Hancornia speciosa Gomes (Apocynaceae), popularly known as “mangabeira,” has been used in folk medicine to treat inflammatory disorders, hypertension, dermatitis, diabetes, liver diseases and gastric disorders. Although the ethnobotany indicates that its fruits can be used for the treatment of ulcers and inflammatory disorders, only few studies have been conducted to prove such biological activities. This study investigated the anti-inflammatory properties of the aqueous extract of the fruits of H. speciosa Gomes as well as its bioactive compounds using in vivo experimental models. The bioactive compounds were identified by High Performance Liquid Chromatography coupled with diode array detector (HPLC-DAD) and Liquid Chromatography coupled with Mass Spectrometry (LC-MS). The anti-inflammatory properties were investigated through in vivo tests, which comprised xylene-induced ear edema, carrageenan-induced peritonitis and zymosan-induced air pouch. The levels of IL-1β, IL-6, IL-12 and TNF-α were determined using ELISA. Rutin and chlorogenic acid were identified in the extract as the main secondary metabolites. In addition, the extract as well as rutin and chlorogenic acid significantly inhibited the xilol-induced ear edema and also reduced the cell migration in both carrageenan-induced peritonitis and zymosan-induced air pouch models. Reduced levels of cytokines were also observed. This is the first study that demonstrated the anti-inflammatory activity of the extract of H. speciosa fruits against different inflammatory agents in animal models, suggesting that its bioactive molecules, especially rutin and chlorogenic acid are, at least in part, responsible for such activity. These findings support the widespread use of Hancornia speciosa in popular medicine and demonstrate that its aqueous extract has therapeutical potential for the development of herbal drugs with anti-inflammatory properties.
Bothrops leucurus is responsible for most cases of snakebite in Northeast Brazil; however, this species is not included in the pool of venoms used in antivenom production in Brazil. The serotherapy has logistical and effectiveness limitations, which stimulates the search for therapeutic alternatives. Chlorogenic acid and rosmarinic acid present several biological activities, but their antiophidic potential has been poorly explored. Thus, the aim of this approach was to evaluate the potential inhibitory effects of these compounds on B. leucurus venom. Initially, the enzymatic inhibition of toxins was evaluated in vitro. Then, anti-hemorrhagic, anti-myotoxic, and anti-edematogenic assays were performed in vivo, as well analysis of several biochemical markers and hemostatic parameters. In addition, the interaction of inhibitors with SVMP and PLA2 was investigated by docking analysis. Results revealed that compounds inhibited in vitro the enzymatic activities and venom-induced edema, with a decrease in both myeloperoxidase and interleukin quantification. The inhibitors also attenuated the hemorrhagic and myotoxic actions and mitigated changes in serum biochemical and hemostatic markers, as well as decreased lipid peroxidation in liver and kidney tissues. Docking analysis revealed attractive interactions of both inhibitors with the zinc-binding site of SVMP and, in the case of PLA2, chlorogenic acid showed a similar inhibition mechanism to that described for rosmarinic acid. The results evidenced the antiophidic potential of both compounds, which showed higher efficiency than antivenom serum. Thus, both inhibitors are promising candidates for future adjuvants to be used to complement antivenom serotherapy.