Lacticaseibacillus paracasei LC86 mitigates age-related muscle wasting and cognitive impairment in SAMP8 mice through gut microbiota modulation and the regulation of serum inflammatory factors.

Purpose: Chronic inflammation contributes to the decline in muscle strength and cognitive abilities associated with aging. This study aims to clarify the effects of oral administration of Lacticaseibacillus paracasei LC86 on these age-related declines, as well as its impact on the composition of gut microbiota. Methods: Senescence-accelerated mouse prone 8 (SAMP8) mice received a 12 week regimen of LC86 (1 × 109 CFU/day). Muscle strength was assessed through forelimb grip strength and four-limb hanging tests. Cognitive function was evaluated through behavioral performance tests, and changes in gut microbiota were analyzed. Results: Administration of LC86 significantly enhanced muscle strength, demonstrated by increased grip strength and higher glycogen content in the gastrocnemius muscle (p = 0.041, p = 0.017, and p = 0.000, respectively). Behavioral tests suggested that LC86 mitigated age-related cognitive decline. Furthermore, there was a significant decrease in serum pro-inflammatory cytokines, such as IL-6, TNF-α, and MCP-1 (p = 0.002, p = 0.000, and p = 0.005, respectively), and an elevation in the anti-inflammatory cytokine IL-10 level (p = 0.000). An increase in hepatic antioxidant capacity was observed. Significant changes in the gut microbiota composition were noted, including increased populations of Bifidobacterium and Lactobacillus and decreased levels of Escherichia/Shigella and Bacteroides. Conclusion: The findings suggest that LC86 supplementation mitigates muscle weakness and cognitive impairment in aging SAMP8 mice, potentially through the modulation of inflammation and gut microbiota composition. LC86 emerges as a promising candidate for ameliorating the decline of muscular and cognitive functions associated with aging.

Polyphyllin VII induces apoptotic cell death via inhibition of the PI3K/Akt and NF­κB pathways in A549 human lung cancer cells.

Polyphyllin VII is an active compound isolated from Paris polyphylla, which is termed Chonglou in China. The present study was designed to investigate the underlying mechanisms of the antitumor effect of Polyphyllin VII in lung cancer cells. The cytotoxic effect of Polyphyllin VII in human lung cancer A549 cells was analyzed; the results revealed an IC50 value of 0.41±0.10 µM at 24 h. The associated mechanisms were investigated by phase­contrast microscopy, fluorescence microscopy, flow cytometry and western blot analysis. Exposure of A549 cells to Polyphyllin VII resulted in apoptosis. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF­κB, and wortmannin, an inhibitor of PI3K, both decreased the proportion of viable A549 cells in the presence of Polyphyllin VII. The ratio of apoptotic cells increased in the presence of wortmannin and PDTC. Western blot analysis revealed that PI3K, phosphorylated (p)­PI3K, Akt, p­Akt, NF­κB and p­NF­κB were downregulated following treatment with Polyphyllin VII. Increased caspase­3 activity, increased poly­(ADP­ribose) polymerase cleavage and a downregulation of inhibitor of caspase­activated DNase were observed following treatment with Polyphyllin VII, and these effects were enhanced by either wortmannin or PDTC. The present results revealed that Polyphyllin VII was able to induce apoptotic cell death in A549 human lung cancer cells via inhibition of the PI3K/Akt and NF­κB pathways.