Comparison of the acute toxicity, analgesic and anti-inflammatory activities and chemical composition changes in Rhizoma anemones Raddeanae caused by vinegar processing.

BACKGROUND: As the dry rhizome of Anemone raddeana Regel, Rhizoma Anemones Raddeanae (RAR), which belongs to Ranunculaceae, is usually used to treat wind and cold symptoms, hand-foot disease and spasms, joint pain and ulcer pain in China. It is well known that the efficacy of RAR can be distinctly enhanced by processing with vinegar due to the reduced toxicity and side effects. However, the entry of vinegar into liver channels can cause a series of problems. In this paper, the differences in the acute toxicity, anti-inflammatory and analgesic effects between RAR and vinegar-processed RAR were compared in detail. The changes in the chemical compositions between RAR and vinegar-processed RAR were investigated, and the mechanism of vinegar processing was also explored. METHODS: Acute toxicity experiments were used to examine the toxicity of vinegar-processed RAR. A series of studies, such as the writhing reaction, ear swelling experiment, complete Freund's adjuvant-induced rat foot swelling experiment and cotton granuloma, in experimental mice was conducted to observe the anti-inflammatory effect of vinegar-processed RAR. The inflammatory cytokines of model rats were determined by enzyme-linked immunosorbent assay (ELISA). Liquid Chromatography-Quadrupole-Time of Flight mass spectrometer Detector (LC-Q-TOF) was used to analyse the chemical compositions of the RARs before and after vinegar processing. RESULTS: Neither obvious changes in mice nor death phenomena were observed as the amount of vinegar-processed RAR in crude drug was set at 2.1 g/kg. Vinegar-processed RAR could significantly prolong the latency, reduce the writhing reaction time to reduce the severity of ear swelling and foot swelling, and remarkably inhibit the secretion of Interleukin-1ß(IL-1ß), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) proinflammatory cytokines. The content of twelve saponins (e.g., Eleutheroside K) in RAR was decreased after vinegar processing, but six other types (e.g., RDA) were increased. CONCLUSIONS: These results revealed that vinegar processing could not only improve the analgesic and anti-inflammatory effects of RAR but also reduce its own toxicity. TRIAL REGISTRATION: Not applicable.

[CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs].

OBJECTIVE: To investigate the effect of CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs. METHOD: Cocktail probe drugs method has been established, an LC-MS/MS analytical method has been established to determine the five probes of midazolam, phenacetin, dextromethorphan, tolbutamide, chlorzoxazone and the internal standard was benzhydramine to evaluate the effect of CYP450 activity following administration of berberine in pooled human liver microsomes. RESULT: Compared with control group, the pharmacokinetics of midazolam, phenacetin and tolbutamide were no significant differences, but the pharmacokinetics of chlorzoxazone was significantly decreased. There were no significant differences for the pharmacokinetics of dextromethorphan when the concentration of berberine was 50 microg x L(-1). The pharmacokinetics of dextromethorphan was significantly decreased when the concentration of berberine was exceed 200 microg x L(-1). CONCLUSION: Berberine has no influence on the activities of CYP3A4, CYP1A2 and CYP2C19 below 2 000 microg x L(-1), but can inhibit the activity of CYP2E1 and CYP2D6 in concentration-dependent.