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Effective parenteral and enteral amino acid replacement is crucial for critically ill patients with altered amino acid metabolism. This study aimed to assess the effects of l-citrulline supplementation on the clinical and laboratory outcomes in critically patients.This was a double-blind placebo-controlled randomized clinical trial. 82 critically ill patients who were expected to receive mechanical ventilation for more than 72 hours were selected. The patients were assigned to either a placebo or an intervention group. The patients in the placebo group received 10 gr of microcrystalline cellulose and the ones in the intervention group were given l-citrulline daily for 7 days. Serum levels of fasting blood sugar (FBS), lipid profile, hepatic enzymes, serum electrolytes, urea nitrogen, creatinine, and C-reactive protein (CRP) were evaluated before and after the intervention. Duration of invasive ventilation, intensive care unit (ICU) length of stay, ventilator-free days, and 28-day mortality rate were recorded and compared between groups.Eighty-two patients completed the trial. No statistically significant differences were observed between the two groups in terms of age (p = 0.46), sex (p = 0.49), body mass index (BMI) (p = 0.41), Sequential Organ Failure Assessment (SOFA) Score (p = 0.08), Clinical Pulmonary Infection Score (CPIS) score (p = 0.76), Acute Physiology and Chronic Health Evaluation (APACHE II) score (p = 0.58), risk factors (p = 0.13), ICU stay before randomization (p = 0.32), and reason of admission (p = 0.50) before the intervention. Citrulline group had a notable reduction in FBS (p = 0.04), total cholesterol (TC) (p = 0.02), low density lipoprotein (LDL-C) (p0.001) and high-sensitivity CRP (hs-CRP) (p0.001). Also, a significant increase in lactate dehydrogenase (LDH) concentration (p0.001) was observed in the intervention group at the end of the trial. Total duration of invasive ventilation and the mean SOFA score on 7th day were significantly lower in the citrulline group compared to the control group. Moreover, a significant increase in days alive and ventilator-free days within 28 days after admission was found in the citrulline group at the end of the trial. Also, there were no significant differences between the groups in terms of mortality rate during intervention, serious adverse events, endotracheal intubation, the use of tracheotomy or non-invasive ventilation after extubation, length of ICU stay, ICU-free days at 28 days, and CPIS and APACHE II scores. For mortality, in the citrulline group, there was two deaths compared to eight deaths in the control group. This resulted in an absolute risk reduction (ARR) of 14.05% (95% CI: 0.39-27.71%) and a number needed to treat (NNT) of 7.1 (95% CI: 3.6-29.5), regarding mortality.The results of the present study demonstrated the probable positive effects of citrulline supplementation on lipid profile, hs-CRP levels, duration of invasive ventilation, and SOFA score. Also, l-citrulline consumption may increase the probability of survival without mechanical ventilation.

Cardiovascular diseases (CVD) are the leading causes of mortality worldwide. Flow-mediated dilation (FMD) is a marker of vascular function. Beneficial cardiometabolic effects of Nigella sativa (N. sativa) have been observed. We evaluated the effect of N. sativa oil on FMD, plasma nitrite, and nitrate (NOx) as nitric oxide (NO) metabolites, and inflammatory markers in subjects with CVD risk factors. Fifty participants were randomly assigned to either the N. sativa (two capsules of 500 mg N. sativa oil) or the placebo group (two capsules of 500 mg mineral oil), for 2 months. The brachial FMD, plasma NOx, vascular cellular adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) were measured. FMD and plasma NOx levels was significantly increased in the N. sativa group compared to the placebo group (changes: 2.97 ± 2.11% vs. 0.71 ± 3.19%, p 0.001 for FMD and 4.73 ± 7.25 μmol/L vs. 0.99 ± 5.37 μmol/L, p = 0.036 for plasma NOx). However, there was no significant difference in ICAM-1 and VCAM-1 levels between groups. Therefore, N. sativa oil improves vascular NO and FMD in subjects with cardiovascular risk factors. However, more studies are warranted to confirm the beneficial impacts of the N. sativa oil on vascular inflammation.

