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

Sajjad Jabbari; Zainul Amiruddin Zakaria; Irwin Rose Alencar de Menezes; Saeed Mohammadi

doi:10.1016/j.jep.2024.119174

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

J Ethnopharmacol. 2024 Nov 28:339:119174. doi: 10.1016/j.jep.2024.119174. Online ahead of print.

Authors

Sajjad Jabbari¹, Zainul Amiruddin Zakaria², Irwin Rose Alencar de Menezes³, Saeed Mohammadi⁴

Affiliations

¹ Department of Biology, Faculty of Sciences, Islamic Azad University, Tehran North Branch, Tehran, Iran. Electronic address: sajjadjabbarighorve@gmail.com.
² Borneo Research on Algesia, Inflammation and Neurodegeneration (BRAIN) Group, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu, 88400, Sabah, Malaysia; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Gedung Nanizar Zaman Joenoes Kampus C, Jl. Mulyorejo, Mulyorejo, Surabaya, East Java 60115, Indonesia. Electronic address: zaz@ums.edu.my.
³ Laboratory of Pharmacology and Molecular Chemistry, Department of Chemical Biology, Regional University of Cariri (URCA), Rua Coronel Antônio Luis 1161, Pimenta, CEP 63105-000, Crato, Ceará, Brazil. Electronic address: Irwin.alencar@urca.br.
⁴ Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. Electronic address: smiauhphd.sm@gmail.com.

PMID: 39613005
DOI: 10.1016/j.jep.2024.119174

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.

Keywords: Acute pain; Chronic pain; Ethnopharmacology; Fritillaria imperialis; Migraine; Verticinone.