Safety assessment of the Quercus brantii gall hydroalcoholic extract: Single and repeated oral dose toxicity studies.

Objectives: Quercus brantii galls (QBGs) are well-known in Iranian traditional medicine for treating various diseases. The aim of study was to assess the acute and repeated oral toxicity of the hydroalcoholic extract of QBG in female rats. Materials and Methods: The ethanolic extract of QBG was administered in rats by gavage in both acute and repeated dose models. In the acute section of the study, a single oral dose of 2000 mg/kg was administered to female rat which were observed for physical symptoms and behavioral changes for 14 days. In the repeated dose toxicity study, the QBG extract (50, 500, and 1000 mg/kg/day) was administered for a period of 28 days to rats. On 28th day of experiment, blood sampling of animals was done for hematological and biochemical analysis and then sacrificed for histopathological examination of the harvested tissues (liver, heart, kidney, lung, spleen, stomach, ovary and uterus). Results: A single oral administration of the QBG extract (2000 mg/kg) did not produce mortality or significant behavioral changes during 14 days of observation. In repeated oral toxicity models, the extract significantly increased (P<0.05) the levels of mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), thyroid-stimulating hormone (TSH) and significantly decreased the levels of triiodothyronine (T3) and thyroxin (T4) in 500 and 1000 mg/kg dosage. The histopathological studies showed the absence of toxic effects of QBG (50 mg/kg dosage) and revealed evidence of microscopic lesions in the liver, kidney, stomach, heart, spleen, lung, uterus, and ovary in the 500- and 1000-mg/kg groups. Conclusion: The results indicate that the oral acute toxicity of QBG extract was of a low order with LD50 being more than 2000 mg/kg in rats. In addition, slight tissue damage was observed in some tissues in the 500 and 1000 mg/kg groups. It was found that prolonged use at higher doses i.e. 500 mg/kg/day of QBG extract should be avoided.

Oral administration of phenylalanine molecularly imprinted polymer (MIP) benefits PKU mouse model.

Phenylketonuria (PKU) is a rare genetic disorder caused by a defect in the metabolism of phenylalanine (Phe). Currently, the most commonly used treatment for PKU is dietary Phe restriction. Problems associated with Phe restricted diets include lack of universal availability, high treatment costs, and reduced adherence to continued treatment with age and finally the development of psychological and neurological problems in a significant proportion of patients despite early start of treatment. One possible approach to decreasing blood Phe level, is inhibition of GI tract absorption of this amino acid. We had previously shown that a Phe selective molecularly imprinted polymer was able to bind Phe in the GI tract and attenuate its plasma concentration. In this work, we used different orally administered Phe selective molecularly imprinted polymer doses in a PKU mouse model to further study the effects of this treatment on biochemical profile and cognitive function in test animals. Treatments started 21 days postnatally. After 3 weeks, brain and plasma amino acid profiles and brain monoaminergic neurotransmitter concentrations were measured. Behavioral profile was also evaluated. Treatment with 2% and 5% Phe selective molecularly imprinted polymer significantly reduced levels of blood Phe in PKU model animals (46% and 48% respectively) meanwhile levels of other amino acids remained unchanged. Brain dopamine concentrations in hippocampus was effectively restored by supplementation of Phe selective molecularly imprinted polymer. Finally, polymer treatment improved locomotor dysfunction in PKU model animals. Our data suggest that the Phe selective molecularly imprinted polymer can be a new candidate for treatment of PKU patients. Take home message: Orally administered Phenylalanine Selective Molecularly Imprinted Polymer is able to inhibit absorption of phenylalanine from the GI tract and may offer a new treatment, in conjunction with dietary restriction, for PKU patients.

Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents.

Rubiadin is identified as a bioactive anthraquinone that exists in some quinone rich plants. The current research was carried out to evaluate the potential anti-inflammatory impact of Rubiadin in acute and chronic inflammation test models in rodents. The anti-inflammatory activity of Rubiadin was examined in cotton pellet-induced granuloma and carrageenan-induced edema as chronic and acute inflammation models in rats. TNF-α level and histopathological changes were assessed using sampled foot tissue of rat in the acute model. Also, the IL-1ß level was assessed in the chronic model. One-way ANOVA (post hoc Tukey's) analysis was used for comparing the groups. Rubiadin (0.5 mg/kg, i.p.) induced a significant reduction in TNF α level and the paw edema compared to the control group in carrageenan test. Also, it was observed that the anti-inflammatory activity of Rubiadin (0.5 mg/kg, i.p.) is comparable to mefenamic acid (30 mg/kg, i.p.) as the standard drug. Rubiadin was effective in granuloma induced by cotton pellet concerning the granuloma and transudate formation amount. Rubiadin's anti-inflammatory effects were associated with a significant IL-1ß decrease in this model. The results suggest that Rubiadin as a natural compound can possess significant peripheral anti-inflammatory impacts.