The aim of this study was to evaluate the analgesic and anti-inflammatory effects of the hydroalcoholic extracts of Malva sylvestris flowers or Carum carvi and Medicago sativa seeds, alone and in combination, which have been used in traditional Iranian medicine.Male Wistar rats were divided into 6 treatment groups: distilled water, sodium salicylate (SS), M. sylvestris extract (600 mg/kg), C. carvi extract (600 mg/kg), M. sativa extract (300 mg/kg) and combined extract (including 300 mg/kg M. sylvestris and C. carvi extracts, and 150 mg/kg M. sativa extract). The formalin pain model was used to evaluate the antinociceptive effects of the treatments. For anti-inflammatory effect, acute (one hour after injection) and chronic (during a week after injection) paw inflammation was measured after subcutaneous injection of 2.5% formalin in the hindpaw. Finally, tissue samples from all groups were prepared for histopathological studies.The combined extract significantly inhibited the nociception in the acute phase of the formalin test (P 0.001). In the chronic phase, all the extracts and SS had significant analgesic effect (P 0.001). Analgesic activity of the combined extract was significantly stronger than SS (P 0.01). In the acute inflammation model, M. sylvestris, C. carvi and the combined drug had significant inhibitory effects against paw edema (P 0.05). All extracts, individually and in combination, significantly alleviated chronic paw inflammation (P 0.01). The combined extract had much more anti-inflammatory activity than SS (P 0.05). Histopathological results indicated improvement and reduction of inflammatory factors in the treatment groups.M. sylvestris, C. carvi and M. sativa have analgesic and anti-inflammatory properties. Potentially, each of these extracts or a mixture of them might be a valuable alternative drug to control pain and inflammation.

Background: Wound healing is an active and complex process. Wounds cause serious problems in many cases, while there is no fast and reliable cure method. Numerous medicines, mostly as ointments, have been used to treat wounds. However, they can have some defects, limitations, and side effects. Therefore, exploration for new natural compounds for curing wounds is important. Traditional Iranian Medicine (TIM) is becoming popular, which can return patients to health with minimal side effects. Pomegranate is well reported for its medicinal properties. In TIM, Punica granatum fruits have been used to treat inflammatory disorders and wounds. Methods: In this study, 60 Wistar rats (male, 180±10 g) were used. The rats were randomly divided into five groups (each containing 12), including Eucerin as control; phenytoin as standard drug; the top layer of pomegranate peel (peel), pomegranate pulp (pulp), and peel + pulp as investigation groups. The back skin of deeply-unconscious animals was wounded (2 cm long). For 14 days from wound establishment, the wounds were treated topically with the medicines above. Wound length and improvement percentage were investigated by analyzing images of wounds. Three rats of each group were killed on days 3,7,10 and 14, and then the wounded skin were cut at a certain area for pathological studies. Epithelization; neovascularization; fibroblast, PMN and macrophage count were investigated. Results: All groups had significant (P

Background: The emergence of drug-resistant strains of herpes simplex virus type 1 (HSV-1) has been increasingly reported. Therefore, attempts to discover new antiviral agents in particular from natural compounds are required. In this study, we evaluated the possible inhibitory effects of hydroalcoholic extract of Sambucus ebulus (S. ebulus ) against HSV-1. Methods: S. ebulus extract was produced by maceration method. MTT assay was used to evaluate the cytotoxicity effects of the S. ebulus extract; also, antiviral effects were measured both by test TCID50 and quantitative real-time PCR methods. To study the inhibitory impact of S. ebulus extract on the expression of HSV-1 antigens, indirect immunofluorescence assay (IFA) was also performed. All analyses were performed using the GraphPad Prism software v. 7.0. Results: In the postexposure assay of HSV-1 with S. ebulus extract at the highest nontoxic concentration (75 μg/mL), S. ebulus extract led to 2.6 log10 TCID50 reduction in infectious virus titer. At the highest nontoxic concentration, the S. ebulus extract led to inhibition rates of 91.2%, based on the quantitative real-time PCR assay results (p

