Wan-Nian-Qing, a Herbal Composite Prescription, Suppresses the Progression of Liver Cancer in Mice by Regulating Immune Response

The Wan-Nian-Qing prescription (WNQP), an herbal composite containing Ornithogalum caudatum, has been used in China for several years for cancer treatment. However, the mechanism of its pharmacological action against liver cancer is not clear. This study aimed to investigate the role of WNQP in inhibiting tumor growth in hepatocellular carcinoma model mice and determine its mechanism of action. We established HepG2- and SMMC-7721-xenografted tumor models in nude mice and BALB/c mice. The mice were administered WNQP for 2 weeks. The bodyweight of each mouse was monitored every day, and the tumor size was measured using vernier caliper before each round of WNQP administration. After the last dose, mice were sacrificed. The tumors were removed, lysed, and subjected to proteome profiling, enzyme-linked immunosorbent assay, and western blotting. The liver, spleen, and kidney were collected for histopathological examination. The effects of WNQP against liver cancer were first systematically confirmed in HepG2- and SMMC-7721-xenografted nude mice and BALB/c mice models. WNQP inhibited tumor growth, but failed to affect bodyweight and organ structures (liver and spleen), confirming that it was safe to use in mice. In BALB/c mice, WNQP regulated immune function, inferred from the modulation of immune-related cytokines such as interleukins, interferon, tumor necrosis factors, and chemokines. Further results confirmed that this regulation occurred via the regulatory effects of WNQP on Nrf2 signaling. WNQP can inhibit the growth of HepG2- and SMMC-7721-xenografted tumors in nude mice and BALB/c mice. This effect manifests at least partially through immunomodulation mediated apoptosis.

OcUGT1-Catalyzing Glycodiversification of Steroids through Glucosylation and Transglucosylation Actions

Steroidal glycosides are important sources of innovative drugs. The increased diversification of steroidal glycosides will expand the probability of discovering active molecules. It is an efficient approach to diversify steroidal glycosides by using steroidal glycosyltransferases. OcUGT1, a uridine diphosphate-d-glucose (UDP-Glc)-dependent glycosyltransferase from Ornithogalum caudatum, is a multifunctional enzyme, and its glycodiversification potential towards steroids has never been fully explored. Herein, the glycodiversification capability of OcUGT1 towards 25 steroids through glucosylation and transglucosylation reactions were explored. Firstly, each of 25 compounds was glucosylated with UDP-Glc. Under the action of OcUGT1, five steroids (testosterone, deoxycorticosterone, hydrocortisone, estradiol, and 4-androstenediol) were glucosylated to form corresponding mono-glucosides and biosides. Next, OcUGT1-mediated transglucosylation activity of these compounds with another sugar donor ortho-nitrophenyl-β-d-glucopyranoside (oNPGlc) was investigated. Results revealed that the same five steroids could be glucosylated to generate mono-glucosides and biosides by OcUGT1 through transglucosylation reactions. These data indicated that OcUGT1-assisted glycodiversification of steroids could be achieved through glucosylation and transglucosylation reactions. These results provide a way to diversify steroidal glycosides, which lays the foundation for the increase of the probability of obtaining active lead compounds.