Ruta graveolens Linn. (RGLE) Reduces Autophagy and Improves Memory in the Rat Model of Dementia through mTOR Signaling Pathway Regulation

Objectives: The present study evaluated Ruta graveolens Linn. extract (RGLE) for its possible role in the treatment of vascular dementia (VD) in the rat model and inhibition of autophagy in hippocampus tissues. Materials and Methods: The spatial working memory of the rats was assessed using the established Tmaze tests. A video camera was used for recording and water maze software (HVS Image 2020; HVS Image Software Ltd.) was used for analysis of the digital images to measure escape latency and swimming distances for each rat. Results: RGLE treatment of the VD rats significantly (p < 0.05) alleviated the impairment in spontaneously altered behaviors and significantly (p < 0.05) reduced escape latency. The VD‑mediated decrease in distance travelled, swim time, and count of platform crossings was significantly (p < 0.02) alleviated by RGLE treatment of the rats. In RGLE‑treated rats, the VD‑mediated increase in Beclin‑1 and Microtubule‑associated protein light chain 3II (LC3II) expression in the hippocampus tissues was significantly (p < 0.05) alleviated. RGLE treatment prevented the suppression of the mammalian target of rapamycin (mTOR) phosphorylation in VD rat hippocampus tissues. The rapamycin‑mediated suppression of p‑mTOR and elevation of Beclin 1 and LC3II expression in the rat hippocampus could not be alleviated by RGLE treatment. Conclusion: In summary, RGLE effectively prevents VD‑mediated cognitive impairment and neuronal damage in the rats. Moreover, autophagy was inhibited and mTOR pathway was activated in rats with VD by RGLE treatment. Therefore, RGLE may be studied further as a therapeutic agent for treatment of dementia.