The Potential of Ectoine as a Brain Anti-Aging Agent in Rat Model of d-Galactose-Accelerated Aging May Be Mediated Through Crosstalk Between Redox/Mitochondrial Homeostasis/Autophagic/Apoptotic Pathways

Aging has emerged as a prominent area of academic inquiry. Brain aging is a complex physiological process characterized by features such as enhanced apoptosis, oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired autophagy. Currently, effective preventative or therapeutic approaches for age-related neurodegenerative disorders remain elusive. Ectoine, a naturally occurring compatible solute, possesses diverse applications in biological engineering, cosmetics, medicine, and the food industry. Ectoine is reported to exhibit anti-inflammatory, antioxidant, and anti-apoptotic properties, making it a potential anti-aging agent. Consequently, the present study investigated the potential neuroprotective effects of Ectoine against D-galactose (D-gal)-induced brain aging. Accelerated aging was induced by subcutaneous injection of D-gal. Rats were subsequently divided into a control group, an aged group, and Ectoine-supplemented groups, receiving daily doses of 10, 20, and 40 mg/kg, respectively. Our findings revealed that Ectoine effectively and dose-dependently protected against D-gal-induced brain aging by inhibiting oxidative stress, enhancing the antioxidant system, decreasing neuroinflammation, restoring autophagy and mitochondrial homeostasis, and inhibiting apoptosis. Furthermore, Ectoine significantly restored the expression of miR-124 and its target genes; however, this effect is correlative and warrants further mechanistic validation. Additionally, while Ectoine's neuroprotective effects were observed at the tissue level, its cell-type specificity remains to be determined. These findings suggest that Ectoine may exert multi-pathway neuroprotective effects in brain aging. However, the current data are exploratory and warrant further validation to define causality and translational applicability.