Neural Network-based Optimization of Silybum Marianum Extract-loaded Chitosan Particles: Modeling, Preparation and Antioxidant Evaluation.

BACKGROUND: Silymarin is a flavonolignan extracted from Silybum marianum with various therapeutic applications. Many studies have focused on improving the bioavailability of silymarin due to its wide range of efficacy and low bioavailability. Chitosan, a naturally occurring polymeric substance, has a strong reputation for increasing the solubility of poorly soluble compounds. OBJECTIVE: This study used artificial neural networks (ANNs) to measure the effects of pH, chitosan to silymarin ratio, chitosan to tripolyphosphate ratio, and stirring time on the loading efficiency of silymarin into chitosan particles. METHODS: A model was developed to investigate the interactions between input factors and silymarin loading efficiency. The DPPH method was utilized to determine the antioxidant activity of an optimized formula and pure raw materials. RESULTS: According to the outcome of the ANN model, pH and the chitosan to silymarin ratio demonstrated significant effects on loading efficiency. In addition, increased stirring time decreased silymarin loading, whereas the chitosan-to-tripolyphosphate ratio showed a negligible effect on loading efficiency. CONCLUSION: Maximum loading efficiency occurred at a pH of approximately~5. Moreover, silymarin- loaded chitosan particles with a lower IC50 value (36.17 ± 0.02 ppm) than pure silymarin (165.04 ± 0.07 ppm) demonstrated greater antioxidant activity.

Fabrication, characterization and optimization of berberine-loaded PLA nanoparticles using coaxial electrospray for sustained drug release.

BACKGROUND: Berberine (BBR) broadly found in medicinal plants has a major application in pharmacological therapy as an anticancer drug. Clinical applications of this promising natural drug are limited due to its poor water solubility and low bioavailability. OBJECTIVE: In this study, for the first time, we synthesized core-shell BBR-loaded PLA nanoparticles (NPBs) by using coaxial electrospray (CES) to solve the poor bioavailability of BBR. METHODS: Three-factor (feeding rate, polymeric solution concentration and applied voltage), three-level, Box-Behnken design was used for optimization of the size and particle size distribution of the prepared NPBs. RESULTS: Based on the results of response surface methodology, the NPBs with the mean size of 265 nm and particle size distribution of 43 nm were synthesized. A TEM image was used to well illustrate the core-shell structure of the NPBs. Encapsulation efficiency and BBR loading capacity for the optimized NPBs were determined at about 81% and 7.5%, respectively. Release of NPBs was examined at pH 7.4 and 5.8. NPBs had a slower release profile than free BBR in both pH values, and the rate of BBR release was more and faster in acidic pH than in physiological one. Effects of the NPBs on the drug release were confirmed by data fitting with six kinetic models. NPBs showed an increased cytotoxic efficacy against HCT116 cells (IC50 = 56 µM), while NIH3T3 cells, non-neoplastic fibroblast cells, (IC50 > 150 µM) were less affected by NPBs. Flow cytometry demonstrated that the cellular uptake of NPBs were higher than BBR at different concentrations. CONCLUSIONS: A new approach was developed in this study to prepare NPBs using the CES process for improving the efficiency and controlled BBR release. It is concluded that nano-scaled NPBs prepared by CES can improve toxicity and chemotherapeutic properties of BBR against cancerous cells. We believe that these NPBs can exhibit further potential in cancer drug delivery systems. Graphical abstract.

Polyphenols targeting diabetes via the AMP-activated protein kinase pathway; future approach to drug discovery.

Regarding the widespread progression of diabetes, its related complications and detrimental effects on human health, investigations on this subject seems compulsory. AMP-activated protein kinase (AMPK) is a serine/threonine kinase and a key player in energy metabolism regulation. AMPK is also considered as a prime target for pharmaceutical and therapeutic studies on disorders such as diabetes, metabolic syndrome and obesity, where the body energy homeostasis is imbalanced. Following the activation of AMPK (physiological or pharmacological), a cascade of metabolic events that improve metabolic health is triggered. While there are several publications on this subject, this is the first report that has focused solely on polyphenols targeting diabetes via AMPK pathway. The multiple characteristics of polyphenolic compounds and their favorable influence on diabetes pathogenesis, as well as their intersections with the AMPK signaling pathway, indicate that these compounds have a beneficial effect on the regulation of glucose homeostasis. PPs could potentially occupy a significant position in the future anti-diabetic drug market.

