Antidiabetic Effects of Quercetin and Silk Sericin in Attenuating Dysregulation of Hepatic Gluconeogenesis in Diabetic Rats Through Potential Modulation of PI3K/Akt/FOXO1 Signaling: In Vivo and In Silico Studies
Type 2 diabetes mellitus (T2DM) is an intricate disease correlated with many metabolic deregulations, including disordered glucose metabolism, oxidative stress, inflammation, and cellular apoptosis due to hepatic gluconeogenesis aberrations. However, there is no radical therapy to inhibit hepatic gl...
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2025-01-01
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| author | Heba M. Abdou Ghada M. Abd Elmageed Hussein K. Hussein Imane Yamari Samir Chtita Lamia M. El-Samad Mohamed A. Hassan |
| author_facet | Heba M. Abdou Ghada M. Abd Elmageed Hussein K. Hussein Imane Yamari Samir Chtita Lamia M. El-Samad Mohamed A. Hassan |
| author_sort | Heba M. Abdou |
| collection | DOAJ |
| description | Type 2 diabetes mellitus (T2DM) is an intricate disease correlated with many metabolic deregulations, including disordered glucose metabolism, oxidative stress, inflammation, and cellular apoptosis due to hepatic gluconeogenesis aberrations. However, there is no radical therapy to inhibit hepatic gluconeogenesis disturbances yet. We thus sought to probe the effectiveness and uncover the potential mechanism of quercetin (QCT) and silk sericin (SS) in mitigating hyperglycemia-induced hepatic gluconeogenesis disorder, which remains obscure. Administration of QCT and SS to diabetic male albino rats markedly restored the levels of glucose, insulin, advanced glycation end-products (AGEs), liver function enzymes, alpha-fetoprotein (AFP), globulin, and glycogen, in addition to hepatic carbohydrate metabolizing enzymes and gluconeogenesis in comparison with diabetic rats. Furthermore, treatment with QCT and SS modulated hepatic malondialdehyde (MD), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), nitric oxide, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β), in addition to serum interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), implying their effectiveness in safeguarding cells against oxidative impairment and inflammation. Remarkably, QCT and SS treatments led to the upregulation of expression of phosphatidylinositol 3-kinases (PI3K), phospho-Akt (p-Akt), and forkhead box-O1 (FOXO1) genes in hepatic tissues compared to diabetic rats, orchestrating these singling pathways for curtailing hyperglycemia and pernicious consequences in hepatic tissues. Importantly, immunohistochemical investigations exhibited downregulation of caspase-3 expression in rats treated with QCT and SS compared to diabetic animals. Beyond that, the histopathological results of hepatic tissues demonstrated notable correlations with biochemical findings. Interestingly, the in silico results supported the in vivo findings, showing notable binding affinities of QCT and SS to PI3K, GPx, and TNF-α proteins. These results imply that QCT and SS could mitigate oxidative stress and inflammation and regulate hepatic gluconeogenesis in diabetic rats. However, QCT revealed greater molecular interactions with the studied proteins than SS. Overall, our results emphasize that QCT and SS have significant therapeutic effects on attenuating hyperglycemia-induced hepatic gluconeogenesis, with QCT showing superior effectiveness. |
| format | Article |
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| issn | 2039-4705 2039-4713 |
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| spelling | doaj-art-673c8b9ab7674e8e830c7992acab5bda2025-08-20T02:01:21ZengMDPI AGJournal of Xenobiotics2039-47052039-47132025-01-011511610.3390/jox15010016Antidiabetic Effects of Quercetin and Silk Sericin in Attenuating Dysregulation of Hepatic Gluconeogenesis in Diabetic Rats Through Potential Modulation of PI3K/Akt/FOXO1 Signaling: In Vivo and In Silico StudiesHeba M. Abdou0Ghada M. Abd Elmageed1Hussein K. Hussein2Imane Yamari3Samir Chtita4Lamia M. El-Samad5Mohamed A. Hassan6Department of Zoology, Faculty of Science, Alexandria University, Alexandria 21321, EgyptDepartment of Zoology, Faculty of Science, Alexandria University, Alexandria 21321, EgyptDepartment of Zoology, Faculty of Science, Alexandria University, Alexandria 21321, EgyptLaboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Casablanca P. O. Box 7955, MoroccoLaboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Casablanca P. O. Box 7955, MoroccoDepartment of Zoology, Faculty of Science, Alexandria University, Alexandria 21321, EgyptProtein Research Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, EgyptType 