PMID- 35026521 OWN - NLM STAT- MEDLINE DCOM- 20220125 LR - 20220125 IS - 1618-095X (Electronic) IS - 0944-7113 (Linking) VI - 96 DP - 2022 Feb TI - Water extract of Cayratia albifolia C.L.Li root relieves zymosan A-induced inflammation by restraining M1 macrophage polarization. PG - 153901 LID - S0944-7113(21)00441-4 [pii] LID - 10.1016/j.phymed.2021.153901 [doi] AB - BACKGROUND: Cayratia albifolia C.L.Li (CAC) is a traditional Chinese herbal medicine used to treat inflammatory diseases. Our laboratory has firstly reported that the water extract from CAC relieved lipopolysaccharide (LPS)-induced inflammation, however stronger evidence is still needed to prove its anti-inflammatory effects and the mechanisms involved are also ambiguous. PURPOSE: This study sought to provide more evidence for the application of CAC in alleviating infectious inflammation and disclose novel pharmacological mechanisms. METHODS: Mice were injected with zymA into their paws or peritoneal cavities, and then treated with CAC. ELISA, immunofluorescence and flow cytometry were performed to detect the cytokines (IL-1beta, IL-6, TNF-alpha and IL-10) generation, the cell infiltration, and the CD86 or CD206 expression of macrophages. Then in vitro assays were performed on bone marrow-derived macrophages (BMDMs) and peritoneal macrophages (PMs) to detect their expression of iNOS, arg-1 and the cytokines above. On mechanisms, western blotting (WB), electrophoretic mobility shift assay (EMSA) and flow cytometry were carried out to measure NF-kappaB transcriptional activity, mitochondrial bioactivity and the mTORC1 activation when BMDMs were stimulated by zymA and treated with CAC. Finally, the chemical components consisted in the extract were analyzed by LC-MS. RESULTS: 200 mg/kg CAC clearly inhibited zymA induced mouse paw edema and reduced the contents of IL-1beta, IL-6 and TNF-alpha rather than IL-10 in local tissues. CAC also reduced CD86 but not CD206 in macrophages in situ. Through in vitro experiments, it was discovered that CAC reduced the protein and mRNA levels of IL-1beta, IL-6 and TNF-alpha, and also inhibited iNOS expression, but showed no influence on IL-10 and arg-1 in macrophages. We found CAC reduced NF-kappaB transcriptional activity, down-regulated mitochondrial membrane potential and ROS levels, and inhibited mTORC1 activity. Finally, we identified 15 major compounds in the extract, among which 4-guanidinobutyric acid and kynurenic acid were the most abundant. CONCLUSION: This study provides further evidence that CAC significantly reduces zymA induced infectious inflammation. In addition, this novel data revealed that CAC restrained M1 rather than promoting M2 macrophages polarization via multi-target inhibitory effects, based on its potentially active components. CI - Copyright (c) 2021 Elsevier GmbH. All rights reserved. FAU - Li, Wei AU - Li W AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - Luo, Li AU - Luo L AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - Zhu, Junyu AU - Zhu J AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - Yan, Huan AU - Yan H AD - College of Public Health, Xinjiang Medical University, Urumqi, 830011, China; Xinjiang Engineering Technology Research center for Green Processing of Nature Product Center, Xinjiang Autonomous Academy of Instrumental Analysis, Urumqi, 830011, China. FAU - Yang, Xue AU - Yang X AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - Tang, Wanqi AU - Tang W AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - Li, Dandan AU - Li D AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - He, Dongmei AU - He D AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - Wang, Jin AU - Wang J AD - The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. FAU - Dai, Weihong AU - Dai W AD - The Second Affiliated Hospital of Hainan Medical University, Haikou, 570216, China. FAU - Ma, Xiaoyuan AU - Ma X AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - Ao, Shengxiang AU - Ao S AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - Ma, Wei AU - Ma W AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - Du, Nana AU - Du N AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - Mao, Chengyi AU - Mao C AD - Department of Pathology, Daping Hospital, Army Medical University, Chongqing, 400042, China. FAU - Diao, Xiaoyan AU - Diao X AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - Yang, Xia AU - Yang X AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - Liu, Daoyan AU - Liu D AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. FAU - Zhang, Zaiqi AU - Zhang Z AD - Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Hunan, 418000, China. Electronic address: qizaizhang@126.com. FAU - Liang, Huaping AU - Liang H AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. Electronic address: 13638356728@163.com. FAU - Wang, Fangjie AU - Wang F AD - State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Center (Daping Hospital), Army Medical University, Chongqing, 400042, China. Electronic address: wangfj10086@163.com. LA - eng PT - Journal Article DEP - 20211229 PL - Germany TA - Phytomedicine JT - Phytomedicine : international journal of phytotherapy and phytopharmacology JID - 9438794 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 059QF0KO0R (Water) RN - 9010-72-4 (Zymosan) SB - IM MH - Animals MH - *Anti-Inflammatory Agents/pharmacology/therapeutic use MH - Cytokines MH - Inflammation/drug therapy MH - Lipopolysaccharides MH - Macrophages MH - Mice MH - *Water MH - Zymosan/therapeutic use OTO - NOTNLM OT - Cayratia albifolia C.L.Li OT - Inflammation OT - Macrophages polarization EDAT- 2022/01/14 06:00 MHDA- 2022/01/27 06:00 CRDT- 2022/01/13 20:22 PHST- 2021/10/19 00:00 [received] PHST- 2021/12/15 00:00 [revised] PHST- 2021/12/18 00:00 [accepted] PHST- 2022/01/14 06:00 [pubmed] PHST- 2022/01/27 06:00 [medline] PHST- 2022/01/13 20:22 [entrez] AID - S0944-7113(21)00441-4 [pii] AID - 10.1016/j.phymed.2021.153901 [doi] PST - ppublish SO - Phytomedicine. 2022 Feb;96:153901. doi: 10.1016/j.phymed.2021.153901. Epub 2021 Dec 29.