First Iranian guidelines for the diagnosis, management, and treatment of hyperlipidemia in adults.

This guideline is the first Iranian guideline developed for the diagnosis, management, and treatment of hyperlipidemia in adults. The members of the guideline developing group (GDG) selected 9 relevant clinical questions and provided recommendations or suggestions to answer them based on the latest scientific evidence. Recommendations include the low-density lipoprotein cholesterol (LDL-C) threshold for starting drug treatment in adults lacking comorbidities was determined to be over 190 mg/dL and the triglyceride (TG) threshold had to be >500 mg/dl. In addition to perform fasting lipid profile tests at the beginning and continuation of treatment, while it was suggested to perform cardiovascular diseases (CVDs) risk assessment using valid Iranian models. Some recommendations were also provided on lifestyle modification as the first therapeutic intervention. Statins were recommended as the first line of drug treatment to reduce LDL-C, and if its level was high despite the maximum allowed or maximum tolerated drug treatment, combined treatment with ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, or bile acid sequestrants was suggested. In adults with hypertriglyceridemia, pharmacotherapy with statin or fibrate was recommended. The target of drug therapy in adults with increased LDL-C without comorbidities and risk factors was considered an LDL-C level of <130 mg/dl, and in adults with increased TG without comorbidities and risk factors, TG levels of <200 mg/dl. In this guideline, specific recommendations and suggestions were provided for the subgroups of the general population, such as those with CVD, stroke, diabetes, chronic kidney disease, elderly, and women.

Involvement of the NO/cGMP/K ATP pathway in the antinociceptive effect of rosemary ( Rosmarinus officinalis ) essential oil in mice.

Rosemary essential oil (REO) has been used for several medical purposes. Previous studies have shown the antinociceptive effect of the oil. This study aimed to investigate the role of some well-known receptors in the antinociceptive effect of REO. Male Swiss mice (25-30 g) were used. To assess the antinociceptive activity, the formalin test was used. At first, the antinociceptive effect of three doses of rosemary oil (150, 300 and 450 µL/kg) was tested, and then a dose of 300 µL/kg was selected for the mechanistic study. Animals were pretreated with several antagonists and enzyme inhibitors to evaluate the role of adrenergic, cholinergic, serotoninergic, dopaminergic and opioid receptors as well as the NO/cGMP/K ATP pathway in the antinociceptive effect of rosemary essential oil. Yohimbine (5 mg/kg), prazocin (2 mg/kg), propranolol (2 mg/kg), atropine (2.5 mg/kg) naloxone (5 mg/kg), cyproheptadine (2 mg/kg), ondansetron (2 mg/kg) and haloperidol (1 mg/kg) could not reverse the antinociceptive effect. Sulpiride (20 mg/kg) only showed preventive activity in the early phase of formalin test while methylene blue (5 mg/kg), L-NAME (20 mg/kg) and glibenclamide (10 mg/kg) significantly attenuated the antinociceptive effect of REO in both phases. Tadalafil (2 mg/kg) potentiated the antinociceptive effect of REO in the late phase of formalin test and arginine (100 mg/kg) had no effect on both phases. Therefore the NO/cGMP/K ATP pathway might have an important role in the antinociceptive effect of REO.

Cycloarta-23-ene-3beta,25-diol a pentacyclic steroid from Euphorbia spinidens, as COX inhibitor with molecular docking, and in vivo study of its analgesic and anti-inflammatory activities in male swiss mice and wistar rats.

