The underlying mechanisms of Jie-Du-Hua-Yu granule for protecting rat liver failure

The underlying mechanisms of Jie-Du-Hua-Yu granule for protecting rat liver failure
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解毒化瘀颗粒保护大鼠肝衰竭的机制研究

DOI:
10.2147/dddt.s180969
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发表时间:
2019-02
期刊:
Drug Des Devel Ther
影响因子:
--
通讯作者:
Wang Xiufeng
Wang Xiufeng
中科院分区:
其他
文献类型:
--
作者:
Qiu Hua;Mao Dewen;Tang Nong;Long Fuli;Zhang Rongzhen;Wang Minggang;Shi Qinglan;Li Jiahuan;Jiang Qin;Chen Yueqiao;Wang Xiufeng

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目的 解毒化瘀(JDHY)颗粒是六种中药的复方,具有治疗急性肝衰竭(ALF)的已知疗效。本研究的目的是探讨 JDHY 对脂多糖/D-半乳糖胺 (LPS/D-GalN) 诱导的大鼠 ALF 的改善效果,并探讨其治疗效果可能的分子机制。材料和方法 JDHY 的功效是通过评估 LPS 和 D-GalN 攻击的 Wistar 大鼠的肝脏病理学和功能来确定的。我们还通过测量炎症细胞因子和确定表型功能来评估 JDHY 对 LPS 诱导的 Kupffer 细胞的影响。通过肝组织的生物信息学分析和库普弗细胞验证,我们确定了 JDHY 药理作用机制的可能途径。结果JDHY可通过抑制细胞凋亡、增加肝活性来减轻LPS引起的大鼠肝损伤。体外研究表明,JDHY可减少促炎细胞因子(肿瘤坏死因子-α、IL6和干扰素-γ)的产生,增加抗炎细胞因子(IL10、IL13)的产生,促进细胞存活和增殖,可能是由于抑制IκB/核因子-κB(NF-κB)信号通路和CD14和CXCL2的表达,这与生物信息学分析的结果一致。结论 我们的结果表明,JDHY 通过抑制 NF-κB 介导的炎症通路,在体外和体内均可预防 LPS 诱导的肝损伤,表明其具有治疗肝病的潜在功能。
Objectives Jie-Du-Hua-Yu (JDHY) granule is a combination of six traditional Chinese medicines with known therapeutic effect in treating acute liver failure (ALF). The aim of this study was to investigate the amelioration efficacy of JDHY in lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced ALF in rat and explore the possible molecular mechanism underlying the therapeutic efficacy. Materials and methods The efficacy of JDHY was determined by assessing hepatic pathology and function in LPS and D-GalN challenged Wistar rat. We also evaluated the effect of JDHY on LPS-induced Kupffer cells by measuring inflammatory cytokines and determining the phenotypic function. By means of bioinformatics analysis of liver tissue and validation in Kupffer cells, we identified possible pathways involved in the pharmacologic action of mechanism of JDHY. Results JDHY could attenuate LPS-induced liver injury in rat by inhibiting apoptosis and increasing hepatic activity. In vitro study showed that JDHY could decrease the production of proinflammatory cytokines (tumor necrosis factor-α, IL6, and interferon-γ), increase anti-inflammatory cytokines (IL10, IL13), and promote cell survival and proliferation, possibly due to inhibition of IκB/nuclear factor-κB (NF-κB) signaling pathway and expression of CD14 and CXCL2, which was consistent with the findings from bioinformatics analysis. Conclusion Our results revealed that JDHY protected against LPS-induced liver damage both in vitro and in vivo, by inhibiting the NF-κB-mediated inflammatory pathway, indicating its potential function to treat liver diseases.
DOI: 10.1155/2017/9819350
发表时间: 2017
期刊: Evidence-based complementary and alternative medicine : eCAM
影响因子: --
作者:
Wang M;Shi Q;Zhang R;Qiu H;Mao D;Long F
通讯作者: Long F
DOI: 10.1002/hep.27849
发表时间: 2015-07-01
期刊: HEPATOLOGY
影响因子: 13.5
作者:
Gustot, Thierry;Fernandez, Javier;Arroyo, Vicente
通讯作者: Arroyo, Vicente
DOI: 10.1007/s00011-005-0060-y
发表时间: 2006-03-01
影响因子: 6.7
作者:
Li, G;Qi, XP;Li, JS
通讯作者: Li, JS
鸡掌大黄对急性肝衰竭小鼠NF-κB信号通路的影响
DOI: 10.1016/j.apjtm.2015.09.011
发表时间: 2015
影响因子: 3.1
作者:
Zhang Rong-Zhen;Qiu Hua;Wang Na;Long Fu-Li;Mao De-Wen
通讯作者: Mao De-Wen
DOI: --
发表时间: 2009
期刊: --
影响因子: --
作者:
Long Fu-li
通讯作者: Long Fu-li