Anti-hyperalgesic and anti-allodynic activities of capillarisin via suppression of inflammatory signaling in animal model

作者：Khan Salman; Shehzad Omer; Chun Jaemoo; Choi Ran Joo; Park Saitbyul; Islam Md Nurul; Choi Jae Sue; Kim Yeong Shik^*

来源：Journal of Ethnopharmacology, 2014, 152(3): 478-486.

DOI：10.1016/j.jep.2014.01.028

• Capillarisin
• Hyperalgesia
• Allodynia
• CFA
• NF-kappa B
• CREB

Ethnopharmacological relevance: Artemisia capillaris has widespread traditional and pharmacological applications such as analgesic, anti-inflammatory, anti-pyretic, enhance immunity and anti-tumor activity properties. To evaluate the pharmacological activities of this plant, capillarisin, one of the potent constituent of Artemisia capillaris was studied based on anti-hyperalgesic and anti-allodynic effects with detailed mechanism. It can be assumed that measurement of anti-nociceptive effects of capillarisin is one of the parameter for the evaluation of this herb. Capillarisin has extensive pharmacological properties and has been considered to have promising ant-inflammatory and anti-nociceptive activities. The aim of the current study is to investigate the effect of capillarisin and underlying molecular mechanisms of action in preventing acute and subchronic inflammatory pain. %26lt;br%26gt;Materials and methods: The inflammatory pain was induced after 40 mm or 1 h of administration of vehicle, 70% EtOH extract of Artemisia capillaris (100 mg/kg) or capillarisin (20 and 80 mg/kg) by intraplantar (i.p.l.) injections of CFA and carrageenan in ICR mice, respectively. Mechanical hyperalgesia and allodynia were evaluated in both acute and subchronic models. Further analysis was performed in CFA-induced mice exploring various molecular and signaling pathways such as NF-kappa B, AP-1, and ERK-CREB involved in the persistent pain sensations. %26lt;br%26gt;Results: In acute model, mechanical hyperalgesia and allodynia were evaluated after every 2 h until 6 h of CFA and after 4 h of carrageenan injections. Whereas, in subchronic inflammatory pain model, mechanical hyperalgesia and paw edema were measured after 4 h of CFA injection and every day after 4 h of daily treatment until 5 days with interval of day four in order to assess the tolerance effect of capillarisin. Further analysis was performed in CFA-induced mice exploring various molecular and signaling pathways such as NF-kappa B, AP-1 and ERK-CREB involved in the persistent of pain sensations. Pretreatment of capillarisin strongly inhibited NF-kappa B mediated genes (iNOS, COX-2), involved in pain. The plasma leading nitrite production was significantly reduced by capillarisin. Moreover, i.p. administration of capillarisin markedly suppressed the adenosine 5%26apos;-triphosphate (ATP) in plasma and substance P in CFA-induced paw tissue. %26lt;br%26gt;Conclusions: The present study indicates that capillarisin possessed promising anti-hyperalgesic and anti-allodynic effects through the inhibition of various inflammatory pain signaling, suggesting that capillarisin constitutes a significant component for the treatment of inflammatory pain.

• 出版日期2014-3-28