Hypoglycemic Mechanism of the Berberine Organic Acid Salt under the Synergistic Effect of Intestinal Flora and Oxidative Stress

Abstract

Both alterations to the intestinal microflora and chronic systemic inflammation predispose towards type 2 diabetes (T2D). Changes in the composition of the intestinal microflora are associated with glucose metabolism changes in rats with T2D. Here, we demonstrate that a berberine fumarate (BF) has a hypoglycemic effect by regulating the intestinal microflora and metabolism of diabetic rats. The T2D rats had disorders of glucose and lipid metabolism, an abnormal intestinal microflora, fewer butyrate-producing and probiotic-type bacteria, larger numbers of potentially pathogenic and sulfate-reducing bacteria, and tissue inflammation. Administration of berberine fumarate significantly ameliorated the metabolic disorder; increased the populations of Bacteroidetes, Clostridia, Lactobacillales, Prevotellaceae, and Alloprevotella; and reduced those of Bacteroidales, Lachnospiraceae, Rikenellaceae, and Desulfovibrio. In addition, it reduced inflammation, inhibiting the overexpression of TLR4 and p-JNK and increasing the expression of PI3K, GLUT2, and other proteins, which are closely related to oxidative stress, thereby promoting the metabolism of glucose.

Figure 1

The effect of BF on the plasma index of T2D rats. The data were expressed as mean ± SD (n = 8), ^∗ P < 0.05 and ^∗∗ P < 0.01 vs T2D group.

Figure 2

The effect of BF on the structure of intestinal flora of T2D rats. (a, b) Analysis of alpha diversity; (c) analysis of beta diversity; (d–h) the relative abundances of main species under different levels (phylum, class, order, family, and genus). n = 5, ^∗ P < 0.05 and ^∗∗ P < 0.01.

Figure 3

The results of Western blot and RT-PCR. (b) Signal pathways, “↑,” activation and “T,” inhibition. The data were expressed as mean ± SD (n = 8), ^∗ P < 0.05 and ^∗∗ P < 0.01 vs T2D group.

Figure 4

The protective effect of BF on liver, pancreas, and ileum of T2D rats (hematoxylin-eosin stain, ×200).