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Toona sinensis modulates autophagy and cytokines in lipopolysaccharide-induced RAW 264.7 macrophages - 28/08/20

Doi : 10.1016/j.biopha.2020.110386 
Chun-En Aurea Kuo a, b, , Szu-Ying Wu a, b, c, d, Chen-Hsiang Lee e, Yun-Ru Lai f, g, Cheng-Hsien Lu f, g, h, Po-Cheng Chen i, Jai-Hong Cheng j, k, Li-Yu Tsai l, Ke-Tien Yen m, Yu Tsao m, n, Shih-Meng Tsai o,
a Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan 
b Department of Nursing, Meiho University, Pingtung, 912009, Taiwan 
c Department of Sports Medicine, Kaohsiung Medical University, Kaohsiung, 807378, Taiwan 
d Department of Chinese Medicine, Xiamen Chang Gung Memorial Hospital, Xiamen, Fujian, 361028, China 
e Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan 
f Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, 804351, Taiwan 
g Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan 
h Department of Neurology, Xiamen Chang Gung Memorial Hospital, Xiamen, Fujian, 361028, China 
i Department of Physical Medicine and Rehabilitation, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan 
j Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan 
k Medical Research, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan 
l Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, 807378, Taiwan 
m Department of Leisure and Sports Management, Cheng Shiu University, Kaohsiung, 833301, Taiwan 
n College of Management, National Kaohsiung University of Science and Technology, Kaohsiung, 807618, Taiwan 
o Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807378, Taiwan 

Corresponding author at: Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan.Department of Chinese MedicineKaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiung833401Taiwan⁎⁎Corresponding author at: Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807378, Taiwan.Department of Public Health and Environmental MedicineSchool of MedicineCollege of MedicineKaohsiung Medical UniversityKaohsiung807378Taiwan

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Highlights

Toona sinensis (TS) leaf extract may modulate autophagy during inflammation.
TS leaf extract does not exhibit toxicity against RAW264.7 cells.
TS leaf extract inhibited mammalian target of rapamycin phosphorylation.
TS leaf extract may prevent cell damage via anti-inflammation and anti-oxidation.
TS leaf extract modulated the expression of interleukin-6 and -10.

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Abstract

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 μg/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.

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Abbreviations : AAPH, ALT, ANOVA, Atg8, ATP, BCA, DMEM, DMSO, DPPH, ECL, ELISA, FBS, GRx, GSH, GSSG, GVHD, HRP, IL, LC, LDL, LPS, MDA, MDCK, mTOR, mTORC1, MTT, NF-κB, NO, NO2, NO3, PVDF, RIPA, SD, SDS-PAGE, SOD, SPSS, siRNA, TBARS, TBS-T, TNF-α, TS

Keywords : Toona sinensis, Autophagy, Natural bioactive compound, Anti-oxidation, Preventive therapy


Esquema


 TS, Toona sinensis


© 2020  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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