BACKGROUND AND AIMS: Euphorbia is a large genus of flowering plants. In Iran, some plants of this family have been used in the treatment of inflammatory disorders and also to relieve back pain. Euphorbia spinidens is a rich source of Cycloarta-23-ene-3beta,25-diol. Cycloartane structures are the starting material for the synthesis of plant steroids, and the aim of this study is to demonstrate COX inhibitory activity, molecular docking and in vivo approach of anti-inflammatory activity of cycloartane compound isolated from Euphorbia spinidens. MATERIAL AND METHODS: Plant material was extracted with acetone-chloroform and submitted to column chromatography for fractionation. Based on preliminary 1H-NMR spectra, cycloartane fraction was selected and purified by repeated recycle HPLC system. The structure and purity of compound were determined by 1H and 13C-NMR, HPTLC, and mass spectra. Inhibitory activities of the tested compounds on COX-1 and COX-2 were evaluated by a colorimetric COX (ovine) inhibitor screening method. Vero cells were used to assess the toxicity against the normal cells, and calculate the selectivity index. COX inhibitory activity results were evaluated and confirmed by molecular docking experiments. In the in vivo approach, analgesic activity was assessed by acetic acid-induced abdominal writhing and formalin tests. Croton oil-induced ear edema in mice and carrageenan-induced rat paw edema in rats were used to evaluate anti-inflammatory activity. Pain tests were carried out on male Swiss mice (25-35 g). Male Wistar rats (160-200 g) were used for the carrageenan test. RESULTS: Cycloart-23-ene-3ß,25-diol showedin vitro cyclooxygenase 1 and 2 inhibitory activities with more selectivity for COX-2. Molecular docking by predicting binding energies in COX protein receptors confirmed in vitro COX inhibitory results, and determined the best position for ligand in COX receptors along with its residue interactions in receptor pockets, which must be considered for designing of their inhibitors. In the in vivo studies, cycloartane inhibited significantly acetic acid-induced abdominal contractions and formalin-induced licking behavior at a dose of 200 mg/kg. The same dose reduced croton oil ear edema in mice and carrageenan-induced paw edema in rats. CONCLUSION: Therefore, according to these findings, cycloart-23-ene-3beta,25-diol showed promising analgesic and anti-inflammatory effects with low toxicity against normal cells and can be suggested as a template lead for designing anti-inflammatory compounds with good selectivity index, and potency for COX-2 inhibitory activity.

The prevalence of lower urinary tract symptoms based on individual and clinical parameters in patients with multiple sclerosis.

BACKGROUND: Most patients with multiple sclerosis (MS) suffer from bladder dysfunction during the course of the disease. This study was conducted to examine the prevalence of these complications among patients with MS. METHODS: This cross-sectional study was performed on 602 patients with MS who referred to the neurology clinics of Kashani and Alzahra Hospitals affiliated to Isfahan University of Medical Sciences, Isfahan, Iran. Multistage random cluster sampling was performed and the informed consent form was signed by the subjects. Then, all the data were collected through interviews using the Lower Urinary Tract Symptom Score (LUTSS) developed in accordance with the definitions presented by the International Continence Society (ICS) and the International Prostate Symptom Score (I-PSS) and DASS-21 questionnaire. The data were analyzed using descriptive and inferential statistical tests in SPSS. RESULTS: The prevalence rate of lower urinary tract symptoms (LUTS) was 87.6% among all the subjects, with a similar rate among women (88.0%) and men (86.0%). There was a significant difference between men and women in terms of the prevalence of stress urinary incontinence (SUI), intermittent urine flow, hesitancy, straining, and dribbling (P <  0.050). There was no significant difference between women and men in terms of the prevalence of other symptoms (P > 0.050). A significant difference was observed in the degree of LUTS with age, marital status, marriage duration, education, illness duration, clinical course, disability, anxiety, depression, and stress (P<  0.05). Moreover, logistic regression analysis revealed that there was a higher probability of a urinary problems among patients with MS and a high EDSS score [0.67 (0.507-0.903), P = 0.008]. CONCLUSIONS: A high prevalence of LUTS was found among patients with MS. There was a higher probability of a urinary tract problem among patients with MS and a high EDSS score. Therefore, it is recommended that the health system take the necessary measures regarding timely detection and treatment of LUTS among these patients in order to prevent secondary outcomes and improve the quality of life (QOL) of patients with MS.

Quality of life among patients with multiple sclerosis and voiding dysfunction: a cross-sectional study.

