scholarly journals Use of Network Pharmacology to Investigate the Mechanism by Which Allicin Ameliorates Lipid Metabolism Disorder in HepG2 Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Bijun Cheng ◽  
Tianjiao Li ◽  
Fenglin Li
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Hepg2 Cells ◽  
Experimental Validation ◽  
Biological Activities ◽  
Lipid Lowering ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder

Allicin has been well documented to exhibit a wide spectrum of biological activities, especially lipid-lowering activity, as a promising candidate for the management of nonalcoholic fatty liver disease (NALFD). However, the mechanisms underlying the therapeutic effects of allicin require further investigation. It is tempting to think of combining network pharmacology and experimental validation to investigate the mechanism by which allicin ameliorates lipid metabolism disorder in HepG2 cells. We established a cell model of hepatic steatosis induced by PA to investigate the antisteatotic effects of allicin. The studies showed that allicin reduced PA-induced lipid accumulation using Nile red staining and TC and TG assays. Then, 219 potential targets of allicin were successfully predicted by PharmMapper. According to Reactome Pathway Analysis, 44 potential targets related to lipid metabolism were screened out. Molecular signaling cascades mediated by allicin included PPARA, PPARG, FABP4, and FABP6 by cytoHubba and qPCR analysis. Results revealed that allicin activated the gene expression of PPARA and FABP6 and suppressed the gene expression of FABP4 and PPARG. Thus, the present study united the methods of network pharmacology and experimental validation to investigate the protein targets of allicin on PA-induced lipid metabolism disorders to supply a reference for related application for the first time.

Lipid-Lowering Therapies for Atherosclerosis: Statins, Fibrates, Ezetimibe and PCSK9 monoclonal antibodies

2021 ◽  
Vol 28 ◽  
Author(s):  
Adel Hajj Ali ◽  
Nour Younis ◽  
Rola Abdallah ◽  
Farah Shaer ◽  
Ali Dakroub ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Lipid Metabolism ◽  
Plasma Cholesterol ◽  
Therapeutic Interventions ◽  
Lipid Lowering ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
Peripheral Arterial Diseases ◽  
Branching Points ◽  
Genetic Interventions

: Cardiovascular disease (CVD) remains the primary cause of global morbidity and mortality. CVD includes various life-threatening conditions such as myocardial infarction, stroke and peripheral arterial diseases. In this context, atherosclerosis continues to play the principal role in the pathogenesis of these conditions. Atherosclerosis emanates from a set of modifiable and non-modifiable risk factors that include age, male gender, family history, obesity, smoking, diabetes mellitus and hypertension. Recent evidence classifies atherosclerosis as a latent disease affecting all-sized arteries with a predilection for arterial branching points of decreased or absent blood supply. Atherosclerosis is not only a lipid metabolism disorder, but is also a chronic inflammatory one. In this review, we provide a synoptic discussion of the underlying pathological mechanisms of atherosclerosis along with the currently applied therapeutic interventions. We then discuss the classical lipid-lowering therapies as well as the newly discovered therapies. For the classical therapies, we point out the importance of statins and ezetimibe in reducing plasma cholesterol levels by virtue of their effects on synthesis, reuptake and intestinal absorption of cholesterol. We also discuss the role of fibrates in modulating lipid metabolism and improving the ratio of high-density to low-density density lipoproteins. We then focus on the more recent molecular and genetic interventions exemplified by proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, evinacumab, and microRNA inhibitors. Special attention is also given to clinical trials involving these therapies.

scholarly journals Free Fatty Acids Impair FGF21 Action in HepG2 Cells

2015 ◽  
Vol 37 (5) ◽  
pp. 1767-1778 ◽  
Author(s):  
Mohamed Asrih ◽  
Christophe Montessuit ◽  
Jacques Philippe ◽  
François R. Jornayvaz
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Free Fatty Acids ◽  
Hepg2 Cells ◽  
Lipid Lowering ◽  
Fibroblast Growth Factor 21 ◽  
Beneficial Effects ◽  
Positive Effects

Background/Aims: Fibroblast growth factor 21 (FGF21) is a key mediator of glucose and lipid metabolism. However, the beneficial effects of exogenous FGF21 administration are attenuated in obese animals and humans with elevated levels of circulating free fatty acids (FFA). Methods: We investigated in vitro how FFA impact FGF21 effects on hepatic lipid metabolism. Results: In the absence of FFA, FGF21 reduced lipogenesis and increased lipid oxidation in HepG2 cells. Inhibition of lipogenesis was associated with a down regulation of SREBP-1c, FAS and SCD1. The lipid-lowering effect was associated with AMPK and ACC phosphorylation, and up regulation of CPT-1α expression. Further, FGF21 treatment reduced TNFα gene expression, suggesting a beneficial action of FGF21 on inflammation. In contrast, the addition of FFA abolished the positive effects of FGF21 on lipid metabolism. Conclusion: In the absence of FFA, FGF21 improves lipid metabolism in HepG2 cells and reduces the inflammatory cytokine TNFα. However, under high levels of FFA, FGF21 action on lipid metabolism and TNFα gene expression is impaired. Therefore, FFA impair FGF21 action in HepG2 cells potentially through TNFα.

