DBZ is a putative PPARγ agonist that prevents high fat diet-induced obesity, insulin resistance and gut dysbiosis
The nuclear receptor PPARγ is an effective pharmacological target for some types of metabolic syndrome, including obesity, diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. However, the current PPARγ-targeting thiazolidinedione drugs have undesirable side effects. Danshensu Bin...
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| Published in | Biochimica et biophysica acta. General subjects Vol. 1861; no. 11; pp. 2690 - 2701 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.11.2017
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0304-4165 1872-8006 |
| DOI | 10.1016/j.bbagen.2017.07.013 |
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| Abstract | The nuclear receptor PPARγ is an effective pharmacological target for some types of metabolic syndrome, including obesity, diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. However, the current PPARγ-targeting thiazolidinedione drugs have undesirable side effects. Danshensu Bingpian Zhi (DBZ), also known as tanshinol borneol ester derived from Salvia miltiorrhiza, is a synthetic derivative of natural compounds used in traditional Chinese medicine for its anti-inflammatory activity.
In vitro, investigations of DBZ using a luciferase reporter assay and molecular docking identified this compound as a novel promising PPARγ agonist. Ten-week-old C57BL/6J mice were fed either a normal chow diet (NCD) or a high-fat diet (HFD). The HFD-fed mice were gavaged daily with either vehicle or DBZ (50mg/kg or 100mg/kg) for 10weeks. The gut microbiota composition was assessed by analyzing the 16S rRNA gene V3+V4 regions via pyrosequencing.
DBZ is an efficient natural PPARγ agonist that shows lower PPARγ-responsive luciferase reporter activity than thiazolidinediones, has excellent effects on the metabolic phenotype and exhibits no unwanted adverse effects in a HFD-induced obese mouse model. DBZ protects against HFD-induced body weight gain, insulin resistance, hepatic steatosis and inflammation in mice. DBZ not only stimulates brown adipose tissue (BAT) browning and maintains intestinal barrier integrity but also reverses HFD-induced intestinal microbiota dysbiosis.
DBZ is a putative PPARγ agonist that prevents HFD-induced obesity-related metabolic syndrome and reverse gut dysbiosis.
DBZ may be used as a beneficial probiotic agent to improve HFD-induced obesity-related metabolic syndrome in obese individuals.
•DBZ showed lower PPARγ-responsive luciferase reporter activity than troglitazone and pioglitazone.•DBZ had excellent effects on the metabolic phenotype and exhibited no unwanted effects in a HFD-induced obese mouse model.•DBZ protected against HFD-induced body weight gain, insulin resistance, hepatic steatosis and inflammation in mice.•DBZ administration stimulated brown adipose tissue (BAT) browning and maintained intestinal barrier integrity.•DBZ treatment reversed HFD-induced intestinal microbiota dysbiosis. |
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| AbstractList | The nuclear receptor PPARγ is an effective pharmacological target for some types of metabolic syndrome, including obesity, diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. However, the current PPARγ-targeting thiazolidinedione drugs have undesirable side effects. Danshensu Bingpian Zhi (DBZ), also known as tanshinol borneol ester derived from Salvia miltiorrhiza, is a synthetic derivative of natural compounds used in traditional Chinese medicine for its anti-inflammatory activity.In vitro, investigations of DBZ using a luciferase reporter assay and molecular docking identified this compound as a novel promising PPARγ agonist. Ten-week-old C57BL/6J mice were fed either a normal chow diet (NCD) or a high-fat diet (HFD). The HFD-fed mice were gavaged daily with either vehicle or DBZ (50mg/kg or 100mg/kg) for 10weeks. The gut microbiota composition was assessed by analyzing the 16S rRNA gene V3+V4 regions via pyrosequencing.DBZ is an efficient natural PPARγ agonist that shows lower PPARγ-responsive luciferase reporter activity than thiazolidinediones, has excellent effects on the metabolic phenotype and exhibits no unwanted adverse effects in a HFD-induced obese mouse model. DBZ protects against HFD-induced body weight gain, insulin resistance, hepatic steatosis and inflammation in mice. DBZ not only stimulates brown adipose tissue (BAT) browning and maintains intestinal barrier integrity but also reverses HFD-induced intestinal microbiota dysbiosis.DBZ is a putative PPARγ agonist that prevents HFD-induced obesity-related metabolic syndrome and reverse gut dysbiosis.DBZ may be used as a beneficial probiotic agent to improve HFD-induced obesity-related metabolic syndrome in obese individuals. The nuclear receptor PPARγ is an effective pharmacological target for some types of metabolic syndrome, including obesity, diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. However, the current PPARγ-targeting thiazolidinedione drugs have undesirable side effects. Danshensu Bingpian Zhi (DBZ), also known as tanshinol borneol ester derived from Salvia miltiorrhiza, is a