Emodin Inhibits Lipopolysaccharide-Induced Inflammation by Activating Autophagy in RAW 264.7 Cells*
Back to article page
Original Article|Updated:2021-09-01
|
Emodin Inhibits Lipopolysaccharide-Induced Inflammation by Activating Autophagy in RAW 264.7 Cells*
Emodin Inhibits Lipopolysaccharide-Induced Inflammation by Activating Autophagy in RAW 264.7 Cells*
Chinese Journal of Integrative Medicine2021年27卷第5期 页码:345-352
Affiliations:
1.Research Centre on Application of Classical Prescriptions, Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai (201203), China
2.Department of Febrile Disease, Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai (201203), China
3.Clinical Pharmacokinetic Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai (201203), China
Author bio:
Prof. YANG Ai-dong, E-mail: aidongy@126.com
Funds:
Ministry of Science and Technology of China(2018YFC1704102);the National Natural Science Foundation of China(81673855;81904072)
Yan-jie TU, Bo TAN, Lei JIANG, 等. Emodin Inhibits Lipopolysaccharide-Induced Inflammation by Activating Autophagy in RAW 264.7 Cells*[J]. Chinese Journal of Integrative Medicine, 2021,27(5):345-352.
Yan-jie TU, Bo TAN, Lei JIANG, et al. Emodin Inhibits Lipopolysaccharide-Induced Inflammation by Activating Autophagy in RAW 264.7 Cells*[J]. Chinese Journal of Integrative Medicine, 2021,27(5):345-352.
Yan-jie TU, Bo TAN, Lei JIANG, 等. Emodin Inhibits Lipopolysaccharide-Induced Inflammation by Activating Autophagy in RAW 264.7 Cells*[J]. Chinese Journal of Integrative Medicine, 2021,27(5):345-352. DOI: 10.1007/s11655-020-3477-9.
Yan-jie TU, Bo TAN, Lei JIANG, et al. Emodin Inhibits Lipopolysaccharide-Induced Inflammation by Activating Autophagy in RAW 264.7 Cells*[J]. Chinese Journal of Integrative Medicine, 2021,27(5):345-352. DOI: 10.1007/s11655-020-3477-9.
Emodin Inhibits Lipopolysaccharide-Induced Inflammation by Activating Autophagy in RAW 264.7 Cells*
摘要
Abstract
Objective:
2
To investigate the effects of emodin on inflammation and autophagy in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and reveal its underlying mechanism.
Methods:
2
3-(4
5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was conducted to find the appropriate dose for emodin. RAW264.7 cells pretreated with different concentrations (0–50 μmol/L) of emodin or vehicle for 2 h prior to exposure to LPS for 16 h. Cell morphology was examined and propidium iodide staining was used to examine cell cycle. Expressions of inflammation-related proteins [nuclear factor-kappaB (NF-κB) and I-kappaB (IκB)α] and autophagy-related proteins [light chain (LC) 3
P62/sequestosome 1
mammalian target of rapamycin (mTOR)
and p-mTOR] were examined using Western blot analysis. Expression of inflammation-related cytokines including tumor necrosis factor (TNF)-α
interleukin (IL)-1β and IL-6 were detected by enzyme-linked immunosorbent assay. Autophagy was examined with LC3B fluorescence intensity and aggregation. The effect of emodin on autophagy was conducted with an autophagy inhibitor
3-methyladenine (3-MA).
Results:
2
The expression of NF-κB in LPS-induced cells was significantly increased (
P
<
0.01) and simultaneously IκBα decreased compared with the normal cell (
P
<
0.05). The expressions of TNF-α
IL-1β
and IL-6 proteins in the LPS-induced RAW264.7 cells were significantly higher than in the normal cell (
P
<
0.05 or
P
<
0.01). LPS increased the percentage of cells in the G0/G1 phase
which was recovered by emodin at different doses (12.5
25
and 50μmol/L
P
<
0.05 or
P
<
0.01). The mediumdose (25 μml/L) emodin decreased the expressions of NF-κB
P62 and p-mTOR (
P
<
0.01) and increased IκBα expression
LC3B Ⅱ/Ⅰ ratio as well as LC3B fluorescence intensity (
P
<
0.05 or
P
<
0.01). Meanwhile
the enhanced autophagic effects of emodin
such as the increment of LC3BⅡ/ ratio and the decrement of P62 expression
were suppressed by autophagy inhibitor 3-MA.
Conclusion:
2
Emodin could inhibit inflammation of mice RAW264.7 macrophages induced by LPS
possibly through activating autophagy.
关键词
Keywords
emodinlipopolysaccharideinflammationautophagy
references
MS Herridge, DC Angus. Acute lung injury—affecting many lives. N Engl J Med 2005;353:1736-1738.
T Granja, D Kohler, V Mirakaj, E Nelson, K Konig, P Rosenberger. Crucial role of Plexin C1 for pulmonary inflammation and survival during lung injury. Mucosal Immunol 2014;7:879-891.
SY Ruan, HH Lin, CT Huang, PH Kuo, HD Wu, CJ Yu.Exploring the heterogeneity of effects of corticosteroids on acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care 2014;18:R63.
