Effect of cubebin against streptozotocin-induced diabetic nephropathy rats via inhibition TNF-α/NF-κB/TGF-β: in vivo and in silico study
Abstract Cubebin, a dibenzyl butyrolactone lignan belonging to several distinct families, including Aristolochiaceae, Myristicaceae, Piperaceae, and Rutaceae, and possesses several pharmacological activities, including analgesic, anti-inflammatory, antioxidant, and vasodilatory. The current study ai...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-87319-7 |
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| author | Rahamat Unissa Syed Sivakumar S. Moni Weiam Hussein Taghreed Mohammad Saad Alhaidan Sondos Mohammed Y. Abumilha Lama Khalid Alnahdi Ling Shing Wong Vetriselvan Subramaniyan Vinoth Kumarasamy |
| author_facet | Rahamat Unissa Syed Sivakumar S. Moni Weiam Hussein Taghreed Mohammad Saad Alhaidan Sondos Mohammed Y. Abumilha Lama Khalid Alnahdi Ling Shing Wong Vetriselvan Subramaniyan Vinoth Kumarasamy |
| author_sort | Rahamat Unissa Syed |
| collection | DOAJ |
| description | Abstract Cubebin, a dibenzyl butyrolactone lignan belonging to several distinct families, including Aristolochiaceae, Myristicaceae, Piperaceae, and Rutaceae, and possesses several pharmacological activities, including analgesic, anti-inflammatory, antioxidant, and vasodilatory. The current study aimed to evaluate the effect of cubebin on streptozotocin (STZ)-evoked diabetic nephropathy (DN). DN is a well-identified complication of diabetes mellitus (DM) characterized by renal hypertrophy that progressively declines kidney function. Wistar rats were randomly divided into groups- normal, STZ control (65 mg/kg/body weight), and STZ + cubebin (10 and 20 mg/kg). Biochemical parameters such as glucose levels, kidney parameters, lipid profile, oxidative stress, endogenous antioxidant markers, inflammatory cytokines and histopathology were performed. Molecular docking [(PDB ID: TNF-α (7JRA), NF-κB (1SVC), TGF-β1 (3TZM)] and dynamic simulation (MDS) were also performed with the selected target. STZ-induced DN was changes in these parameters. In contrast, DN + cubebin at 10 and 20 mg/kg doses improved the biochemical parameters and histological changes. Furthermore, molecular docking and simulation studies showed a binding affinity with negative binding energy with TNF-α (7jra, − 11.342 kcal/mol), TGF-β1 (3tzm, − 9.162 kcal/mol) and NF-κB (1svc, − 6.665 kcal/mol). The results of MDS provided insight into the mechanisms that associate proteins TNF-α, NF-κB, and TGF-β1 in conformational dynamics upon binding to cubebin. In conclusion, these findings exhibit a potential effect of cubebin in STZ-evoked DN rats. |
| format | Article |
| id | doaj-art-b0732e2b3aef4483a0d5245c1879438a |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-b0732e2b3aef4483a0d5245c1879438a2025-02-09T12:33:16ZengNature PortfolioScientific Reports2045-23222025-02-0115112610.1038/s41598-025-87319-7Effect of cubebin against streptozotocin-induced diabetic nephropathy rats via inhibition TNF-α/NF-κB/TGF-β: in vivo and in silico studyRahamat Unissa Syed0Sivakumar S. Moni1Weiam Hussein2Taghreed Mohammad Saad Alhaidan3Sondos Mohammed Y. Abumilha4Lama Khalid Alnahdi5Ling Shing Wong6Vetriselvan Subramaniyan7Vinoth Kumarasamy8Department of Pharmaceutics, College of Pharmacy, University of Ha’ilDepartment of Pharmaceutics, College of Pharmacy, Jazan UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, University of HailDepartment of Clinical Toxicology, College of Medicine, Umm Al-Qura UniversityCollege of Medicine, King Khalid