Possible Mechanism of Dysphania ambrosioides (L.) Mosyakin & Clemants Seed Extract Suppresses the Migration and Invasion of Human Hepatocellular Carcinoma Cells SMMC-7721.

Mexican tea (Dysphania ambrosioides (L.) Mosyakin & Clemants) is rich in phenolic acids and flavonoids and could be a potential medicinal herb that can be used for prevention of human hepatocellular carcinoma. The objective of this study was to elaborate the possible mechanism for the prevention or treatment of hepatocellular carcinoma using Mexican tea, and to provide new avenues for the utilization of the invasive plant. In this study, the D. ambrosioides seed extracts (CSE) were analyzed by gas chromatography-mass spectrometry, and the effects of CSE on proliferation, migration, invasion, and gene expression of SMMC-7721 cells were investigated. Eight compounds were identified in CSE, and the compound with the highest content was ascaridole (25.82 %). The proliferation was significantly inhibited by CSE (p<0.05), and IC50 values were 0.587 g/L, 0.360 g/L, and 0.361 g/L at 24 h, 36 h, and 48 h, respectively. Migration and invasion were significantly inhibited (p<0.05). The network pharmacology and transcriptome analysis indicated that 2-hydroxy-2,6,6-trimethylbicyclo[3.1.1]heptan-3-one, cis-11-eicosenoic acid and 2-ethylcyclohexanone might be the active compounds. Transcriptome analysis indicated that the Wnt signaling pathway, which is related to migration and invasion, was significantly altered; this was verified by western blot assay. The expression of wnt11, lef1 and mmp7 genes in SMMC-7721 cells was significantly down-regulated (p<0.05), while gsk-3ß was significantly up-regulated (p<0.05). These results indicate that CSE inhibits the invasion and migration of SMMC-7721 cells in hepatocellular carcinoma through the Wnt signaling pathway.

Cremastra appendiculata polysaccharides improve stress resistance and prolong the lifespan of Caenorhabditis elegans via daf-16 in the insulin signaling pathway.

Cremastra appendiculata polysaccharide (CAP) exhibits potential anti-aging and stress resistance effects. In this study, we investigated the structure, antioxidant properties, and mechanism of action of CAP in Caenorhabditis elegans. The results showed that CAP primarily comprises mannose and glucose and exerts antioxidant activity in vitro. In vivo, CAP prolonged the lifespan of C. elegans in a concentration-dependent manner, with 2.0 mg/mL CAP prolonging the lifespan by 39.97 %. Compared with the control, the activities of superoxide dismutase (SOD) and catalase (CAT) antioxidant enzymes increased by 46 % and 57 %, respectively. However, the reactive oxygen species (ROS) and malondialdehyde (MDA) contents decreased by 38 % and 19.92 %, respectively, at the same CAP concentration, oxidative and heat stress resistance increased. The target genes of the insulin/insulin-like growth factor (IGF) signaling pathway, daf-16, sod-3, ctl-1, and hsp-16.2, were activated by CAP; their mRNA expression levels were upregulated by 7.23 %, 69.78 %, 43.62 %, and 58.62 %, respectively. A transgenic worm assay indicated that CAP regulates the lifespan of C. elegans through daf-16. These results suggest that CAP improves stress resistance and prolongs the lifespan of C. elegans through daf-16 in the insulin/IGF signaling pathway.