Antinociceptive Activity of Borreria verticillata: In vivo and In silico Studies

Abstract

Borreria verticillata (L.) G. Mey. known vassourinha has antibacterial, antimalarial, hepatoprotective, antioxidative, analgesic, and anti-inflammatory, however, its antinociceptive action requires further studies. Aim of the study evaluated the antinociceptive activity of B. verticillata hydroalcoholic extract (EHBv) and ethyl acetate fraction (FAc) by in vivo and in silico studies. In vivo assessment included the paw edema test, writhing test, formalin test and tail flick test. Wistar rats and Swiss mice were divided into 6 groups and given the following treatments oral: 0.9% NaCl control group (CTRL), 10 mg/kg memantine (MEM), 10 mg/kg indomethacin (INDO), 500 mg/kg EHBv (EHBv 500), 25 mg/kg FAc (FAc 25) and 50 mg/kg FAc (FAc 50). EHBv, FAc 25 and 50 treatments exhibited anti-edematous and peripheral antinociceptive effects. For in silico assessment, compounds identified in FAc were subjected to molecular docking with COX-2, GluN1a and GluN2B. Ursolic acid (UA) was the compound with best affinity parameters (binding energy and inhibition constant) for COX-2, GluN1a, GluN2B, and was selected for further analysis with molecular dynamics (MD) simulations. In MD simulations, UA exhibited highly frequent interactions with residues Arg120 and Glu524 in the COX-2 active site and NMDA, whereby it might prevent COX-2 and NMDA receptor activation. Treatment with UA 10 mg/Kg showed peripheral and central antinociceptive effect. The antinociceptive effect of B. verticillata might be predominantly attributed to peripheral actions, including the participation of anti-inflammatory components. Ursolic acid is the main active component and seems to be a promising source of COX-2 inhibitors and NMDA receptor antagonists.

Anti-Inflammatory and Antinociceptive Activity of Pollen Extract Collected by Stingless Bee Melipona fasciculata

“…After 60 min of treatment, paw edema was induced by subplantar administration of 50 µL of 1% carrageenan into the right paw of the animal. The paw volume of the animal was measured by the digital plethysmometer (Ugo Basile Model, Verese, Italy) during 0, 1, 2, 3, 4 and 5 h after induction [60,61]. The edema value was also obtained by the difference between the right paw volume in the respective hour comparing with the basal volume, being expressed as the variation of the paw volume (mL) over time.…”

Anti-Inflammatory and Antioxidant Activity of Pollen Extract Collected by Scaptotrigona affinis postica: in silico, in vitro, and in vivo Studies

“…A digital plethysmometer (Ugo Basile Model, Verese, Italy) was used to evaluate the variation of edema for 5 h, with a 60 min interval between each measurement. The difference between induced paw-volume versus basal time in each evaluation hour was used to evaluate the effect of treatment [20,21].…”

“…To perform this test, 1 h before writhes induction with acetic acid solution at 0.8% (10 mL/kg) by intraperitonial administration, the mice (n = 5) were treated orally with TbHPE 250 mg/kg, indomethacin (10 mg/kg) or vehicle (saline) (10 mL/kg). During the first 20 min after induction, the animals were evaluated regarding the number of writhes [21,23].…”

“…One hour after the oral treatment with TbHPE 250 mg/kg, indomethacin (10 mg/kg), or vehicle (saline) (10 mL/kg), the mice (n = 5) were administrated, by subplantar injection, 20 µL of formalin 2.5% in the right paw and the animal responses in the first 5 min (neurogenic phase) and 15-30 min after the induction (peripheral phase) were evaluated [21,24].…”

“…COX-2 structure was obtained on Protein Data Bank (PDB ID 1DDX) with original ligands and artifacts removed and compound from TBHPE prepared with AutoDock Tools (Scripps Research, San Diego, California, USA) version 1.5.6 [29]. Docking protocol described in literature was used [30] with adjustment [7,21,31]. We used the oxygen atom from residue Arg120, catalytic site residue from COX-2, to position the grid box and Lamarckian genetic algorithm (LGA), with 100 runs for each compound.…”