Effect of co-existent components in CO2 supercritical fluid extract of Angelica Sinensis Radix on metabolism of Z-ligustilide after oral administration in rats

Abstract

Objective: To establish a basis for Angelica Sinensis Radix (ASR) as a dietary supplement for colorectal cancer chemoprevention, the effect of co-existent components in supercritical fluid extract (SFE) of ASR on the pharmacokinetics of Z-ligustilide after oral administration was investigated in vitro and in vivo. Methods: Incubation in gastrointestinal contents and incubation in rat liver tissue homogenates post-mitochondrial supernatant (PMS) experiments were used to study changes in the levels of Z-ligustilide in vitro. Results: Within 4 hours, the level of Z-ligustilide in SFE declined at a slower rate than in its pure form. Clearance of Z-ligustilide after administration in its pure form was significantly slower than that of SFE of ASR (CL, 0.96 ± 0.16 mL·min/kg versus 1.24 ± 0.21 mL·min/kg P < 0.05; AUC, 243.37 ± 16.84 versus 176.69 ± 12.59 mg·min/L). Conclusion: These phenomena may be attributed to the interactions between the co-existent components in SFE of ASR and Z-ligustilide enhancing the stability of Z-ligustilide. These results suggest that the bioavailability of Z-ligustilide in SFE of ASR is improved. However, stabilization of plasma concentration was not sustained, so that the efficacy of active components could not be maintained. Thus, further processing of SFE of ASR is required.

Keywords

• Angelica Sinensis Radix
• Supercritical fluid extract
• Z-ligustilide
• Metabolism