Effects of methyl jasmonate and phloroglucinol on thebaine and sanguinarine production in cell suspension culture of Persian poppy (Papaver bracteatum Lindl.).

The biosynthesis path engineering could be very promising for mass production of alkaloids by applying elicitors in the cell suspension culture of Persian poppy (Papaver bracteatum Lindl.). In this work, the effects of different concentrations of methyl jasmonate (MJ) and phloroglucinol (PG) on thebaine and sanguinarine productions in vitro were investigated. Roots as explant and supplementing 3 mg L-1 2,4-Dichlorophenoxyacetic acid with 0.5 mg L-1 Benzyl amino purine to modified MS medium were selected to achieve the most efficient combination for callus induction and production of callus fresh and dry weights. At 48 h after treatment, the addition of PG and MJ individually and in combination together significantly increased both thebaine and sanguinarine contents than the control. The results of high-performance liquid chromatography (HPLC) detection indicated that the highest production rate has been achieved through a synergic effect of two elicitors after 48 h. Results revealed that adding 200 µM of MJ and 100 mg L-1 PG increased thebaine and sanguinarine contents by 56.36 and 107.71-fold than control cells, respectively.

Safety and efficacy of Melissa officinalis (lemon balm) on ApoA-I, Apo B, lipid ratio and ICAM-1 in type 2 diabetes patients: A randomized, double-blinded clinical trial.

BACKGROUND: The purpose of this study was to investigate the safety and effects of Melissa officinalis, a good source of bioactive components, on apolipoprotein (Apo)B, Apo A-I, and their ratio, lipids ratios and intercellular adhesion molecule-1(ICAM-1) in patients with type 2 diabetes. METHODS: For the present randomized, double-blinded, placebo-controlled clinical trial, 70 type 2 diabetic patients aged 20-65 years old were randomly assigned to receive hydroalcoholic extract of M. officinalis (HEMO) (700 mg/d) or placebo twice-daily for 12 weeks. RESULTS: There were significant differences in serum Apo A-I, TC/ HDL-c and LDL-c/ HDL-c between the two groups at the end of the study (p < 0.05), but we did not show significant differences in the values for Apo B, Apo B/Apo A-I, TG/HDL-c, ICAM-1 and liver enzymes include AST, ALT, and ALP between the study groups. Although both groups showed a significant reduction in ICAM-1, AST and, ALP (p < 0.05), no significant differences in ICAM-1, AST and, ALP were observed. At end, in M. officinalis group, there was a significant increase in Apo A-I (p = 0.003) and significant reduction in TG/HDL-c (p = 0.05) compared with initial values, as well as in placebo group, there was a significant rising in Apo B/Apo A-I (p = 0.02) and significant reduction in Apo A-I (p = 0.001) compared with baseline values. CONCLUSIONS: M. officinalis is safe and effective in improvement of Apo A-I, Apo B/Apo A-I, and lipids ratios as key factors promoting cardiovascular disease (CVD) in type II diabetic patients.

Antitrypanosomal isothiocyanate and thiocarbamate glycosides from Moringa peregrina.

O-Methyl (1), O-ethyl (2), and O-butyl (3) 4-[(α-L-rhamnosyloxy) benzyl] thiocarbamate (E), along with 4-(α-L-rhamnosyloxy) benzyl isothiocyanate (4) have been isolated from the aerial parts of Moringa peregrina. The compounds were tested for in vitro activity against Trypanosoma brucei rhodesiense and cytotoxicity in rat skeletal myoblasts (L6 cells). The most potent compound was 4 with an IC50 of 0.10 µM against T.b. rhodesiense and a selectivity index of 73, while the thiocarbamate glycosides 1, 2, and 3 showed only moderate activity. Intraperitoneal administration of 50 mg/kg body weight/day of 4 in the T.b. rhodesiense STIB 900 acute mouse model revealed significant in vivo toxicity. Administration of 10 mg/kg body weight/day resulted in a 95% reduction of parasitemia on day 7 postinfection, but did not cure the animals. Because of its high in vitro activity and its ability to irreversibly inhibit trypanothione reductase, an attractive parasite-specific target enzyme, 4-[(α-L-rhamnosyloxy) benzyl] isothiocyanate (4), can be considered as a lead structure for the development and characterization of novel antitrypanosomal drugs.

