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Erchen Decoction Ameliorates Lipid Metabolism by the Regulation of the Protein CAV-1 and the Receptors VLDLR, LDLR, ABCA1, and SRB1 in a High-Fat Diet Rat Model.

ABSTRACT: Lipid metabolism disorder is a common metabolic disorder characterized by abnormal lipid levels in blood. Erchen decoction (ECD) is a traditional Chinese medicine prescription, which is used for the treatment of diseases caused by retention of phlegm dampness. It has been reported to ameliorate the disorder of lipid metabolism. The aim of the present study was to investigate the effects and underlying mechanisms of ECD in lipid metabolism disorder induced by a high-fat diet (HFD) in rats. ECD (4.35g/kg/d) and atorvastatin (10mg/kg/d, positive control) were orally administered to HFD-fed rats for four weeks. The parameters, food, water consumption, body weight, body length, liver, and visceral fat weight and the content of serum lipids and lipid transporters were assessed. The effects of ECD on the mRNA and protein expression levels of lipid transport factors were measured by real-time PCR and western blotting. The present study demonstrated that ECD improved the disorders of serum lipid and lipid transporters in HFD-fed rats, TG (0.70±0.08 mmol/L, p<0.01), LDL-C (1.50±0.19 mmol/L, p<0.01), LDL (1.38±0.21 mmol/L, p<0.05), and oxLDL (1.77±0.39 ng/mL, p<0.05) were downregulated, while HDL-C (0.87±0.13 mmol/L, p<0.01), FFA (0.62±0.13 mmol/L, p<0.05), HDL (38.8±4.0 mg/dL, p<0.05), and CETP (903.6±120.0 ng/mL, p<0.05) were upregulated. But ECD obviously had no effects on the indices food/water/energy intake, body/tissue (liver and fat) weight, and BMI (p>0.05). Concomitantly, ECD reversed the abnormal expressions of those lipid transport factors in the liver and visceral fat.

SUBMITTER: Ding S

PROVIDER: S-EPMC6196931 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Obesity is a chronic metabolic disease caused by genetic and environmental factors that has become a serious global health problem. There is evidence that gut microbiota is closely related to the occurrence and development of obesity. Erchen Decoction (ECD), a traditional Chinese medicine, has been widely used for clinical treatment and basic research of obesity and related metabolic diseases in recent years. It can significantly improve insulin resistance (IR) and lipid metabolism disorders. However, there is no microbiological study on its metabolic regulation. In this study, we investigated the effects of ECD on obesity, especially lipid metabolism and the composition and function of gut microbiota in Zucker diabetic fatty (ZDF) rats, and explored the correlation between the biomarkers of gut microbiota and metabolite and host phenotype. The results showed that ECD could reduce body weight, improve IR and lipid metabolism, and reduce the concentration of free fatty acids (FFA) released from white adipose tissue (WAT) due to excessive lipolysis by interfering with the insulin receptor substrate 1 (IRS1)/protein kinase B (AKT)/protein kinase A (PKA)/hormone-sensitive triglyceride lipase (HSL) signaling pathway in ZDF rats. Additionally, ECD gradually adjusted the overall structure of changed gut microbiota, reversed the relative abundance of six genera, and changed the function of gut microbiota by reducing the content of propionic acid, a metabolite of gut microbiota, in ZDF rats. A potentially close relationship between biomarkers, especially Prevotella, Blautia, and Holdemania, propionic acid and host phenotypes were demonstrated through correlation analysis. The results suggested that the beneficial effects of ECD on obesity, especially lipid metabolism disorders, are related to the regulation of gut microbiota in ZDF rats. This provides a basis for further research on the mechanism and clinical application of ECD to improve obesity via gut microbiota.