synthetic derivative of natural compounds used in traditional Chinese medicine for its anti-inflammatory activity. In vitro, investigations of DBZ using a luciferase reporter assay and molecular docking identified this compound as a novel promising PPARγ agonist. Ten-week-old C57BL/6J mice were fed either a normal chow diet (NCD) or a high-fat diet (HFD). The HFD-fed mice were gavaged daily with either vehicle or DBZ (50mg/kg or 100mg/kg) for 10weeks. The gut microbiota composition was assessed by analyzing the 16S rRNA gene V3+V4 regions via pyrosequencing. DBZ is an efficient natural PPARγ agonist that shows lower PPARγ-responsive luciferase reporter activity than thiazolidinediones, has excellent effects on the metabolic phenotype and exhibits no unwanted adverse effects in a HFD-induced obese mouse model. DBZ protects against HFD-induced body weight gain, insulin resistance, hepatic steatosis and inflammation in mice. DBZ not only stimulates brown adipose tissue (BAT) browning and maintains intestinal barrier integrity but also reverses HFD-induced intestinal microbiota dysbiosis. DBZ is a putative PPARγ agonist that prevents HFD-induced obesity-related metabolic syndrome and reverse gut dysbiosis. DBZ may be used as a beneficial probiotic agent to improve HFD-induced obesity-related metabolic syndrome in obese individuals. The nuclear receptor PPARγ is an effective pharmacological target for some types of metabolic syndrome, including obesity, diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. However, the current PPARγ-targeting thiazolidinedione drugs have undesirable side effects. Danshensu Bingpian Zhi (DBZ), also known as tanshinol borneol ester derived from Salvia miltiorrhiza, is a synthetic derivative of natural compounds used in traditional Chinese medicine for its anti-inflammatory activity.BACKGROUNDThe nuclear receptor PPARγ is an effective pharmacological target for some types of metabolic syndrome, including obesity, diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. However, the current PPARγ-targeting thiazolidinedione drugs have undesirable side effects. Danshensu Bingpian Zhi (DBZ), also known as tanshinol borneol ester derived from Salvia miltiorrhiza, is a synthetic derivative of natural compounds used in traditional Chinese medicine for its anti-inflammatory activity.In vitro, investigations of DBZ using a luciferase reporter assay and molecular docking identified this compound as a novel promising PPARγ agonist. Ten-week-old C57BL/6J mice were fed either a normal chow diet (NCD) or a high-fat diet (HFD). The HFD-fed mice were gavaged daily with either vehicle or DBZ (50mg/kg or 100mg/kg) for 10weeks. The gut microbiota composition was assessed by analyzing the 16S rRNA gene V3+V4 regions via pyrosequencing.METHODSIn vitro, investigations of DBZ using a luciferase reporter assay and molecular docking identified this compound as a novel promising PPARγ agonist. Ten-week-old C57BL/6J mice were fed either a normal chow diet (NCD) or a high-fat diet (HFD). The HFD-fed mice were gavaged daily with either vehicle or DBZ (50mg/kg or 100mg/kg) for 10weeks. The gut microbiota composition was assessed by analyzing the 16S rRNA gene V3+V4 regions via pyrosequencing.DBZ is an efficient natural PPARγ agonist that shows lower PPARγ-responsive luciferase reporter activity than thiazolidinediones, has excellent effects on the metabolic phenotype and exhibits no unwanted adverse effects in a HFD-induced obese mouse model. DBZ protects against HFD-induced body weight gain, insulin resistance, hepatic steatosis and inflammation in mice. DBZ not only stimulates brown adipose tissue (BAT) browning and maintains intestinal barrier integrity but also reverses HFD-induced intestinal microbiota dysbiosis.RESULTSDBZ is an efficient natural PPARγ agonist that shows lower PPARγ-responsive luciferase reporter activity than thiazolidinediones, has excellent effects on the metabolic phenotype and exhibits no unwanted adverse effects in a HFD-induced obese mouse model. DBZ protects against HFD-induced body weight gain, insulin resistance, hepatic steatosis and inflammation in mice. DBZ not only stimulates brown adipose tissue (BAT) browning and maintains intestinal barrier integrity but also reverses HFD-induced intestinal microbiota dysbiosis.DBZ is a putative PPARγ agonist that prevents HFD-induced obesity-related metabolic syndrome and reverse gut dysbiosis.CONCLUSIONSDBZ is a putative PPARγ agonist that prevents HFD-induced obesity-related metabolic syndrome and reverse gut dysbiosis.DBZ may be used as a beneficial probiotic agent to improve HFD-induced obesity-related metabolic syndrome in obese individuals.GENERAL SIGNIFICANCEDBZ may be used as a beneficial probiotic agent to improve HFD-induced obesity-related metabolic syndrome in obese individuals. The nuclear receptor PPARγ is an effective pharmacological target for some types of metabolic syndrome, including obesity, diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. However, the current PPARγ-targeting thiazolidinedione drugs have undesirable side effects. Danshensu Bingpian Zhi (DBZ), also known as tanshinol borneol ester derived from Salvia miltiorrhiza, is