BACKGROUND: Evaluating the usefulness of treatment requires a direct measurement of the health-related quality of life (QOL). Therefore, this study was carried out aiming to determine the QOL of patients with MS and voiding dysfunction. METHODS: This cross-sectional study was carried out using multi-stage random cluster sampling method on 602 patients with MS in Isfahan, Iran. All data were collected through interviews using standard questionnaires including International Prostate Symptom Score (IPSS), and the Multiple Sclerosis Quality of Life-54 (MSQOL-54). Data were analyzed using descriptive and inferential statistical tests. RESULTS: The prevalence rate of mixed, irritative, and obstructive urinary symptoms was 52.2, 25.5, and 6.5%, respectively. The mixed symptom had the highest prevalence among men and women with rates of 56.5 and 51.1%, respectively. The prevalence of irritative and obstructive symptoms was, respectively, higher and statistically significant among women alone and men alone (P <  0.05). The prevalence of irritative symptoms was higher among patients with MS, EDSS score ≤ 3, disease duration of less than 5 years, and with clinically isolated syndrome. In addition, the prevalence of mixed symptoms was higher among patients with MS of over 30 years of age with a Pre-high school degree, severe disability, disease duration of over 10 years, and progressive MS; the difference was statistically significant (P <  0.05). There was a difference in the combined dimensions of physical and mental health of QOL between the two groups with and without urinary symptoms (P <  0.05). Logistic regression analysis revealed that there was a higher probability of a urinary problems among patients with MS and high age [3.273 (1.083-9.860); P = 0.035]. CONCLUSIONS: Mixed urinary symptoms are highly prevalent among MS patients and affect QOL dimensions. In order to improve QOL, more attention and focus should be paid to urinary problems in MS patients.

Sexual dysfunction in women with multiple sclerosis: prevalence and impact on quality of life.

BACKGROUND: Sexual function is a component of quality of life, and sexual dysfunction entails reduced satisfaction with life and impaired mood and quality of relationships and affects not only the individual's quality of life, but her partner's life as well. Since Sexual Dysfunction (SD) is among the most common complaints of patients with Multiple Sclerosis (MS), this study was conducted to determine the prevalence of SD among women with MS and its effect on quality of life. MATERIALS AND METHODS: This cross-sectional study was conducted in 2018 on 300 women with MS aged 22-50 years in Isfahan, Iran, selected through systematic random sampling. Data were collected using the standard Female Sexual Function Index (FSFI) and MSQOL-54 and analyzed in SPSS using descriptive and analytical statistics. RESULTS: The overall prevalence of SD was found as 69.8% in women with MS, with the dimension of sexual desire being affected in 38.6% of the cases, sexual arousal in 38.6%, lubrication in 23.7%, orgasm in 37.3%, satisfaction in 23.4% and pain in 16.9%. SD was found to have significant relationships with age, duration of marriage, fatigue, EDSS and the combined physical and mental health aspects of quality of life (P <  0.05). Moreover, logistic regression analysis revealed that there was a higher probability of a sexual dysfunction among patients with MS and a high fatigue score [1.228(1.003 to 1.504); P = 0.047]. The mean score of the combined physical and mental health aspects of quality of life was lower in the group of women with MS and SD compared to those without SD, and the difference between the two groups was statistically significant (P <  0.05). CONCLUSION: Sexual dysfunction is highly prevalent among women with MS and affects various dimensions of quality of life. Greater attention should be paid to the sexual problems faced by MS patients in order to improve their quality of life.

The effect of vitamin B6 on dexamethasone-induced depression in mice model of despair.

Objective: Glucocorticoid receptors (GRs) have an important role in mediating the effects of glucocorticoids (GCs) on brain plasticity and mood. GC drugs and elevated cortisol level can cause psychiatric disorders including depression. The B-vitamins have numerous benefits on general health as well as mood, and cognition. The aim was evaluating the effect of vitamin B6 following dexamethasone (DEX)-induced depression in mice, to see if it can be proposed as a remedy for psychiatric problems following GC therapy. Methods: Male mice were housed by six. The immobility time was measured, in the forced swimming test as an animal model of despair and sucrose preference was measured in order to test anhedonia (<65% was taken as a criterion for anhedonia). DEX was administered either single dose (15, 60, 250 mcg/kg) or 15 mcg/kg for 7 consecutive days, vitamin B6 (100 mg/kg) was administered for 7 days. Results: DEX dose dependently increased immobility time that denoted animal depression; as it was 177.5 seconds ± 3 following 60 mcg/kg and 188.3 seconds ± 5 following 250 mcg/kg administration (vs. control animals 164 seconds ± 6, P < 0.01). Premedication with vitamin B6 prevented DEX-induced depression and demonstrated antidepressant effect. It also reduced the immobility time following 7days DEX injection (192.5 seconds ± 6) to 100 seconds ± 5.5; sucrose preference escalated from 50%±3 to 87%±4. Conclusion: Vitamin B6 prevented DEX-induced depression possibly by altering the GR function. Thus Vitamin B6 could be promising in patients suffering from GC-induced psychiatric adverse effects and probably controlling stress and preventing its affective disorder out comes.