Protective effects of allicin on 1,3-DCP-induced lipid metabolism disorder in HepG2 cells

2017 ◽  
Vol 96 ◽  
pp. 1411-1417 ◽  
Author(s):  
Jing Lu ◽  
Bijun cheng ◽  
Baochen Fang ◽  
Zhuoqun Meng ◽  
Yiying Zheng ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Hepg2 Cells ◽  
Protective Effects ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder

Exploring miRNA-related Molecular Targets of Erchen Decoction against Lipid Metabolism Disorder using A Network Pharmacologic Approach

2021 ◽  
Vol 24 ◽  
Author(s):  
Shanshan Ding ◽  
Qiliang Chen ◽  
Yiqing Huang ◽  
Xiaomei Li ◽  
Yujuan Chai ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Molecular Targets ◽  
Confidence Score ◽  
Network Pharmacology ◽  
Sprague Dawley ◽  
Lipid Metabolism Disorder ◽  
Protein Protein Interaction ◽  
Metabolism Disorder ◽  
Sprague Dawley Rats ◽  
Mirna Sequencing

Background: Erchen Decoction (ECD) is a complex herbal formulation widely used for treating lipid metabolism disorder (LMD) in China. This study aims to explore the microRNA (miRNA)-related molecular targets of ECD against LMD using a network pharmacology approach (NPA) Methods: We randomly divided 20 male Sprague Dawley rats into two groups; 10 rats were normal controls, and the other 10 rats were fed a high-fat diet (HFD) for 12 weeks to establish an LMD model. Differentially expressed miRNAs (DE-miRs, HFD vs. Control) in the rats’ liver tissues were identified by miRNA sequencing and validated with qRT-PCR. Finally, the miRNA-related molecular targets for ECD activity against LMD were identified using a standard NPA by finding the intersection between identified DE-miRs-related targets and ECD-related targets. Result: We identified 8 DE-miRs and 968 targets and compared them to 262 ECD-related targets. A final list of 22 candidate targets was identified. Using a confidence score of >0.4, the network of (protein-protein interaction) PPI relationships exhibited 22 nodes and 67 edges. The GO and KEGG enrichment analyses revealed 171 molecular targets and 59 pathways, which were associated with ECD against LMD. Conclusion: The identified molecular targets and pathways suggest that complex mechanisms are involved in ECD’s mechanism of action, and immune-inflammation-related mechanisms are closely associated with the effects of ECD. The targets obtained in this study will guide future studies on the pharmacologic effects of ECD.

scholarly journals Phenolic Compounds of Propolis Alleviate Lipid Metabolism Disorder

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Lingjie Kong ◽  
Yuhao Zhang ◽  
Zhouxu Feng ◽  
Jie Dong ◽  
Hongcheng Zhang
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Caffeic Acid ◽  
Significant Risk ◽  
Caffeic Acid Phenethyl Ester ◽  
Benzyl Ester ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder

Lipid metabolism disorder is one of the significant risk factors for a multitude of human diseases and has become a serious threat to human health. The present study aimed to evaluate the effects of phenolics from poplar-type propolis on regulating lipid metabolism by using cell models of steatosis induced by palmitic acid (PA). Our study shows that phenolic esters have higher lipid-lowering activities than phenolic acids, especially for three caffeic acid esters, including caffeic acid phenethyl ester (CAPE), caffeic acid cinnamyl ester (CACE), and caffeic acid benzyl ester (CABE). Most notably, CACE presents prominent properties to prevent intracellular lipid accumulation and to amend extracellular adipokine secretion abnormalities. In addition, our results firstly reveal that CACE can alleviate lipid metabolism disorder through mediating protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6) signaling pathway-associated protein expression, suppressing endoplasmic reticulum (ER) stress, and activating peroxisome proliferator-activated receptors (PPARs) by distinct upregulation of PPARα and downregulation of PPARγ.

scholarly journals Integrating Constituents Absorbed into Blood, Network Pharmacology, and Quantitative Analysis to Reveal the Active Components in Rubus chingii var. suavissimus that Regulate Lipid Metabolism Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Man-jing Jiang ◽  
Wan-fang Huang ◽  
Shuai Huang ◽  
Yi-xiang Lu ◽  
Yong Huang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Quantitative Analysis ◽  
Target Genes ◽  
Rat Plasma ◽  
Network Pharmacology ◽  
Active Components ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
Effective Components ◽  
Rubus Chingii

