Protective role of vitamin B6 against mitochondria damage in Drosophila models of SCA3.

Polyglutamine (polyQ)-mediated mitochondria damage is one of the prime causes of polyQ toxicity, which leads to the loss of neurons and the injury of non-neuronal cells. With the discovery of the crucial role of the gut-brain axis and gut microbes in neurological diseases, the relationship between visceral damage and neurological disorders has also received extensive attention. This study successfully simulated the polyQ mitochondrial damage model by expressing 78 or 84 polyglutamine-containing Ataxin3 proteins in Drosophila intestinal enterocytes. In vivo, polyQ expression can reduce mitochondrial membrane potential, mitochondrial DNA damage, abnormal mitochondrial morphology, and loose mitochondrial cristae. Expression profiles evaluated by RNA-seq showed that mitochondrial structural genes and functional genes (oxidative phosphorylation and tricarboxylic acid cycle-related) were significantly down-regulated. More importantly, Bioinformatic analyses demonstrated that pathological polyQ expression induced vitamin B6 metabolic pathways abnormality. Active vitamin B6 participates in hundreds of enzymatic reactions and is very important for maintaining mitochondria's activities. In the SCA3 Drosophila model, Vitamin B6 supplementation significantly suppressed ECs mitochondria damage in guts and inhibited cellular polyQ aggregates in fat bodies, indicating a promising therapeutic strategy for the treatment of polyQ. Taken together, our results reveal a crucial role for the Vitamin B6-mediated mitochondrial protection in polyQ-induced cellular toxicity, which provides strong evidence for this process as a drug target in polyQ diseases treatment.

Pinoresinol Diglucoside Alleviates oxLDL-Induced Dysfunction in Human Umbilical Vein Endothelial Cells.

Atherosclerotic cardiovascular diseases are the leading causes of morbidity and mortality worldwide. Deposition of oxidized low-density lipoprotein (oxLDL) is one of the initiators and promoters of atherosclerosis. Eucommia lignans were shown to possess antihypertensive effects. This study aimed to investigate the effects of pinoresinol diglucoside (PD), a Eucommia lignan, on oxLDL-induced endothelial dysfunction. HUVECs were treated with oxLDL and/or PD followed by assessing radical oxygen species (ROS), apoptosis, nitrogen oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD) activity with specific assays kits, mRNA levels with quantitative real-time polymerase chain reaction (PCR), and protein levels with western blot. PD abolished oxLDL-induced ROS and MDA production, apoptosis, upregulation of lectin-like oxidized LDL recptor-1 (LOX-1), intercellular Adhesion Molecule 1 (ICAM-1), and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB), and activation of p38MAPK (mitogen-activated protein kinases)/NF-κB signaling. Meanwhile, PD alleviated oxLDL-caused inhibition of SOD activity, eNOS expression, and NO production. These data demonstrated that PD was effective in protecting endothelial cells from oxLDL-caused injuries, which guarantees further investigation on the clinical benefits of PD on cardiovascular diseases.