Obesity, characterized by abnormal or excessive fat accumulation, has become a chronic degenerative health condition that poses significant threats to overall well-being. Pharmacological intervention stands at the forefront of strategies to combat this issue. Recent studies, notably by Umut Ozcan's team, have uncovered the remarkable potential of Celastrol, a small-molecule compound derived from the traditional Chinese herb thunder god vine (Tripterygium wilfordii) as an anti-obesity agent. In this research, computational chemical analysis was employed, incorporating the "TriDimensional Hierarchical Fingerprint Clustering with Tanimoto Representative Selection (3DHFC-TRS)" algorithm to systematically explore 139 active small molecules from thunder god vine. These compounds were classified into six categories, with a particular focus on Category 1 molecules for their exceptional binding affinity to obesity-related targets, offering new avenues for therapeutic development. Using advanced molecular docking techniques and Cytoscape prediction models, six representative Celastrol-like molecules were identified, namely 3-Epikatonic Acid, Hederagenin, Triptonide, Triptotriterpenic Acid B, Triptotriterpenic Acid C, and Ursolic Acid. These compounds demonstrated superior binding affinity and specificity toward two key obesity targets, PPARG and PTGS2, suggesting their potential to regulate fat metabolism and mitigate inflammatory responses. To further substantiate these findings, molecular dynamics simulations and MM-PBSA free-energy calculations were applied to analyze the dynamic interactions between these small molecules and the enzymatic active sites of their targets. The results provide robust theoretical evidence that support the feasibility of these molecules as promising candidates for anti-obesity therapies. This study underscores the power of the 3DHFC-TRS algorithm in uncovering bioactive compounds from natural sources, such as thunder god vine, and highlights the therapeutic promise of PPARG and PTGS2 as novel obesity-related targets. Furthermore, it emphasizes the essential role of computational science in expediting drug discovery, paving the way for personalized and precision-based treatments for obesity and heralding a future of more effective healthcare solutions.
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http://dx.doi.org/10.3390/ijms252312501 | DOI Listing |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11641352 | PMC |
Int J Mol Sci
November 2024
Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun 130012, China.
Obesity, characterized by abnormal or excessive fat accumulation, has become a chronic degenerative health condition that poses significant threats to overall well-being. Pharmacological intervention stands at the forefront of strategies to combat this issue. Recent studies, notably by Umut Ozcan's team, have uncovered the remarkable potential of Celastrol, a small-molecule compound derived from the traditional Chinese herb thunder god vine (Tripterygium wilfordii) as an anti-obesity agent.
View Article and Find Full Text PDFLupus Sci Med
March 2024
Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Chinese Medicine, Beijing, China
Objective: Celastrol is a bioactive constituent extracted from (thunder god vine). It has been demonstrated to have a therapeutic effect on experimental disease models for chronic inflammatory and immune disorders. In the present study, we investigated whether and how celastrol exerts a regulatory effect on the autoimmune response in MRL/lpr mice.
View Article and Find Full Text PDFAnal Bioanal Chem
January 2024
State Key Laboratory for Fine Exploration and Intelligent Development of Coal Resources, Ding11 Xueyuan Road, Beijing, 100083, China.
Natural bioactive compounds (NBCs) are widely used in clinical treatment. For example, Tripterygium wilfordii Hook f. is commonly known in China as Lei-Gong-Teng which means thunder god vine.
View Article and Find Full Text PDFBioorg Chem
December 2023
Natural Product Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China. Electronic address:
Extensive phytochemical investigation of the seeds of Tripterygium wilfordii led to the identification of 54 polyesterified dihydro-β-agarofuran-type sesquiterpenoids, including 27 previously undescribed ones, named Tripwilin I-XXVII (1-27). Comprehensive spectroscopic and single-crystal X-ray diffraction analyses, along with electronic circular dichroism (ECD) calculations were used for the structural elucidation of the new compounds. Biological assay revealed that 37 compounds among the isolates exhibited significant inhibition against osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL) at 10 µM.
View Article and Find Full Text PDFJ Burn Care Res
January 2024
Department of Pharmacy, Hospital of Huazhong University of Science and Technology, Wuhan, China.
Keloids are benign skin tumors characterized by excessive fibroblast proliferation and collagen deposition. The current treatment of keloids with hormone drug injection, surgical excision, radiotherapy, physical compression, laser therapy, cryotherapy often have unsatisfactory outcomes. The phytochemical compounds have shown great potential in treating keloids.
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