scholarly journals Improving the ameliorative effects of berberine and curcumin combination via dextran-coated bilosomes on non-alcohol fatty liver disease in mice

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yi Chen ◽  
Zhaohui Jiang ◽  
Jinzhuan Xu ◽  
Jiyuan Zhang ◽  
Runbin Sun ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Oral Delivery ◽  
Fatty Liver Disease ◽  
Oral Absorption ◽  
Synergistic Effects ◽  
Drug Combinations ◽  
Promising Strategy ◽  
Anti Inflammation

Abstract Background The combination of berberine (BER) and curcumin (CUR) has been verified with ameliorative effects on non-alcohol fatty liver disease (NAFLD). However, discrepant bioavailability and biodistribution of BER and CUR remained an obstacle to achieve synergistic effects. Multilayer nanovesicles have great potential for the protection and oral delivery of drug combinations. Therein lies bile salts inserted liposomes, named as bilosomes, that possesses long residence time in the gastrointestinal tract (GIT) and permeability across the small intestine. Diethylaminoethyl dextran (DEAE-DEX) is generally used as an outside layer on the nanovesicles to increase the mucinous stability and promote oral absorption. Herein, we developed a DEAE-DEX-coated bilosome with BER and CUR encapsulated (DEAE-DEX@LSDBC) for the treatment of NAFLD. Results DEAE-DEX@LSDBC with 150 nm size exhibited enhanced permeation across mucus and Caco-2 monolayer. In vivo pharmacokinetics study demonstrated that DEAE-DEX@LSDBC profoundly prolonged the circulation time and improved the oral absorption of both BER and CUR. Intriguingly, synchronized biodistribution of BER and CUR and highest biodistribution at liver was achieved by DEAE-DEX@LSDBC, which contributed to the optimal ameliorative effects on NAFLD. It was further verified to be mainly mediated by anti-oxidation and anti-inflammation related pathways Conclusion DEAE-DEX coated bilosome displayed promoted oral absorption, prolonged circulation and synchronized biodistribution of BER and CUR, leading to improved ameliorative effects on NAFLD in mice, which provided a promising strategy for oral administration of drug combinations. Graphic abstract

scholarly journals The Evaluation of Drug Delivery Nanocarrier Development and Pharmacological Briefing for Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

2021 ◽  
Vol 14 (3) ◽  
pp. 215
Author(s):  
Reem Abou Assi ◽  
Ibrahim M. Abdulbaqi ◽  
Chan Siok Yee
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Synergistic Effects ◽  
Herbal Medicines ◽  
Alcoholic Fatty Liver ◽  
Intrahepatic Lipids ◽  
Inflammatory Processes ◽  
Drug Compound ◽  
Alcoholic Fatty Liver Disease

Current research indicates that the next silent epidemic will be linked to chronic liver diseases, specifically non-alcoholic fatty liver disease (NAFLD), which was renamed as metabolic-associated fatty liver disease (MAFLD) in 2020. Globally, MAFLD mortality is on the rise. The etiology of MAFLD is multifactorial and still incompletely understood, but includes the accumulation of intrahepatic lipids, alterations in energy metabolism, insulin resistance, and inflammatory processes. The available MAFLD treatment, therefore, relies on improving the patient’s lifestyle and multidisciplinary pharmacotherapeutic options, whereas the option of surgery is useless without managing the comorbidities of the MAFLD. Nanotechnology is an emerging approach addressing MAFLD, where nanoformulations are suggested to improve the safety and physicochemical properties of conventional drugs/herbal medicines, physical, chemical, and physiological stability, and liver-targeting properties. A wide variety of liver nanosystems were constructed and delivered to the liver, only those that addressed the MAFLD were discussed in this review in terms of the nanocarrier classes, particle size, shape, zeta potential and offered dissolution rate(s), the suitable preparation method(s), excipients (with synergistic effects), and the suitable drug/compound for loading. The advantages and challenges of each nanocarrier and the focus on potential promising perspectives in the production of MAFLD nanomedicine were also highlighted.

scholarly journals Circ_0057558 promotes nonalcoholic fatty liver disease by regulating ROCK1/AMPK signaling through targeting miR-206

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Xi Chen ◽  
Qing-Qing Tan ◽  
Xin-Rui Tan ◽  
Shi-Jun Li ◽  
Xing-Xing Zhang
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Luciferase Assay ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling ◽  
Related Proteins

AbstractNonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders that is featured by the extensive deposition of fat in the hepatocytes. Current treatments are very limited due to its unclear pathogenesis. Here, we investigated the function of circ_0057558 and miR-206 in NAFLD. High-fat diet (HFD) feeding mouse was used as an in vivo NAFLD model and long-chain-free fatty acid (FFA)-treated liver cells were used as an in vitro NAFLD model. qRT-PCR was used to measure levels of miR-206, ROCK1 mRNA, and circ_0057558, while Western blotting was employed to determine protein levels of ROCK1, p-AMPK, AMPK, and lipogenesis-related proteins. Immunohistochemistry were performed to examine ROCK1 level. Oil-Red O staining was used to assess the lipid deposition in cells. ELISA was performed to examine secreted triglyceride (TG) level. Dual-luciferase assay was used to validate interactions of miR-206/ROCK1 and circ_0057558/miR-206. RNA immunoprecipitation was employed to confirm the binding of circ_0057558 with miR-206. Circ_0057558 was elevated while miR-206 was reduced in both in vivo and in vitro NAFLD models. miR-206 directly bound with ROCK1 3’-UTR and suppressed lipogenesis and TG secretion through targeting ROCK1/AMPK signaling. Circ_0057558 directly interacted with miR-206 to disinhibit ROCK1/AMPK signaling. Knockdown of circ_0057558 or overexpression of miR-206 inhibited lipogenesis, TG secretion and expression of lipogenesis-related proteins. ROCK1 knockdown reversed the effects of circ_0057558 overexpression. Injection of miR-206 mimics significantly ameliorated NAFLD progression in vivo. Circ_0057558 acts as a miR-206 sponge to de-repress the ROCK1/AMPK signaling and facilitates lipogenesis and TG secretion, which greatly contributes to NAFLD development and progression.

scholarly journals Activation of TAF9 via Danshensu-Induced Upregulation of HDAC1 Expression Alleviates Non-alcoholic Fatty Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruiwen Wang ◽  
Zhecheng Wang ◽  
Ruimin Sun ◽  
Rong Fu ◽  
Yu Sun ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Protective Effect ◽  
Fatty Liver Disease ◽  
Cell Model ◽  
Signaling Mechanism ◽  
Alcoholic Fatty Liver

Fatty acid β-oxidation is an essential pathogenic mechanism in nonalcoholic fatty liver disease (NAFLD), and TATA-box binding protein associated factor 9 (TAF9) has been reported to be involved in the regulation of fatty acid β-oxidation. However, the function of TAF9 in NAFLD, as well as the mechanism by which TAF9 is regulated, remains unclear. In this study, we aimed to investigate the signaling mechanism underlying the involvement of TAF9 in NAFLD and the protective effect of the natural phenolic compound Danshensu (DSS) against NAFLD via the HDAC1/TAF9 pathway. An in vivo model of high-fat diet (HFD)-induced NAFLD and a palmitic acid (PA)-treated AML-12 cell model were developed. Pharmacological treatment with DSS significantly increased fatty acid β-oxidation and reduced lipid droplet (LD) accumulation in NAFLD. TAF9 overexpression had the same effects on these processes both in vivo and in vitro. Interestingly, the protective effect of DSS was markedly blocked by TAF9 knockdown. Mechanistically, TAF9 was shown to be deacetylated by HDAC1, which regulates the capacity of TAF9 to mediate fatty acid β-oxidation and LD accumulation during NAFLD. In conclusion, TAF9 is a key regulator in the treatment of NAFLD that acts by increasing fatty acid β-oxidation and reducing LD accumulation, and DSS confers protection against NAFLD through the HDAC1/TAF9 pathway.

scholarly journals Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Peng Yu ◽  
Xi Xu ◽  
Jing Zhang ◽  
Xuan Xia ◽  
Fen Xu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling

A glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LR) had been experimentally and clinically shown to ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the beneficial effect of LR on NAFLD in vivo and in vitro and its underlying molecular mechanism. The effects of LR were examined on the high-fat diet-induced in vivo model in mice and in vitro model of NAFLD in human HepG2 cells. Liver tissues and HepG2 cells were procured for measuring lipid metabolism, histological examination, and western blot analysis. LR administration significantly lowered the serum lipid profile and lipid disposition in vitro and in vivo because of the altered expression of enzymes on hepatic gluconeogenesis and lipid metabolism. Moreover, LR significantly decreased Src homology region 2 domain-containing phosphatase-1 (SHP1) and then increased the expression of phosphorylated-AMP-activated protein kinase (p-AMPK). However, the overexpression of SHP1 mediated by lentivirus vector reversed LR-induced improvement in lipid deposition. Moreover, SHP1 silencing could further increase the expression of p-AMPK to ameliorate lipid metabolism and relative lipogenic gene induced by LR. In addition, abrogation of AMPK by Compound C eliminated the protective effects of LR on lipid metabolism without changing the expression of SHP1. LR markedly prevented NAFLD through adjusting lipid metabolism via SHP1/AMPK signaling pathway.

P0975 : Characterization of an in vivo model of juvenile non-alcoholic fatty liver disease

2015 ◽  
Vol 62 ◽  
pp. S711-S712
Author(s):  
V. Marin ◽  
N. Rosso ◽  
M. Dal Ben ◽  
A. Raseni ◽  
C. Degrassi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
In Vivo Model ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease
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