Antinociceptive, antineuropathic, and antimigraine-like activities of Fritillaria imperialis L. rich in verticinone on rats: Mechanisms of action

Abstract

Ethnopharmacological relevance

Fritillaria imperialis L. (Fabaceae), commonly known as “Laleh vazhgon”, ethnomedicinally utilized in Iranian traditional medicine to treat joint pain, chronic daily headaches, and back pain.

Aim of the study

To investigate the antinociceptive, anti-neuropathic, and anti-migraine activities of Fritillaria imperialis bulbs essential oil (FIEO) as well as to uncover the potential mechanisms of action involved.

Materials and methods

The antinociceptive activity of FIEO and its main constituent, Verticinone (Vt), was assessed using the formalin-induced paw licking assay. The potential mechanisms of antinociception were investigated through various antagonists. Additionally, their antineuropathic activity was examined using the cervical spinal cord contusion (CCS) technique and the possible role of Stat3 was evaluated using Western blot analysis. The nitroglycerin-induced model (NTG) was also employed for the evaluation of migraine.

Results

FIEO demonstrated significant antinociceptive activity in both phases of the formalin-induced test. However, the FIEO activity was more pronounced effect observed in the second phase. Modulators of the NO-cGMP-K⁺ channel pathway significantly reversed the antinociceptive activity of FIEO (P < 0.05). Additionally, antagonists of TRPV1, PPARα, dopamine D1, GABA_A, and δ-opioid receptors also significantly reversed the antinociceptive effects of FIEO (P < 0.05). In a separate study, both FIEO and Vt were found to attenuate hyperalgesia and mechanical allodynia (P < 0.01) when evaluated using the CCS-induced pain model. Furthermore, FIEO may alleviate migraine behaviors, likely related to the regulation of NO and CGRP levels.

Conclusion

FIEO exerts an antineuropathic effect through the phosphorylation of Stat3. Furthermore, the antinociceptive activity is partially modulated via the NO-cGMP-K⁺ channel pathway, as well as the activation of TRPV, PPAR, opioid, and GABA receptors. Vt may be involved in the antinociceptive, antineuropathic, and antimigraine activities induced by FIEO.