2 diabetes mellitus (T2DM) is an intricate disease correlated with many metabolic deregulations, including disordered glucose metabolism, oxidative stress, inflammation, and cellular apoptosis due to hepatic gluconeogenesis aberrations. However, there is no radical therapy to inhibit hepatic gluconeogenesis disturbances yet. We thus sought to probe the effectiveness and uncover the potential mechanism of quercetin (QCT) and silk sericin (SS) in mitigating hyperglycemia-induced hepatic gluconeogenesis disorder, which remains obscure. Administration of QCT and SS to diabetic male albino rats markedly restored the levels of glucose, insulin, advanced glycation end-products (AGEs), liver function enzymes, alpha-fetoprotein (AFP), globulin, and glycogen, in addition to hepatic carbohydrate metabolizing enzymes and gluconeogenesis in comparison with diabetic rats. Furthermore, treatment with QCT and SS modulated hepatic malondialdehyde (MD), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), nitric oxide, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β), in addition to serum interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), implying their effectiveness in safeguarding cells against oxidative impairment and inflammation. Remarkably, QCT and SS treatments led to the upregulation of expression of phosphatidylinositol 3-kinases (PI3K), phospho-Akt (p-Akt), and forkhead box-O1 (FOXO1) genes in hepatic tissues compared to diabetic rats, orchestrating these singling pathways for curtailing hyperglycemia and pernicious consequences in hepatic tissues. Importantly, immunohistochemical investigations exhibited downregulation of caspase-3 expression in rats treated with QCT and SS compared to diabetic animals. Beyond that, the histopathological results of hepatic tissues demonstrated notable correlations with biochemical findings. Interestingly, the in silico results supported the in vivo findings, showing notable binding affinities of QCT and SS to PI3K, GPx, and TNF-α proteins. These results imply that QCT and SS could mitigate oxidative stress and inflammation and regulate hepatic gluconeogenesis in diabetic rats. However, QCT revealed greater molecular interactions with the studied proteins than SS. Overall, our results emphasize that QCT and SS have significant therapeutic effects on attenuating hyperglycemia-induced hepatic gluconeogenesis, with QCT showing superior effectiveness.https://www.mdpi.com/2039-4713/15/1/16type 2 diabetes mellitusquercetinsilk sericinhepatic gluconeogenesiscaspase-3PI3K/Akt/FOXO1 signal |
| spellingShingle | Heba M. Abdou Ghada M. Abd Elmageed Hussein K. Hussein Imane Yamari Samir Chtita Lamia M. El-Samad Mohamed A. Hassan Antidiabetic Effects of Quercetin and Silk Sericin in Attenuating Dysregulation of Hepatic Gluconeogenesis in Diabetic Rats Through Potential Modulation of PI3K/Akt/FOXO1 Signaling: In Vivo and In Silico Studies Journal of Xenobiotics type 2 diabetes mellitus quercetin silk sericin hepatic gluconeogenesis caspase-3 PI3K/Akt/FOXO1 signal |
| title | Antidiabetic Effects of Quercetin and Silk Sericin in Attenuating Dysregulation of Hepatic Gluconeogenesis in Diabetic Rats Through Potential Modulation of PI3K/Akt/FOXO1 Signaling: In Vivo and In Silico Studies |
| title_full | Antidiabetic Effects of Quercetin and Silk Sericin in Attenuating Dysregulation of Hepatic Gluconeogenesis in Diabetic Rats Through Potential Modulation of PI3K/Akt/FOXO1 Signaling: In Vivo and In Silico Studies |
| title_fullStr | Antidiabetic Effects of Quercetin and Silk Sericin in Attenuating Dysregulation of Hepatic Gluconeogenesis in Diabetic Rats Through Potential Modulation of PI3K/Akt/FOXO1 Signaling: In Vivo and In Silico Studies |
| title_full_unstemmed | Antidiabetic Effects of Quercetin and Silk Sericin in Attenuating Dysregulation of Hepatic Gluconeogenesis in Diabetic Rats Through Potential Modulation of PI3K/Akt/FOXO1 Signaling: In Vivo and In Silico Studies |
| title_short | Antidiabetic Effects of Quercetin and Silk Sericin in Attenuating Dysregulation of Hepatic Gluconeogenesis in Diabetic Rats Through Potential Modulation of PI3K/Akt/FOXO1 Signaling: In Vivo and In Silico Studies |
| title_sort | antidiabetic effects of quercetin and silk sericin in attenuating dysregulation of hepatic gluconeogenesis in diabetic rats through potential modulation of pi3k akt foxo1 signaling in vivo and in silico studies |
| topic | type 2 diabetes mellitus quercetin silk sericin hepatic gluconeogenesis caspase-3 PI3K/Akt/FOXO1 signal |
| url | https://www.mdpi.com/2039-4713/15/1/16 |
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