PMID- 24495472 OWN - NLM STAT- MEDLINE DCOM- 20141128 LR - 20140317 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 152 IP - 3 DP - 2014 Mar 28 TI - Anti-hyperalgesic and anti-allodynic activities of capillarisin via suppression of inflammatory signaling in animal model. PG - 478-86 LID - S0378-8741(14)00075-0 [pii] LID - 10.1016/j.jep.2014.01.028 [doi] AB - 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. MATERIALS AND METHODS: The inflammatory pain was induced after 40 min or 1h of administration of vehicle, 70% EtOH extract of Artemisia capillaris (100mg/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-kappaB, AP-1, and ERK-CREB involved in the persistent pain sensations. RESULTS: In acute model, mechanical hyperalgesia and allodynia were evaluated after every 2h until 6h of CFA and after 4h of carrageenan injections. Whereas, in subchronic inflammatory pain model, mechanical hyperalgesia and paw edema were measured after 4h of CFA injection and every day after 4h 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-kappaB, AP-1 and ERK-CREB involved in the persistent of pain sensations. Pre-treatment of capillarisin strongly inhibited NF-kappaB 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׳-triphosphate (ATP) in plasma and substance P in CFA-induced paw tissue. 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. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Khan, Salman AU - Khan S AD - Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. FAU - Shehzad, Omer AU - Shehzad O AD - Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea; Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan. FAU - Chun, Jaemoo AU - Chun J AD - Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. FAU - Choi, Ran Joo AU - Choi RJ AD - Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. FAU - Park, Saitbyul AU - Park S AD - Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. FAU - Islam, Md Nurul AU - Islam MN AD - Department of Food Science and Nutrition, Pukyong National University, Pusan 608-737, Republic of Korea. FAU - Choi, Jae Sue AU - Choi JS AD - Department of Food Science and Nutrition, Pukyong National University, Pusan 608-737, Republic of Korea. FAU - Kim, Yeong Shik AU - Kim YS AD - Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: kims@snu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140202 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Analgesics) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Chromones) RN - 0 (Plant Extracts) RN - 56365-38-9 (capillarisin) RN - 9000-07-1 (Carrageenan) SB - IM MH - Analgesics/administration & dosage/isolation & purification/pharmacology MH - Animals MH - Anti-Inflammatory Agents/administration & dosage/isolation & purification/pharmacology MH - Artemisia/*chemistry MH - Carrageenan/toxicity MH - Chromones/administration & dosage/isolation & purification/*pharmacology MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Edema/drug therapy/pathology MH - Hyperalgesia/drug therapy/pathology MH - Inflammation/*drug therapy/pathology MH - Male MH - Mice MH - Mice, Inbred ICR MH - Pain/drug therapy/pathology MH - Plant Extracts/administration & dosage/*pharmacology MH - Signal Transduction/drug effects OTO - NOTNLM OT - Allodynia OT - CFA OT - CREB OT - Capillarisin OT - Hyperalgesia OT - NF-kappaB EDAT- 2014/02/06 06:00 MHDA- 2014/12/15 06:00 CRDT- 2014/02/06 06:00 PHST- 2013/05/09 00:00 [received] PHST- 2014/01/22 00:00 [revised] PHST- 2014/01/25 00:00 [accepted] PHST- 2014/02/06 06:00 [entrez] PHST- 2014/02/06 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] AID - S0378-8741(14)00075-0 [pii] AID - 10.1016/j.jep.2014.01.028 [doi] PST - ppublish SO - J Ethnopharmacol. 2014 Mar 28;152(3):478-86. doi: 10.1016/j.jep.2014.01.028. Epub 2014 Feb 2.