Sub-acute and acute toxicity of Ferula asafoetida and Silybum marianum formulation and effect of the formulation on delaying gastric emptying.

BACKGROUND: Delayed gastric emptying play an important role in the pathology of functional dyspepsia. Owing to their functional attributes in alleviating the gastrointestinal disorders, single or polyherbal formulations have gained attention to treat the symptoms of functional dyspepsia. We have investigated the safety and efficacy of a novel formulation of Ferula asafoetida oleo resin and standardized Silybum marianum extract (Asdamarin). METHODS: The effect of asdamarin on delayed gastric emptying was investigated in Sprague Dawley rats using phenol red method. The acute and sub-acute oral toxicity was evaluated in wistar rats following OECD guidelines 425 and 407 respectively. The data were analyzed by one-way ANOVA using GraphPad Prism 5.0 software. RESULTS: Oral administration of Asdamarin dose-dependently improved the delay in gastric emptying as evident from the significant increase in the gastrointestinal transit time (p < 0.001). The LD50 of asdamarin was estimated to be more than 2000 mg/kg. Further, in the 28-day sub-acute toxicity study, the administration of 250, 500 and 1000 mg/kg of Asdamarin did not significantly altered the feed and water consuption, body weight change, biochemical and haematological parameters compared to control animals. Macroscopic and histopathological examination of vital organs revealed no toxic signs. CONCLUSION: The preliminary data from the present study provides the first evidence on the possible effectiveness of novel formulation of F. Asafoatida and S. marianum extracts in alleviating the associated symptoms of functional dyspepsia. The toxicity data indicated that Asdamarin can be considered safe up to 1000 mg/kg dose.

Toxicity assessment of Ferula gummosa administration during pregnancy, lactation, and juvenile period in rat.

Ferula gummosa is widely used in traditional medicine to treat a variety of ailments. This work evaluated the safety of F. gummosa root in pregnancy, lactation, and juvenile periods. This study was performed in three parts: (1) pregnant rats were received diet containing 0 (control), 150 , or 700 mg/kg of F. gummosa root during pregnancy; (2) Lactating rats were treated with diet containing the root (0, 150, or 700 mg/kg) during lactation period; (3) juvenile rats were received 4 weeks diet containing the root (0, 150, or 700 mg/kg). F. gummosa at both doses had no significant effects on the duration of pregnancy, maternal weight, and the number of delivered pups, but at dose of 700 mg/kg decreased birthweight of the pups. In lactation period, F. gummosa had no significant effects on mortality, body weight, body length, the weight of organs, and blood biochemical parameters of offspring. In juvenile rats, food consumption, body weight, and WBCs number were decreased in treated groups. No histopathological lesions were detected in the brain, heart, liver, lungs and kidney of offspring, and juvenile rats in treated groups. LC/MS/MS analysis confirmed systemic absorption of active constituents of the root by the oral route of administration. In conclusion, F. gummosa root did not produce significant toxic effects during pregnancy, lactation, and juvenile period. But, decrease in birthweight of delivered pups and in weight gain of juvenile rats should be considered in the long-term consumption of this plant.

Toxicity evaluation of hydroalcoholic extract of Ferula gummosa root.

Traditionally, people use harvested Ferula gummosa for medicinal purposes. However, no information about its safety and toxicity is available. In the present study, the toxicological profile of sub-chronic oral administration of hydroalcoholic extract of F. gummosa radix is evaluated in rats. The extract was orally administrated at 100 and 600 mg/kg to male rats for 28 days. After 28 days, clinical signs, mortality, body weights, food and water consumption, organ weights, hematology, serum biochemistry, as well as histopathological and neurobehavioral changes were examined. Also, the sedative effect of this extract was evaluated in mice at the doses of 100, 600, and 800 mg/kg. Its cytotoxicity against human stroma-vascular cells and human renal epithelial cells were also evaluated. No lethality or adverse toxic signs were seen during the experimental period. There were no significant changes in body and organ weights, hematology, serum biochemistry, and histopathological examination. The extract decreased the rotarod performance, but did not increase pentobarbital-induced hypnosis. Also, F. gummosa extract significantly decreased cell viability at the concentrations of higher than 400 µg/mL. In conclusion, the sub-chronic toxicity study of F. gummosa hydroalcoholic extract demonstrated the extract to be safe for the tested dosage and route of administration.

Analytical discrimination of poisonous and nonpoisonous chemotypes of giant fennel (Ferula communis L.) through their biologically active and volatile fractions.

Giant fennel (Ferula communis L.) from Sardinia is characterized by two chemotypes with different biological activities. One chemotype is poisonous, due to prenylcoumarins, and responsible for ferulosis, which mainly affects sheep and goats, cattle, and horses; the other chemotype is nonpoisonous and contains daucane esters. The two chemotypes cannot be distinguished botanically. High-performance liquid chromatography-diode array-ultraviolet detection-mass spectrometry (HPLC-DAD-UV-MS) analysis of the composition of the fractions containing the biologically active metabolites and of the volatile fractions, by gas chromatography-mass spectrometry (GC-MS), of both essential oil and headspace sampled by headspace solid-phase microextraction (HS-SPME) are here shown to be effective in discriminating the poisonous and nonpoisonous chemotypes. HS-SPME with CAR/PDMS/DVB in combination with GC-MS has also been found to be a successful, fully automated one-step method for rapid and unequivocal discrimination of the two chemotypes, using aristolene and allohedycaryol as markers of the poisonous and nonpoisonous chemotypes, respectively.