Walnut green husk (WGH) has been mentioned as a wound-healing agent in traditional Iranian medicine. Although previous studies indicated that WGH is a good source of pharmaceutical ingredients, they did not assess its wound healing activity; so the present study set out the scientific validation of the wound healing potential of the Persian walnut. Total phenolic content, reducing power, DPPH, and nitric oxide scavenging activity of aqueous ethanol extract of WGH was evaluated. Forty-eight male Wistar albino rats were divided into four groups of 12 each. An incision wound was created on the dorsal region of each rat. WGH extract (20% w/w), WGH burnt residues (20% w/w), Eucerin, and Phenytoin ointments were used in each group. Wound length, contraction percentage, and histopathological evaluations were recorded on days 3, 7, 10, and 14. Total phenolic content and EC50 values of reducing power, DPPH and nitric oxide scavenging activity of the WGH extract were 61.34 ± 0.64 mg/g dry extract, 0.95 ± 0.02 mg/mL, 0.35 ± 0.01 mg/mL, and 0.28 ± 0.01 mg/mL, respectively. Treated animals with WGH extract showed significantly (p ≤ 0.05) better results for physical and pathological parameters compared to the control group; overall, WGH extract showed better results than WGH burnt residues. The present study indicated that the WGH aqueous ethanol extract has a promising potential for wound healing in the animal model and could be a valuable resource for developing new wound-healing medicines for humans.

Background: One of the most significant symptoms in many acute and chronic diseases is pain. While many researches reveal side effects of many synthetic analgesic drugs, which are commonly used, new surveys are searching for new alternative analgesic drugs (especially by use of medicinal plants) with few side effects. Objectives: This study was designed to evaluate the analogous function of Ficus carica L. (one of the important medicinal plants in Persian medicine) as an anti-nociceptive in allopathic medicine. Methods: Subcutaneous injection of formalin in rat paw was performed to establish the pain. Formalin test was applied to assess the severity of pain every 15 seconds for one hour. In two parts of this study, two different types of Ficus extract were used in intraperitoneal injections; the aqueous boiled Ficus extract (500, 1000, 2000 mg/kg) in comparison with distilled water (DW) and the petroleum ether extract (500, 1000 mg/kg) in comparison with DMSO. Results: The aqueous boiled Ficus extract showed no significant difference between control (DW) group and groups that had received extracts (P > 0.05). While a significant difference between the petroleum ether extract (1000 mg/kg) and the DMSO group in the last five minutes of the study (P < 0.05) was recorded. Anti-inflammatory examination of aqueous and ethanolic extract of Ficus fruit showed no anti-inflammatory effect; however, the petroleum ether extract displayed a dose-dependent (1000 mg/kg) anti-inflammatory effect even in comparison with sodium salicylate. Conclusions: According to the achieved results, it was concluded that there are no anti-nociceptive and anti-inflammatory effects of Ficus carica fruit aqueous extract on the formalin test in the male rat paw in doses mentioned above. However, there is a delayed anti-nociceptive effect dose-dependently and a dose-dependent anti-inflammatory effect of petroleum ether extract.

One of the most important issues which medical science has been facing is wound healing for the tissue repair with the least complications. In this study, we aimed to isolate, purify and quantitate tannins and phenolic compounds from exocarp and pulp of fruits of Iranian pomegranate cultivars. Our findings demonstrate that the highest amount of tannin extracts from ethanol extract of the black peel exocarp was 201.76 ± 1.93. The highest amount of flavonoids from the ethanol extract of Sweet Alac exocarp was119.69 ± 1.02 as well as antioxidant compounds activity in the exocarp and pulp showed that the highest activity is in the ethanol extract of the black peel was 95.65 ± 3.1. The total phenolic activity indicated that the Sour white peel ethanol extract has the highest phenolic activity 327.05 ± 863. Our data suggest that the ethanol extract of pomegranate exocarp has the higher amounts of tannins and flavonoids, compounds that are known to be beneficial for wound healing. Taken together, these data suggest that compounds isolated from Iranian pomegranate cultivars offer new options for managements of wound healing.

