PMID- 31589967 OWN - NLM STAT- MEDLINE DCOM- 20200323 LR - 20200323 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 247 DP - 2020 Jan 30 TI - Euryops arabicus displays anti-inflammatory activities in experimental models. PG - 112278 LID - S0378-8741(19)30783-4 [pii] LID - 10.1016/j.jep.2019.112278 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Euryops arabicus (Asteraceae) is grown in Arab Peninsula. Its aerial parts possess ethnomedicinal applications against several inflammatory conditions. AIM OF THE STUDY: To evaluate the anti-inflammatory activity of Euryops arabicus (E. arabicus) organic extract as well as its major polymethoxylated flavonoids. MATERIALS AND METHODS: Acute toxicity of the total extract of E. ararbicus was evaluated by assessing LD(50). In vivo anti-inflammatory activity was evaluated in rats injected with carrageenan in the plantar area. Paw edema volume, histological changes and rats'stair climbing and motility were assessed. In vitro anti-inflammatory activity of the isolated compounds was evaluated in peripheral blood mononuclear cells (PBMCs) challenged with carrageenan. Inflammation markers were assessed in cellular lysates and collected media. RESULTS: The extract was found safe and considered unclassified with an oral LD(50) > 2000 mg/kg in rats. Pretreatment of rats with a total extract of E. arabicus at doses of 100 and 250 mg/kg significantly inhibited carrageenan-induced increase in paw edema volume and histopathological changes. Also, it significantly ameliorated diminution of climbing and motility. Phytochemical studies led to the isolation and identification of five polymethoxylated flavonoids. The anti-inflammatory properties of the isolated compounds were evaluated in carrageenan-challenged peripheral blood mononuclear cells (PBMCs). All compounds exhibited appreciable antioxidant activities. Further, pre-incubation of the cells with the isolated metabolites significantly ameliorated the rise in cyclo-oxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and monocyte chemoattractant protein-1 (MCP-1) induced by carrageenan challenge. Further, the compounds inhibited the leakage of interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and myeloperoxidase (MPO) in media collected from stimulated cells. CONCLUSION: E. arabicus exhibited in vivo anti-inflammatory effects in the carrageenan model as it ameliorated rat paw edema, histopathological changes and movement dysfunction. in vitro activity of isolated compounds was confirmed in stimulated PBMCs. Thus, the anti-inflammatory activity of E. arabicus can be attributed, at least partly, to its anti-oxidant, anti-inflammatory and anti-chemotactic properties. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Abdel-Lateff, Ahmed AU - Abdel-Lateff A AD - Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah, PO Box 80260, 21589, Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, PO. Box 61511, 61519, Egypt. Electronic address: aabdellatteff@kau.edu.sa. FAU - Alarif, Walied Mohamed AU - Alarif WM AD - Department of Marine Chemistry, Faculty of Marine Science, King Abdulaziz University, Jeddah, PO. Box 80207, 21589, Saudi Arabia. FAU - Algandaby, Mardi Mohamed AU - Algandaby MM AD - Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, PO. Box 80203, 21589, Saudi Arabia. FAU - Alburae, Najla Ali AU - Alburae NA AD - Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, PO. Box 80203, 21589, Saudi Arabia; Biology Department, College of Science, Princess Nourah Bint Abdulrahman University, PO. Box 84428, Riyadh, 11671, Saudi Arabia. FAU - Abdel-Naim, Ashraf B AU - Abdel-Naim AB AD - Department of Pharmacology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, PO Box 80260, 21589, Saudi Arabia. LA - eng PT - Journal Article DEP - 20191004 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Flavonoids) RN - 0 (Plant Extracts) RN - 9000-07-1 (Carrageenan) SB - IM MH - Administration, Oral MH - Animals MH - Anti-Inflammatory Agents/*pharmacology/therapeutic use MH - Asteraceae/*chemistry MH - Carrageenan/immunology MH - Chemotaxis/drug effects MH - Disease Models, Animal MH - Ethnopharmacology MH - Flavonoids/*pharmacology/therapeutic use MH - Humans MH - Inflammation/*drug therapy/immunology MH - Lethal Dose 50 MH - Leukocytes, Mononuclear MH - Male MH - Medicine, Arabic/methods MH - Plant Extracts/*pharmacology/therapeutic use MH - Rats MH - Toxicity Tests, Acute OTO - NOTNLM OT - Asteraceae OT - Carrageenan OT - Climbing OT - Inflammation OT - Motility OT - PBMCs OT - Paw edema EDAT- 2019/10/08 06:00 MHDA- 2020/03/24 06:00 CRDT- 2019/10/08 06:00 PHST- 2019/02/25 00:00 [received] PHST- 2019/09/05 00:00 [revised] PHST- 2019/10/03 00:00 [accepted] PHST- 2019/10/08 06:00 [pubmed] PHST- 2020/03/24 06:00 [medline] PHST- 2019/10/08 06:00 [entrez] AID - S0378-8741(19)30783-4 [pii] AID - 10.1016/j.jep.2019.112278 [doi] PST - ppublish SO - J Ethnopharmacol. 2020 Jan 30;247:112278. doi: 10.1016/j.jep.2019.112278. Epub 2019 Oct 4.