Comparison of distribution of verbascoside in normoxic and hypoxic rats

Abstract

This study established a high performance liquid chromatography(HPLC) method for the simultaneous determination of verbascoside(VB) and its main metabolite caffeic acid(CA) in rat tissue samples. A low-pressure low-oxygen animal experimental chamber was used to simulate the plateau environment for establishing the hypoxic rat model. After intragastric administration of 300 mg·kg~(-1) VB, the normoxic and hypoxic rats were sacrificed for the collection of heart, liver, spleen, lung, kidney, brain, muscle, large intestine, small intestine, and stomach tissue samples at the time points of 30, 60, and 90 min. VB and CA concentrations in each tissue sample were measured by HPLC, and the distribution of VB and CA in normoxic and hypoxic rats was compared. The results showed that after intragastric administration, VB can be rapidly absorbed and distributed into various tissues including brain in both normoxic and hypoxic rats, indicating that VB can pass through the blood-brain barrier. In the gastrointestinal tract, VB was mainly distributed in small intestine, which suggested that the main absorption site of VB was small intestine. A large amount of VB was detected in muscle and lung, and only a small amount in other tissues. CA was detected in other tissues except brain, heart, and muscle. Small intestine had the most abundant CA, followed by stomach, large intestine, and kidney, and only a small amount of CA was detected in the liver, spleen, and lung(<50 ng·mL~(-1)). The results indicated that VB may be mainly absorbed and metabolized in the gastrointestinal tract to produce CA and was possibly excreted through kidney. Compared with normoxic rats, hypoxic rats had reduced and slow distribution of VB and increased ratio of VB concentration in tissue to plasma, which implied that the relative proportion of VB from systemic circulation to tissues was increased in hypoxic rats. This study provides a basis for the application of VB in anti-hypoxia therapy and for the formulation of anti-hypoxia dosing regimens.