Maprotiline inhibits COX2 and iNOS gene expression in lipopolysaccharide-stimulated U937 macrophages and carrageenan-induced paw edema in rats.

Maprotiline, a tetracyclic antidepressant, is used for the management of mental disorders and various types of chronic pain. In our previous work, we found the inhibitory effect of maprotiline on inflammatory mediator's expression like tumor necrosis factor α (TNF-α and interleukin 1ß (IL-1ß. As part of that study, we sought to evaluate the effect of maprotiline on the expression of some inflammatory mediators such as cyclooxygenases 2 (COX2) and inducible nitric oxide synthase (iNOS). For this reason we used an in vitro model system of lipopolysaccharide (LPS)-stimulated human U937 macrophages and also an in vivo model of carrageenan-induced paw edema in rats. We measured the expression of these genes by quantitative RT-real time PCR. The expression of COX2 and iNOS significantly decreased by maprotiline in U937 macrophages and carrageenan-induced paw inflammation in rats. Our finding also confirmed that intraperitoneal (i.p.) injection of maprotiline inhibited carrageenan-induced paw edema. Moreover, maprotiline significantly decreased the migration of polymorphonuclear (PMN) leukocytes to the site of inflammation. The results of the present study provide further evidence for the anti-inflammatory effect of maprotiline. This effect appears to be mediated by down regulation of inflammatory genes. Further studies are needed to evaluate the complex cellular and molecular mechanisms of maprotiline.

A comparison of the effect of certain inorganic salts on suppression acute skin irritation by human biometric assay: A randomized, double-blind clinical trial.

BACKGROUND: Strontium, zinc, and potassium salts have been demonstrated to inhibit irritation and inflammation when applied topically. Particularly, strontium chloride (SC) and potassium nitrate (KN) are reported to reduce skin and tooth sensitivity. The aim of the present study was to compare the anti-irritant effects of four inorganic salts and assign the ingredient which can suppress skin irritation due to chemical or environmental exposure, more effectively. We compared the anti-inflammatory effects of SC, strontium nitrate (SN), KN, and zinc chloride (ZC). MATERIALS AND METHODS: This double-blind trial was conducted on 32 healthy volunteers with sensitive skin. Irritation was induced by 24 h exposure with 1.0% sodium lauryl sulfate on arms. Treatments were applied by an ointment of SN, SC hexahydrate, KN, and ZC and their 1%, 3%, and 5% (w/v) concentrations were prepared. The dosage was twice daily for 6 days to the irritated areas. Skin reactions were evaluated instrumentally. RESULTS: SC had a beneficial effect that was significant overall. All other treatments exert a protective effect in skin barrier function but not significantly. With the exception of ZC, all test substances improved skin hydration but the effect of SC was significant. In respect of colorimetric assessment, all treatments, excluding ZC, reduced erythema significantly compared with an untreated control 7 days after treatment start. There was no support for a dose-response effect. CONCLUSION: Analysis of the biometric measurements revealed that the strontium salts are best, not treating is worst, and there is little difference between the other treatments. Hence, the skin care products containing SC and SN may reduce the signs and symptoms of irritant contact dermatitis.

A Comparison of the Effects of Chlorhexidine and Sodium Bicarbonate Mouthwashes on COVID-19-Related Symptoms.