Hepatoprotective effects of Juglans regia extract against CCl4-induced oxidative damage in rats.

CONTEXT: Different parts of the walnut [Juglans regia L. (Juglandaceae)] have been used in folk medicine for protection against liver injury, although its actual efficacy remains uncertain. OBJECTIVE: The present study investigated the protective effect of walnut leaf extract against carbon tetrachloride (CCl4)-induced liver damage in rats. MATERIALS AND METHODS: The rats were randomly divided into seven groups: control, CCl4 (i.p., 0.5 mL/kg b.w., 50% CCl4 in olive oil), walnut extract (at dose level of 0.2 g/kg b.w.) alone, walnut extract (at dose levels of 0.05, 0.1, 0.2 and 0.4 g/kg b.w.) with CCl4, and treatment was carried out accordingly. On the 28th day, rats were sacrificed and blood was withdrawn by cardiac puncture. Liver damage was assessed by serum biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and albumin), antioxidant enzymes (superoxide dismutase and catalase) and histopathological observation. RESULTS: Administration of walnut leaf extract (ranging from 0.2 to 0.4 g/kg b.w.) significantly lowered serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in CCl4-treated rats. Walnut leaf extract increased antioxidant enzymes, including superoxide dismutase and catalase. Histopathological examination of livers showed that walnut leaves extract reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl4-treated rats. DISCUSSION AND CONCLUSION: These results suggest that walnut extract has a protective effect over CCl4-induced oxidative damage in rat liver. These results demonstrate that walnut extract acts as a good hepatoprotective and antioxidant agent in attenuating hepatocellular damage.

Urease inhibitory activities of ß-boswellic acid derivatives.

BACKGROUND AND THE PURPOSE OF THE STUDY: Boswellia carterii have been used in traditional medicine for many years for management different gastrointestinal disorders. In this study, we wish to report urease inhibitory activity of four isolated compound of boswellic acid derivative. METHODS: 4 pentacyclic triterpenoid acids were isolated from Boswellia carterii and identified by NMR and Mass spectroscopic analysis (compounds 1, 3-O-acetyl-9,11-dehydro-ß-boswellic acid; 2, 3-O-acetyl-11-hydroxy-ß-boswellic acid; 3. 3-O- acetyl-11-keto-ß-boswellic acid and 4, 11-keto-ß-boswellic acid. Their inhibitory activity on Jack bean urease were evaluated. Docking and pharmacophore analysis using AutoDock 4.2 and Ligandscout 3.03 programs were also performed to explain possible mechanism of interaction between isolated compounds and urease enzyme. RESULTS: It was found that compound 1 has the strongest inhibitory activity against Jack bean urease (IC50 = 6.27 ± 0.03 µM), compared with thiourea as a standard inhibitor (IC50 = 21.1 ± 0.3 µM). CONCLUSION: The inhibition potency is probably due to the formation of appropriate hydrogen bonds and hydrophobic interactions between the investigated compounds and urease enzyme active site and confirms its traditional usage.

A double-blind placebo controlled trial of Ginkgo biloba added to risperidone in patients with autistic disorders.

