Chemical characterization, pharmacological effects, and toxicity of an ethanol extract of Celtis pallida Torr. (Cannabaceae) aerial parts

Abstract

Ethnopharmacological relevance: Celtis pallida Torr (Cannabaceae) is employed as a folk medicine for the treatment of inflammation, pain, skin infections, and diarrhea, among other diseases.

Aim of the study: The purpose of this work was to assess the chemical composition, the in vitro and in vivo toxicity, the antimicrobial, anti-inflammatory, antidiarrheal, antinociceptive, locomotor, and sedative effects of an ethanolic extract obtained from Celtis pallida aerial parts (CPE).

Materials and methods: The composition of CPE was carried out by GC-MS. The in vitro and in vivo toxic activity of CPE was estimated with the comet assay (10-1000 µg/ml) for 5 h in peripheral blood mononuclear cells, and the acute toxicity test (500-5000 mg/kg p.o.), for 14 days, respectively. The antimicrobial effect of CPE was evaluated using the minimum inhibitory concentration (MIC) assay, whereas the antidiarrheal activity (10-200 mg/kg p.o.) was calculated using the castor oil test. The antinociceptive effects of CPE (50-200 mg/kg p.o.) were estimated with the acetic acid and formalin tests, as well as the hot plate test. The sedative and locomotor activities of CPE (50-200 mg/kg p.o.) were assessed with the pentobarbital-induced sleeping time test and the rotarod test, respectively.

Results: The main compound found in CPE was the triterpene ursolic acid (22% of the extract). CPE at concentrations of 100 µg/ml or higher induced genotoxicity in vitro and showed low in vivo toxicity (LD₅₀ > 5000 mg/kg p.o.). Additionally, CPE lacked (MIC > 400 µg/ml) antimicrobial activity but exerts antinociceptive (ED₅₀ = 12.5 ± 1.5 mg/kg) and antidiarrheal effects (ED₅₀ = 2.8 mg/kg), without inducing sedative effects or altering the locomotor activity. The antinociceptive activity of CPE suggests the participation of adrenoceptors, as well as the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway.

Conclusion: C. pallida exerts its antinociceptive effects probably mediated by the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway.

Keywords: Antimicrobial; Carbamoyl choline (PubChem CID:5831); Celtis pallida; Clonazepam (PubChem CID:2802); Diarrhea; Dimethyl sulfoxide (PubChem CID:679); Glibenclamide (PubChem CID:3488); Inflammation; Naloxone (PubChem CID:5464092); Naproxen sodium (PubChem CID: 23681059); Pain; Tramadol hydrochloride (PubChem CID:63013); pentobarbital (PubChem CID: 4737).