Background: Some studies have reported that mouthwashes can decrease the viral load in the mouth, but there is not much information about the effectiveness of mouthwashes on coronavirus disease 2019 (COVID-19). This study was conducted to compare the impact of using two types of mouthwash, chlorhexidine and sodium bicarbonate, on COVID-19 symptoms and infection. Materials and Methods: The present three-group, double-blind clinical trial examined 116 operating room nurses and anesthesia personnel of certain hospitals of Isfahan University of Medical Sciences, Isfahan, Iran. The participants were randomly assigned to three groups: intervention group 1 (chlorhexidine mouthwash), intervention group 2 (sodium bicarbonate mouthwash), and the control group (placebo). Mouthwash was used twice a day (morning and night) for 2 weeks. The participants were monitored in terms of COVID-19-related symptoms for 4 weeks, from the first day of mouthwash use. Results: Fisher's exact test indicated a significant difference between the chlorhexidine and control groups in terms of the onset of COVID-19-related symptoms (p = 0.02). There was no significant difference in the symptoms of COVID-19 between the groups, but the groups were significantly different in terms of all symptoms at a 4-week interval (p = 0.04). Furthermore, headache was less observed in the chlorhexidine (p = 0.007) and sodium bicarbonate (p = 0.03) groups compared to the control group. Conclusions: The use of 0.2% chlorhexidine mouthwash can decrease the onset of COVID-19-related symptoms in health-care workers. In addition, this mouthwash can partially reduce the symptoms of this disease in comparison to the control and sodium bicarbonate groups.

Anti-inflammatory and antinociceptive effects of sitagliptin in animal models and possible mechanisms involved in the antinociceptive activity.

Background: Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of sitagliptin in formalin and carrageenan tests and determine the possible mechanism(s) of its antinociceptive activity. Methods: Male Swiss mice (25-30 g) and male Wistar rats (180-220 g) were used for formalin and carrageenan tests, respectively. In the formalin test, paw licking time and in the carrageenan test, paw thickness were considered as indexes of pain behavior and inflammation respectively. Three doses of sitagliptin (2.5, 5, and 10 mg/kg) were used in these tests. Also, several antagonists and enzyme inhibitors were used to evaluate the role of adrenergic, serotonergic, dopaminergic, and opioid receptors as well as the NO/cGMP/KATP pathway in the antinociceptive effect of sitagliptin (5 mg/kg). Results: Sitagliptin showed significant antinociceptive and anti-inflammatory effects in the formalin and carrageenan tests respectively. In the carrageenan test, all three doses of sitagliptin significantly (P < 0.001) reduced paw thickness. Pretreatment with yohimbine, prazosin, propranolol, naloxone, and cyproheptadine could not reverse the antinociceptive effect of sitagliptin (5 mg/Kg), which indicates that adrenergic, opioid, and serotonin receptors (5HT2) are not involved in the antinociceptive effects. L-NAME, methylene blue, glibenclamide, ondansetron, and sulpiride were able to reverse this effect. Conclusions: NO/cGMP/KATP, 5HT3 and D2 pathways play an important role in the antinociceptive effect of sitagliptin. Additionally significant anti-inflammatory effects observed in the carrageenan test might contribute in reduction of pain response in the second phase of the formalin test.

Evaluation of the effectiveness of topical oily solution containing frankincense extract in the treatment of knee osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: Pharmacological treatments of osteoarthritis (OA) have several side effects. Boswellia serrata resin (frankincense) is rich in boswellic acids that have antioxidant and anti-inflammatory effects; though, their oral bioavailability is low. The aim of this study was evaluation of the clinical effectiveness of frankincense extract in the treatment of knee OA. In a randomized double-blind placebo-controlled clinical trial, eligible patients with knee OA were randomly divided into two groups of drug (33 patients) and control (37 patients), to use oily solution of frankincense extract or placebo, respectively, on the involved knee three times daily for four weeks. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), VAS (visual analogue scale; for pain severity), and PGA (patient global assessment) scores were determined before and after intervention. RESULTS: For all evaluated outcome variables, there was a significant decrease from baseline in both groups (P < 0.001 for all). Furthermore, the end-of-intervention values for all parameters were significantly lower in drug group than placebo group (P < 0.001 for all), showing more effectiveness of drug compared to placebo. CONCLUSION: Topical oily solution containing enriched extract of boswellic acids could decrease pain severity and improve the function in patients with knee OA. Trial Registration Trial registration number: IRCT20150721023282N14. Trial registration date: September 20, 2020. The study was retrospectively registered in Iranian Registry of Clinical Trials (IRCT).

Smart redox-sensitive micelles based on chitosan for dasatinib delivery in suppressing inflammatory diseases.