Ajowan, thyme and fenugreek are spice and aromatic crops with a number of medicinal properties which are known as important sources of essential phytochemicals. The purpose of this study was to investigate the antioxidant capacity, total phenolic content and antifungal activities of these plant extracts on growth of Fusarium solani, an important plant pathogen, soil saprophyte and one of the causal agents of fusariosis in human and animals. Their total antioxidant activity was measured using DPPH radical scavenging assay and their antimicrobial activity was determined through poison food assay at two concentrations (1000 and 1500 ppm) and spore germination assay in vitro. All methanolic extracts showed high antioxidant activity which among them methanolic extract of thyme demonstrated higher antioxidant potential with a low IC50 (16.50 mg ascorbic acid/g). Also, the highest phenolic content (70.55 mg GAE g-1) was observed in methanolic extract of thyme. The highest and lowest amount of thymol was determined in methanolic extract of thyme and aqueous extract of ajowan. Methanolic extracts of thyme leaves and ajowan seeds at concentration of 1500 ppm were potentially effective against F. solani over the control treatments by 90.33% and 85.73%, respectively. Followed by hydro-ethanolic and aqueous extracts exhibited a lesser percentage of inhibition. The MIC value for methanolic extract of thyme and ajowan was 3.75 mg/ml followed by hydro-ethanolic and aqueous extracts, respectively. The amount of calculated MFC was ranging from 7.5 to 30 mg/ml for thyme methanolic and fenugreek aqueous extracts, respectively.

The present study was conducted to assess the antifungal activity of essential oils of medicinal plants Mentha piperita (peppermint), Foeniculum vulgare, Satureja hortensis (Savory), Ferula asafoetida and Cuminum cyminum against Alternaria sp., Bipolaris sorokiniana and Acremonium sclerotigenum. The antifungal activity was evaluated by Broth Microdilution Method. Minimum Inhibitory Concentration (MICs) and Minimum Fungicidal Concentration (MFCs) of the essential oils were compared with Amphotricin B and Captan as standard drug. MIC values for all essential oils were between 1 to 8 mg/mL. MIC value of Fennel essential oil was comparable to MFC value obtained from fungicide Captan. Peppermint essential oil exhibited maximum inhibitory and fungicide activity in concentrations of 2 mg/ml and 4 mg/ml against Alternaria sp. The essential oil was more effective than Fennel against Bipolaris, but MFC values of both essential oils were 4 mg/ml. C. cyminum displayed less susceptibility against all of the fungi. Regarding our finding, peppermint and Fennel oil seem to be a promising solution to control plant diseases.

We sought to determine the effect of ischemic preconditioning (IPC) and hirudotherapy (leech therapy) on cutaneous pedicle flaps after they underwent prolonged ischemia (global ischemia) in a mouse model. Twenty cutaneous pedicle flaps were elevated in 20 mice, and the animals were randomized into four groups: sham, control, IPC and leech (5 flaps in each group). Except in the sham group, all flaps were subjected to global ischemia for 5 h via pedicle clamping. The control group did not receive any treatment before or after global ischemia. In the IPC group, global ischemia was preceded by three 10-min episodes of ischemia, each followed by 10 min of reperfusion. In the leech therapy group, after global ischemia, hirudotherapy was performed. Flap survival area and histopathological changes were evaluated on the 10th day after surgery. Flap survival areas were significantly higher in both the IPC and leech groups than in the control group and were significantly higher in the leech group than in the IPC group (p < 0.05). In conclusion IPC and hirudotherapy had definite effects on the survival area of cutaneous pedicle flaps that underwent prolonged ischemia in a mouse model.

