No abstract

Chrysanthemum zawadskii var. latilobum (CZ) has been used for beverage or tea and also as folk medicine for the remedy of diverse inflammatory diseases. Nevertheless, the therapeutic effect of CZ on arthritis remains to be unknown. In this paper we aim to investigate the CZ's antiarthritic effect and mechanism of action both in vitro and in vivo. To assess CZ's antiarthritic effect, mouse models of type II collagen-induced arthritis (CIA) were used. Mice were used to gauge clinical arthritis index and histopathological changes. Reverse transcriptase-polymerase chain reaction (RT-PCR), western blotting, electrophoretic mobility shift assay (EMSA), and other biological methods were adopted to measure CZ's effect on arthritis and to understand the veiled mechanism of action. CZ greatly suppressed CIA, histopathological score, bone erosion, and osteoclast differentiation. Mechanistically, CZ inhibited the production of various inflammatory and arthritic mediators like inflammatory cytokines, matrix metalloproteinases (MMPs), and chemokines. Of note, CZ significantly suppressed the activation of the NF-κB pathway in vivo. CZ exerted an antiarthritic effect in CIA mice by curbing the production of crucial inflammatory and arthritis mediators. This study warrants further investigation of CZ for the use in human rheumatoid arthritis (RA).

1. BST204, a purified ginseng dry extract containing a high concentration of racemic Rh2 and Rg3 mixtures, is being developed for supportive care use in cancer patients in Korea. This study investigates the pharmacokinetics and tissue distribution of BST204 in rats. 2. After oral administration of BST204, only the S epimers, S-Rh2 and S-Rg3, could be determined in rat plasma. The poor absorption of the R-epimers, R-Rh2 and R-Rg3, may be attributed to lower membrane permeability and extensive intestinal oxygenation and/or deglycosylation into metabolites. The AUC and Cmax values of both S-Rh2 and S-Rg3 after BST204 oral administration were proportional to the administered BST204 doses ranged from 400 mg/kg to 2000 mg/kg, which suggested linear pharmacokinetic properties. 3. There were no statistically significant differences in the pharmacokinetics of S-Rh2 and S-Rg3 after oral administration of pure S-Rh2 (31.5 mg/kg) and S-Rg3 (68 mg/kg) compared with oral administration of BST204, 1000 mg/kg. These indicated that the presence of other components of BST204 extract did not influence the pharmacokinetic behavior of S-Rh2 and S-Rg3. 4. After oral dosing of BST204, S-Rh2 and S-Rg3 were distributed mainly to the liver and gastrointestinal tract in rats. 5. Our finding may help to understand pharmacokinetic characteristics of S-Rh2, R-Rh2, S-Rg3, and R-Rg3, comprehensively, and provide useful information in clinical application of BST204.

We developed and validated an accurate and sensitive LC-MS/MS method for the simultaneous quantitation of ginsenoside Rg3 and Rh2 epimers (R-Rg3, S-Rg3, R-Rh2, and S-Rh2) in rat plasma. Analytes were extracted from 0.1 mL aliquots of rat plasma by liquid-liquid extraction, using 2 mL of ethyl acetate. In this assay, dioscin (500 ng/mL) was used as an internal standard. Chromatographic separation was conducted using an Acclaim RSLC C18 column (150 × 2.1 mm, 2.2 μm) at 40°C, with a gradient mobile phase consisting of 0.1% formic acid in distilled water and in acetonitrile, a flow rate of 0.35 mL/min, and a total run time of 20 min. Detection and quantification were performed using a mass spectrometer in selected reaction-monitoring mode with negative electrospray ionization at m/z 783.4 → 161.1 for R-Rg3 and S-Rg3, m/z 621.3 → 161.1 for R-Rh2 and S-Rh2, and m/z 867.2 → 761.5 for the internal standard. For R-Rg3 and S-Rg3, the lower limit of quantification was 5 ng/mL, with a linear range up to 500 ng/mL; for R-Rh2 and S-Rh2, the lower limit of quantification was 150 ng/mL, with a linear range up to 6000 ng/mL. The coefficient of variation for assay precision was less than 10.5%, with an accuracy of 86.4-112%. No relevant cross-talk or matrix effect was observed. The method was successfully applied to a pharmacokinetic study after oral administration of 400 mg/kg and 2000 mg/kg of BST204, a fermented ginseng extract, to rats. We found that the S epimers exhibited significantly higher plasma concentrations and area under curve values for both Rg3 and Rh2. This is the first report on the separation and simultaneous quantification of R-Rg3, S-Rg3, R-Rh2, and S-Rh2 in rat plasma by LC-MS/MS. The method should be useful in the clinical use of ginseng or its derivatives.

Cancer related fatigue (CRF) is one of the most common side effects of cancer and its treatments. A large proportion of cancer patients experience cancer-related physical and central fatigue so new strategies are needed for treatment and improved survival of these patients. BST204 was prepared by incubating crude ginseng extract with ginsenoside-β-glucosidase. The purpose of the present study was to examine the effects of BST204, mixture of ginsenosides on 5-fluorouracil (5-FU)-induced CRF, the glycogen synthesis, and biochemical parameters in mice. The mice were randomly divided into the following groups: the naïve normal (normal), the HT-29 cell inoculated (xenograft), xenograft and 5-FU treated (control), xenograft + 5-FU + BST204-treated (100 and 200 mg/kg) (BST204), and xenograft + 5-FU + modafinil (13 mg/kg) treated group (modafinil). Running wheel activity and forced swimming test were used for evaluation of CRF. Muscle glycogen, serum inflammatory cytokines, aspartic aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CRE), white blood cell (WBC), neutrophil (NEUT), red blood cell (RBC), and hemoglobin (HGB) were measured. Treatment with BST204 significantly increased the running wheel activity and forced swimming time compared to the control group. Consistent with the behavioral data, BST204 markedly increased muscle glycogen activity and concentrations of WBC, NEUT, RBC, and HGB. Also, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), AST, ALT, and CRE levels in the serum were significantly reduced in the BST204-treated group compared to the control group. This result suggests that BST204 may improve chemotherapy-related fatigue and adverse toxic side effects.