a synthetic derivative of natural compounds used in traditional Chinese medicine for its anti-inflammatory activity. In vitro, investigations of DBZ using a luciferase reporter assay and molecular docking identified this compound as a novel promising PPARγ agonist. Ten-week-old C57BL/6J mice were fed either a normal chow diet (NCD) or a high-fat diet (HFD). The HFD-fed mice were gavaged daily with either vehicle or DBZ (50mg/kg or 100mg/kg) for 10weeks. The gut microbiota composition was assessed by analyzing the 16S rRNA gene V3+V4 regions via pyrosequencing. DBZ is an efficient natural PPARγ agonist that shows lower PPARγ-responsive luciferase reporter activity than thiazolidinediones, has excellent effects on the metabolic phenotype and exhibits no unwanted adverse effects in a HFD-induced obese mouse model. DBZ protects against HFD-induced body weight gain, insulin resistance, hepatic steatosis and inflammation in mice. DBZ not only stimulates brown adipose tissue (BAT) browning and maintains intestinal barrier integrity but also reverses HFD-induced intestinal microbiota dysbiosis. DBZ is a putative PPARγ agonist that prevents HFD-induced obesity-related metabolic syndrome and reverse gut dysbiosis. DBZ may be used as a beneficial probiotic agent to improve HFD-induced obesity-related metabolic syndrome in obese individuals. •DBZ showed lower PPARγ-responsive luciferase reporter activity than troglitazone and pioglitazone.•DBZ had excellent effects on the metabolic phenotype and exhibited no unwanted effects in a HFD-induced obese mouse model.•DBZ protected against HFD-induced body weight gain, insulin resistance, hepatic steatosis and inflammation in mice.•DBZ administration stimulated brown adipose tissue (BAT) browning and maintained intestinal barrier integrity.•DBZ treatment reversed HFD-induced intestinal microbiota dysbiosis. |
| Author | Zhai, Yonggong Hong, Fan Xue, Tingting Wang, Jialin Zheng, Xiaohui Xu, Pengfei Zhao, Xia Wang, Jing Xu, Jingwei Wang, Sheng |
| Author_xml | – sequence: 1 givenname: Pengfei surname: Xu fullname: Xu, Pengfei organization: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China – sequence: 2 givenname: Fan surname: Hong fullname: Hong, Fan organization: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China – sequence: 3 givenname: Jialin surname: Wang fullname: Wang, Jialin organization: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China – sequence: 4 givenname: Jing surname: Wang fullname: Wang, Jing organization: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China – sequence: 5 givenname: Xia surname: Zhao fullname: Zhao, Xia organization: Shijingshan Teaching Hospital of Capital Medical University, Beijing Shijingshan Hospital, Beijing, 100043, China – sequence: 6 givenname: Sheng surname: Wang fullname: Wang, Sheng organization: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China – sequence: 7 givenname: Tingting surname: Xue fullname: Xue, Tingting organization: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China – sequence: 8 givenname: Jingwei surname: Xu fullname: Xu, Jingwei organization: Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China – sequence: 9 givenname: Xiaohui surname: Zheng fullname: Zheng, Xiaohui email: Zhengxh@nwu.edu.cn organization: Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi'an, 710069, China – sequence: 10 givenname: Yonggong surname: Zhai fullname: Zhai, Yonggong email: ygzhai@bnu.edu.cn organization: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28736228$$D View this record in MEDLINE/PubMed |
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| Keywords | PCoA Gut microbiota NAFLD TNFα UCP HFD ITT LPL WAT ADRB ORO LPS RDA OTU Per-WAT QUICKI FATP SREBP1c TLR DBZ ACC Obesity LDL-c T2D NMDS IL-6 NCD PPARγ FFDS PCA TC LEfSe Epi-WAT HOMA-IR TG BAT FAS Insulin resistance Mes-WAT IGTT CPT1β TCM TZD |
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| SubjectTerms | adverse effects agonists animal disease models body weight changes Bornanes - administration & dosage Bornanes - chemistry borneol brown adipose tissue cardiovascular diseases danshensu diabetes Diet, High-Fat - adverse effects digestive system drugs dysbiosis Dysbiosis - drug therapy Dysbiosis - genetics Dysbiosis - pathology fatty liver Gastrointestinal Microbiome - drug effects Gastrointestinal Microbiome - genetics genes Gut microbiota high fat diet Humans inflammation Insulin Resistance intestinal microorganisms luciferase Medicine, Chinese Traditional metabolic syndrome mice Molecular Docking Simulation molecular models Obesity Obesity - drug therapy Obesity - etiology Obesity - physiopathology Oriental traditional medicine peroxisome proliferator-activated receptors phenotype Phenylpropionates - administration & dosage Phenylpropionates - chemistry PPAR gamma - agonists PPAR gamma - chemistry PPAR gamma - genetics PPARγ probiotics ribosomal RNA RNA, Ribosomal, 16S - genetics Salvia miltiorrhiza Salvia miltiorrhiza - chemistry thiazolidinediones |
| Title | DBZ is a putative PPARγ agonist that prevents high fat diet-induced obesity, insulin resistance and gut dysbiosis |
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