PMID- 32563986 OWN - NLM STAT- MEDLINE DCOM- 20210301 LR - 20211204 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 129 DP - 2020 Sep TI - Toona sinensis modulates autophagy and cytokines in lipopolysaccharide-induced RAW 264.7 macrophages. PG - 110386 LID - S0753-3322(20)30579-5 [pii] LID - 10.1016/j.biopha.2020.110386 [doi] AB - Toona sinensis (TS) is a medicinal herb possessing anti-apoptotic, anti-oxidant, and anti-inflammatory properties and is used to treat diabetes, cancer, and inflammatory diseases. In traditional Chinese medicine theory, TS clears dampness and heat, strengthens the stomach function, and regulates vital energy flow. TS is also used as an astringent and a pesticide. In this study, we aimed to evaluate how TS influences autophagy and cytokines during the inflammatory process in RAW 264.7 macrophages. The treatment groups were pre-supplemented with TS leaf extract; rapamycin was used to enhance autophagy and lipopolysaccharide (LPS) was used to induce inflammation. The expression of autophagy-related proteins was analyzed by western blotting. The survival rate of, and chemokine expression and oxidative stress in the cells were also assessed. TS leaf extract inhibited mammalian target of rapamycin (mTOR) phosphorylation at site S2448 in the macrophages. At relatively higher concentrations (50 and 75 mug/mL), TS elevated the expression of light chain 3 II (LC3-II), which further modulated autophagy. Pre-supplementation with TS leaf extract elevated the total glutathione (GSH) level and GSH/oxidized GSH (GSSG) ratio, but it decreased the GSSG, total nitric oxide, nitrate, nitrite, malondialdehyde, and superoxide anion levels. TS reversed the effects of LPS-induced cytokines, including interleukin (IL)-6 and IL-10. TS did not induce significant toxicity at the studied concentrations. In conclusion, TS leaf extract may modulate autophagy during inflammation. Furthermore, it may prevent cell damage via anti-inflammation and anti-oxidation. Thus, this study supports the ethnomedical use of TS in the prevention of inflammation-related diseases. CI - Copyright (c) 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Kuo, Chun-En Aurea AU - Kuo CA AD - Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan; Department of Nursing, Meiho University, Pingtung, 912009, Taiwan. Electronic address: lecherries@gmail.com. FAU - Wu, Szu-Ying AU - Wu SY AD - Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan; Department of Nursing, Meiho University, Pingtung, 912009, Taiwan; Department of Sports Medicine, Kaohsiung Medical University, Kaohsiung, 807378, Taiwan; Department of Chinese Medicine, Xiamen Chang Gung Memorial Hospital, Xiamen, Fujian, 361028, China. FAU - Lee, Chen-Hsiang AU - Lee CH AD - Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan. FAU - Lai, Yun-Ru AU - Lai YR AD - Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, 804351, Taiwan; Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan. FAU - Lu, Cheng-Hsien AU - Lu CH AD - Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, 804351, Taiwan; Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan; Department of Neurology, Xiamen Chang Gung Memorial Hospital, Xiamen, Fujian, 361028, China. FAU - Chen, Po-Cheng AU - Chen PC AD - Department of Physical Medicine and Rehabilitation, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan. FAU - Cheng, Jai-Hong AU - Cheng JH AD - Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan; Medical Research, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan. FAU - Tsai, Li-Yu AU - Tsai LY AD - Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, 807378, Taiwan. FAU - Yen, Ke-Tien AU - Yen KT AD - Department of Leisure and Sports Management, Cheng Shiu University, Kaohsiung, 833301, Taiwan. FAU - Tsao, Yu AU - Tsao Y AD - Department of Leisure and Sports Management, Cheng Shiu University, Kaohsiung, 833301, Taiwan; College of Management, National Kaohsiung University of Science and Technology, Kaohsiung, 807618, Taiwan. FAU - Tsai, Shih-Meng AU - Tsai SM AD - Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807378, Taiwan. Electronic address: tsaism@kmu.edu.tw. LA - eng PT - Journal Article DEP - 20200618 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (Autophagy-Related Proteins) RN - 0 (Cytokines) RN - 0 (IL10 protein, mouse) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Plant Extracts) RN - 0 (interleukin-6, mouse) RN - 0 (lipopolysaccharide, Escherichia coli O111 B4) RN - 130068-27-8 (Interleukin-10) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Anti-Inflammatory Agents/isolation & purification/*pharmacology MH - Antioxidants/isolation & purification/pharmacology MH - Autophagy/*drug effects MH - Autophagy-Related Proteins/metabolism MH - Cytokines/*metabolism MH - Inflammation/metabolism/pathology/*prevention & control MH - Interleukin-10/metabolism MH - Interleukin-6/metabolism MH - Lipopolysaccharides/*toxicity MH - Macrophages/*drug effects/metabolism/pathology MH - Mice MH - Oxidative Stress/drug effects MH - Phosphorylation MH - Plant Extracts/isolation & purification/*pharmacology MH - Plant Leaves MH - RAW 264.7 Cells MH - Signal Transduction MH - TOR Serine-Threonine Kinases/metabolism MH - *Toona/chemistry OTO - NOTNLM OT - Anti-oxidation OT - Autophagy OT - Natural bioactive compound OT - Preventive therapy OT - Toona sinensis EDAT- 2020/06/22 06:00 MHDA- 2021/03/02 06:00 CRDT- 2020/06/22 06:00 PHST- 2020/04/15 00:00 [received] PHST- 2020/06/01 00:00 [revised] PHST- 2020/06/07 00:00 [accepted] PHST- 2020/06/22 06:00 [pubmed] PHST- 2021/03/02 06:00 [medline] PHST- 2020/06/22 06:00 [entrez] AID - S0753-3322(20)30579-5 [pii] AID - 10.1016/j.biopha.2020.110386 [doi] PST - ppublish SO - Biomed Pharmacother. 2020 Sep;129:110386. doi: 10.1016/j.biopha.2020.110386. Epub 2020 Jun 18.