Components in SLPE Alleviate AD Model Nematodes by Up-Regulating Gene gst-5

<i>Salvia leucantha</i> is a perennial herb of the genus <i>Salvia</i> in the family Labiatae, which has a wide range of biological activities, mainly including inhibition of acetylcholinesterase, antibacterial, and anti-inflammatory activity. To explore the protective effects and mechanism of action of <i>S. leucantha</i> on Alzheimer's disease (AD), the anti-AD activity of SLE (extracts of <i>S. leucantha</i>) was determined by using a transgenic <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) model (CL4176). Analyses included paralysis assay, phenotypic experiments, transcriptome sequencing, RNA interference (RNAi), heat shock assays, and gas chromatography-mass spectrometry (GC-MS). SLPE (<i>S. leucantha</i> petroleum ether extract) could significantly delay CL4176 paralysis and extend the longevity of <i>C. elegans</i> N2 without harmful effects. A total of 927 genes were significantly changed by SLPE treatment in <i>C. elegans,</i> mainly involving longevity regulatory pathways-nematodes, drug metabolism-cytochrome P450, and glutathione metabolic pathways. RNAi showed that SLPE exerted its anti-AD activity through up-regulation of the gene <i>gst-5</i>; the most abundant compound in SLPE analyzed by GC-MS was 2,4-Di-tert-butylphenol (2,4-DTBP), and the compound delayed nematode paralysis. The present study suggests that active components in <i>S. leucantha</i> may serve as new-type anti-AD candidates and provide some insights into their biological functions.