Anti-inflammatory effects and pharmacokinetics study of geniposide on rats with adjuvant arthritis.

The aim of this study was to explore the anti-inflammatory effects of Geniposide (GE), an iridoid glycoside compound extracted from Gardenia jasminoides Ellis (GJ) fruit in adjuvant-induced arthritis (AA) rats and its pharmacokinetic (PK) basis. AA was induced by injecting with Freund's complete adjuvant (FCA). Male SD rats were subjected to treatment with GE (30, 60 and 120mg/kg) from day 17 to 24 after immunization. Fibroblast-like synoviocyte (FLS) proliferation was assessed by MTT. Interleukin (IL)-1, IL-6, TNF-α and IL-10 were determined using double-sandwich enzyme-linked immunosorbent assay (ELISA). Expression of p38 mitogen-activated protein kinases (p38MAPKs) related proteins in FLS was detected by Western blotting. PK profiles were simultaneously detected by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) in AA rat plasma after oral administration of GE on day 17 after immunization. As a result, GE promoted the recovery of arthritis and inhibited the colonic inflammation damage in AA rats by decreasing the expression level of TNF-α, IL-1 and IL-6, increasing the production of IL-10 and inhibiting the expression of phospho-p38 (p-p38) related proteins in FLS. PK parameters (AUC, Cmax and t1/2) tended to be associated with dosage-related decreasing of efficacy index.

Identification and distribution of four metabolites of geniposide in rats with adjuvant arthritis.

Geniposide (GE), also called Jasminoidin, is the major active ingredient of Gardenia jasminoides Ellis (GJ) fruit, which has long been used in traditional Chinese medicine (TCM). Growing evidences suggested that GE has a great potentiality for treating rheumatoid arthritis (RA). However, GE is rapidly metabolized, and we know little about its availability or metabolites in tissues. To elucidate the distribution of GE and its metabolites in tissues, three groups of adjuvant arthritis (AA) rats were given GE (33, 66 and 120 mg/kg) from days 18 to 24, and the biotransformation of GE in plasma, liver, spleen, synovium, urine and mesenteric lymph node (MLN) of rats was investigated by a novel approach named Information-Dependent Acquisition (IDA)-Mediated LC-MS/MS method. As a result, GE and its four major metabolites were detected as follows: GE, G1, G2 in plasma; GE, G2 in MLNs; only GE in liver and synovium; GE, G2, G3 and G4 in spleen; and GE, G1, G2 and G4 in urine. In total four metabolites (G1-G4) involved in the in vivo metabolism processes were identified. The results of this work have demonstrated the IDA-Mediated LC-MS/MS could screen rapidly and reliably the characterization of metabolites from iridoid compounds.

Ablation of leiomyomas using a combination of HIFU and iodized oil in vitro.

This study investigates the enhancement effects of iodized oil and the features of hyperechoic focus changes in a target region of high-intensity focused ultrasound (HIFU) ablated uterine fibroids. Leiomyomas in the experimental group of 20 randomly assigned patients were ablated by HIFU under certain parameters 30 min after 1 mL of iodized oil was injected into the center of the myomas. The value of the gray scale and its area were observed by B-mode ultrasound in the target region and were carefully recorded at 0, 2, 4, and 5 min, respectively, after HIFU ablation. The samples were sectioned successively in a thickness of 1∼2 mm and stained by 2,3,5-triphenyltetrazolium chloride solution within 1 h after HIFU ablation. The TTC non-staining volumes were measured afterwards. All procedures in the control group of the other 20 randomly assigned patients were the same except that iodized oil was replaced by physiologic saline. The hyperechoic areas in the target region were observed in all fibroids of both groups. Compared with the control group, the gray scale values in the target region of the experimental group were higher 4 min after HIFU ablation. The enhanced gray scale area in the target region and the 2,3,5-triphenyltetrazolium chloride non-staining volumes in the experimental group were bigger. Based on our experience, HIFU sonication of leiomyomas injected with iodized oil produces hyperechoic foci that are greater than areas injected with saline. More studies are required to understand the clinical implications of these observations.