YB Chen, Q Liu, H Xie, SM Yin, L Wu, XH Yu, et al. Is Chinese medicine injection applicable for treating acute lung injury and acute respiratory distress syndrome? A systematic review and meta-analysis of randomized controlled trials. Chin J Integr Med 2019;10.1007/s11655-019-3078-7http://doi.org/10.1007/s11655-019-3078-7.
X Dong, J Fu, X Yin, S Cao, X Li, L Lin, et al. Emodin: a review of its pharmacology, toxicity and pharmacokinetics.Phytother Res 2016;30:1207-1218.
J Gao, F Wang, W Wang, Z Su, C Guo, S Cao. Emodin suppresses hyperglycemia-induced proliferation and fibronectin expression in mesangial cells via inhibiting cFLIP. PLoS One 2014;9:e93588.
W Zhang, X Lu, W Wang, Z Ding, Y Fu, X Zhou, et al.Inhibitory effects of emodin, thymol, and astragalin on leptospira interrogans-induced inflammatory response in the uterine and endometrium epithelial cells of mice.Inflammation 2017;40:666-675.
G Meng, Y Liu, C Lou, H Yang. Emodin suppresses lipopolysaccharide-induced pro-inflammatory responses and NF-kappaB activation by disrupting lipid rafts in CD14-negative endothelial cells. Br J Pharmacol 2010;161:1628-1644.
M Xiao, T Zhu, W Zhang, T Wang, YC Shen, QF Wan, et al. Emodin ameliorates LPS-induced acute lung injury, involving the inactivation of NF-kappaB in mice. Int J Mol Sci 2014;15:19355-19368.
SA Jones, KH Mills, J Harris. Autophagy and inflammatory diseases. Immunol Cell Biol 2013;91:250-258.
MC Tal, M Sasai, HK Lee, B Yordy, GS Shadel, A Iwasaki.Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc Natl Acad Sci USA 2009;106:2770-2775.
K Nakahira, JA Haspel, VA Rathinam, SJ Lee, T Dolinay, HC Lam, et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol 2011;12:222-230.
R Zhou, AS Yazdi, P Menu, J Tschopp. A role for mitochondria in NLRP3 inflammasome activation. Nature 2011;469:221-225.
V Russotto, G Bellani, G Foti. Respiratory mechanics in patients with acute respiratory distress syndrome. Ann Transl Med 2018;6:382.
EH Joh, W Gu, DH Kim. Echinocystic acid ameliorates lung inflammation in mice and alveolar macrophages by inhibiting the binding of LPS to TLR4 in NF-kappaB and MAPK pathways. Biochem Pharmacol 2012;84:331-340.
MR Looney, N Roubinian, O Gajic, MA Gropper, RD Hubmayr, CA Lowell, et al. Transfusion-Related Acute Lung Injury Study Group. Prospective study on the clinical course and outcomes in transfusion-related acute lung injury. Crit Care Med 2014;42:1676-1687.
E Fan, D Brodie, AS Slutsky. Acute respiratory distress syndrome: advances in diagnosis and treatment. JAMA 2018;319:698-710.
Y Maruyama, YS Sou, S Kageyama, T Takahashi, T Ueno, K Tanaka, et al. LC3B is indispensable for selective autophagy of p62 but not basal autophagy. Biochem Biophys Res Commun 2014;446:309-315.
N Mizushima. Autophagy: process and function. Genes Dev 2007;21:2861-2873.
M Niklaus, O Adams, S Berezowska, I Zlobec, F Graber, J Slotta-Huspenina, et al. Expression analysis of LC3B and p62 indicates intact activated autophagy is associated with an unfavorable prognosis in colon cancer. Oncotarget 2017;8:54604-54615.
Y Fujishima, S Nishiumi, A Masuda, J Inoue, NM Nguyen, Y Irino, et al. Autophagy in the intestinal epithelium reduces endotoxin-induced inflammatory responses by inhibiting NF-kappaB activation. Arch Biochem Biophys 2011;506:223-235.
YT Yen, HR Yang, HC Lo, YC Hsieh, SC Tsai, CW Hong, et al. Enhancing autophagy with activated protein C and rapamycin protects against sepsis-induced acute lung injury. Surgery 2013;153:689-698.
T Hussell, TJ Bell. Alveolar macrophages: plasticity in a tissue-specific context. Nat Rev Immunol 2014;14:81-93.
SL Tian, Y Yang, XL Liu, QB Xu. Emodin attenuates bleomycin-induced pulmonary fibrosis via anti-inflammatory and anti-oxidative activities in rats. Med Sci Monit 2018;24:1-10.
GL Chen, JJ Zhang, X Kao, LW Wei, ZY Liu. Emodin ameliorates lipopolysaccharides-induced corneal inflammation in rats. Int J Ophthalmol 2015;8:665-669.
Emodin Ameliorates High Glucose-Induced Podocyte Apoptosis via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway
Protective Effect of Brassica napus L. Hydrosols against Inflammation Response in RAW 264.7 Cells
Heat-Clearing Chinese Medicines in Lipopolysaccharide-Induced Inflammation
Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/mTOR Signaling Pathway
Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes
相关作者
暂无数据
相关机构
Department of Nephrology, Wuhan No. 1 Hospital
Department of Central Laboratory, Wuhan No. 1 Hospital
Chuncheon Center, Korea Basic Science Institute
Traditional Chinese Pharmacological Laboratory, Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University
Academic Affairs Office, Chengdu University of Traditional Chinese Medicine