Baicalein Induces Mitochondrial Autophagy to Prevent Parkinson's Disease in Rats via miR-30b and the SIRT1/AMPK/mTOR Pathway

Abstract

Parkinson's disease (PD) is a prevailing neurodegenerative disorder. Baicalein has neuroprotective effects on PD animals, but its mechanism is not clarified. We explored baicalein effects on PD rats. PD rat models were established by injecting 6-hydroxydopamine into the striatum of substantia nigra on the left side of the rat brain and treated with baicalein. Dopamine (DA) content, neuronal apoptosis, neuronal injury, neuronal mitochondria, and autophagy were assessed. Baicalein-treated PD rats were treated with autophagy inhibitor 3-methyladenine to identify the role of autophagy in PD. PD rats were injected with AgomiR-30b-5p or sh-SIRT1 plasmids and treated with baicalein. PD rats elicited decreased neurological score and DA secretion of the striatum, increased neuronal apoptosis, and injury, and reduced number of mitochondria and autophagy, whereas baicalein alleviated neuronal injury and partly recovered mitochondrial dysfunction, 3-methyladenine inhibited the protection of baicalein. miR-30b-5p was elevated and SIRT1 was diminished in PD rats and inhibited by baicalein. miR-30b-5p targeted SIRT1. miR-30b-5p overexpression or SIRT1 silencing annulled the protection of baicalein. The phosphorylation level of AMPK in the substantia nigra of PD rats was decreased and mTOR was increased, whereas baicalein annulled these trends. Briefly, baicalein activated mitochondrial autophagy via miR-30b-5p and the SIRT1/AMPK/mTOR pathway, thus protecting PD rats.

New Insights into Baicalein’s Effect on Chlorpyrifos-Induced Liver Injury in Carp: Involving Macrophage Polarization and Pyropto sis

“…Bai works on the SIRT1/ AMPK/mTOR pathway to exert neuroprotective effects in Parkinson's rats. 47 Bai protects against fructose-induced hepatic steatosis in rats by activating the AMPK/PGC-1α and PPARα pathways to promote fatty acid oxidation. 48 According to our results, CPF exposure significantly inhibited the expression of the AMPK/SIRT1/pGC-1α pathway, accompanied by reduced mitochondrial biogenesis and mitochondrial dynamic imbalance, and excessive oxidative stress.…”

“…Recent studies have shown that Bai can act on AMPK and play a beneficial role in a variety of diseases. Bai works on the SIRT1/AMPK/mTOR pathway to exert neuroprotective effects in Parkinson’s rats . Bai protects against fructose-induced hepatic steatosis in rats by activating the AMPK/PGC-1α and PPARα pathways to promote fatty acid oxidation .…”

MiR‐30b‐5p attenuates the inflammatory response and facilitates the functional recovery of spinal cord injury by targeting the NEFL/mTOR pathway

“…In our study, we found that the mTOR signaling pathway is suppressed by miR‐30b‐5p overexpression in LPS‐induced PC12 cells, which was rescued after NEFL upregulation. Overexpression of miR‐30b‐5p has also been reported to partially reverse the inhibitory effect of baicalein on the AMPK/mTOR pathway in Parkinson's disease (Chen et al., 2021 ). The difference from our findings may be explained by the different animal and cell models we used and the influence of other interventions such as baicalein treatments.…”

Autophagy and Its Association with Genetic Mutations in Parkinson Disease

“…Baicalein has been shown to exert neuroprotective effects in the substantia nigra of 6-hydroxydopamine-induced Parkinson disease model rats by stimulating mitochondrial autophagy via enhancing the phosphorylation level of AMPK and reducing mTOR [ 127 ].…”