Feng Xu, Mei Zhang, Hongmei Wu, Yuanmin Wang, Ye Yang, Xiangpei Wang
{"title":"结合药理评价和网络药理学研究lupenone治疗2型糖尿病的作用机制。","authors":"Feng Xu, Mei Zhang, Hongmei Wu, Yuanmin Wang, Ye Yang, Xiangpei Wang","doi":"10.1080/13880209.2022.2067568","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>Lupenone (LUP) is the active ingredient of <i>Musa basjoo</i> Sieb. et Zucc. (Musaceae) with antidiabetes effects, but an unclear underlying mechanism of action.</p><p><strong>Objective: </strong>Animal experiments combined with network pharmacology were used to explore the mechanism of LUP for treating diabetes.</p><p><strong>Materials and methods: </strong>Insulin resistance (IR) in male Sprague-Dawley rats with type 2 diabetic was induced using a high-fat diet and streptozotocin. The selected rats were divided into normal group, model group, positive group and LUP (2.0, 4.0 and 8.0 mg/kg) groups, and orally administrated twice daily with Tween 80, rosiglitazone or LUP. Fasting blood glucose (FBG), oxidative stress index, blood lipids and IR-related targets were detected. A network pharmacology analysis was performed.</p><p><strong>Results: </strong>Compared to the model group, LUP (8.0 mg/kg) significantly decreased the levels of FBG (22.3%), LEP (9.5%), HbA1c (14.9%) and MDA (12.3%), increased the ADPN (24.2%) levels and GSH-PX activity (12.4%) (<i>p</i> < 0.05), improved oxidative stress, lipid metabolism disorders and pancreas pathological changes, increased the mRNA and protein expression of InsR (3.7-fold and 1.3-fold), IRS-1 (3-fold and 2-fold), IRS-2 (2-fold and 1.6-fold), GLUT-4 (2-fold and 2.4-fold) in skeletal muscle and IRS-1 (6-fold and 1.6-fold), IRS-2 (5.8-fold and 1.5-fold), GLUT-4 (2.5-fold and 1.7-fold) and PPAR-γ (7-fold and 1.4-fold) in adipose tissue (<i>p</i> < 0.05). Network pharmacology analysis revealed that LUP improves IR by multiple targets and signal pathways.</p><p><strong>Conclusions: </strong>The mechanism of LUP for treating diabetes is related to improving IR. LUP has the potential to be developed as a new drug for treating type 2 diabetes.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"60 1","pages":"997-1010"},"PeriodicalIF":3.9000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154797/pdf/","citationCount":"4","resultStr":"{\"title\":\"Study on the mechanism of lupenone for treating type 2 diabetes by integrating pharmacological evaluation and network pharmacology.\",\"authors\":\"Feng Xu, Mei Zhang, Hongmei Wu, Yuanmin Wang, Ye Yang, Xiangpei Wang\",\"doi\":\"10.1080/13880209.2022.2067568\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Context: </strong>Lupenone (LUP) is the active ingredient of <i>Musa basjoo</i> Sieb. et Zucc. (Musaceae) with antidiabetes effects, but an unclear underlying mechanism of action.</p><p><strong>Objective: </strong>Animal experiments combined with network pharmacology were used to explore the mechanism of LUP for treating diabetes.</p><p><strong>Materials and methods: </strong>Insulin resistance (IR) in male Sprague-Dawley rats with type 2 diabetic was induced using a high-fat diet and streptozotocin. The selected rats were divided into normal group, model group, positive group and LUP (2.0, 4.0 and 8.0 mg/kg) groups, and orally administrated twice daily with Tween 80, rosiglitazone or LUP. Fasting blood glucose (FBG), oxidative stress index, blood lipids and IR-related targets were detected. A network pharmacology analysis was performed.</p><p><strong>Results: </strong>Compared to the model group, LUP (8.0 mg/kg) significantly decreased the levels of FBG (22.3%), LEP (9.5%), HbA1c (14.9%) and MDA (12.3%), increased the ADPN (24.2%) levels and GSH-PX activity (12.4%) (<i>p</i> < 0.05), improved oxidative stress, lipid metabolism disorders and pancreas pathological changes, increased the mRNA and protein expression of InsR (3.7-fold and 1.3-fold), IRS-1 (3-fold and 2-fold), IRS-2 (2-fold and 1.6-fold), GLUT-4 (2-fold and 2.4-fold) in skeletal muscle and IRS-1 (6-fold and 1.6-fold), IRS-2 (5.8-fold and 1.5-fold), GLUT-4 (2.5-fold and 1.7-fold) and PPAR-γ (7-fold and 1.4-fold) in adipose tissue (<i>p</i> < 0.05). Network pharmacology analysis revealed that LUP improves IR by multiple targets and signal pathways.</p><p><strong>Conclusions: </strong>The mechanism of LUP for treating diabetes is related to improving IR. LUP has the potential to be developed as a new drug for treating type 2 diabetes.</p>\",\"PeriodicalId\":19942,\"journal\":{\"name\":\"Pharmaceutical Biology\",\"volume\":\"60 1\",\"pages\":\"997-1010\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2022-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154797/pdf/\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutical Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/13880209.2022.2067568\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13880209.2022.2067568","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
Study on the mechanism of lupenone for treating type 2 diabetes by integrating pharmacological evaluation and network pharmacology.
Context: Lupenone (LUP) is the active ingredient of Musa basjoo Sieb. et Zucc. (Musaceae) with antidiabetes effects, but an unclear underlying mechanism of action.
Objective: Animal experiments combined with network pharmacology were used to explore the mechanism of LUP for treating diabetes.
Materials and methods: Insulin resistance (IR) in male Sprague-Dawley rats with type 2 diabetic was induced using a high-fat diet and streptozotocin. The selected rats were divided into normal group, model group, positive group and LUP (2.0, 4.0 and 8.0 mg/kg) groups, and orally administrated twice daily with Tween 80, rosiglitazone or LUP. Fasting blood glucose (FBG), oxidative stress index, blood lipids and IR-related targets were detected. A network pharmacology analysis was performed.
Results: Compared to the model group, LUP (8.0 mg/kg) significantly decreased the levels of FBG (22.3%), LEP (9.5%), HbA1c (14.9%) and MDA (12.3%), increased the ADPN (24.2%) levels and GSH-PX activity (12.4%) (p < 0.05), improved oxidative stress, lipid metabolism disorders and pancreas pathological changes, increased the mRNA and protein expression of InsR (3.7-fold and 1.3-fold), IRS-1 (3-fold and 2-fold), IRS-2 (2-fold and 1.6-fold), GLUT-4 (2-fold and 2.4-fold) in skeletal muscle and IRS-1 (6-fold and 1.6-fold), IRS-2 (5.8-fold and 1.5-fold), GLUT-4 (2.5-fold and 1.7-fold) and PPAR-γ (7-fold and 1.4-fold) in adipose tissue (p < 0.05). Network pharmacology analysis revealed that LUP improves IR by multiple targets and signal pathways.
Conclusions: The mechanism of LUP for treating diabetes is related to improving IR. LUP has the potential to be developed as a new drug for treating type 2 diabetes.
期刊介绍：
Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine.
Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.
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