scholarly journals Scutellarein Aggravated Carbon Tetrachloride-Induced Chronic Liver Injury in Gut Microbiota-Dysbiosis Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhimin Miao ◽  
Yong Lai ◽  
Yingying Zhao ◽  
Lingmin Chen ◽  
Jianeng Zhou ◽  
...  

Scutellarein (SCU) is an herbal flavonoid, showing hepatoprotective potentials. The study was aimed to investigate whether the hepatoprotective effect of SCU is dependent on the integrity of gut microbiota. Mice received repeated intraperitoneal injections of CCl4, followed with or without SCU treatment (15, 30, and 60 mg/kg). Gut microbial community of mice was disrupted by administrating a cocktail of antibiotics (ampicillin, neomycin sulfate, metronidazole, and vancomycin) in drinking water. The results showed SCU plus antibiotics aggravated CCl4-induced chronic liver injury, as demonstrated by liver function analysis, histological analysis, and TUNEL assay. SCU activated CYP2E1 expression and worsened CYP2E1-mediated lipid peroxidation and oxidative stress as coadministered with antibiotics. Moreover, when gut microbiota was disrupted by antibiotics, SCU activated IκBα/NF-κB pathway and promoted the release of subsequent proinflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Remarkably, the 16 S rRNA sequencing demonstrated that SCU greatly decreased the relative abundance of Bifidobacterium and Lactobacillus and increased the relative abundance of Enterococcus in gut microbiota-dysbiosis mice. Spearman correlation analysis showed that Lactobacillus was positively correlated with SOD and negatively correlated with AST. Collectively, the hepatoprotective effect of SCU is reversed under antibiotics intervention, which may partly involve the activation of CYP2E1 and IκBα/NF-κB pathway and diminishment of Lactobacillus.

2020 ◽  
Author(s):  
Zhimin Miao ◽  
Yingying Zhao ◽  
Chunyan Li ◽  
Lingmin Chen ◽  
Jianeng Zhou ◽  
...  

Abstract Background: Erigeron breviscapus (Vant.) Hand. -Mazz. is an edible and traditional medical herb and its extract scutellarin (SCU) is a widely used flavonoid showing anti-oxidant and anti-inflammatory activities. The purpose of this study was to evaluate the hepatoprotective effect of SCU on carbon tetrachloride (CCl4)-induced chronic liver injury in mice and reveal the underlying mechanisms. Methods: Chronic liver injury in mice was induced by intraperitoneal injection of 1 ml/kg CCl4 every three days. SCU (15 mg/kg, 30 mg/kg and 60 mg/kg) was administered through gavage every day. Bifendate (120 mg/kg) serves as a positive drug to validate the effectiveness of SCU.Results: The hepatoprotective effect of SCU was confirmed by liver function analysis, histological analysis and TUNEL assay. Administration of SCU recovered the activities of superoxide dismutase (SOD) and reduced the production of malondialdehyde (MDA). Additionally, treatment with SCU significantly decreased the mRNA levels of pro-inflammatory cytokines including IL-6, IL-1β and TNF-α. Moreover, SCU treatment suppressed the activation of NF-κB by decreasing the degradation of IκBα and inhibited the expression of CYP2E1. The 16S rRNA sequencing demonstrated that intake of SCU significantly remodeled gut microbiota, especially enriching the following: Lactobacillus, Coprobacillus, Akkermansia, Bifidobacterium, Parabacteroides. Conclusion: Our findings showed that SCU effectively ameliorated CCl4-induced chronic liver injury. This hepatoprotective effects might be attributed to inhibition of CCl4-induced NF-κB and CYP2E1 activation and enrichment of beneficial microbial community.


2016 ◽  
Vol 17 (12) ◽  
pp. 2056 ◽  
Author(s):  
Wen-Huang Peng ◽  
Yi-Wen Chen ◽  
Meng-Shiou Lee ◽  
Wen-Te Chang ◽  
Jen-Chieh Tsai ◽  
...  

2013 ◽  
Vol 51 (7) ◽  
pp. 930-935 ◽  
Author(s):  
Jing-Hua Wang ◽  
Jian Wang ◽  
Min-Kyung Choi ◽  
Fang Gao ◽  
Dong-Soo Lee ◽  
...  

2016 ◽  
Vol 49 (1) ◽  
pp. 35
Author(s):  
Aml Hashem ◽  
Nabil Taha ◽  
AbdElwahab Mandour ◽  
Mohamed Lebda ◽  
Mahmoud Balbaa ◽  
...  

Phytomedicine ◽  
2009 ◽  
Vol 16 (9) ◽  
pp. 805-813 ◽  
Author(s):  
Fei Yan ◽  
Qiao-Yan Zhang ◽  
Lei Jiao ◽  
Ting Han ◽  
Hong Zhang ◽  
...  

2018 ◽  
Vol 83 (2) ◽  
pp. 525-534 ◽  
Author(s):  
Mohammed Hamid ◽  
Yassin Abdulrahim ◽  
Dandan Liu ◽  
Gang Qian ◽  
Alamzeb Khan ◽  
...  

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