PMID- 31843575 OWN - NLM STAT- MEDLINE DCOM- 20201109 LR - 20220413 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 252 DP - 2020 Apr 24 TI - Anti-inflammatory and anticoagulant effects of polyphenol-rich extracts from Thymus atlanticus: An in vitro and in vivo study. PG - 112475 LID - S0378-8741(19)31515-6 [pii] LID - 10.1016/j.jep.2019.112475 [doi] AB - ETHNOPHARMACOLOGICAL EVIDENCE: Thymus atlanticus (TA) is used in traditional medicine in Morocco to treat chronic inflammatory diseases, after local and oral treatment. AIM OF STUDY: This study aimed to investigate the in vitro and in vivo anti-inflammatory and anticoagulant activities of an aqueous extract (AE) and polyphenol fraction (PF) derived from TA. MATERIALS AND METHODS: The effect of AE and PF on monocyte chemoattractant protein-1 (MCP-1) production by naive and LPS-stimulated peritoneal macrophages isolated from C57Bl/6 mice was assessed by ELISA assay. The effect of chronic administration of the extracts at three different doses by oral rout for 2 weeks on blood coagulation and inflammation induced by carrageenan in Wistar rats was evaluated. In addition, the in vitro anticoagulant effect was tested on blood plasma collected from healthy rats using the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) tests. The acute toxicity of AE was investigated. Phytochemical analysis was carried out by HPLC. RESULTS: Analysis by HPLC indicated rosmarinic acid as the main phenolic acid in TA extracts. Compared to control macrophages, MCP-1 level was lower in medium supplemented with AE at 50 and 500 mug/mL and PF at 500 mug/mL, but higher in medium with PF at 50 mug/mL. Rosmarinic and chicoric acids, served as controls, significantly decreased MCP-1 production. Chronic oral administration of TA extracts prevented inflammation induced by carrageenan and induced a significant prolongation of blood coagulation time, in a dose dependant manner, in Wistar rats. The results of the in vitro assay showed that the coagulation time was significantly prolonged in plasma incubated with extracts in APTT, PT and TT tests. Lethal dose 50 of AE in mice was 27.90 +/- 1.19 g/kg. CONCLUSION: This study indicated TA as an herb with anti-inflammatory and anticoagulant proprieties and supports the traditional use of this plant for the treatment of inflammatory diseases. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Khouya, Tarik AU - Khouya T AD - Biochemistry and Natural Substances Team, Department of Biology, Faculty of Sciences & Techniques, University Moulay Ismail, 52000, Errachidia, Morocco. Electronic address: tarikkhouya@yahoo.com. FAU - Ramchoun, Mhamed AU - Ramchoun M AD - Biochemistry and Natural Substances Team, Department of Biology, Faculty of Sciences & Techniques, University Moulay Ismail, 52000, Errachidia, Morocco; Laboratory of Biotechnology & Sustainable Development of Natural Resources, Polydisciplinary Faculty, 23000, Beni Mellal, Morocco; Laboratory of Biochemistry and Biotechnologies, Department of Biology, Faculty of Sciences, University Mohamed I, 60 000, Oujda, Morocco. Electronic address: ramchoun_10@yahoo.fr. FAU - Amrani, Souliman AU - Amrani S AD - Laboratory of Biochemistry and Biotechnologies, Department of Biology, Faculty of Sciences, University Mohamed I, 60 000, Oujda, Morocco. Electronic address: amrani137@yahoo.fr. FAU - Harnafi, Hicham AU - Harnafi H AD - Laboratory of Biochemistry and Biotechnologies, Department of Biology, Faculty of Sciences, University Mohamed I, 60 000, Oujda, Morocco. Electronic address: hhicham02@gmail.com. FAU - Rouis, Mustapha AU - Rouis M AD - Biological Adaptation and Ageing (B2A), CNRS UMR-8256/INSERM ERL U-1164, University Pierre et Marie Curie, Paris, France. Electronic address: mustapha.rouis@upmc.fr. FAU - Couchie, Dominique AU - Couchie D AD - Biological Adaptation and Ageing (B2A), CNRS UMR-8256/INSERM ERL U-1164, University Pierre et Marie Curie, Paris, France. Electronic address: dominique.couchie@upmc.fr. FAU - Simmet, Thomas AU - Simmet T AD - Ulm University, Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm, Germany. Electronic address: thomas.simmet@uni-ulm.de. FAU - Alem, Chakib AU - Alem C AD - Biochemistry and Natural Substances Team, Department of Biology, Faculty of Sciences & Techniques, University Moulay Ismail, 52000, Errachidia, Morocco. Electronic address: alem04@yahoo.fr. LA - eng PT - Journal Article DEP - 20191213 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Anticoagulants) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Lipopolysaccharides) RN - 0 (Plant Extracts) RN - 0 (Polyphenols) RN - 9000-07-1 (Carrageenan) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology/*therapeutic use/toxicity MH - Anticoagulants/pharmacology/*therapeutic use/toxicity MH - Blood Coagulation/drug effects MH - Carrageenan MH - Chemokine CCL2/immunology MH - Edema/chemically induced/drug therapy MH - Female MH - Lethal Dose 50 MH - Lipopolysaccharides/pharmacology MH - Macrophages, Peritoneal/drug effects/immunology MH - Male MH - Medicine, Traditional MH - Mice, Inbred C57BL MH - Morocco MH - Plant Extracts/pharmacology/*therapeutic use/toxicity MH - Polyphenols/pharmacology/*therapeutic use/toxicity MH - Rats, Wistar MH - *Thymus Plant OTO - NOTNLM OT - Aspirin OT - Atherosclerosis OT - Chicoric acid OT - Heparin OT - MCP-1 OT - Macrophage OT - Rosmarinic acid OT - Thymus atlanticus COIS- Declaration of competing interest None. EDAT- 2019/12/18 06:00 MHDA- 2020/11/11 06:00 CRDT- 2019/12/18 06:00 PHST- 2019/04/16 00:00 [received] PHST- 2019/11/26 00:00 [revised] PHST- 2019/12/09 00:00 [accepted] PHST- 2019/12/18 06:00 [pubmed] PHST- 2020/11/11 06:00 [medline] PHST- 2019/12/18 06:00 [entrez] AID - S0378-8741(19)31515-6 [pii] AID - 10.1016/j.jep.2019.112475 [doi] PST - ppublish SO - J Ethnopharmacol. 2020 Apr 24;252:112475. doi: 10.1016/j.jep.2019.112475. Epub 2019 Dec 13.