Analgesic effect of the flavonoid herbacetin in nociception animal models

M. Oqal, E. Qnais, A. Alqudah, O. Gammoh

Department of Pharmaceutics and Pharmaceutical Technologies, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa, Jordan. abdelrahim@hu.edu.jo

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• Phytomedicine

OBJECTIVE: This study aimed to assess the antinociceptive activity of herbacetin using chemically and thermally induced nociception in a mouse model.

MATERIALS AND METHODS: The antinociceptive effects of various herbacetin 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. Pro-inflammatory mediators: Interleukin-1-beta (IL-1β), Tumour Necrosis Factor alpha (TNF-α), Interferon-gamma (IFN-γ), and Nitric Oxide (NO) were also assessed.

RESULTS: Herbacetin produced significant dose-dependent inhibition of nociceptive behavior in the acetic acid-induced writhing test, showing 65% inhibition at a dose of 200 µg/kg. Herbacetin also caused a significant increase in the latency period in response to the hot plate test (70% 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 herbacetin in both the hot plate and formalin-induced paw-licking test. Moreover, herbacetin significantly inhibited the neurogenic nociception induced by intraplantar injections of capsaicin and glutamate (75% and 48%, respectively, at a dose of 200 µg/kg). Pro-inflammatory cytokines IL-1β, TNF-α, IFN-γ, and NO in the serum of mice were assessed. These cytokines were significantly inhibited by herbacetin (100 and 200  µg/kg). Thus, herbacetin exhibited peripheral and central antinociception through the modulation of vanilloid receptors, opioid receptors, and the glutamatergic system.

CONCLUSIONS: Herbacetin possesses antinociceptive activity in adult mice that is mediated through both central and peripheral pathways.

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