Rubus chingii var. suavissimus (S. K. Lee) L. T. Lu (RS)—a sweet plant also known as Tiancha distributed in the south of China where it is used as a beverage—recently gained extensive attention as adjuvant therapy of diabetes and hypertension. Although pharmacological studies indicate that RS has beneficial effects in regulating lipid metabolism disorder characteristics, the active chemicals responsible for this effect remains unclear. The present study aims to predict the effective substances of RS on regulating lipid metabolism disorder through the analysis of the chemical profile of RS, the absorbed prototype components in rat plasma, and network pharmacology. Also, a UPLC method able to quantify the screened potential effective chemicals of RS products was established. First, a total of 69 components—including diterpene, triterpenoids, flavonoids, polyphenols, and lignans—were systematically characterized in RS. Of those, 50 compounds were detected in the plasma of rats administered with RS extract. Through network pharmacology, 9 potential effective components, 71 target genes, and 20 pathways were predicted to be involved in RS-mediated regulation of lipid metabolism disorder. The quantitative analysis suggested that the contents of potential effective components varied among samples from different marketplaces. In conclusion, the presented results provide a chemical basis for further research of Rubus chingii var. suavissimus.

scholarly journals Integrating Network Pharmacology and Experimental Validation to Investigate the Effects and Mechanism of Astragalus Flavonoids Against Hepatic Fibrosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Lin An ◽  
Yuefang Lin ◽  
Leyan Li ◽  
Muyan Kong ◽  
Yanmei Lou ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Experimental Validation ◽  
Biological Activities ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Pharmacological Effects ◽  
Validation Data ◽  
Matrix Deposition

Hepatic fibrosis (HF) represents the excessive wound healing where an excess amount of connective tissues is formed within the liver, finally resulting in cirrhosis or even hepatocellular carcinoma (HCC). Therefore, it is significant to discover the efficient agents and components to treat HF, thus restraining the further progression of hepatopathy. Astragalus membranaceus (Fisch.) Bunge [also called Astragali Radix (AR)] is a famous herb in traditional Chinese medicine (TCM), which possesses a variety of biological activities and exerts good therapeutic effects in the treatment of HF. Flavonoids account for the major active ingredients related to the AR pharmacological effects. Total AR flavonoids have been proved to exert inhibitory effects on hepatic fibrosis. This study aimed to further undertake network pharmacology analysis coupled with experimental validation and molecular docking to investigate the effects and mechanism of multiple flavonoid components from AR against liver fibrosis. The results of the network pharmacology analysis showed that the flavonoids from AR exerted their pharmacological effects against liver fibrosis by modulating multiple targets and pathways. The experimental validation data showed that the flavonoids from AR were able to suppress transforming growth factor beta 1 (TGF-β1)-mediated activation of hepatic stellate cells (HSCs) and reduce extracellular matrix deposition in HSC-T6 cells via regulating the nuclear factor kappa B (NF-κB) signal transduction pathway. The results of the molecular docking study further showed that the flavonoids had a strong binding affinity for IκB kinase (IKKβ) after docking into the crystal structure. The above results indicated that, flavonoids possibly exerted the anti-inflammatory effect on treating HF by mediating inflammatory signaling pathways. The potential mechanism of these flavonoids against liver fibrosis may be related to suppression of the NF-κB pathway through effective inhibition of IKKβ. This study not only provides a scientific basis for clarifying the effects and mechanism of AR flavonoids against liver fibrosis but also suggests a novel promising therapeutic strategy for the treatment of liver fibrosis.

scholarly journals Crosstalk Between Polygonatum kingianum, the miRNA, and Gut Microbiota in the Regulation of Lipid Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Jincai Dong ◽  
Wen Gu ◽  
Xingxin Yang ◽  
Linxi Zeng ◽  
Xi Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Therapeutic Effects ◽  
Lipid Metabolism Disorder ◽  
Polysaccharide Fraction ◽  
The Core ◽  
Metabolism Disorder ◽  
Differentially Expressed Mirnas ◽  
Reduce Insulin Resistance

Objectives:Polygonatum kingianum is a medicinal herb used in various traditional Chinese medicine formulations. The polysaccharide fraction of P. kingianum can reduce insulin resistance and restore the gut microbiota in a rat model of aberrant lipid metabolism by down regulating miR-122. The aim of this study was to further elucidate the effect of P. kingianum on lipid metabolism, and the roles of specific miRNAs and the gut microbiota.Key findings:P. kingianum administration significantly altered the abundance of 29 gut microbes and 27 differentially expressed miRNAs (DEMs). Several aberrantly expressed miRNAs closely related to lipid metabolism were identified, of which some were associated with specific gut microbiota. MiR-484 in particular was identified as the core factor involved in the therapeutic effects of P. kingianum. We hypothesize that the miR-484-Bacteroides/Roseburia axis acts as an important bridge hub that connects the entire miRNA-gut microbiota network. In addition, we observed that Parabacteroides and Bacillus correlated significantly with several miRNAs, including miR-484, miR-122-5p, miR-184 and miR-378b.Summary:P. kingianum alleviates lipid metabolism disorder by targeting the network of key miRNAs and the gut microbiota.

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