Polyurethane Nanoparticle-Loaded Fenofibrate Exerts Inhibitory Effects on Nonalcoholic Fatty Liver Disease in Mice

Cao, Yini; Baiyisaiti, Asiya; Wong, Chui‐Wei; Hsu, Shan‐hui; Qi, Rong

doi:10.1021/acs.molpharmaceut.8b00548

Cited by 19 publications

(14 citation statements)

References 43 publications

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“…In recent times, safe, smart, and highly efficient nanomaterials have been gaining importance for their roles in treating different diseases, including NAFLD and dyslipidemia (Wang et al, 2016;Cao et al, 2018;Wan et al, 2018;Lee et al, 2019). Moreover, nanocarriers are promising carriers for gene delivery (Canup et al, 2017;Wang et al, 2018;Zai et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Delivery of microRNA-33 Antagomirs by Mesoporous Silica Nanoparticles to Ameliorate Lipid Metabolic Disorders

Tao

Wang

et al. 2020

Front. Pharmacol.

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Lipid metabolic disorders have become a major global public health concern. Fatty liver and dyslipidemia are major manifestations of these disorders. Recently, MicroRNA-33 (miR-33), a post-transcriptional regulator of genes involved in cholesterol efflux and fatty acid oxidation, has been considered as a good therapeutic target for these disorders. However, the traditional methods of gene therapy impede their further clinical transformation into a mature treatment system. To counter this problem, in this study we used mesoporous silica nanoparticles (MSNs) as nanocarriers to deliver miR-33 antagomirs developing nanocomposites miR-MSNs. We observed that the hepatocellular uptake of miR-33 antagomirs increased by ∼5 times when they were delivered using miR-MSNs. The regulation effects of miR-MSNs on miR-33 and several genes involved in lipid metabolism were confirmed in L02 cells. In a high-fat diet fed mice, miR-33 intervention via miR-MSNs lowered the serum triglyceride levels remarkably by 18.9% and reduced hepatic steatosis. Thus, our results provide a proof-of-concept for a potential strategy to ameliorate lipid metabolic disorders.

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Section: Introductionmentioning

confidence: 99%

Delivery of microRNA-33 Antagomirs by Mesoporous Silica Nanoparticles to Ameliorate Lipid Metabolic Disorders

Tao

Wang

et al. 2020

Front. Pharmacol.

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“…In order to explore the effect of NP-RAPA on NAFLD, and compare the therapeutic efficacy, mPEG-PLGA, RAPA, and NP-RAPA were intravenously injected into C57BL/6J mice during the period of HFD feeding (Figure 4). Hematoxylin and eosin (H&E) staining showed that HFD treatment resulted in lipid droplets in the hepatocytes compared with ND-treated mice, indicating the successful establishment of a mouse model of NAFLD, which has been described previously (Cao et al, 2018;Zhao et al, 2018). However, administration of mPEG-PLGA polymers did not induce the reduction in the hepatic lipid accumulation at all.…”

Section: Effects Of Np-rapa On Nafld In Micementioning

confidence: 73%

“…In vitro release profile can be used to determine whether dissolution of the targeted drug into carrier is enhanced by the novel drug delivery platform (Cao et al, 2018). The release curve of RAPA from NP-RAPA in vitro at pH 5.5 and 7.4 was shown in Figure 2A with zero time corresponding to the start of the incubation period.…”

