the end of the study, it was 134.6 ± 18.25 mmHg and mean diastolic blood pressure (DBP) was 97.41 ± 10.36 at the baseline and was 85.71 ± 7.481 after 8 weeks. OSE significantly reduced SBP and DBP at the end of 8 weeks (P=0.003, 95% CI: -19.7, -15.1; P=0.0006, 95% CI: -10.23, -13.15; respectively). No evidence of hepatic or renal toxicity was detected. Conclusion: Based on the results of this study OSE has antihypertensive property with no significant adverse effects. However, because of the low number of samples, this medication may be not safely administered. The results of this study could be the basis for further studies with larger sample size. IRCT registration number: IRCT2013020712391N.

Efficacy and safety of Amla (Phyllanthus emblica L.) in non-erosive reflux disease: a double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal complaints. GERD, caused by the reflux of stomach contents into the esophagus, leads to troublesome symptoms such as heartburn and regurgitation. It is classified into two types: erosive esophagitis, characterized by visible esophageal mucosa erosion in endoscopy, and non-erosive reflux disease (NERD). GERD is a chronic and recurrent disease that impairs the quality of life and imposes socioeconomic and therapeutic burdens to both patients and society. OBJECTIVE: Due to the failure of the conventional treatments for GERD and to the traditional use of Amla (Phyllanthus emblica L.), in addition to beneficial effects shown in recent studies, we evaluated the safety and efficacy of Amla tablet for improvement of symptoms of patients with NERD. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We designed a double-arm, randomized, double-blind, placebo-controlled clinical trial. Sixty-eight patients who had classic symptoms of GERD (heartburn, regurgitation and epigastralgia) for at least three months before the start of the trial were randomized in two parallel groups. Patients in the Amla group received two 500 mg Amla tablets twice a day, after meals, for 4 weeks. In the control group, patients received placebo tablets similar to the Amla prescription. MAIN OUTCOME MEASURES: The patients were visited at baseline, and at the end of the 2nd and 4th weeks of intervention; their symptoms were measured on a frequency and severity scale for the symptoms of NERD, according to the quality of life in reflux-associated disease questionnaire. RESULTS: Frequencies of heartburn and regurgitation in both groups of the study were significantly reduced after intervention (P < 0.001). Repeated measures logistic regression analysis showed that, in the Amla group, there was a more significant reduction in regurgitation frequency, heartburn frequency, regurgitation severity and heartburn severity during the study period, compared with the placebo group (P < 0.001). CONCLUSION: This randomized double-blind, placebo-controlled clinical trial demonstrated that Amla could reduce frequencies of heartburn and regurgitation and improve heartburn and regurgitation severity in patients with NERD. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT2016061428469N1.

Sulfur-containing compounds from the roots of Ferula latisecta and their cytotoxic activities.

Five new sulfur-containing compounds, with a new geometry (cis) of the propenyl moiety, and five known compounds were isolated from the roots of Ferula latisecta. The structures of these compounds, were elucidated on the basis of spectroscopic data including 1D and 2D NMR experiments and HRMS. All of the isolated compounds were tested against A2780, A549, HeLa, and HCT116 human cancer cell lines and some of them showed moderate cytotoxic activities.

Antihypoxic activities of Crataegus pentaegyn and Crataegus microphylla fruits-an in vivo assay

ABSTRACT The aim of this study was to evaluate anti-hypoxia activity of polyphenolic extracts of Crataegus microphylla and Crataegus pentaegyn on mice. Three experimental models of hypoxia were considered, including asphyctic hypoxia, haemic hypoxia, and circulatory hypoxia. Polyphenolic extract of both plants exhibited significant anti-hypoxic activity and prolonged animal survival time. Anti-hypoia activity of C. pentaegyn was found to be superior to that of C. microphylla in circulatory and asphyctic hypoxia. Antihypoxic activity of these extracts may be attributed to their phenolic compounds.

Protective Effect of a Polyherbal Traditional Formula Consisting of Rosa damascena Mill., Glycyrrhiza glabra L. And Nardostachys jatamansi DC., Against Ethanol-induced Gastric Ulcer.

"VARD" formula consisting of Rosa damascena Mill. (Rosaceae) petals, and rhizomes of Glycyrrhiza glabra L. (Papilionaceae) and Nardostachys jatamansi DC. (Valerianaceae), has been proposed for gastric ulcer in Iranian traditional medicine. We investigated the antiulcer activity of each plant separately and in combination. The biochemical and molecular functions of extracts were also evaluated. Each plant hydroalcoholic extract was standardized via determination of total phenolic and flavonoid contents, also via some phenolic compounds determination and specially glycyrrhizic acid in G. glabra by using HPLC. Rats received orally extracts of the plants (20, 40 and 80 mg/Kg) and "VARD" (45 mg/Kg) 1 h before ethanol administration. Two h after receiving ethanol, animals were sacrificed; the stomach was removed for macroscopic and microscopic assessment. Also heme-oxygenase-1, glutathione, and catalase were measured in the gastric tissue of the rats pretreated by "VARD" and dose of 20 mg/Kg of extracts. Among three extracts, R. damascena and G. glabra contained more total phenolic and flavonoid content respectively. Gallic acid was prominent compound in R. damascena. The extracts of R. damascena, G. glabra, and N. jatamansi significantly decreased ulcer index. ED50 values were 8.2, 31.86 and 25.08 mg/Kg respectively. "VARD" significantly decreased ulcer index compared to 20 mg/Kg of G. glabra (p < 0.0001) and N. jatamansi (p < 0.001). Pretreatment with "VARD" and each plant extracts (20 mg/Kg) increased glutathione, catalse and heme-oxygenase-1 significantly (p < 0.05) in comparison with control group. Our findings indicate that "VARD" partly via antioxidant activity can be considered as an effective antiulcer formula.

Evaluation of phytochemicals, antioxidant and burn wound healing activities of Cucurbita moschata Duchesne fruit peel.

OBJECTIVES: Cucurbita moschata Duchesne (pumpkin) is a well-known plant with several pharmacological effects. The aim of the present study was to assess burn wound healing activity of C. moschata peel extract (CE). Also, standardized CE was assessed for antioxidant activity and antibacterial effects against major pathogens of burns. MATERIALS AND METHODS: Healing properties of topical preparation of 10% and 20% concentrations of CE were assessed on second degree burn in rats during a 14-day period as well as histological studies, total antioxidant power, lipid peroxidation and total thiol content of skin tissue samples. RESULTS: Radical scavenging IC50 and ferric-reducing antioxidant power value were 4.015±0.20 mg/ml and 142.63±2.65 mmol Fe2+/g, respectively. Total mucilage content was 13.8%. The optimal results were obtained by 20% CE that showed 90.80±5.86 % wound closure and tissue repair as well as significant reduction of tissue oxidative stress biomarkers. Histological analyses confirmed wound healing activity of pumpkin peel extract. CONCLUSION: Considering the high mucilage content of the plant, providing a moist environment for wound, C. moschata peel extract could be a natural remedy for treatment of burns. Further clinical studies are suggested to confirm C. moschata peel extract as a wound healing agent.