UniversityCollege of Medicine, King Khalid UniversityFaculty of Health and Life Sciences, INTI International UniversityDivision of Pharmacology, School of Medical and Life Sciences, Sunway UniversityDepartment of Parasitology and Medical Entomology, Faculty of Medicine, Universiti Kebangsaan MalaysiaAbstract Cubebin, a dibenzyl butyrolactone lignan belonging to several distinct families, including Aristolochiaceae, Myristicaceae, Piperaceae, and Rutaceae, and possesses several pharmacological activities, including analgesic, anti-inflammatory, antioxidant, and vasodilatory. The current study aimed to evaluate the effect of cubebin on streptozotocin (STZ)-evoked diabetic nephropathy (DN). DN is a well-identified complication of diabetes mellitus (DM) characterized by renal hypertrophy that progressively declines kidney function. Wistar rats were randomly divided into groups- normal, STZ control (65 mg/kg/body weight), and STZ + cubebin (10 and 20 mg/kg). Biochemical parameters such as glucose levels, kidney parameters, lipid profile, oxidative stress, endogenous antioxidant markers, inflammatory cytokines and histopathology were performed. Molecular docking [(PDB ID: TNF-α (7JRA), NF-κB (1SVC), TGF-β1 (3TZM)] and dynamic simulation (MDS) were also performed with the selected target. STZ-induced DN was changes in these parameters. In contrast, DN + cubebin at 10 and 20 mg/kg doses improved the biochemical parameters and histological changes. Furthermore, molecular docking and simulation studies showed a binding affinity with negative binding energy with TNF-α (7jra, − 11.342 kcal/mol), TGF-β1 (3tzm, − 9.162 kcal/mol) and NF-κB (1svc, − 6.665 kcal/mol). The results of MDS provided insight into the mechanisms that associate proteins TNF-α, NF-κB, and TGF-β1 in conformational dynamics upon binding to cubebin. In conclusion, these findings exhibit a potential effect of cubebin in STZ-evoked DN rats.https://doi.org/10.1038/s41598-025-87319-7AntioxidantCubebinDiabetic nephropathyStreptozotocinDiabetes |
| spellingShingle | Rahamat Unissa Syed Sivakumar S. Moni Weiam Hussein Taghreed Mohammad Saad Alhaidan Sondos Mohammed Y. Abumilha Lama Khalid Alnahdi Ling Shing Wong Vetriselvan Subramaniyan Vinoth Kumarasamy Effect of cubebin against streptozotocin-induced diabetic nephropathy rats via inhibition TNF-α/NF-κB/TGF-β: in vivo and in silico study Scientific Reports Antioxidant Cubebin Diabetic nephropathy Streptozotocin Diabetes |
| title | Effect of cubebin against streptozotocin-induced diabetic nephropathy rats via inhibition TNF-α/NF-κB/TGF-β: in vivo and in silico study |
| title_full | Effect of cubebin against streptozotocin-induced diabetic nephropathy rats via inhibition TNF-α/NF-κB/TGF-β: in vivo and in silico study |
| title_fullStr | Effect of cubebin against streptozotocin-induced diabetic nephropathy rats via inhibition TNF-α/NF-κB/TGF-β: in vivo and in silico study |
| title_full_unstemmed | Effect of cubebin against streptozotocin-induced diabetic nephropathy rats via inhibition TNF-α/NF-κB/TGF-β: in vivo and in silico study |
| title_short | Effect of cubebin against streptozotocin-induced diabetic nephropathy rats via inhibition TNF-α/NF-κB/TGF-β: in vivo and in silico study |
| title_sort | effect of cubebin against streptozotocin induced diabetic nephropathy rats via inhibition tnf α nf κb tgf β in vivo and in silico study |
| topic | Antioxidant Cubebin Diabetic nephropathy Streptozotocin Diabetes |
| url | https://doi.org/10.1038/s41598-025-87319-7 |
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