Ginkgo biloba has been reported to affect the neurotransmitter system and to have antioxidant properties that could impact the pathogenesis of Autism Spectrum Disorder. Based on these studies, we decided to assess the effectiveness of Ginkgo biloba extract (Ginko T.D., Tolidaru, Iran) as an adjunctive agent to risperidone in the treatment of autism. Forty-seven outpatients with a DSM-IV-TR diagnosis of autism ages between 4 and 12 years were assigned to this double blinded clinical trial and were randomly divided into two groups. One group received risperidone plus Ginko T.D and the other received risperidone plus placebo. The dose of risperidone was 1-3 mg/day and the dose of Ginko T.D. was 80 mg/day for patients under 30 kg and 120 mg/day for patients above 30 kg. Patients were assessed using Aberrant Behavior Checklist-Community (ABC-C) rating scale and the side effect check list every 2 weeks until the endpoint. None of the 5 subscales of ABC-C rating scale showed significant differences between the two groups. Incidents of side effects were not significantly different between the two groups. Adding Ginkgo biloba to risperidone did not affect the treatment outcome of ADs. Nevertheless, further observations are needed to confirm this result.

Antinociceptive and anti-inflammatory effects of olive oil (Olea europeae L.) in mice.

CONTEXT: Olive [Olea europaea L. (Oleaceae)] is a long-lived evergreen tree that is widespread in different parts of the world. OBJECTIVE: Olive oil has been reported to relieve pain; however, there is still insufficient data in the literature on the subject. Thus, it is considered worthwhile investigating the antinociceptive and anti-inflammatory effects of olive oil in adult male Balb/C mice. MATERIALS AND METHODS: The antinociceptive effects were studied using formalin, hot plate and writhing tests. The acute anti-inflammatory effects of olive oil in mice were studied using xylene ear edema test. Olive oil (1, 5 and 10 ml/kg body wt.) was injected intraperitoneally. Intact animals served as controls. RESULTS: Our results showed that the olive oil only decreased the second phase of formalin-induced pain. In the hot plate test, olive oil did not raise the pain threshold over the 60 min duration of the test. Olive oil exhibited antinociceptive activity against writhing-induced pain by acetic acid. In the xylene ear edema test, olive oil showed significant anti-inflammatory activity in the mice. DISCUSSION AND CONCLUSION: The present data indicated that olive oil has antinociceptive and anti-inflammatory effects in mice but further investigation of these effects is required to elucidate the mechanism(s) involved in analgesic and anti-inflammatory effects of Olea europaea oil.

Biological Activities of Various Extracts and Chemical Composition of Trigonella monantha C. A. Mey. subsp. monantha Grown in Iran.

The objective of this research was to study the biological activities of various extracts and the chemical composition of the essential oil Trigonella monantha C. A. Mey. subsp. monantha by gas chromatography (GC) and gas chromatography-mass spectroscopy (GC-MS), from the compounds derived from the aerial parts. The overall results of T. monantha tests allow us to conclude various extracts [hexane extract (HE), methanol extract (ME) and chloroform extract (CE)] of the test total phenolic, ABTS and DPPH while also testing ß-carotene largest property antioxidant. The property antioxidant shows the extracts of both mechanisms of electron transfer and the hydrogen transfer it has gone through. The antimicrobial activity of the extracts of both samples was determined against seven Gram-positive and Gram-negative bacteria. The strongest activity exhibited by the T. monantha of ME was determined to be 49.58 µg/mL and was exhibited by ME.

Analgesic effects of methanolic extracts of the leaf or root of Moringa oleifera on complete Freund's adjuvant-induced arthritis in rats.

