Ethyl 2-Succinate-Anthraquinone Attenuates Inflammatory Response and Oxidative Stress via Regulating NLRP3 Signaling Pathway

Aloe-emodin widely possesses antibacterial, anti-inflammatory, antioxidant, antiviral, and anti-infectious properties. This study investigated the effect of ethyl 2-succinate-anthraquinone (Luhui derivative, LHD) on inflammation. In vitro, a THP-1 macrophage inflammation model, made by 100 ng/ml pho...

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Autores principales:	Burong Feng, Xiuye Zhao, Wei Zhao, Huiwei Jiang, Zijing Ren, Yingfu Chen, Ye Yuan, Zhimin Du
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Luhui derivative (LHD) inflammation oxidative stress NLRP3 THP-1 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/18481a4896fa4d4ca4a2f7115d3d2ab7
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spelling	oai:doaj.org-article:18481a4896fa4d4ca4a2f7115d3d2ab72021-11-08T09:21:53ZEthyl 2-Succinate-Anthraquinone Attenuates Inflammatory Response and Oxidative Stress via Regulating NLRP3 Signaling Pathway1663-981210.3389/fphar.2021.719822https://doaj.org/article/18481a4896fa4d4ca4a2f7115d3d2ab72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.719822/fullhttps://doaj.org/toc/1663-9812Aloe-emodin widely possesses antibacterial, anti-inflammatory, antioxidant, antiviral, and anti-infectious properties. This study investigated the effect of ethyl 2-succinate-anthraquinone (Luhui derivative, LHD) on inflammation. In vitro, a THP-1 macrophage inflammation model, made by 100 ng/ml phorbol-12-myristate-13-acetate (PMA) and 1 μg/ml LPS for 24 h, was constructed. The LHD group (6.25 μmol/L, 12.5 μmol/L, 25 μmol/L, 50 μmol/L) had no effect on THP-1 cell activity, and the expression of IL-6 mRNA was down-regulated in a concentration-dependent manner, of which the 25 μmol/L group had the best inhibitory effect. The migration of THP-1 macrophages induced by LPS was decreased by the LHD. Moreover, the LHD suppressed ROS fluorescence expression by inhibiting MDA expression and increasing SOD activity. In vivo, we revealed that the LHD, in different doses (6.25 mg/kg, 12.5 mg/kg, 25 mg/kg, 50 mg/kg), has a protective effect on stress physiological responses by assessing the body temperature of mice. Interestingly, acute lung injury (e.g., the structure of the alveoli disappeared and capillaries in the alveolar wall were dilated and congested) and liver damage (e.g., hepatocyte swelling, neutrophil infiltration, and hepatocyte apoptosis) were obviously improved at the same condition. Furthermore, we initially confirmed that the LHD can down-regulate the expression of NLRP3, IL-1β, and caspase-1 proteins, thereby mediating the NLRP3 inflammasome signaling pathway to produce anti-inflammatory effects. In conclusion, our results indicate that the LHD exerts anti-inflammatory activity via regulating the NLRP3 signaling pathway, inhibition of oxidative stress, and THP-1 macrophage migration.Burong FengBurong FengXiuye ZhaoXiuye ZhaoWei ZhaoWei ZhaoHuiwei JiangHuiwei JiangZijing RenZijing RenYingfu ChenYingfu ChenYe YuanYe YuanZhimin DuZhimin DuZhimin DuFrontiers Media S.A.articleLuhui derivative (LHD)inflammationoxidative stressNLRP3THP-1Therapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Luhui derivative (LHD) inflammation oxidative stress NLRP3 THP-1 Therapeutics. Pharmacology RM1-950
