Analgesic effect of the flavonoid herbacetin in nociception animal models.

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-1ß), 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-1ß, 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.