Isorhamnetin exerts neuroprotective effects in STZ-induced diabetic rats via attenuation of oxidative stress, inflammation and apoptosis

Objective: Isorhamnetin, a derivative of quercetin, exerts antioxidant and anti-inflammatory effects in different diseases, and we examined its protective effects against diabetes-related changes in the brain. Methods: A single dose of a freshly prepared solution of streptozotocin (STZ) (60 mg/kg body weight) was intraperitoneally injected to establish STZ-induced diabetic model in male Wistar rats. The animals were randomly divided into four groups: control, control + isorhamnetin, diabetic, diabetic + isorhamnetin. Isorhamnetin at a dose of 10 mg/kg body weight was intraperitoneally administrated once a day for 12 weeks. Formalin and tail immersion tests were performed to evaluate the severity of pain. Astrogliosis markers such as GFAP and APO-E4, DNA fragments, MDA level, and TNF alpha expressions were evaluated using ELISA assay. Neuronal density in the hippocampus region was evaluated using Nissl staining. The method of Ellman and fluorescent probe 2, 7-dichlorofluorescein diacetate (DCFH-DA) was used to measure brain acetyl-cholinesterase activity and detect reactive nitrogen and oxygen species (RNS and ROS), respectively. Results: Isorhamnetin reduced pain, blood glucose levels, and increased body weight significantly compared to control. Moreover, isorhamnetin inhibited astroglial activation, acetyl-cholinesterase activity, oxidative stress, apoptosis, and inflammation. Conclusion: These findings suggested that isorhamnetin has potential effects as neuroprotective agents against diabetes-related changes in the brain.