| Berberine (Ber) as a traditional Chinese medicine has been used to treat gastroenteritis and secretory diarrhea for over two million years. Recently, many investigations have reported the role of berberine in the treatment of cardiac arrhythmia, hypertension, backward failure, diabetes, hyperlipemia and tumours. However, it also displays numerous limitations or side effects as lower bioavailability, poorer intestinal absorption, need repeatedly administration. High doses administration usually causes gastrointestinal side effects. Consequently, its clinical application has been greatly limited. The aim of present study was to improve the intestinal absorption of berberine by using the intestinal absorption enhancers Sodium Caprate (SC) in order to increase its bioavailability, cut down the clinical dosis and avoids its side effects.Objective:Investigate the absorption kinetics and site of berberine in the small intestine in rats. Observe the role of sodium caprate in improving the absorption of berberine; examine the site of the promoting absorption and its mechanisms.Methods:In situ recirculation model was employed to evaluate the effect of sodium caprate on the absorption amount and the absorption rate constant (Ka) of different doses of Ber (50, 100, 200μmol·L-1) at different time in entire small intestine. Using high performance liquid chromatography (HPLC) to detect Ber concentration in the intestinal circulate medium. Rat everted gut sacs model were developed to discover the absorption amount of Ber at duodenum, jejunum and ileum. Meanwhile, the effect of sodium caprate on the absorption amount and Papp of Ber also has been observed. The concentration of Ber in sacs was determined by liquid chromatography with tandem mass spectrometric (LC–MS/MS). The P-glycoprotein inhibitors verapamil (Ver) has been applied to study the enhancing absorption mechanism of SC. Determination of lactate dehydrogenase (LDH) activity in the intestinal circulate medium and intestinal mucosa morphology has been conducted to explore the effect of SC on intestinal mucosa cells.RESULTS:1. The uptake of Ber presented dose-dependent manner. The absorption rates of small intestine at 1h, 2h, 3h, and 4h were 20.05%, 17.59%, 24.18%, and Ka were 0.044,0.061 and 0.063 h-1at the dosage of 50,100 and 200μmol.L-1 respectively. There was no significant difference among these groups (P>0.05); Ber can be absorbed at various intestinal segments and the order of absorption amount as jejunum> duodenum> ileum. However, there was no significant difference at various intestinal segments. Papp were 3.56×10-7,4.64×10-7,1.88×10-7cm·s-1 at various intestinal segments.2. SC can significantly increase the absorption of Ber in the small intestine. Low dose group shows the most notable promoting effect on absorption, absorbed amount in 4h was [(272.75±50.03) ng vs. (526.6±30.9) ng, P <0.05] respectively. However, SC didn't play any significant effect on the absorption rate constant Ka of Ber (P>0.05). SC can significantly promote the absorption of Ber at various intestinal segments (P<0.05 or P <0.01); Ileal shows a higher sensitivity on SC and the strength order of promoting permeation was: ileum > duodenum> jejunum. Meanwhile, Papp have increased in a different level in all groups when SC was added (P <0.05, P <0.01), the enhancement ratio (ER) were 2.08,1.49, and 3.49 respectively.3. P-glycoprotein inhibitor verapamil can remarkably increase absorption amount of Ber compared with the control group (P<0.05).There was no significant difference between group Ber+SC and group Ber+verapamil (P> 0.05).4. Compared tothe control group, the activity of LDH in the intestinal circulate medium was no significant difference in Ber group and SC added group. Morphology of intestinal mucosal shows that Ber Group and SC added group had not significantly increased the impairment of intestinal mucosal injury compared to the control group,Conclusion:Ber has a poor intestinal absorption and can be absorbed at various intestinal segments. P-gp can influence the absorption kinetics of Ber. Significantly increase the absorption of Ber in the small intestine by SC may be related to its inhibition of P-gp activity. SC is a safe and effective intestinal absorption enhancer.
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