Dasatinib (DAS) exhibits anti-inflammatory effects by retrieving the balance between inflammatory and anti-inflammatory cytokines secreted by macrophages. The aim of this study was the development of redox-responsive micelles with the potential of passive targeting and on-demand drug release for DAS delivery to macrophages. For this purpose, two molecular weights of chitosan (CHIT) were conjugated to DAS at different molar ratios using 3,3'-dithiodipropionic anhydride (DTDPA) as disulfide bond containing linker to synthesize a series of CHIT-S-S-DAS amphiphilic conjugates. Micelles obtained by the sonication method had particle sizes of 129.3-172.2 nm, zeta potentials of +17.5 to +20.9 mV, drug contents of 0.90-7.20 %, CMC values of 35.3-96.6 µg/ml, and exhibited redox-responsive in vitro drug release. Optimized micelles were non-toxic and dramatically more efficient than non-redox responsive micelles in reducing TNF-α and IL-6 and increasing IL-10 secretion from LPS-stimulated RAW264.7 cells. Furthermore, the redox-responsive micelles were able to reduce the mice paw edema, reduce the plasma levels of pro-inflammatory cytokines and increase plasma level of IL-10, considerably more than free DAS and non-redox responsive micelles in carrageenan-induced mice paw edema model of inflammation.

Efficacy of an Oral Solution Containing Five Herbal Extracts in the Treatment of Urolithiasis: A Randomized, Single-blind, Placebo-controlled Clinical Trial.

Objective: The high prevalence of urolithiasis and its recurrence entail the preparation of an efficient drug with the least side effects. Tribulus terrestris, Urtica dioica, Adiantum capillus-veneris, Stigma maydis (corn silk), and Cucumis melo are herbal remedies utilized in traditional medicine for urolithiasis. This study aimed to assess the efficiency of these plants' extracts in treating urolithiasis. Methods: In a randomized, single-blind, placebo-controlled clinical trial, participants meeting inclusion criteria were randomly allocated to the drug (n = 27) and placebo (n = 27) groups to take herbal or placebo solutions, respectively, at a dose of 60 drops 3 times daily for 4 weeks with standard treatment. Before and after the intervention, 24-h urine volume and the quantities of calcium, sodium, citrate, oxalate, urea, creatinine, and uric acid in 24-h urine, and urinary pH were measured. The number and size (diameter in mm) of stones were determined by ultrasonography and recorded for each patient. Findings: Except for 24 h urine volume, other urinary parameters did not alter significantly at the end of the intervention compared to baseline. Furthermore, the two groups had no significant difference regarding these indices. Regarding stone parameters, the stone size decreased significantly in the drug group compared to the placebo group (P = 0.049). The number of cases with complete stone expulsion in the drug group was significantly higher than in the placebo group (12 cases vs. 4 cases, respectively, P = 0.017). Conclusion: Oral consumption of the herbal solution causes stone size reduction and stone expulsion in patients with urolithiasis.

Antinociceptive and anti-inflammatory activities of Satureja hortensis seed essential oil, hydroalcoholic and polyphenolic extracts in animal models.

OBJECTIVE: The aim of this study was to evaluate the anti-inflammatory and analgesic effects of Satureja hortensis seed extracts and to analyze their essential oil constituents. MATERIALS AND METHODS: Hydroalcoholic and polyphenolic extracts and essential oil of S. hortensis seeds were prepared using standard methods. Analgesic activity was assessed in male mice (25-35 g) using standard methods (acetic acid and formalin tests). For the evaluation of anti-inflammatory activity, the carrageenan-induced rat paw edema test was used. The mice were pretreated with 50, 100 or 200 mg/kg, i.p., hydroalcoholic or polyphenolic extracts or 100 or 200 µl/kg, p.o. RESULTS: Hydrodistillation of the seeds of S. hortensis afforded a pale yellowish oil in a yield of 0.05% (v/w). Pretreatment of mice with hydroalcoholic or polyphenolic extracts or essential oil significantly (p < 0.001) reduced acetic acid-induced abdominal twitches. Hydroalcoholic extracts also significantly reduced pain responses in early and late phases of the formalin test whereas the polyphenolic extract and essential oil were only effective in the late phase of the formalin test. All three fractions were found to reduce paw edema in the carrageenan test. CONCLUSION: These results clearly demonstrate the analgesic and anti-inflammatory activity of S. hortensis seeds and since the hydroalcoholic extract relieved pain in the first phase of the formalin test, it seems that at least part of its analgesic activity may be mediated centrally. The results of this study substantiated the traditional use of S. hortensis plant seeds in painful and inflammatory ailments.

