Nephroprotective and Gastroprotective potential of Aerva javanica (L.) green synthesized nanoparticles, supported by Molecular Networking

NSAIDs pose a significant risk to the stomach and kidneys, with oxidative stress being a key driver in the development of indomethacin-induced gastric ulcers and acute kidney injury by disrupting the balance between oxidation and antioxidation. Effective management of oxidative stress and bolstering antioxidant defenses are crucial strategies for preventing and treating these conditions. This study explored the potential of Aerva javanica, a plant abundant in Saudi Arabia and used in traditional medicine, to mitigate these adverse effects. Researchers identified 27 phytochemicals in its leaf extract using LC-MS and synthesized silver nanoparticles (SNPs), characterizing them with TEM and UV-visible spectrophotometry. Network analysis suggested a link between procyanidin dimer and kaempferol 4’-O-methyl ether with genes protecting the kidneys and stomach, possibly involving the AGE-RAGE and HIF-1 signaling pathways. In vivo experiments using an indomethacin-induced injury model demonstrated that administering A. javanica resulted in a dose-dependent decrease in gastric ulcer severity and a return of elevated serum renal markers to normal levels. Furthermore, the treatment reduced oxidative stress markers (MDA) and increased antioxidant levels (GSH) in both the stomach and kidneys. A. javanica also suppressed the expression of pro-inflammatory markers and inhibited the NF-κB p65 and STAT-3 signaling pathways. Histological examination corroborated these protective effects. The observed scavenging activity of A. javanica is attributed to its rich content of flavonoids and phenolic compounds. These findings suggest that A. javanica offers promising gastroprotective and nephroprotective properties against NSAID-induced complications by reducing oxidative stress and inflammation through the coordinated regulation of key signaling pathways.