A novel low molecular weight polysaccharide (LMW-CPS) was identified from a specific combination of Chinese herb ingredients. The monosaccharide composition of LMW-CPS was consisted of single arabinose, which had an α-L-furanose configuration with an average molecular weight of 2.06 kDa. NMR spectra and monosaccharide constitution analyses revealed that it had a backbone of →5)-α-L-Araf-(1→ with α-L-Araf-(1→ as the terminal residue. In vitro experiments found that it could lead to apoptosis and inhibit hepatocellular carcinoma cell proliferation by arresting them in the S phase. In vivo experiments showed that it protected immune organs such as the thymus and spleen, enhanced immune cell activities, stimulated cytokine release, augmented the abundance of CD8, CD3, CD4, and CD19 positive lymphocytes, and markedly impeded solid hepatocellular carcinoma progression in mice. H&E staining and cell cycle examination also indicated that LMW-CPS arrested hepatocellular carcinoma cells at the S phase to induce apoptosis. These findings indicated its promising potential for the treatment of hepatocellular carcinoma.

Hyperoside and quercetin are similar in molecular structures. In this study, the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor (erythroid-2-derived)-related factor 2 (Nrf2) pathway predicted by network pharmacology. And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H₂O₂-induced HepG2 cells and Caenorhabditis elegans. The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage, which was proved by improved cell viability, decreased reactive oxygen species (ROS) production, decreased cellular apoptosis, and alleviated mitochondrial damage. In addition, quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated mRNAs, increasing the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and reducing the cellular malondialdehyde (MDA) content. Quercetin was superior to hyperoside in prolonging the lifespan of worms, decreasing the accumulation of lipofuscin, inhibiting ROS production, and increasing the proportion of skn-1 in the nucleus. With the Nrf2 inhibitor ML385, we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway. Furthermore, molecular docking and dynamics simulations demonstrated that the quercetin- Kelch-like ECH-associated protein 1 (Keap1) complex was more stable than the hyperoside-Keap1 complex. The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role. Overall, quercetin had a better antioxidant than hyperoside.