scholarly journals Recombinant Lactococcus lactis Expressing Ling Zhi 8 Protein Ameliorates Nonalcoholic Fatty Liver and Early Atherogenesis in Cholesterol-Fed Rabbits

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Mey-Fann Lee ◽  
Chu-Hui Chiang ◽  
Shyh-Jye Lin ◽  
Pei-Pong Song ◽  
Hsin-Chun Liu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Lactococcus Lactis ◽  
Low Cost ◽  
Rabbit Model ◽  
Herbal Medicines ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
Subendothelial Space ◽  
Anti Inflammatory

Atherosclerosis is an inflammatory disease characterized by lipid deposits in the subendothelial space leading to severe inflammation. Nonalcoholic fatty liver disease (NAFLD) shares several risk factors with atherosclerosis, including dyslipidemia, type 2 diabetes mellitus, and metabolic syndrome, all of which lead to lipid deposition in the liver causing inflammation and fibrosis. Several clinical trials have shown that certain Chinese herbal medicines with anti-inflammatory effects can be used as adjuvant therapy to prevent the development of cardiovascular events and liver disease. Ling Zhi 8 (LZ8) is an immunomodulatory protein isolated from a medicinal mushroom and has been well documented to possess a broad range of pharmacological properties. This study aimed to evaluate the protective effects of recombinant Lactococcus lactis expressing LZ8 protein on NAFLD and atherogenesis in a cholesterol-fed rabbit model. Twelve rabbits were divided into three groups and fed with syrup only, L. lactis vehicle, or recombinant L. lactis-LZ8 once a day on weekdays for five weeks, respectively. The gene expression of IL-1β in the aorta was significantly suppressed after oral administration of L. lactis-LZ8. Moreover, in hematoxylin and eosin staining of the aorta, the intima-medial thickness was decreased, and foam cells were significantly reduced in the subendothelial space. LZ8 also inhibited the expression of IL-1β in the liver, decreased fat droplet deposits and infiltration of inflammatory cells, and improved liver function by decreasing liver enzymes in an animal model. Our results suggest that the Lactococcus-expressing LZ8 appears to be a promising medicine for improving both NAFLD and early atherogenesis owing to its anti-inflammatory effect. Furthermore, it is available as a low-cost food-grade product.

P6204Oral vaccination of Lactococcus lactis expressing Ling Zhi 8 protein prevents nonalcoholic fatty liver and early atherogenesis in cholesterol-fed rabbits

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
W W Lin ◽  
M F Lee ◽  
S J Lin ◽  
T J Wu
Keyword(s):  
Fatty Liver ◽  
Lactococcus Lactis ◽  
Expression System ◽  
Inflammatory Cells ◽  
Nonalcoholic Fatty Liver ◽  
Subendothelial Space ◽  
Anti Inflammatory ◽  
Intima Medial Thickness ◽  
Epidemiology Studies ◽  
Anti Inflammation

Abstract Background Atherosclerosis is an inflammatory disease characterized by lipid deposits in the subendothelial space leading to severe inflammation. Nonalcoholic fatty liver disease (NAFLD) shares several risk factors with atherosclerosis. Epidemiology studies have indicated that NAFLD may be an independent risk factor for atherosclerosis. Anti-inflammation therapy by inhibiting IL-1β led to a significantly lower cardiovascular event rate in recent clinical trial (CANTOS trial). Ling Zhi 8 (LZ8) is an immunomodulatory protein that possesses a broad range of pharmacological properties, including anti-inflammatory activities. Methods and findings In this study, we developed an oral vaccination of Lactococcus lactis expressing LZ8 protein in a nisin-controlled gene expression system and investigated its anti-inflammation properties. Experimental rabbits received commercial rabbit chow supplemented with 2% cholesterol for 5 weeks and recombinant LZ8 L. lactis vaccine once a day on weekdays. The expression of IL-1β in the aorta (Figure A) was significantly suppressed after LZ8 vaccination. Moreover, in hematoxylin and eosin staining of the aorta, the intima-medial thickness was decreased, and foam cells were significantly reduced in the sub-endothelial space (Figure C). LZ8 also inhibited the expression of IL-1β in the liver (Figure B), decreased fat droplet deposits and infiltration of inflammatory cells (Figure D), and improved liver function by decreasing liver enzymes. Figure 1 Conclusions Our results suggest that LZ8 could be used as a therapeutic tool to improve both atherosclerosis and NAFLD due to its anti-inflammatory effect. Acknowledgement/Funding TCVGH-1067317C, TCVGH-1063108C

Polyphenol intakes and risk of impaired lipid profile, elevated hepatic enzymes and nonalcoholic fatty liver disease

2019 ◽  
Vol 49 (5) ◽  
pp. 903-910 ◽  
Author(s):  
Mehrnaz Nikkhah-Bodaghi ◽  
Matin Ghanavati ◽  
Azita Hekmatdoost
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Profile ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Separate Analysis ◽  
Protective Effects ◽  
Hepatic Enzymes ◽  
Content Type ◽  
Nonalcoholic Fatty Liver

