PMID- 33242622 OWN - NLM STAT- MEDLINE DCOM- 20210305 LR - 20210305 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 268 DP - 2021 Mar 25 TI - Water extract of Artemisia scoparia Waldst. & Kitam suppresses LPS-induced cytokine production and NLRP3 inflammasome activation in macrophages and alleviates carrageenan-induced acute inflammation in mice. PG - 113606 LID - S0378-8741(20)33494-2 [pii] LID - 10.1016/j.jep.2020.113606 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia scoparia Waldst. & Kitam (A. scoparia) is a perennial herbal plant that is widely used as a folk remedy in Asian countries. Several studies have demonstrated that A. scoparia has various physiological effects, including anti-inflammation, anti-hypertension, anti-obesity, anti-hepatotoxicity, and anti-oxidant effects. AIM OF THE STUDY: The objective of the present study was to examine the anti-inflammatory effects of water extract of A. scoparia (WAS). MATERIALS AND METHODS: Murine bone marrow-derived macrophages (BMDMs), human monocyte THP-1 and murine fibroblast 3T3-L1 cells were used for the in vitro experiments. Cell viability and cytokine production were determined by the MTT assay and ELISA, respectively. RT-PCR was performed to determine iNOS gene expression and the Griess reaction was used to measure nitrite levels. iNOS protein expression, activation of NF-kappaB and MAPKs, and cleavage of caspase-1 and IL-1beta were determined by Western blot analysis. A carrageenan-induced mouse model of acute inflammation was used in the in vivo experiments. RESULTS: Pretreatment with WAS concentration-dependently suppressed gene expression and IL-6, TNF-alpha, CXCL1 and iNOS protein levels in BMDMs stimulated with LPS. In addition, pretreatment with WAS inhibited LPS-induced production of IL-6 and TNF-alpha in THP-1 cells and CXCL1 in 3T3-L1. Furthermore, LPS induced phosphorylation of p65 in BMDMs, and this induction was dramatically suppressed by WAS pretreatment. We further investigated whether WAS regulates activation of the NLRP3 inflammasome, which is known to be essential for IL-1beta processing. WAS inhibited the production of IL-1beta, but not IL-6, in response to adenosine triphosphate (ATP) and monosodium uric acid (MSU) crystals in LPS-primed BMDMs. Cleavage of caspase-1 and IL-1beta was also reduced by WAS. We finally evaluated the in vivo anti-inflammatory effects of WAS in a mouse model of carrageenan-induced acute inflammation. Subcutaneous administration of WAS reduced production of the inflammatory cytokines IL-6, TNF-alpha, CXCL1, and IL-1beta. Recruitment of immune cells, mostly neutrophils, was also reduced by administration of WAS. Infiltration of inflammatory cells and edema in the submucosa of air pouch tissues were markedly improved in the WAS-treated groups. CONCLUSIONS: Our results indicate that WAS possesses potent anti-inflammatory properties. These findings suggest that A. scoparia is a candidate functional food targeting several inflammatory diseases. CI - Copyright (c) 2020 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Ahn, Jae-Hun AU - Ahn JH AD - Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address: hun2wawa@hanmail.net. FAU - Park, Yae-Lyeon AU - Park YL AD - Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address: curoyaong@naver.com. FAU - Song, A-Young AU - Song AY AD - Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address: 4107say@naver.com. FAU - Kim, Wan-Gyu AU - Kim WG AD - Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address: namootneep@naver.com. FAU - Je, Chang-Yun AU - Je CY AD - Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address: jchy0207@naver.com. FAU - Jung, Do-Hyeon AU - Jung DH AD - Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address: jdh6221@naver.com. FAU - Kim, Yeong-Jun AU - Kim YJ AD - Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address: kimyj0587@naver.com. FAU - Oh, Jisu AU - Oh J AD - Department of Food and Science and Technology, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address: dhwltn7117@naver.com. FAU - Cho, Jeong-Yong AU - Cho JY AD - Department of Food and Science and Technology, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address: jyongcho17@jnu.ac.kr. FAU - Kim, Dong-Jae AU - Kim DJ AD - Laboraotry Animal Resource Center, DGIST, Daegu, Republic of Korea. Electronic address: kimdj@dgist.ac.kr. FAU - Park, Jong-Hwan AU - Park JH AD - Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address: jonpark@jnu.ac.kr. LA - eng PT - Journal Article DEP - 20201123 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, mouse) RN - 0 (Plant Extracts) RN - 059QF0KO0R (Water) RN - 9000-07-1 (Carrageenan) SB - IM MH - 3T3-L1 Cells MH - Animals MH - Anti-Inflammatory Agents/isolation & purification/pharmacology/*therapeutic use MH - *Artemisia MH - Carrageenan/*toxicity MH - Cytokines/*antagonists & inhibitors/biosynthesis MH - Dose-Response Relationship, Drug MH - Female MH - Humans MH - Inflammation/drug therapy/metabolism MH - Lipopolysaccharides/*toxicity MH - Macrophages/drug effects/metabolism MH - Mice MH - Mice, Inbred C57BL MH - NLR Family, Pyrin Domain-Containing 3 Protein/*antagonists & inhibitors/metabolism MH - Plant Extracts/isolation & purification/pharmacology/*therapeutic use MH - Water/pharmacology OTO - NOTNLM OT - Artemisia scoparia OT - Carrageenan-induced inflammation OT - Inflammation OT - NLRP3 inflammasome EDAT- 2020/11/27 06:00 MHDA- 2021/03/06 06:00 CRDT- 2020/11/26 20:08 PHST- 2020/08/31 00:00 [received] PHST- 2020/11/13 00:00 [revised] PHST- 2020/11/18 00:00 [accepted] PHST- 2020/11/27 06:00 [pubmed] PHST- 2021/03/06 06:00 [medline] PHST- 2020/11/26 20:08 [entrez] AID - S0378-8741(20)33494-2 [pii] AID - 10.1016/j.jep.2020.113606 [doi] PST - ppublish SO - J Ethnopharmacol. 2021 Mar 25;268:113606. doi: 10.1016/j.jep.2020.113606. Epub 2020 Nov 23.