This study investigated the effects of gastrodin (GAS) on analgesic, anxiolytic, ferroptosis, and jejunal microbiota in chronic inflammatory pain mice. The chronic inflammatory pain model of C57BL/6J mice was established by hindpaw injection of complete Freund’s adjuvant (CFA). After GAS treatment, thermal hyperalgesia test, mechanical allodynia test, elevated plus-maze (EPMT), and open-field test (OFT) were performed to assess the behavioral changes of pain and anxiety. mRNAs of FTHI, GPX4, HO-1, and PTGS2 and jejunal microbiota were measured by qPCR. In CFA-injected C57BL/6 mice, we found that the mechanical and thermal pain threshold were increased with treatment of GAS. In EPMT, the number of entries in open arms and retention times of open arms were increased by GAS. In the OFT, the time spent in the central area was also increased. Furthermore, GAS enhanced mRNA expressions of FTHI, GPX4, and HO-1 but decreased the expression of PTGS2 in a dose-dependent manner. GAS is effective in the treatment of mice chronic inflammatory pain and anxiety-like behaviors. It may be exhibits potential neuroprotective effects through inhibition of ferroptosis independently of the intestinal microbiota.

To investigate the transport mechanism of isorhynchophylline (IRN) by using the specific inhibitors of organic cation transporters (OCTs) and organic anion transporting polypeptides (OATPs) and attempt illustrate the metabolic mechanism of IRN in the liver. All animals were randomly divided into three groups: control group (only inject IRN), RIF group (inject IRN and rifampicin), and ADR group (inject IRN and adrenalone). The control group was injected with IRN via the caudal vein. The RIF group was injected with rifampicin (RIF) by gavage, and after 1 h, IRN was injected into the caudal vein. Similarly, the ADR group received adrenalone by the caudal vein, and after 0.5 h, IRN was injected into the caudal vein. Thereafter, blood samples were obtained by the heart punctures at 90 min, 180 min, and 300 min following drug administration. Rats were sacrificed at 300 min after drug administration; then, the liver tissue was harvested. The level of IRN was measured by using high-performance liquid chromatography (HPLC), and the Kp values were calculated. After RIF administration (OATPs inhibitors), the Kp value of IRN was slightly decreased when compared with that of the control group. Meanwhile, the Kp value of IRN was dramatically reduced compared to that of the control group following ADR administration (OCTs inhibitors). The results suggested that OCTs have mainly participated in the hepatic uptake process of IRN.