PMID- 34563177 OWN - NLM STAT- MEDLINE DCOM- 20211230 LR - 20211230 IS - 2662-7671 (Electronic) IS - 2662-7671 (Linking) VI - 21 IP - 1 DP - 2021 Sep 25 TI - Effect of supercritical carbon dioxide fluid extract from Chrysanthemum indicum Linne on bleomycin-induced pulmonary fibrosis. PG - 240 LID - 10.1186/s12906-021-03409-9 [doi] LID - 240 AB - BACKGROUND: As a prevalent type of cryptogenic fibrotic disease with high mortality, idiopathic pulmonary fibrosis (IPF) still lacks effective therapeutic drugs. The compounds extracted from buds and flowers of Chrysanthemum indicum Linne with supercritical-carbon dioxide fluid (CI(SCFE)) has been confirmed to have antioxidant, anti-inflammatory, and lung-protective effects. This paper aimed to clarify whether CI(SCFE) could treat IPF induced by bleomycin (BLM) and elucidate the related mechanisms. METHODS: Rats (Sprague-Dawley, male) were separated into the following groups: normal, model, pirfenidone (50 mg/kg), CI(SCFE)-L, -M, and -H (240, 360, and 480 mg/kg/d, i.g., respectively, for 4 weeks). Rats were given BLM (5 mg/kg) via intratracheal installation to establish the IPF model. A549 and MRC-5 cells were stimulated by Wnt-1 to establish a cell model and then treated with CI(SCFE). Haematoxylin-eosin (H&E) and Masson staining were employed to observe lesions in the lung tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) were performed to observe changes in genes and proteins connected with the Wnt/beta-catenin pathway. RESULTS: CI(SCFE) inhibited the proliferation of MRC-5 cells (IC(50): 2.723 +/- 0.488 mug/mL) and A549 cells (IC(50): 2.235 +/- 0.229 mug/mL). In rats, A549 cells, and MRC-5 cells, BLM and Wnt-1 obviously induced the protein expression of alpha-smooth muscle actin (alpha-SMA), vimentin, type I collagen (collagen-I), and Nu-beta-catenin. The mRNA levels of matrix metalloproteinase-3 (MMP-3) and - 9 (MMP-9), two enzymes that degrade and reshape the extracellular matrix (ECM) were also increased while those of tissue inhibitor of metalloproteinase 1 (TIMP-1) were decreased. However, CI(SCFE) reversed the effects of BLM and Wnt-1 on the expression pattern of these proteins and genes. CONCLUSION: These findings showed that CI(SCFE) could inhibit IPF development by activating the Wnt/beta-catenin pathway and may serve as a treatment for IPF after further investigation. CI - (c) 2021. The Author(s). FAU - Nie, Juan AU - Nie J AD - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China. FAU - Liu, Yanlu AU - Liu Y AD - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China. FAU - Sun, Chaoyue AU - Sun C AD - 2nd Clinical Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China. FAU - Zheng, Jingna AU - Zheng J AD - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China. FAU - Chen, Baoyi AU - Chen B AD - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China. FAU - Zhuo, Jianyi AU - Zhuo J AD - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China. FAU - Su, Ziren AU - Su Z AD - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China. AD - Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. FAU - Lai, Xiaoping AU - Lai X AD - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China. AD - Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. FAU - Chen, Jiannan AU - Chen J AD - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China. AD - Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. FAU - Zheng, Jibiao AU - Zheng J AD - Department of Pharmacy, Central People's Hospital of Zhanjiang, Zhanjiang, 524000, China. 13828280428@163.com. FAU - Li, Yucui AU - Li Y AD - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China. liyucui@gzucm.edu.cn. AD - Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. liyucui@gzucm.edu.cn. LA - eng PT - Comparative Study PT - Journal Article DEP - 20210925 PL - England TA - BMC Complement Med Ther JT - BMC complementary medicine and therapies JID - 101761232 RN - 0 (Antibiotics, Antineoplastic) RN - 0 (Plant Extracts) RN - 11056-06-7 (Bleomycin) RN - 142M471B3J (Carbon Dioxide) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Animals MH - Antibiotics, Antineoplastic/adverse effects MH - Bleomycin/adverse effects MH - Carbon Dioxide/*administration & dosage MH - Chrysanthemum/*metabolism MH - Male MH - Matrix Metalloproteinases/metabolism MH - Plant Extracts/pharmacology MH - Pulmonary Fibrosis/chemically induced/*drug therapy/pathology MH - Rats MH - Rats, Sprague-Dawley PMC - PMC8464116 OTO - NOTNLM OT - Chrysanthemum indicum Linne OT - Idiopathic pulmonary fibrosis OT - Supercritical carbon dioxide extraction OT - Wnt/beta-catenin signalling pathway COIS- The authors declare that they have no competing interests. EDAT- 2021/09/27 06:00 MHDA- 2021/12/31 06:00 PMCR- 2021/09/25 CRDT- 2021/09/26 20:25 PHST- 2020/08/28 00:00 [received] PHST- 2021/09/08 00:00 [accepted] PHST- 2021/09/26 20:25 [entrez] PHST- 2021/09/27 06:00 [pubmed] PHST- 2021/12/31 06:00 [medline] PHST- 2021/09/25 00:00 [pmc-release] AID - 10.1186/s12906-021-03409-9 [pii] AID - 3409 [pii] AID - 10.1186/s12906-021-03409-9 [doi] PST - epublish SO - BMC Complement Med Ther. 2021 Sep 25;21(1):240. doi: 10.1186/s12906-021-03409-9.