Haojing Li, Wenli Li, Yuanyuan Wu, Huimin Wu, Xiaojun Cai
{"title":"Integrating network pharmacology and animal experimental validation to investigate the mechanism of lotus leaf in obesity.","authors":"Haojing Li, Wenli Li, Yuanyuan Wu, Huimin Wu, Xiaojun Cai","doi":"10.1016/j.intimp.2024.113719","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Lotus leaf and its extracts have been reported to exert various beneficial effects; however, their anti-obesity mechanisms remain relatively unclear. Therefore, we investigated the mechanism by which lotus leaf regulates obesity using network pharmacology, molecular docking, and animal experimentation.</p><p><strong>Methods: </strong>Network pharmacology was used to identify potential targets and pathways through which lotus leaf regulates obesity. Molecular docking technology was used to verify the interaction between lotus leaves and core targets of obesity. Additionally, a rat model of obesity induced using a high-fat diet was established to examine the anti-obesity effects of lotus leaf. Moreover, western blotting was performed to examine the expression levels of the target proteins and elucidate the molecular mechanisms of lotus leaf.</p><p><strong>Results: </strong>Quercetin, nuciferin, catechin, kaempferol, and isorhamnetin were identified as the main active compounds in the lotus leaves involved in obesity treatment. Network pharmacology analysis identified fibroblast growth factor (FGF) 15 and farnesoid X receptor (FXR) as core targets of lotus leaf, and the AGE-RAGE signaling pathway in diabetic complications, neuroactive ligand-receptor interactions, insulin resistance, and cancer pathways, as biomechanistic pathways by which lotus leaf ameliorates obesity. Additionally, molecular docking analysis indicated a strong binding affinity between the main active ingredients of lotus leaf and the core targets. Moreover, western blotting showed that lotus leaf significantly downregulated FGF15 and FXR protein expression in intestinal tissues.</p><p><strong>Conclusions: </strong>Lotus leaf ameliorates obesity through several pathways, including by downregulating FGF15 and FXR, providing a novel basis for the development of natural drug therapy for obesity.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113719"},"PeriodicalIF":4.8000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.intimp.2024.113719","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/8 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Lotus leaf and its extracts have been reported to exert various beneficial effects; however, their anti-obesity mechanisms remain relatively unclear. Therefore, we investigated the mechanism by which lotus leaf regulates obesity using network pharmacology, molecular docking, and animal experimentation.
Methods: Network pharmacology was used to identify potential targets and pathways through which lotus leaf regulates obesity. Molecular docking technology was used to verify the interaction between lotus leaves and core targets of obesity. Additionally, a rat model of obesity induced using a high-fat diet was established to examine the anti-obesity effects of lotus leaf. Moreover, western blotting was performed to examine the expression levels of the target proteins and elucidate the molecular mechanisms of lotus leaf.
Results: Quercetin, nuciferin, catechin, kaempferol, and isorhamnetin were identified as the main active compounds in the lotus leaves involved in obesity treatment. Network pharmacology analysis identified fibroblast growth factor (FGF) 15 and farnesoid X receptor (FXR) as core targets of lotus leaf, and the AGE-RAGE signaling pathway in diabetic complications, neuroactive ligand-receptor interactions, insulin resistance, and cancer pathways, as biomechanistic pathways by which lotus leaf ameliorates obesity. Additionally, molecular docking analysis indicated a strong binding affinity between the main active ingredients of lotus leaf and the core targets. Moreover, western blotting showed that lotus leaf significantly downregulated FGF15 and FXR protein expression in intestinal tissues.
Conclusions: Lotus leaf ameliorates obesity through several pathways, including by downregulating FGF15 and FXR, providing a novel basis for the development of natural drug therapy for obesity.
期刊介绍:
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.