Lactobacillus paracasei PS23 improves cognitive deficits via modulating the hippocampal gene expression and the gut microbiota in D-galactose-induced aging mice.

Probiotic supplements are potential therapeutic agents for age-related cognitive deficits. A prior study showed that probiotic Lactobacillus paracasei PS23 (PS23) supplementation delayed age-related cognitive decline in mice. However, the underlying mechanisms remain unclear. This study aimed to investigate the effects of live or heat-killed PS23 (HK-PS23) on cognitive function in D-galactose (D-gal)-induced aging mice and explore the underlying mechanisms. We designed four groups of mice: control, D-gal aging mice, and PS23 supplemented and HK-PS23 supplemented D-gal aging mice. We evaluated memory function and anxiety using Morris water maze and open field tests, respectively. Neural monoamines and activities of superoxide dismutase (SOD) in the hippocampus were evaluated. RNA-seq was used to evaluate hippocampal gene expression profiles in each group, and the composition of the gut microbiota was analyzed. We revealed that PS23 and HK-PS23 supplementation ameliorated D-gal-induced memory deficits and improved motor and anxiety-behaviors in aging mice. In the hippocampus, serotonin levels (5-HT) were increased and the genes involved in neuroplasticity, anti-inflammatory, and antioxidant functions were upregulated in PS23 and HK-PS23 supplemented groups. The gut microbiota showed specific changes. Our results suggest that PS23 and HK-PS23 supplements could ameliorate age-related cognitive decline, possibly by upregulating the genes involved in synaptic plasticity and preventing oxidation and inflammation.

3'-Hydroxypterostilbene Inhibits 7,12-Dimethylbenz[a]anthracene (DMBA)/12-O-Tetradecanoylphorbol-13-Acetate (TPA)-Induced Mouse Skin Carcinogenesis.

BACKGROUND: A natural pterostilbene analogue isolated from the herb Sphaerophysa salsula, 3'-hydroxypterostilbene (HPSB), exhibits antiproliferative activity in several cancer cell lines; however, the inhibitory effects of HPSB on skin carcinogenesis remains unclear. PURPOSE: The aim of this study was to evaluate the inhibitory effects of HPSB on two-stage skin carcinogenesis in mice and its potential mechanism. STUDY DESIGN AND METHODS: This study investigated the anti-inflammatory and anti-tumor effects of HPSB in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated acute skin inflammation and 7,12-dimethylbenz[a]anthracene (DMBA)/TPA-induced two-stage skin carcinogenesis model. In addition, the effects of HPSB on the modulation of the phase I and phase II metabolizing enzymes in the DMBA-induced HaCaT cell model were investigated. RESULTS: The results provide evidence that topical treatment with HPSB significantly inhibits TPA-induced epidermal hyperplasia and leukocyte infiltration through the down-regulation of cyclooxygenase-2 (COX-2), matrix metalloprotein-9 (MMP-9), and ornithine decarboxylase (ODC) protein expression in mouse skin. Furthermore, HPSB suppresses DMBA/TPA-induced skin tumor incidence and multiplicity via the inhibition of proliferating cell nuclear antigen (PCNA), Cyclin B1 and cyclin-dependent kinase 1 (CDK1) expression in the two-stage skin carcinogenesis model. In addition, pretreatment with HPSB markedly reduces DMBA-induced cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) gene expression in human keratinocytes; however, HPSB does not significantly affect the gene expression of the phase II enzymes. CONCLUSION: This is the first study to show that topical treatment with HPSB prevents mouse skin tumorigenesis. Overall, our study suggests that natural HPSB may serve as a novel chemopreventive agent capable of preventing carcinogen activation and inflammation-associated tumorigenesis.