spellingShingle	Luhui derivative (LHD) inflammation oxidative stress NLRP3 THP-1 Therapeutics. Pharmacology RM1-950 Burong Feng Burong Feng Xiuye Zhao Xiuye Zhao Wei Zhao Wei Zhao Huiwei Jiang Huiwei Jiang Zijing Ren Zijing Ren Yingfu Chen Yingfu Chen Ye Yuan Ye Yuan Zhimin Du Zhimin Du Zhimin Du Ethyl 2-Succinate-Anthraquinone Attenuates Inflammatory Response and Oxidative Stress via Regulating NLRP3 Signaling Pathway
description	Aloe-emodin widely possesses antibacterial, anti-inflammatory, antioxidant, antiviral, and anti-infectious properties. This study investigated the effect of ethyl 2-succinate-anthraquinone (Luhui derivative, LHD) on inflammation. In vitro, a THP-1 macrophage inflammation model, made by 100 ng/ml phorbol-12-myristate-13-acetate (PMA) and 1 μg/ml LPS for 24 h, was constructed. The LHD group (6.25 μmol/L, 12.5 μmol/L, 25 μmol/L, 50 μmol/L) had no effect on THP-1 cell activity, and the expression of IL-6 mRNA was down-regulated in a concentration-dependent manner, of which the 25 μmol/L group had the best inhibitory effect. The migration of THP-1 macrophages induced by LPS was decreased by the LHD. Moreover, the LHD suppressed ROS fluorescence expression by inhibiting MDA expression and increasing SOD activity. In vivo, we revealed that the LHD, in different doses (6.25 mg/kg, 12.5 mg/kg, 25 mg/kg, 50 mg/kg), has a protective effect on stress physiological responses by assessing the body temperature of mice. Interestingly, acute lung injury (e.g., the structure of the alveoli disappeared and capillaries in the alveolar wall were dilated and congested) and liver damage (e.g., hepatocyte swelling, neutrophil infiltration, and hepatocyte apoptosis) were obviously improved at the same condition. Furthermore, we initially confirmed that the LHD can down-regulate the expression of NLRP3, IL-1β, and caspase-1 proteins, thereby mediating the NLRP3 inflammasome signaling pathway to produce anti-inflammatory effects. In conclusion, our results indicate that the LHD exerts anti-inflammatory activity via regulating the NLRP3 signaling pathway, inhibition of oxidative stress, and THP-1 macrophage migration.
format	article
author	Burong Feng Burong Feng Xiuye Zhao Xiuye Zhao Wei Zhao Wei Zhao Huiwei Jiang Huiwei Jiang Zijing Ren Zijing Ren Yingfu Chen Yingfu Chen Ye Yuan Ye Yuan Zhimin Du Zhimin Du Zhimin Du
author_facet	Burong Feng Burong Feng Xiuye Zhao Xiuye Zhao Wei Zhao Wei Zhao Huiwei Jiang Huiwei Jiang Zijing Ren Zijing Ren Yingfu Chen Yingfu Chen Ye Yuan Ye Yuan Zhimin Du Zhimin Du Zhimin Du
author_sort	Burong Feng
title	Ethyl 2-Succinate-Anthraquinone Attenuates Inflammatory Response and Oxidative Stress via Regulating NLRP3 Signaling Pathway
title_short	Ethyl 2-Succinate-Anthraquinone Attenuates Inflammatory Response and Oxidative Stress via Regulating NLRP3 Signaling Pathway
title_full	Ethyl 2-Succinate-Anthraquinone Attenuates Inflammatory Response and Oxidative Stress via Regulating NLRP3 Signaling Pathway
title_fullStr	Ethyl 2-Succinate-Anthraquinone Attenuates Inflammatory Response and Oxidative Stress via Regulating NLRP3 Signaling Pathway
title_full_unstemmed	Ethyl 2-Succinate-Anthraquinone Attenuates Inflammatory Response and Oxidative Stress via Regulating NLRP3 Signaling Pathway
title_sort	ethyl 2-succinate-anthraquinone attenuates inflammatory response and oxidative stress via regulating nlrp3 signaling pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/18481a4896fa4d4ca4a2f7115d3d2ab7
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Ethyl 2-Succinate-Anthraquinone Attenuates Inflammatory Response and Oxidative Stress via Regulating NLRP3 Signaling Pathway

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