Scholarlink

<p>Diabetes-induced liver damage is a significant complication of hyperglycemia, which results in oxidative stress, inflammation, and fibrosis. Conventional treatment strategies remain limited, necessitating novel therapeutic approaches. This study evaluates the hepatoprotective effects of valsartan-loaded self-nanoemulsifying drug delivery system (SNEDDS) in streptozotocin (STZ)-induced hyperglycemic rats, focusing on oxidative stress modulation, suppression of inflammatory cytokines, and metabolic regulation. Male Sprague-Dawley rats were divided into six groups: control, STZ-induced diabetic model, and treatment diabetic groups receiving valsartan (Val) or valsartan/hydrochlorothiazide (Val/HCT) in either SNEDDS-loaded liquisolid tablets or directly compressed tablets. Liver function, oxidative stress biomarkers, lipid profiles, histopathological changes, and gene expression levels of NF-κB, TGF-β, and Nrf2 were assessed. Val and Val/HCT-loaded-SNEDDS significantly reduced fasting blood glucose to ~ 95&#xa0;mg/dl, serum ALT levels (34–50%), and pro-inflammatory cytokines (NF-κB and IL-1) (21% and 40%, respectively). They also enhanced antioxidant defenses by increasing hepatic glutathione levels (34–39%) while reducing malondialdehyde (36–39%) and nitric oxide (50%). Histopathological analysis confirmed improved liver architecture with diminished inflammatory cell infiltration and fibrosis. Gene expression analysis revealed a downregulation of TGF-β and NF-κB, alongside upregulation of Nrf2, indicating reduced fibrogenesis and an oxidative stress response. In conclusion, Val-loaded SNEDDS effectively mitigates STZ-induced hepatotoxicity. This hepatoprotective effect is due to blocking the angiotensin II type 1 receptor (AT1R), leading to inhibition of TGF-β and other TGF-β-mediated inflammatory markers, such as NF-κB and IL-1. This nanoformulation offers a promising therapeutic strategy for diabetes-associated liver injury and warrants further investigation for clinical applications.</p> Graphical abstract <p></p> <p>Schematic diagram showing the mechanism of SNEDDS-loaded VST and SNEDDS-loaded VST/HCTZ as potential treatment strategies for type-2 diabetes mellitus. This mechanism includes the reduction of Nrf2 expression, antioxidant activity, and activation of the ATR1/TGF-β/ NF-κB signaling cascade.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Innovative valsartan-loaded self-nanoemulsifying drug delivery system combat liver inflammation and oxidative stress in streptozotocin-induced diabetic rats

  • 期刊论文

  • 发表日期：

    2026年5月12日

查看全文
  • Hanan Elimam,
  • Jihan Hussein,
  • Mona El-Banna,
  • Zakaria El-Khayat,
  • Mohamed Bakr Zaki,
  • Sami H. Alamri,
  • Tarek A. Ahmed,
  • Khalid M. El-Say

摘要

Diabetes-induced liver damage is a significant complication of hyperglycemia, which results in oxidative stress, inflammation, and fibrosis. Conventional treatment strategies remain limited, necessitating novel therapeutic approaches. This study evaluates the hepatoprotective effects of valsartan-loaded self-nanoemulsifying drug delivery system (SNEDDS) in streptozotocin (STZ)-induced hyperglycemic rats, focusing on oxidative stress modulation, suppression of inflammatory cytokines, and metabolic regulation. Male Sprague-Dawley rats were divided into six groups: control, STZ-induced diabetic model, and treatment diabetic groups receiving valsartan (Val) or valsartan/hydrochlorothiazide (Val/HCT) in either SNEDDS-loaded liquisolid tablets or directly compressed tablets. Liver function, oxidative stress biomarkers, lipid profiles, histopathological changes, and gene expression levels of NF-κB, TGF-β, and Nrf2 were assessed. Val and Val/HCT-loaded-SNEDDS significantly reduced fasting blood glucose to ~ 95 mg/dl, serum ALT levels (34–50%), and pro-inflammatory cytokines (NF-κB and IL-1) (21% and 40%, respectively). They also enhanced antioxidant defenses by increasing hepatic glutathione levels (34–39%) while reducing malondialdehyde (36–39%) and nitric oxide (50%). Histopathological analysis confirmed improved liver architecture with diminished inflammatory cell infiltration and fibrosis. Gene expression analysis revealed a downregulation of TGF-β and NF-κB, alongside upregulation of Nrf2, indicating reduced fibrogenesis and an oxidative stress response. In conclusion, Val-loaded SNEDDS effectively mitigates STZ-induced hepatotoxicity. This hepatoprotective effect is due to blocking the angiotensin II type 1 receptor (AT1R), leading to inhibition of TGF-β and other TGF-β-mediated inflammatory markers, such as NF-κB and IL-1. This nanoformulation offers a promising therapeutic strategy for diabetes-associated liver injury and warrants further investigation for clinical applications.

Graphical abstract

Schematic diagram showing the mechanism of SNEDDS-loaded VST and SNEDDS-loaded VST/HCTZ as potential treatment strategies for type-2 diabetes mellitus. This mechanism includes the reduction of Nrf2 expression, antioxidant activity, and activation of the ATR1/TGF-β/ NF-κB signaling cascade.