Project description:Background: Metabolic syndrome is characterized by central obesity, hyperglycemia and hyperlipidemia. Insulin resistance is the leading risk factor for metabolic syndrome. Kun-Dan decoction (KD), a traditional Chinese medicine, has been applied to treat patients with metabolic syndrome for over ten years. It is increasingly recognized that autophagy deficiency is the key cause of metabolic syndrome. Therefore, we aimed to explore whether KD can activate autophagy to improve metabolic syndrome. Methods: Network pharmacology was used to explore the underlying mechanism of KD in the treatment of metabolic syndrome. The high-fat diet-fed rats and oleic acid-induced LO2 cells were employed in our study. Oral glucose tolerance test and insulin tolerance test, obesity and histological examination, serum cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity in high-fat diet-fed rats were analyzed. Furthermore, the protein expressions of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), phospho-AMPK, mammalian target of rapamycin (mTOR), phospho-mTOR, p62, autophagy related protein (Atg) 5, Atg7, Atg12, Atg13, Atg16L1 and microtubule-associated protein 1A/1B-light chain 3 (LC3)-Ⅱ/Ⅰ were examined in rats and LO2 cells. Moreover, autophagy activator rapamycin and inhibitor 3-methyladenine, and small interfering RNA against Atg7 were utilized to verify the role of autophagy in the treatment of metabolic syndrome by KD in oleic acid-induced LO2 cells. Results: Results from network pharmacology indicated that targeted insulin resistance might be the critical mechanism of KD in the treatment of metabolic syndrome. We found that KD significantly suppressed obesity, serum cholesterol, triglyceride and LDL-C levels and increased serum HDL-C level in high-fat diet-fed rats. Furthermore, KD enhanced insulin sensitivity and attenuated HOMA-IR in high-fat diet-fed rats. Western blot showed that KD could enhance autophagy to increase the insulin sensitivity of high-fat diet-fed rats and oleic acid-induced LO2 cells. Furthermore, 3-methyladenine and small interfering RNA against Atg7 could reverse the protective effect of KD on LO2 cells. However, rapamycin could cooperate with KD to enhance autophagic activation to increase insulin sensitivity in LO2 cells. Conclusion: The induction of autophagy may be the major mechanism for KD to improve insulin resistance and metabolic syndrome.

Project description:Objective: Erchen Decoction (ECD), a well-known traditional Chinese medicine, exerts metabolism-regulatory, immunoregulation, and anti-tumor effects. However, the action and pharmacological mechanism of ECD remain largely unclear. In the present study, we explored the effects and mechanisms of ECD in the treatment of CRC using network pharmacology, molecular docking, and systematic experimental validation. Methods: The active components of ECD were obtained from the TCMSP database and the potential targets of them were annotated by the STRING database. The CRC-related targets were identified from different databases (OMIM, DisGeNet, GeneCards, and DrugBank). The interactive targets of ECD and CRC were screened and the protein-protein interaction (PPI) networks were constructed. Then, the hub interactive targets were calculated and visualized from the PPI network using the Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. In addition, the molecular docking was performed. Finally, systematic in vitro, in vivo and molecular biology experiments were performed to further explore the anti-tumor effects and underlying mechanisms of ECD in CRC. Results: A total of 116 active components and 246 targets of ECD were predicted based on the component-target network analysis. 2406 CRC-related targets were obtained from different databases and 140 intersective targets were identified between ECD and CRC. 12 hub molecules (STAT3, JUN, MAPK3, TP53, MAPK1, RELA, FOS, ESR1, IL6, MAPK14, MYC, and CDKN1A) were finally screened from PPI network. GO and KEGG pathway enrichment analyses demonstrated that the biological discrepancy was mainly focused on the tumorigenesis-, immune-, and mechanism-related pathways. Based on the experimental validation, ECD could suppress the proliferation of CRC cells by inhibiting cell cycle and promoting cell apoptosis. In addition, ECD could inhibit tumor growth in mice. Finally, the results of molecular biology experiments suggested ECD could regulate the transcriptional levels of several hub molecules during the development of CRC, including MAPKs, PPARs, TP53, and STATs. Conclusion: This study revealed the potential pharmacodynamic material basis and underlying molecular mechanisms of ECD in the treatment of CRC, providing a novel insight for us to find more effective anti-CRC drugs.

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Erchen Decoction Ameliorates Lipid Metabolism by the Regulation of the Protein CAV-1 and the Receptors VLDLR, LDLR, ABCA1, and SRB1 in a High-Fat Diet Rat Model.

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