Intestinal absorption characteristics of Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats via everted intestinal sac models / 中国中药杂志

The present study is to investigate the absorption characteristics of the main components in Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats with everted intestinal sac models. Intestinal sac fluid samples were collected in different part of intestine(duodenum, jejunum, ileum, colon) at different time after administration of different concentration of P. orientale extract(5.0,10.0, 20.0 mg·mL~(-1)). An UPLC-TQD method was employed for the determination of six components including orientin, isoorientin, vitexin, protocatechuic acid, kaempferol-3-O-β-D-glucoside and quercitrin in the intestinal sac samples. The absorption rate and cumulative absorption were calculated to analyze the intestinal absorption characteristics of six components in normal and myocardial ischemia model rats. The P-glycoprotein(P-gp) inhibitor was applied to investigate influence of intestinal absorption of six components in P. orientale extract. The results showed that the main absorption sites were concentrated on the duodenum at low concentration, while they were the colon at the medium concentration and the ileum at high concentration in control groups. In the condition of myocardial ischemia model, the main absorption sites focus on the ileum and jejunum at low concentration; the main absorption sites were in the ileum at the medium concentration and main absorption sites were the duodenum and ileum at high concentration. Compared with the normal group, the absorption rate and cumulative absorption of the six components significantly decreased in the model group. P-gp inhibitor markedly increased the absorption rate and cumulative absorption of six components in the model group, inferring that the 6 components may be the substrates of P-gp, and the mechanism needs further study. In this study, it is revealed that the six components of P. orientale extract can be absorbed into the intestinal sac, and it is an effective method to assess the intestinal absorption characteristics of P. orientale extract through everted intestinal sac model, providing data support for the clinical application and further development of P. orientale.

Establishment and application of STING agonist in-vitro screening model / 药学学报

Tumor immunotherapy is a critical field in the development of anticancer drugs. The research of stimulator of interferon genes (STING) agonist provides a new idea for immunotherapy. Innate immune response can effectively be induced by nucleic acids in mammalian cytoplasm. In recent years, a large number of studies have confirmed that the cGAS-cGAMP-STING signaling pathway plays a key role in cytoplasmic DNA recognition and immune defense activation. The dysfunction of cGAS-cGAMP-STING is closely related to the tumorigenesis, and is a potent target for drug development. In this study, based on THP-1 dual cells which are stably expressing cGAS-STING pathway and THP-1 KO-STING cells which are stably depleted STING, a screening method for STING agonists was established by detection of luciferase. Furthermore, the accuracy and sensitivity of the model were verified using positive compound, providing a simple, efficient and accurate screening platform for high-throughput screening of STING agonists.