OBJECTIVE: Moringa oleifera (family Moringaceae) has been widely used in African folk medicine, and researchers have recently revealed its anti-inflammatory effects in human. This study aimed to evaluate the analgesic properties of methanolic extracts of M. oleifera in complete Freund's adjuvant (CFA)-induced arthritis in rats. METHODS: Adult male Wistar rats, weighing 200 to 220 g, were used in this study. Adjuvant arthritis was induced on day 0 by a single subcutaneous injection of CFA. The prepared extracts from both the root and leaf (200, 300 and 400 mg/kg) of M. oleifera were administered intraperitonealy to rats in the treatment groups 0, 3 and 6 d after CFA injection and indomethacin (5 mg/kg) was used as a positive control drug. Thermal hyperalgesia and mechanical allodynia were evaluated for the analgesic effect 0, 3 and 6 d after CFA injection. Combined methanolic root and leaf extracts of M. oleifera (200 mg/kg) were also tested for the analgesic effect. RESULTS: The potency of the root or leaf extracts of M. oleifera (300 and 400 mg/kg) was similar to that of indomethacin, resulted in significant reductions in both thermal hyperalgesia and mechanical allodynia in rats with CFA-induced arthritis compared with the control group after 3 and 6 d, respectively (P<0.01 or P<0.05). Combined root and leaf extracts (200 mg/kg) of M. oleifera resulted in a significant reduction in thermal hyperalgesia compared with the control group after 3 and 6 d, respectively (P<0.01). Prophylactic injections of combined root and leaf extracts of M. oleifera (200 mg/kg) resulted in a significant reduction in thermal hyperalgesia compared with the control group, the root extracts group, and the leaf extracts group after 3 and 6 d, respectively (P<0.01). CONCLUSION: The methanolic extracts of the root or leaf of M. oleifera are effective in the reduction of pain induced by CFA in rats. A comparison of single and combination therapies of root and leaf extracts also showed a synergistic effect on pain reduction.

Sildenafil adjunctive therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled trial.

RATIONAL: It has been suggested that phosphodiesterase 5 inhibitors such as sildenafil may be effective in the treatment of negative symptoms of schizophrenia. OBJECTIVE: This study was designed to investigate the effect of sildenafil added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in a double-blind and randomized clinical trial. METHODS: Eligible participants in the study were 40 patients with chronic schizophrenia with ages ranging from 18 to 45 years. All patients were inpatients and were in the active phase of the illness and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion: 20 to risperidone (6 mg/day) plus sildenafil (75 mg/day) and 20 to risperidone (6 mg/day) plus placebo. The principal measure of outcome was Positive and Negative Syndrome Scale (PANSS). RESULTS: Although both protocols significantly decreased the score of the positive, negative, and general psychopathological symptoms over the trial period, the combination of risperidone and sildenafil showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores over the 8-week trial (between-subjects factor; F = 4.77, df = 1; P = 0.03; F = 5.91, df = 1, P = 0.02 respectively). CONCLUSION: Therapy with 75 mg/day of sildenafil was well tolerated, and no clinically important side effects were observed. The present study indicates sildenafil as a potential adjunctive treatment strategy for treatment of negative symptoms of schizophrenia. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N11).

Achillea santolina reduces serum interleukin-6 level and hyperalgesia during complete Freund's adjuvant-induced inflammation in male Wistar rats.

OBJECTIVE: Immune system is involved in the etiology and pathophysiologic mechanisms of inflammation. Medicinal plants are an important source of substances which are claimed to induce non-specific immunomodulatory effects. In view of this and on account of the interleukin (IL)-6's role in inflammation and pain induction, this study investigated the effects of Achillea santolina extracts on inflammation which was induced by complete Freund's adjuvant (CFA) in male Wistar rats. METHODS: Both methanolic and defatted extracts prepared from aerial parts of the plant were examined. Inflammatory symptoms such as hyperalgesia and paw edema in CFA-injected rats' paw were measured by radiant heat and plethysmometer during different stages of study respectively. Serum IL-6 level was checked by rat standard enzyme-linked immunosorbent assay specific kit. RESULTS: The results indicated dose-related effects of methanolic extract on paw edema, hyperalgesia and serum IL-6 level reduction in rats. Methanolic extract of A. santolina exhibited significant antihyperalgesic and anti-inflammatory effects during pretreatment and short-term treatment at dose of 200 mg/kg and there was no significant difference between 200 and 400 mg/kg doses of this extract. Defatted extract did not show significant effect on CFA-induced inflammation during different stages of treatment (P>0.05). Short-term treatment with methanolic extract at dose of 200 mg/kg was more effective than indomethacin in edema, hyperalgesia and serum IL-6 level reduction (P<0.01, P<0.01 and P<0.05 respectively). CONCLUSION: These results suggest that methanolic extract of A. santolina possesses potent anti-inflammatory and immunomodulatory activities during pretreatment and short-term administration.