Evaluation of the antinociceptive effects of a selection of triazine derivatives in mice.

Background: The authors showed in a previous study that some novel triazine derivatives had an anti-inflammatory effect. The present study was designed to evaluate the antinociceptive effect of five out of nine compounds including two vanillin-triazine (5c and 5d) and three phenylpyrazole-triazine (10a, 10b, 10e) derivatives which showed the best anti-inflammatory effect. Methods: Male Swiss mice (25-30 g) were used. To assess the antinociceptive effect, acetic acid-writhing, formalin, and hot plate tests were used after intraperitoneal injection of each compound. Results: All compounds significantly (P < 0.001) reduced acetic acid-induced writhing at tested doses (50, 100, and 200 mg/kg). Also, the percent inhibition of writhing in the acetic acid test showed that at the maximum tested dose of these compounds (200 mg/kg), the order of potencies is as follows: 10b > 10a > 10e > 5d > 5c. In the formalin test, compounds 5d, 10a, and 10e showed an antinociceptive effect in the acute phase and all compounds were effective in the chronic phase. In the hot plate test, compounds 5c, 5d, and 10a demonstrated an antinociceptive effect. Conclusions: The results clearly showed that both vanillin-triazine and phenylpyrazole-triazine derivatives had an antinociceptive effect. Also, some compounds which showed activity in the early phase of formalin test as well as in the hot plate test could control acute pain in addition to chronic or inflammatory pain.

Antinociceptive and anti-inflammatory activities of Bunium persicum essential oil, hydroalcoholic and polyphenolic extracts in animal models.

OBJECTIVE: Fruits of Bunium persicum (Boiss.) B. Fedtsh. (Apiaceae) are widely used in Iranian folkloric medicine for controlling colic pain and dysmenorrhea. This study was aimed to evaluate the anti-inflammatory and analgesic effects of the plant fruits and analyzing its essential oil. MATERIALS AND METHODS: Hydroalcoholic extract, polyphenolic extract and essential oil were prepared using standard methods. The acetic acid and formalin tests were used in male mice (25-35 g) to assess analgesic activity. For evaluation of anti-inflammatory effect, carrageenan-induced rat paw edema and croton oil-induced ear edema were used. RESULTS: Hydrodistillation of the fruits of B. persicum afforded a pale yellowish oil in a yield of 2%. GC/MS analysis identified 10 compounds, and gamma-terpinene (46.1%), cuminal (23.9%) and p-cymene (15.9%) were the main components. Hydroalcoholic and polyphenolic extracts (400 and 800 mg/kg, i.p.) and essential oil (100-400 µl/kg, p.o.) significantly (p < 0.01) reduced acetic acid-induced writhings. They also significantly reduced the pain response of both early and late phases of the formalin test. In the carrageenan test and croton oil-induced ear edema both extracts and essential oil showed considerable anti-inflammatory response. DISCUSSION AND CONCLUSIONS: These results clearly show the analgesic and anti-inflammatory effects of the plant fruits, and since extracts and essential oil relieved the pain of the first phase of the formalin test, it seems that at least a part of analgesic activity is mediated centrally. Meanwhile, the effects observed in this study provide evidence for folkloric uses of the plant fruits in painful and inflammatory conditions.

Effect of a Selection of Skin Penetration Enhancers on Topical Anti-Inflammatory Effect of Boswellic Acids in Carrageenan-Induced Paw Edema in Rats.

