Pellucidin A promotes antinociceptive activity by peripheral mechanisms inhibiting COX-2 and NOS: In vivo and in silico study

PLoS One. 2020 Sep 17;15(9):e0238834. doi: 10.1371/journal.pone.0238834. eCollection 2020.

Abstract

Peperomia pellucida (PP) belongs to the Peperomia genus, which has a pantropic distribution. PP is used to treat a wide range of symptoms and diseases, such as pain, inflammation, and hypertension. Intriguingly, PP extract is used by different tropical countries for its anti-inflammatory and antinociceptive effects. In fact, these outcomes have been shown in animal models, though the exact bioactive products of PP that exert such results are yet to be discovered. To determine and elucidate the mechanism of action of one of these compounds, we evaluated the antinociceptive effect of the novel dimeric ArC2 compound, Pellucidin A by using in vivo and in silico models. Animals were then subjected to chemical, biphasic and thermal models of pain. Pellucidin A induced an antinociceptive effect against chemical-induced pain in mice, demonstrated by the decrease of the number of writhes, reaching a reduction of 43% and 65% in animals treated with 1 and 5 mg/kg of Pellucidin A, respectively. In the biphasic response (central and peripheral), animals treated with Pellucidin A showed a significant reduction of the licking time exclusively during the second phase (inflammatory phase). In the hot-plate test, Pellucidin A did not have any impact on the latency time of the treated animals. Moreover, in vivo and in silico results show that Pellucidin A's mechanism of action in the inflammatory pain occurs most likely through interaction with the nitric oxide (NO) pathway. Our results demonstrate that the antinociceptive activities of Pellucidin A operate under mechanism(s) of peripheral action, involving inflammatory mediators. This work provides insightful novel evidence of the biological properties of Pellucidin A, and leads to a better understanding of its mechanism of action, pointing to potential pharmacological use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Cyclobutanes / pharmacology*
  • Cyclooxygenase 2 / drug effects
  • Cyclooxygenase 2 / metabolism
  • Inflammation / drug therapy
  • Mice
  • Molecular Docking Simulation
  • Nitric Oxide / metabolism
  • Pain / drug therapy
  • Pain / physiopathology
  • Pain Measurement
  • Peperomia
  • Plant Extracts / pharmacology

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Cyclobutanes
  • Plant Extracts
  • pellucidin A
  • Nitric Oxide
  • Cyclooxygenase 2

Grants and funding

The authors received funding for National Council of Scientific and Technological Development (CNPq), CAPES and Fundação Amazônia Paraense de Amparo à Pesquisa (FAPESPa).