Estudo químico e avaliação anti-inflamatória, neuroprotetiva e toxicológica em camundongos das folhas de Allophylus edulis (A.St.-Hil., Cambess. & A. Juss.) Radlk.

Abstract

The Brazilian native tree Allophylus edulis (A.St.-Hil., Cambess. & A. Juss.) Radlk., known as "vacum", has its leaves commonly used for the treatment of inflammatory conditions such as sore throat, cholecystitis, and fever, described as rich in flavonoids. This research aimed to: (1) analyze the variation in the chemical composition of the essential oil from A. edulis leaves; (2) conduct chemical, histochemical, in vitro antioxidant, in vivo pharmacological studies (anti-inflammatory, anti-hyperalgesic, and antinociceptive) of the leaves, with in silico predictions of vitexin 2''-O-rhamnoside; and (3) investigate the anxiolytic, anti-amnesic effects, and subacute toxicity of the leaves, along with the molecular remodeling of vitexin 2''-O-rhamnoside on acetylcholinesterase (AChE). In the first manuscript (1), fresh A. edulis leaves collected in Bonito and Dourados/MS (2018 to 2019) had their essential oils extracted and analyzed. The yield varied from 0.07% to 0.6%, increasing with higher temperatures and during the flowering phase. In Dourados, the main component was caryophyllene oxide (20 to 29%), and in Bonito, α-zingiberene (25 to 45%). In the second manuscript (2), histochemical analysis revealed secretory structures in fresh A. edulis leaves. An infusion of the leaves (ILAE) was obtained from fresh leaves, fractionated into fractions, including hydromethanolic (HMf). From the latter, vitexin 2''-O-rhamnoside was isolated, undergoing in silico prediction, showing low predicted toxicity. Better antioxidant effects were observed in free radical scavenging models. Oral administration of ILAE (3, 30, and 100 mg/kg) and HMf (3 mg/kg) was tested in acute inflammation models (induced by carrageenan), mechanical hyperalgesia, thermal allodynia, and nociception (induced by formalin), showing a significant reduction in induced effects. The ILAE (30 mg/kg), HMf (3 and 30 mg/kg), and vitexin 2''-O-rhamnoside (AE-1, 3 mg/kg) were tested in a prolonged inflammation model (induced by complete Freund's adjuvant - CFA), resulting in a significant reduction in edema, mechanical hyperalgesia, and thermal allodynia, including for the isolated flavonoid (AE-1). In the third manuscript (3), oral administration of ILAE (3, 30, and 100 mg/kg) and HMf (3 mg/kg) was evaluated in anxiety and amnesia models (induced by scopolamine). The treatments reduced anxiety and improved parameters related to short-term memory. The decrease in AChE activity and lipid peroxidation, along with the intermolecular interactions of vitexin 2''-O-rhamnoside with AChE (in silico), may explain, at least in part, the observed results. It is concluded that A. edulis has a diversity of metabolites and potential anti-inflammatory, antinociceptive, and neuroprotective properties.