In vivo analgesic and anti-inflammatory effects of the essential oil from Tanacetum balsamita L

Tanacetum balsamita locally called Shahesparam is an aromatic plant that grows widely in Azerbaijan Province, Iran. Due to the widespread use of T. balsamita as a pain killer and relief of inflammatory based disorders in Iranian folk medicine and considering the high content of essential oil in T. balsamita aerial parts, we were prompted to investigate the anti-nociceptive and anti-inflammatory properties of T. balsamita essential oil (TBEO) for the first time. The carrageenan-induced Paw Edema was used for inflammation evaluation in rat, and hot-plate method was used for pain assessment in mice. Different doses of TBEO were administered. Morphine and Mefenamic acid were used as the standard drugs in anti-nociceptive and anti-inflammatory evaluation tests, respectively. TBEO (100 mg/kg) showed significantly anti-nociceptive activity in hot-plate test. The anti-inflammatory activity of TBEO was found to be more than mefenamic acid. The studied oil was analyzed by GC and GC-MS. The major component of the oil was characterized as carvone (39.8%) which might be responsible for the observed activities. The results suggested that TBEO possessed biologically active constituents that had significant analgesic and anti-inflammatory effects which support the ethno-medicinal claims of the plant application in the management of pain and inflammation.

Safety Assessment of Mentha mozaffarianii Essential Oil: Acute and Repeated Toxicity Studies.

BACKGROUND: Mentha mozaffarianii, an endemic species from the Labiatae family, is used in Iranian traditional medicine. This study evaluated the acute and repeated oral toxicity of the Mentha mozaffarianii essential oil (MMEO) in rats and mice. METHODS: To assess the toxicity profile of the MMEO, we administered the essential oil to 48 rats and mice of both sexes by gavage in acute and repeated models. In acute toxicity, the animals were administered the MMEO (2000 mg/kg) and were monitored for 14 days. In the repeated toxicity, the MMEO was administered (100 mg/kg) daily for 4 weeks. On the 28th day, all the animals were scarified and blood and tissue samples were prepared. All the clinical, biochemical, and histopathological changes were assessed and compared with those in the controls. Statistical significance was determined by one- and two-way analyses of variance, followed by the Tukey test using GraphPad Prism 6. RESULTS: In the acute test, there was no mortality; therefore, the oral LD50 value determined in the mice and rats of both sexes was greater than 2000 mg/kg. In the repeated test, the animals received the MMEO and there was no mortality. In the biochemical analysis, there were significant increases in blood glucose, cholesterol, ALT, AST, ALP, and TSH in the female rats and also in BUN in the male rats. The histopathological studies revealed evidence of microscopic lesions in the liver, kidney, stomach, and small intestine tissues of the MMEO group. CONCLUSION: The results indicated that the acute toxicity of the MMEO in the mice and rats was of a low order and it revealed slight tissue damage to several organs when given subchronically at a dose of 100 mg/kg.

The evaluation of the clinical effect of topical St Johns wort (Hypericum perforatum L.) in plaque type psoriasis vulgaris: a pilot study.

In this case series, ten patients with plaque-type psoriasis were treated with Hypericum perforatum ointment. The hypericum ointment was applied to one side of each patient's body and the vehicle to the opposite side twice daily for 4 weeks in a single blinded manner. Modified psoriasis area severity index (PASI) scores were significantly lowered where the formulated ointment had been applied. In determining PASI scores, three factors, erythema, scaling and thickness, were evaluated; all were significantly lower where the formulated ointment had been applied (P = 0.01, P = 0.004, P = 0.04). Hypericum perforatum ointment applied twice daily may be effective in reducing PASI scores in mild plaque-type psoriasis, however, further larger studies need be conducted to achieve a more conclusive result.