Venlafaxine versus methylphenidate in pediatric outpatients with attention deficit hyperactivity disorder: a randomized, double-blind comparison trial.

OBJECTIVE: The present report aimed to investigate the efficacy and tolerability of venlafaxine compared to methylphenidate in children and adolescents with Attention Deficit/Hyperactivity Disorder (ADHD). METHODS: This was a 6-week, parallel group, randomized clinical trial. Thirty-eight patients (27 boys and 11 girls) with a DSM-IV-TR diagnosis of ADHD were the study population of this trial. All study subjects were randomly assigned to receive treatment using capsules of venlafaxine at doses of 50-75 mg/day depending on weight (50 mg/day for <30 kg and 75 mg/day for >30 kg (group 1) or methylphenidate at a dose of 20-30 mg/day depending on weight (group 2) for a 6-week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent Attention Deficit/Hyperactivity Disorder Rating Scale-IV. RESULTS: No significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores (df = 1; F = 1.77; p = 0.19 and df = 1; F = 1.64; p = 0.20, respectively). Side effects of headaches and insomnia were observed more frequently in the methylphenidate group. CONCLUSIONS: The results suggest that venlafaxine may be useful for the treatment of ADHD. In addition, a tolerable side-effect profile is one of the advantages of venlafaxine in the treatment of ADHD.

Double-blind, placebo-controlled trial of risperidone plus topiramate in children with autistic disorder.

BACKGROUND: Autism is a complex neurodevelopmental disorder that forms part of a spectrum of related disorders referred to as Autism Spectrum Disorders. The present study assessed the effects of topiramate plus risperidone in the treatment of autistic disorder. METHOD: Forty children between the ages of 4 and 12 years with a DSM IV clinical diagnosis of autism who were outpatients from a specialty clinic for children were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to topiramate+risperidone (Group A) or placebo+risperidone (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 2 mg/day for children between 10 and 40 kg and 3 mg/day for children weighting above 40 kg. The dose of topiramate was titrated up to 200 mg/day depending on weight (100 mg/day for <30 kg and 200 mg/day for >30 kg). Patients were assessed at baseline and after 2, 4, 6 and 8 weeks after starting medication. Measure of outcome was the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale. RESULTS: Difference between the two protocols was significant as the group that received topiramate had a greater reduction in ABC-C subscale scores for irritability, stereotypic behavior and hyperactivity/noncompliance. CONCLUSION: The results suggest that the combination of topiramate with risperidone may be superior to risperidone monotherapy for children with autistic disorder. However the results need to be further confirmed by a larger randomized controlled trial.

Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial.

OBJECTIVE: The aim of the present study was to further evaluate, under double blind and controlled conditions, the efficacy of amantadine for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents as compared to methylphenidate. METHODS: This was a 6-week randomized clinical trial. Forty patients (28 boys and 12 girls) with a DSM-IV-TR diagnosis of ADHD were the study population of this trial. All study subjects were randomly assigned to receive the treatment using capsule of amantadine at a dose of 100-150 mg/day depending on weight (100 mg/day for <30 kg and 150 mg/day for >30 kg) or methylphenidate at a dose of 20-30 mg/day for a 6-week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent Attention deficit/hyperactivity disorder Rating Scale-IV. RESULTS: No significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores (df = 1; F = 0.02; p = 0.86 and df = 1; F = 0.01; p = 0.89, respectively). Side effects of decreased appetite and restlessness were observed more frequently in the methylphenidate group. CONCLUSION: The results of this study indicate that amantadine significantly improved symptoms of ADHD and was well tolerated and it may be beneficial in the treatment of children with ADHD. Nevertheless, the present results do not constitute proof of efficacy.

Double-blind placebo-controlled trial of pentoxifylline added to risperidone: effects on aberrant behavior in children with autism.

