Mitigating Hyperglycemia-Induced learning and memory impairment: Insulin Combined with Lemon Peel Essential Oil effects on Hippocampal Oxidative Stress, Neuroinflammation, and BDNF Expression in Type 1 Diabetic Rats

The present work aims to assess if insulin combined with Lemon peels essential oil (EO) prevents chronic hyperglycemia-related learning and memory impairments by restoring normal oxidative stress levels, reducing neuroinflammation, upregulating BDNF expression, and restoring Acetylcholinesterase (AChE) activity in streptozotocin (STZ)-induced type 1 diabetic rats. After confirming hyperglycemia, rats were divided into five groups: Normal Control, Diabetic Control, Insulin-treated Diabetic, and two Diabetic groups receiving a combination of Insulin (6UI/day) and EO at doses of 0.5 ml/kg and 1 ml/kg. Treatment was administered orally over seven weeks. Fasting blood glucose (FBG) levels were assessed, and an Oral Glucose Tolerance Test was conducted at the end of the six-week period. Behavioral tests to evaluate learning and memory were conducted after 42 days. Upon euthanasia, blood samples were collected immediately to evaluate lipid parameters and cardiovascular risk indices. Bilateral hippocampi were dissected to measure levels and activity of oxidative stress markers, TNF-alpha, BDNF, and AChE. The study reveals compelling evidence that combining insulin with EO surpasses the efficacy of insulin treatment alone. This combination therapy not only stabilizes FBG to normal levels but also reduces markers of oxidative stress (Malondialdehyde and Nitric Oxide), enhances antioxidant enzyme activity (Superoxide Dismutase and Glutathione Peroxidase), decreases TNF-alpha levels, and reverses the decline in hippocampal BDNF while restoring AChE activity to normal levels. These findings highlight the potential of insulin combined with EO for managing diabetes more effectively and regulating long-term glycemic levels. Additionally, the results suggest that this combination therapy could help alleviate cognitive impairments linked to hyperglycemia by addressing oxidative balance, neuroinflammation, BDNF expression, and AChE function. This approach presents a comprehensive strategy for treating diabetes and its complications.