Lysionotin exerts antinociceptive effects in various models of nociception induction

Abdelrahim Alqudah; Esam Y Qnais; Mohammed A Wedyan; Hakam AlKhateeb; Shtaywy S Abdalla; Omar Gammoh; Mohammad A AlQudah

doi:10.1016/j.heliyon.2023.e15619

Lysionotin exerts antinociceptive effects in various models of nociception induction

Heliyon. 2023 Apr 18;9(4):e15619. doi: 10.1016/j.heliyon.2023.e15619. eCollection 2023 Apr.

Authors

Abdelrahim Alqudah¹, Esam Y Qnais², Mohammed A Wedyan², Hakam AlKhateeb³, Shtaywy S Abdalla⁴, Omar Gammoh⁵, Mohammad A AlQudah⁶

Affiliations

¹ Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa, Jordan.
² Department of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa, Jordan.
³ Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan.
⁴ Department of Biological Sciences, Faculty of Science, University of Jordan, Amman, Jordan.
⁵ Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan.
⁶ Department of Physiology, Jordan University of Science and Technology, Irbid, Jordan.

Abstract

Background: Lysionotin, a natural flavonoid extracted from Lysionotus pauciflorus Maxim (Gesneriaceae), has several pharmacological effects including anti-bacterial, anti-hypertensive and anti-inflammatory effects. However, its analgesic effect has not been investigated. This study aimed to assess the antinociceptive activity of lysionotin using chemically and thermally induced nociception in a mouse model.

Methods: The antinociceptive effects of various lysionotin doses (50, 100, 150, and 200 μg/kg) were assessed in mice using the acetic acid-induced writhing test, hot plate test, and formalin-induced paw licking assay. The effects were compared to those of mice treated with acetylsalicylic acid or morphine in the presence or absence of naloxone (an opioid receptor antagonist). Capsaicin- and glutamate-induced paw licking tests were also used to evaluate the involvement of the vanilloid and glutamatergic systems, respectively.

Results: Lysionotin produced significant dose-dependent inhibition of nociceptive behavior in the acetic acid-induced writhing test, showing 60% inhibition at a dose of 200 μg/kg. Lysionotin also caused a significant increase in the latency period in response to the hot plate test (76.4% at 200 μg/kg), and significantly inhibited both the neurogenic and inflammatory phases in the formalin-induced paw licking test. Naloxone significantly reverses the effect of lysionotin in both hot plate test and formalin-induced paw licking test. Moreover, lysionotin significantly inhibited the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin (57% and 67.2%, respectively at a dose of 200 μg/kg). Thus, lysionotin exhibited peripheral and central antinociception through the modulation of vanilloid receptors, opioid receptors, and the glutamatergic system.

Conclusion: Lysionotin possesses antinociceptive activity on adult mice that is mediated through both central and peripheral pathways.

Keywords: Flavonoids; Glutamate; Lysionotin; Naloxone; Nociception; Vanilloid.