PurposePolyphenols are plant-derived bioactive compounds with some known hepato-protective effects. The purpose of this study is to evaluate the association between polyphenol consumption and risk of nonalcoholic fatty liver disease (NAFLD) and its related conditions such as impaired lipid profile and elevated hepatic enzymes.Design/methodology/approachA total of 196 NAFLD patients and 803 controls were enrolled in this case-control study. Biochemical and anthropometric measurements as well as polyphenol consumption during the previous year were assessed.FindingsIn unadjusted model, participants who consumed the third and fourth quartiles of polyphenols intake were less likely to have NAFLD in comparison to those who consumed the first quartile [odds ratio, OR: 0.48; 95 per cent confidence interval, CI: (0.30-0.77) and OR: 0.62; 95 per cent CI: (0.40-0.96), respectively]. In separate analysis of genders, this effect was seen only in male participants [OR: 0.29; 95 per cent CI: (0.14-0.58) and OR: 0.21; 95 per cent CI (0.10-0.42), respectively], and the association remained significant after adjustment for energy, body mass index, age and smoking.Originality/valueHigher total polyphenol intake is associated with a decreased risk of NAFLD. Prospective studies are needed to confirm these results.

scholarly journals Protective Effects of MitoTEMPO on Nonalcoholic Fatty Liver Disease via Regulating Myeloid-Derived Suppressor Cells and Inflammation in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Jiayuan Wu ◽  
Li Zheng ◽  
Juanfen Mo ◽  
Xiujuan Yao ◽  
Chenliang Fan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Calcium Binding ◽  
Fatty Liver Disease ◽  
Calcium Binding Protein ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
S100 Calcium Binding Protein ◽  
Protein Expressions

MitoTEMPO, a mitochondrial antioxidant, has protective effects on liver-related diseases. However, the role of MitoTEMPO on nonalcoholic fatty liver disease (NAFLD) and its possible mechanisms are largely unknown. Here, we investigated the effects of MitoTEMPO on NAFLD using high fat diet- (HFD-) induced obese mice as animal models. MitoTEMPO was intraperitoneally injected into HFD mice. Liver morphological changes were observed by H&E and Oil Red O staining, and the frequency of MDSCs in peripheral blood was analyzed by flow cytometry. Moreover, real-time quantitative PCR, western blot, and immunohistochemistry were conducted to detect the mRNA and protein expressions in the liver tissues. The results showed that the hepatic steatosis in liver tissues of HFD mice injected with MitoTEMPO was significantly ameliorated. Additionally, MitoTEMPO reduced the frequency of CD11b+Gr-1+ MDSCs in peripheral circulation and decreased Gr-1+ cell accumulation in the livers. Further studies demonstrated that MitoTEMPO administration suppressed the mRNA and protein expressions of MDSC-associated proinflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1), S100 calcium-binding protein A8 (S100A8), and S100 calcium-binding protein A9 (S100A9). Our results suggest that MitoTEMPO appears to be a potential chemical compound affecting certain immune cells and further ameliorates inflammation in obese-associated NAFLD.

scholarly journals Network Pharmacology-Based Analysis of Pogostemon cablin (Blanco) Benth Beneficial Effects to Alleviate Nonalcoholic Fatty Liver Disease in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Yizhe Cui ◽  
Qiuju Wang ◽  
Renxu Chang ◽  
Ahmad Aboragah ◽  
Juan J. Loor ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Network Pharmacology ◽  
Nonalcoholic Fatty Liver ◽  
Pogostemon Cablin ◽  
Anti Oxidant ◽  
Anti Inflammatory

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is associated with high morbidity and mortality. Pogostemon cablin (Blanco) Benth/Huo Xiang (HX) is a perennial herb with unique anti-oxidant and anti-inflammatory properties, and thus, can positively affect liver function. In this study, we used network pharmacology to predict the potential mechanism of HX on NAFLD. Pharmacological experiments were used to verify the effect of HX on the functions of NAFLD. Network pharmacology identified nine components that interacted with 82 NAFLD-related targets, revealing four target genes: TNF, IL6, TP53, and AKT1. HX prevents the development and progression of NAFLD through different pathways and targets with quercetin-regulated lipid metabolism, anti-inflammatory, and anti-oxidant pathways playing an essential role in the treatment of NAFLD. Compared with feeding HFD, HX significantly attenuated lipid accumulation in vivo with mice and also in vitro with mouse liver cells. A high dose of HX decreased hepatocyte lipid accumulation and the abundance of SREBF1 and FASN. Validation experiments revealed that HX inhibited the activation of NF-κB/IκB signaling and decreased the release and levels of pro-inflammatory factors (TNF-α and IL-6). These data suggest that HX can attenuate abnormal lipid metabolic responses and enhance antioxidant mechanisms. Thus, the pharmacological effects from plants used in traditional Chinese medicine are achievde through a multi-level response.

scholarly journals Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanism and Therapy

2017 ◽  
Author(s):  
Junli Ma ◽  
Qihang Zhou ◽  
Houkai Li
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Targeted Therapies ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Herbal Medicines ◽  
Active Components ◽  
Nonalcoholic Fatty Liver

Gut microbiota play critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance, which highlighted the potential of gut microbiota-targeted therapies on these diseases. There are various ways that can manipulate gut microbiota including probiotics, prebiotics, synbiotics, antibiotics and some active components from herbal medicines. In this review, we first reviewed the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies on NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future.

scholarly journals Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanism and Therapy

2017 ◽  
Author(s):  
Junli Ma ◽  
Qihang Zhou ◽  
Houkai Li
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Targeted Therapies ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Herbal Medicines ◽  
Active Components ◽  
Nonalcoholic Fatty Liver

Gut microbiota play critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance, which highlighted the potential of gut microbiota-targeted therapies on these diseases. There are various ways that can manipulate gut microbiota including probiotics, prebiotics, synbiotics, antibiotics and some active components from herbal medicines. In this review, we first described the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies in NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future.

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