Background: The aim of this study was to investigate the effects of leech therapy (LT), in comparison with topical phenytoin (PHT), on incisional skin-wound healing in animal models. Methods: This experimental study included 15 male rats (5 animals in 3 groups) with approximately equal body weights (350 10 g). Skin wounds with lengths of 20 mm and depths of 0.5 mm were made on the dorsolateral region of rats 4 cm from the spine. The first group (PHT group) was treated daily with topical PHT (1%) while the second group (LT group) received LT at the beginning of the experiment. The control group received neither the drug nor the therapy. Wound healing was evaluated every day, and the study was continued until the wound had completely healed. Changes in the areas and the appearances of the skin wounds and histological differences (at the end of the experiment) were used to investigate the differences in wound healing among the groups. Results: The process of wound healing was significantly faster in the group treated with LT (p < 0.05) than in the group treated with the PHT. Conclusion: The study results showed that LT improved incisional skin-wound healing in rats.

The phenomenon of inflammation is the base of many acute and chronic diseases. New effective antiinflammatory drugs are needed to battle side effects of acute and especially chronic inflammation and incomplete treatment of patients suffering from these side effects. For this purpose, in the present study, we evaluated Ruta graveolens L. (R. graveolens) as a folk herb for treatment of inflammation.In an experimental-interventional study, anti - inflammatory effects of R. graveolens, a Persian Medicine (PM) plant, were examined with formalin-induced hind paw edema model in rats. Sodium Salicylate (300mg/kg, ip, SS) was injected as a positive control group and compared with three doses of methanolic extract of R. graveolens (Meth) (50, 100 and 200 mg/kg; i.p.), two doses of ethanolic extract of R. graveolens (Eth) (50 and 100 mg/kg; i.p.) and a group of distilled water (6 mL/kg; i.p.).The results showed that R. graveolens has acute and chronic anti-inflammatory properties and prevents inflammation. These effects were found to be effective like SS.

OBJECTIVE: Echinophora platyloba DC is a widely used herbal medicine and food seasoning in Iran. It is claimed to exert antimicrobial, antifungal, and antispasmodic effects. Despite the prevalent use of this plant as a food and medicine, there are no reports on its possible toxic effects. To evaluate the safety of E. platyloba, we tested its acute and sub-chronic toxicity in male and female Wistar rats. METHODS: Rats were orally treated with four different single doses of E. platyloba total extract and screened for signs of toxicity two weeks after administration. In the sub-chronic toxicity study, E. platyloba was administered for 45 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological markers were monitored during the study. RESULTS: We found no mortality and no abnormality in clinical signs, body weight, or necropsy findings in any of the animals in the acute study. The results of the subchronic study showed no significant difference in hematological parameters in either sex. There was a significant increase in lactate dehydrogenase in the female groups. A significant increase in the relative lung weight of female rats was noted at 500 mg/kg. Histopathological examinations revealed intra-alveolar hemorrhage in the male rats (500 mg/kg). In the females, congestion of the alveolar capillaries (at 500 mg/kg) and liver bridging necrosis (at 200 mg/kg) were significantly increased. CONCLUSION: The no observed adverse effect level of E. platyloba was determined to be 200 and 50 mg/kg for male and female rats, respectively.

Background: “Teucrium polium L.” (TP) has been long recommended in Iranian folk medicine for its anti-diabetic activities. We attempt here to evaluate the effect of TP extract on insulin secretion in rat pancreas. Methods: Rat pancreas was isolated in situ and perfused with Krebs solution containing low glucose (LG, 2.8 mM) or high glucose (HG, 16.7 mM) as perfusate. The aqueous extract (Aq. E) and methanolic extract (Met. E) of TP aerial parts and two partition fractions of Met. E were added to perfusate to evaluate insulin release. Diazoxide (DZX) and verapamil (VPM) were also used for assessing the probable mechanism of the effects. In each experimental group, the peak and baseline of insulin levels in effluent samples were compared. The GC/MS analysis was carried out to detect active ingredients in the extracts. Results: Adding Met. E to the LG caused a significant increase (P