Gazwi Hanaa S S, Ragab Amany E, Soltan Osama I A, Abdein Mohamed A, Shakoor Bushra, Shafiq Nusrat, Refaat Inas Hussein, Al-Rejaie Salim S, Djurasevic Sinisa, Mohany Mohamed, Zaki Asmaa H
Departments of Agricultural Chemistry, Faculty of Agriculture, Minia University, El-Minia, 61519, Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, 32527, Egypt.
Regul Toxicol Pharmacol. 2025 Nov;162:105913. doi: 10.1016/j.yrtph.2025.105913. Epub 2025 Jul 18.
The study explored the nephroprotective potential of Rosa canina (dog rose) ethanolic fruit extract against carbon tetrachloride (CCl4)-induced nephrotoxicity in rats, while also analyzing its phytochemical composition using UPLC-ESI-MS/MS. Male Wistar rats were allocated into five groups: control, R. canina extract alone, CCl4-induced nephrotoxicity, CCl4 with R. canina extract and CCl4 with silymarin. UPLC-ESI-MS/MS revealed 15 compounds in R. canina extract, predominantly anthocyanins, flavonoids, and lycopene. Treatment with R. canina extract significantly ameliorated CCl4-induced kidney dysfunction, abating oxidative stress and inflammation. Enhanced expression of HO-1 (heme oxygenase-1) and Nrf2 (nuclear factor erythroid 2-related factor 2) mRNA in the kidney suggested their involvement in protective mechanisms. Inhibition of HO-1 attenuated R. canina's protective effect against CCl4-induced kidney injury, underscoring the significance of the Nrf2/HO-1 pathway. For further validation, high throughput molecular docking analysis were performed. The docking analysis revealed the interaction between HO-1 and Nrf2 against Pelarginidin, Malvidin and Petunidin. Among all the three compounds, pelargonidin showed the highest binding score of -9.3 kcal/mol and -7.7 kcal/mol against Nrf2 and HO-1 respectively. In conclusion, R. canina extract, rich in phenolics, exhibited nephroprotective effects via inflammation and oxidative stress attenuation, potentially mediated through Nrf2/HO-1 pathway modulation against CCl4-induced nephrotoxicity.