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Tanreqing injection inhibits dengue virus encephalitis by suppressing the activation of NLRP3 inflammasome

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机构: [1]Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, People’s Republic of China. [2]Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, People’s Republic of China. [3]Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, People’s Republic of China. [4]Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China.
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关键词: Tanreqing injection Dengue Encephalitis NLRP3

摘要:
Encephalitis caused by dengue virus (DENV) is considered a manifestation of severe dengue. Tanreqing injection (TRQ) is a well-known Chinese patented medicine, which has been used to treat brain-related disorders by inhibiting inflammation. Nevertheless, the effects of TRQ on DENV encephalitis have not been studied. The aim of this study was to evaluate the effects of TRQ on DENV encephalitis and to explore its potential mechanisms.The cytotoxicity of TRQ was examined by MTT assay, and the anti-DENV activities of TRQ in BHK-21 baby hamster kidney fibroblast were evaluated through CCK-8 and plaque assays. The expression levels of NO, IL1B/IL-1β, TNFα and IL6 were measured by qRT‒PCR and ELISA in the BV2 murine microglial cell line. The inhibitory effects of TRQ on NLRP3 inflammasome activation in BV2 cells were examined by Western blotting, qRT‒PCR and ELISA. The effects of TRQ on HT22 mouse hippocampal neuronal cells were examined by CCK-8 assay, morphology observation and flow cytometry. Moreover, a DENV-infected ICR suckling mouse model was developed to investigate the protective role of TRQ in vivo.TRQ decreased the release of NO, IL6, TNFα and IL1B from BV2 cells and inhibited the activation of NLRP3. The presence of the NLRP3 agonist nigericin reversed the anti-inflammatory activities of TRQ. Furthermore, TRQ inhibited the death of HT22 cells by decreasing IL1B in DENV-infected BV2 cells. In addition, TRQ significantly attenuated weight loss, reduced clinical scores and extended the survival in DENV-infected ICR suckling mice. Critically, TRQ ameliorated pathological changes in ICR suckling mice brain by inhibiting microglia and NLRP3 activation and decreasing the production of inflammatory factors and the number of dead neurons.TRQ exerts potent inhibitory effects on dengue encephalitis in vitro and in vivo by reducing DENV-2-induced microglial activation and subsequently decreasing the inflammatory response, thereby protecting neurons. These findings demonstrate the potential of TRQ in the treatment of dengue encephalitis.© 2024. The Author(s).

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出版当年[2023]版:
大类 | 3 区 医学
小类 | 2 区 全科医学与补充医学 2 区 药学
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 全科医学与补充医学 2 区 药学
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出版当年[2022]版:
Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Q1 PHARMACOLOGY & PHARMACY
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Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Q1 PHARMACOLOGY & PHARMACY

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第一作者机构: [1]Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, People’s Republic of China.
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通讯机构: [1]Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, People’s Republic of China. [3]Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, People’s Republic of China. [4]Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China.
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