Section: Drug Loading and Release Profile Of Rapamycin From Np-rapamentioning

confidence: 99%

Rapamycin-Loaded mPEG-PLGA Nanoparticles Ameliorate Hepatic Steatosis and Liver Injury in Non-alcoholic Fatty Liver Disease

et al. 2020

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Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and liver injury, and is the leading cause of chronic liver disease worldwide. There is an urgent need to develop novel pathophysiology-oriented therapy in human. Rapamycin (RAPA) has been recognized as a promising drug for alleviating hepatic steatosis on NAFLD, but the poorly water-soluble properties and side effects of RAPA limit their clinical use. In this study, we aimed to investigate the in vitro and in vivo therapeutic efficacy of biodegradable mPEG-PLGA polymers loaded with RAPA (NP-RAPA) on NAFLD. NP-RAPA were prepared by a green process using an emulsion/solvent evaporation method, the therapeutic efficacy on NAFLD were investigated on HepG2 cells incubated with oleic acid (OA) and in the livers of mice with NAFLD induced by high-fat diet (HFD). Compared with free RAPA, NP-RAPA significantly reduced lipid accumulation in HepG2 cells, and obviously ameliorated hepatic steatosis and liver injury in mice though enhancing the therapeutic efficacy of RAPA through reducing SREBP-1c-dependent de novo lipogenesis (DNL) and promoting PPARα-mediated fatty acid oxidation. This study suggests that mPEG-PLGA can be used as the potential therapeutic strategy and novel drug delivery for improving the efficacy of rapamycin for treatment of NAFLD.

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“…H20030569), which is a peroxisome proliferator-activated receptor- γ (PPAR γ ) agonist used as a positive drug in vivo [ 23 ], was purchased from Chengdu Hengrui Pharmaceutical Co. Ltd. Fenofibrate (FNF) (Lot. S5812), which is a PPAR α agonist used as a positive drug in vitro [ 24 ], was purchased from Selleck Chem, Inc., (Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Efficacy and Mechanism of a Chinese Classic Prescription of Yueju in Treating Nonalcoholic Steatohepatitis and Protecting Hepatocytes from Apoptosis

Zhang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Yueju, a famous classic Chinese prescription, has been extensively used in treating depression syndromes for hundreds of years. Recent studies have reported that Yueju showed good effects in treating metabolic diseases, such as obesity and hyperlipidemia. Nonalcoholic steatohepatitis (NASH), which leads to cirrhosis and severe cardiovascular diseases, is closely linked to obesity and abnormal lipid metabolism. In this study, Yueju could decrease the levels of alanine aminotransferase, aspartate transaminase, triglyceride, cholesterol, and low-density lipoprotein-C but increase the high-density lipoprotein-C in the serum of the NASH rat model induced by high-fat and high-cholesterol diet. Yueju could alleviate hepatosteatosis by increasing the phosphorylation of acetyl-CoA carboxylase and inhibiting the expression of fatty acid synthase and stearoyl-CoA desaturase 1. Yueju downregulated the expression of α-smooth muscle actin and collagen type 1A1, ameliorating the liver fibrilization. Yueju could also protect the hepatocytes from apoptosis by upregulating antiapoptosis protein Bcl-2 and X-linked inhibitor of apoptosis protein and downregulating apoptotic proteins Bax and cleaved poly ADP-ribose polymerase. Thus, Yueju could improve liver function, regulate lipid metabolism, alleviate hepatosteatosis and fibrosis, and protect hepatocytes from apoptosis against NASH. Yueju may be used as an alternative effective medicine for NASH treatment.

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Polyurethane Nanoparticle-Loaded Fenofibrate Exerts Inhibitory Effects on Nonalcoholic Fatty Liver Disease in Mice

Cited by 19 publications

References 43 publications

Delivery of microRNA-33 Antagomirs by Mesoporous Silica Nanoparticles to Ameliorate Lipid Metabolic Disorders

Delivery of microRNA-33 Antagomirs by Mesoporous Silica Nanoparticles to Ameliorate Lipid Metabolic Disorders

Rapamycin-Loaded mPEG-PLGA Nanoparticles Ameliorate Hepatic Steatosis and Liver Injury in Non-alcoholic Fatty Liver Disease

Efficacy and Mechanism of a Chinese Classic Prescription of Yueju in Treating Nonalcoholic Steatohepatitis and Protecting Hepatocytes from Apoptosis

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