Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine

Abstract

Abstract. Berberine, a plant alkaloid used in traditional Chinese medicine, has a wide spectrum of pharmacological actions, but the poor bioavailability limits its clinical use. The present aim was to observe the effects of sodium caprate on the intestinal absorption and antidiabetic action of berberine. The in situ, in vitro, and in vivo models were used to observe the effect of sodium caprate on the intestinal absorption of berberine. Intestinal mucosa morphology was measured to evaluate the toxic effect of sodium caprate. Diabetic model was used to evaluate antidiabetic effect of berberine coadministrated with sodium caprate. The results showed that the absorption of berberine in the small intestine was poor and that sodium caprate could significantly improve the poor absorption of berberine in the small intestine. Sodium caprate stimulated mucosal-to-serosal transport of berberine; the enhancement ratios were 2.08, 1.49, and 3.49 in the duodenum, jejunum, and ileum, respectively. After coadministration, the area under the plasma concentration-time curve of berberine was increased 28% than that in the absence of sodium caprate. Furthermore, both berberine and coadministration with sodium caprate orally could significantly decrease fasting blood glucose and improve glucose tolerance in diabetic rats (P<0.05). The hypoglycemic effect of coadministration group was remarkably stronger, and the areas under the glucose curves was decreased 22.5%, compared with berberine treatment group (P< 0.05). Morphologic analysis indicated that sodium caprate was not significantly injurious to the intestinal mucosa. The study demonstrates that sodium caprate could significantly promote the absorption of berberine in intestine and enhance its antidiabetic effect without any serious mucosal damage.

Sodium caprate augments the hypoglycemic effect of berberine via AMPK in inhibiting hepatic gluconeogenesis

“…Although hypoglycemic effect of BER is so enticing, it has not yet been used clinically as an anti-diabetic drug, mainly because of its low bioavailability (<5%) (Maeng et al, 2002). We also observed its poor intestinal absorption in vivo and in vitro in our previous study (Lv et al, 2010). As a result, BER has to be administered repeatedly and at high doses (1500–2000 mg/d) when used in diabetic patients (Yin et al, 2008).…”

“…It increases the paracellular permeability through enlarging the tight junctions, and then expanding paracellular routes for water-soluble, low lipophilic, and poorly absorbable drugs. Our previous data showed that sodium caprate could significantly increase the bioavailability of BER without any serious mucosal damage (Lv et al, 2010). In this study, we investigated whether co-administration of sodium caprate would alter the hypoglycemic effect of BER in diabetes mellitus in rats.…”

Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies

“…Sodium caprate is a medium chain fatty acid that promotes the absorption of poorly absorbable drugs by increasing the permeability of intestinal epithelium and by inhibiting the function of P-gp [116]. In the presence of sodium caprate, the absorption rate of BBR in the small intestine increases, leading to higher plasma levels of BBR and to a stronger hypoglycemic effect in diabetic rats (Table 5) [116; 117].…”

Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles

“…Strategies to improve the absorption and efficacy of BBR have been investigated in other studies such as the combination with sodium caprate. 27,28 The abnormal immune status in db/db mice, which directly leads to the lack of islet function, may be systemically improved by BBR, thus facilitating islet regeneration, while the independent effect of lipid nanoparticles in regulating insulin and other lipoproteins should also be considered. Additionally, the carrier materials, mainly including lecithin and tripalmitin, did not show toxic side effects in the experimental or pathological examination.…”