Evaluation of acute and sub-chronic toxicity of Semelil (ANGIPARS™), a new phytotherapeutic drug for wound healing in rodents

Semelil (ANGIPARS™), an herbal formulation containing Melilotus officinalis extract, is a novel compound being developed for treatment of chronic wounds, particularly diabetic foot ulcers. The purpose of this study was to investigate toxicological, pharmacological, and pathomorphological effects of I.M. and I.P. administration of Semelil in animals. The acute toxicity parameters of Semelil diluted in normal saline (1:10 or 1:5) were determined after a single injection into BALB/c mice and Wistar rats in two steps. First, the LD50 was approximately assessed and then the precise lethal dose indices were estimated by the probit-analysis method. Specific single-dose effects of Semelil were monitored for clinical signs of toxicity, including general state of the animals, changes in their behavior, hematological and biochemical parameters for 14 days after drug administration. Then, subacute-chronic toxicity was evaluated in rats treated with Semelil for 3 months. In acute toxicity study, the calculated LD50 for drug diluted at 1:5 was in the range of 44-52 ml/kg. The adverse effects at drug doses close to the LD50 included depressed mood, narcosis, and sleep. No adverse pharmacological or toxicological effects of the drug diluted at 1:10 and administered in the single-dose (25-50 ml/kg body wt.) or chronically (daily doses of 0.07 and 0.21 ml/kg body wt.) were noted. Thus, the animal studies demonstrated a favorable safety profile for the phytotherapeutic Semelil.