Avaliação farmacológica e toxicológica do extrato etanólico das folhas de Salvia lachnostachys Benth e de Fruticulina A em modelo experimental com roedores

Abstract

Salvia lachnostachys Benth is endemic in southern Brazil, the phytochemical evaluation revealed the presence of ursolic and oleanolic acids, as well as fruticuline A, which may be responsible for the anti-inflammatory and antinociceptive activity reported in the literature by our group. In this study, we investigated the pharmacological activities: antihyperalgesic, antiarthritic, antidepressive and antinociceptive, as well as the genotoxic and mutagenic potential of the S. lachnostachys (SLEE) leaves and the fruticuline A, in rodents. SLEE (100 mg / kg, p.o.) was evaluated in the sciatic nerve injury (SNI) model in rats and the animals were submitted to mechanical sensitivity, cold sensitivity and forced swimming 10 and 15 days after surgery. In the chronic, arthritis-like, induced pain model induced by the complete Freund's adjuvant (CFA), The animals received the SLEE (50 and 100 mg/kg/day) all 21 days of treatment, being evaluated the mechanical and thermal sensitivity (cold and heat) on days 5, 7, 10, 15 and 21. SLEE (100 mg/kg, p.o.) and fruticuline A (3 mg/kg, v.o.) were also evaluated in the formalin-induced nociceptive response with the animals being treated one hour prior to formalin injection into the paw. In the clonidine-induced depression model, the animals received an injection of clonidine (0.8 mg / kg) for 7 days, while treatment was started from day 5 to day 7 with SLEE (100mg/kg/day) and fruticuline A (3 mg/kg/day). For toxicogenic evaluation (genotoxicity and micronucleus test), apoptosis and splenic phagocytosis, the animals were orally treated with SLEE (10, 100 and 1000 mg / kg). In the neuropathy model (SNI), oral administration of SLEE for 15 days and a subcutaneous dose of 10 mg / kg ketamine (positive control) significantly inhibited SNI-induced mechanical hyperalgesia and decreased the time of immobility in the forced swim test. On the 15th day of oral treatment, SLEE prevented increased sensitivity to cold stimuli induced by neuropathy. In the pain chronic model, SLEE significantly reduced mechanical and thermal hyperalgesia and edema caused by CFA injection, suggesting antiarthritic activity. In the formalin test, SLEE and fruticulin A significantly reduced the nociceptive response (paw licking frequency) in the first And second stage and decreased the formation of edema. SLEE and fruticuline A significantly attenuated the effects induced by clonidine - increasing spontaneous locomotor activity (invaded squares and lifting) and decreasing emotionality (licking and freezing) compared to controls, the results were similar to the naive (non-depressive) group. The results of the comet and micronuclei tests revealed that SLEE did not cause damage to DNA but there was an increase in the number of apoptotic cells of the spleen after 72h of treatment with SLEE (1000 mg / kg). Based on the results, SLEE exhibits antihyperalgesic, antiarthritic, antidepressive, and antinociceptive activity, and fruticuline A appears to be one of the compounds responsible for the effects of SLEE. These results reinforce the antidepressant actions of SLEE and fruticuline A. The results still show low toxicity in the models tested, but other tests should be performed.