Efeitos farmacológicos do extrato etanólico das cascas do fruto de Nephelium lappaceum L. na nocicepção e na úlcera gástrica

• Ano de defesa: 2022
• Autor(a) principal: Oliveira, Alan Santos
• Orientador(a): Camargo, Enilton Aparecido
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Programa de Pós-Graduação: Pós-Graduação em Ciências da Saúde
• Palavras-chave em Português: Rabutan; Atividade motora; Toxidade; Mucosa gástrica; Úlcera gástrica
• Palavras-chave em Inglês: Locomotor activity; Toxicity; Gastric mucosa; Gastric ulcer
• Área do conhecimento CNPq: CIENCIAS DA SAUDE
• Link de acesso: http://ri.ufs.br/jspui/handle/riufs/16772

Introduction: Rambutan, the fruit of Nephelium lappaceum L. (Sapindaceae) is popularly used to treat fever, stomach pain and diarrhea. The peels of rambutan contain a variety of phytochemicals, such as phenolic compounds, flavonoids and carotenoids, which add potential for several biological activities. Its use is suggested in cosmeceutical, nutraceutical and pharmaceutical preparations. Objective: The present study evaluated the antinociceptive and gastroprotective activities of the ethanolic extract of the fruit peels of N. lappaceum L. (EENL) in non-clinical models, as well as it evaluated whether this extract induces acute toxicity in zebrafish. Material and methods: EENL was characterized by chromatography coupled to mass spectrometry (RP-UHPLC-DAD). The experimental protocols were approved by the Animal Research Ethics Committee of Instituto Butantan – São Paulo (nº 6438210220) and UFS (nº 1122270819). An acute toxicity test was performed on zebrafish. Male Swiss mice were treated with EENL (50, 100 or 200 mg/kg, po, 1 hour before) and submitted to nociception assessment (abdominal writhing, paw formalin and capsaicin, carrageenan-induced mechanical hyperalgesia and hot plate test) and locomotor activity (open field). The ulcer model induced by acidified ethanol (60% ethanol/0.3 mol/L HCl) was used to evaluate the gastroprotective effect of EENL. In this model, the concentration of sulfhydryl compounds and lipid peroxidation in the gastric mucosa were also evaluated. The participation of non-protein sulfhydryl compounds (NP-SH), nitric oxide (NO), prostaglandins (PG), ATP-sensitive K+ channels (KATP) and hydrogen sulfide (H2S) in the gastroprotective effect of EENL was investigated in this model of ulcer using pharmacological tools. The effect of EENL on gastric volume, acidity and pH was evaluated in the pylorus ligation model, as well as mucus on gastric contents. Results: Procyanidin B, epicatechin, ellagic acid and their derivatives (such as punicalin and pedunculagin) were identified in the EENL. No toxicity was observed after incubating EENL with zebrafish embryos. Oral pretreatment of mice with EENL (200 mg/kg) did not alter locomotor activity, but pretreatment with doses of 50, 100 and 200 mg/kg reduced (p<0.05 or p<0.001) the abdominal writhing induced by acetic acid. Pretreatment with EENL (100 and 200 mg/kg, p.o.) reduced (p<0.001) the licking/biting time in both first and second phases of the formalin test and in the capsaicin test, as well as decreased (p<0.001) carrageenan-induced mechanical paw hyperalgesia. In the hot plate test, oral pretreatment with EENL (50,100 and 200 mg/kg) increased (p<0.001) the latency time. This antinociceptive effect was reversed by naloxone (opioid antagonist), L-arginine (a precursor of nitric oxide) and glibenclamide (a KATP blocker). Pretreatment with EENL (50, 100 and 200 mg/kg) reduced the area of gastric injury induced by acidified ethanol (p<0.01) and lipid peroxidation (p<0.001), and the doses of 100 and 200 mg/kg increased sulfhydryl content in the stomach (p<0.01 or 0.05, respectively) compared to the vehicle group. Pretreatment with N-ethylmaleimide (a non-protein sulfhydryl group blocker, 10 mg/kg, ip), indomethacin (inhibitor of prostaglandin synthesis, 10 mg/kg) or L-NAME (inhibitor of nitric oxide synthase, 70 mg/kg) inhibited the gastroprotective response caused by EENL (100 mg/kg; p<0.05 or 0.001), but there were no changes due to pretreatments with glibenclamide (a KATP channel blocker, 10 mg/kg, ip) or DL-propargylglycine (an inhibitor of hydrogen sulfide synthesis, 10 mg/kg). In addition, treatment with EENL (100 mg/kg) increased mucus production (p<0.001) and pH (p<0.01) and reduced the volume (p<0.001) and acidity (p<0.001) of the gastric secretion after pylorus ligation. Conclusion: The results demonstrate that EENL did not cause changes in zebrafish, contains anthocyanins, catechins and phenolic compounds, induces antinociceptive effect with the participation of opioid receptors, NO and KATP channels and promotes gastroprotective effect with the participation of sulfhydryl groups, prostaglandins, NO and increased mucus production and modulation of parameters of gastric secretion.