BACKGROUND: There are several lines of evidence to indicate that the immune system plays an important role in the pathophysiology of autism. The objective of this study was to access the effects of pentoxifylline plus risperidone in the treatment of autistic disorder. METHODS: Forty children between the ages 4 and 12 years with a DSM IV-TR clinical diagnosis of autism were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to pentoxifylline+risperidone or placebo+risperidone for a 10-week, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 3 mg/day, pentoxifylline was titrated to 600 mg/day. Patients were assessed at baseline and after 2, 4, 6, 8 and 10 weeks of starting medication. The measure of the outcome was the Aberrant Behavior Checklist-Community (ABC-C). RESULTS: The difference between the two protocols was significant as the group that received pentoxifylline had greater reduction in ABC-C subscale scores for Irritability, Lethargy/Social Withdrawal, Stereotypic Behavior, Hyperactivity/Noncompliance and Inappropriate Speech. CONCLUSION: The results suggest that combination of atypical antipsychotic medications and pentoxifylline might have synergistic effects in treatment of behavioral problems of children with autism.

Ginkgo biloba for attention-deficit/hyperactivity disorder in children and adolescents: a double blind, randomized controlled trial.

BACKGROUND: Although stimulants are highly effective in controlling the symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD), some children will not respond to, or are intolerant of stimulants. Thus, the desire for safe and effective nonstimulant medications has risen during the past several years. Ginkgo biloba has been suggested in the treatment of dementia and memory impairment. We hypothesized that G.biloba would be beneficial for treatment of ADHD, and this could be evaluated in a double blind, randomized, parallel group comparison of G.biloba (Ginko T.D. Tolidaru, Iran) and methylphenidate. METHODS: Fifty outpatients (39 boys and 11 girls) with a DSM-IV-TR diagnosis of ADHD were study population of this trial. Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind, randomized clinical trial. All study subjects were randomly assigned to receive treatment using tablet of Ginko T.D. at a dose of 80-120 mg/day depending on weight (80 mg/day for <30 kg and 120 mg/day for >30 kg) (group 1) or methylphenidate at a dose of 20-30 mg/day depending on weight (20 mg/day for <30 kg and 30 mg/day for >30 kg (group 2) for a 6 week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent ADHD Rating Scale- IV. Patients were assessed at baseline and at 21 and 42 days after the medication started. RESULTS: Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores. The changes at the endpoint compared to baseline were: -6.52+/-11.43 (mean+/-S.D.) and -15.92+/-11.44 (mean+/-S.D.) for Ginko T.D. and methyphenidate, respectively for Parent ADHD Rating Scale. The changes at the endpoint compared to baseline were: -0.84+/-6.79 (mean+/-S.D.) and -14.04+/-8.67 (mean+/-S.D.) for Ginko T.D. and methyphenidate, respectively for Teacher ADHD Rating Scale. The difference between the Ginko T.D. and methylphenidate groups in the frequency of side effects was not significant except for decreased appetite, headache and insomnia that were observed more frequently in the methylphenidate group. CONCLUSION: The results of this study suggest that administration of G.biloba was less effective than methylphenidate in the treatment of ADHD.

A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease.

RATIONALE: There is increasing evidence to suggest the possible efficacy of Crocus sativus (saffron) in the management of Alzheimer's disease (AD). OBJECTIVE: The purpose of the present investigation was to assess the efficacy of C. sativus in the treatment of patients with mild-to-moderate AD. METHODS: Fifty-four Persian-speaking adults 55 years of age or older who were living in the community were eligible to participate in a 22-week, double-blind study of parallel groups of patients with AD. The main efficacy measures were the change in the Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical Dementia Rating Scale-Sums of Boxes scores compared with baseline. Adverse events (AEs) were systematically recorded. Participants were randomly assigned to receive a capsule saffron 30 mg/day (15 mg twice per day) or donepezil 10 mg/day (5 mg twice per day). RESULTS: Saffron at this dose was found to be effective similar to donepezil in the treatment of mild-to-moderate AD after 22 weeks. The frequency of AEs was similar between saffron extract and donepezil groups with the exception of vomiting, which occurred significantly more frequently in the donepezil group. CONCLUSION: This phase II study provides preliminary evidence of a possible therapeutic effect of saffron extract in the treatment of patients with mild-to-moderate Alzheimer's disease. This trial is registered with the Iranian Clinical Trials Registry (IRCT138711051556N1).