BACKGROUND: Boswellia species have been used for treatment of chronic inflammatory disease. Several studies have documented the anti-inflammatory effect of Boswellic acids (BAs) after systemic administration. This study was aimed to evaluate the effect of some skin penetration enhancers on topical anti-inflammatory effect of BAs in rats. MATERIALS AND METHODS: Male Wistar rats weighting 180-220 were used. Anti-inflammatory activity was assessed using carrageenan test. BAs dissolved in ethanol, propylene glycol 2%, 5%, olive oil and applied topically. Menthol, D-limonene, or eucalyptus oil 0.5%, 1% were also tested as other skin penetration enhancers and applied topically 30 min prior to subplantar injection of carrageenan into the right hind paw of rats. The volume of the paw was measured at 0 and 4 h after carrageenan with a digital plethysmometer and the difference was used as an index of inflammation. Piroxicam gel was used as a standard drug. RESULTS: A 4% ethanolic solution of BAs showed significant anti-inflammatory effect. Propylene glycol (2% and 5%) in alcohol did not change the effect. Olive oil also enhanced penetration of BAs. Menthol 0.5%, 1% and D-limonene 0.5%, 1% did not show any significant change compared to olive oil alone. In the present study, eucalyptus oil 1% in olive oil was known as the best carrier for transdermal delivery of BAs. CONCLUSION: BAs have considerable topical anti-inflammatory effects and olive oil alone or especially in combination with eucalyptus oil can be promising vehicles for skin penetration of topical BAs.

Anti-nociceptive and anti-inflammatory effects of hydroalcoholic extract and essential oil of Pinus eldarica in animal models.

OBJECTIVE: Several species of Pinus have shown anti-nociceptive and anti-inflammatory properties. This study was aimed to evaluate anti-nociceptive and anti-inflammatory effects of hydroalcoholic extract of bark and essential oil of leaves of P. eldarica in animal models. MATERIALS AND METHODS: Hydroalcoholic extract of bark and essential oil of leaves of P. eldarica were prepared and phenolic content and essential oil composition were analyzed using Folin-Ciocalteu method and GC/MS, respectively. Anti-nociceptive effect was assessed using acetic acid, formalin and hot plate tests in male Swiss mice (25-30 g) and for evaluation of anti-inflammatory activity, carrageenan test in male Wistar rats (180-200 g) and croton oil-induced ear edema in male mice, were used. Involvement of opioid, α2-adrenergic, 5-HT3 receptors and adenosine triphosphate (ATP)-dependent K+ channels in pain relief was tested using naloxone, ondansetron, yohimbine and glibenclamide. RESULTS: The total phenolic content of the extract in terms of gallic acid equivalent was 404.9±7.7 mg/g of the extract powder. P. eldarica hydroalcoholic extract (200 and 400 mg/kg) and essential oil (100 and 200 µl/kg) significantly (all, p<0.001) decreased pain behavior in acetic acid and formalin tests but not in hot plate test. The extract and essential oil suppressed edema in carrageenan and croton tests. Glibenclamide partially reversed the anti-nociceptive effect of hydroalcoholic extract while the other antagonists were ineffective. CONCLUSION: Hydroalcoholic extract of bark and essential oil of leaves of P. eldarica significantly decreased acute and chronic pain as well as inflammation. ATP-dependent K+ channels mediate a part of the observed anti-nociceptive effect.

Analgesic and Anti-Inflammatory Effects of Hydroalcoholic and Hexane Extracts of Smyrniopsis aucheri in Animal Models.

BACKGROUND: The fruits of Apiaceae family have been widely used in traditional medicine for the treatment of pain and inflammation. In this study, we evaluated the analgesic and anti-inflammatory effects of wild celery (Smyrniopsis aucheri) seeds, as a member of the Apiaceae family. METHODS: Hydroalcoholic and hexane extracts of seeds were prepared and for the evaluation of analgesic activity, acetic acid, formalin, and hotplate tests in male mice (20-30 g) and for anti-inflammatory assessment carrageenan-induced paw edema in rats and croton oil-induced ear edema in mice were used. RESULTS: Hydroalcoholic and hexane extracts (100-400 mg/kg) significantly reduced abdominal spasms in the acetic acid test. In the formalin test, the hydroalcoholic extract at doses of 200 and 400 mg/kg reduced the pain of the chronic phase while hexane extract was effective in both acute and chronic phases. In the hot plate test, both extracts were ineffective. In the carrageenan and croton tests, both extracts at a dose of 400 mg/kg significantly reduced edema. CONCLUSIONS: The results revealed the analgesic and anti-inflammatory effects of plant seed extracts. Due to the lack of response of the extracts in the hot plate test, it seems that the plant mainly has a peripheral analgesic effect.