Beneficial effects of naringenin in liver diseases: Molecular mechanisms

Figure 2 Absorption and metabolism of naringenin. Small intestine: Naringenin (N, orange arrows) is absorbed through the intestinal epithelium by passive diffusion into enterocytes; then, it can pass to general circulation by multidrug resistance associated proteins (Mrp1) or transported by active efflux protein carriers P-glycoprotein (P-gp) and Mrp2, back to the intestinal lumen, out of the enterocytes. Inside the enterocyte, naringenin is glucuronized by UDP-glucuronosyl transferase (UGT), and after that, naringenin-glucuronides (red arrows) leave cells by Mrp2 protein or pass into blood via breast cancer-resistant protein (Bcrp1). Moreover, naringenin-glucuronides can be cleaved by β-glucuronidases (GUSB), resulting in release of the aglycone. Large intestine: Naringenin undergoes same processes as in small intestine but also is highly metabolized by Streptococcus S-2, Lactobacillus L-2, and Bacteroides JY-6 to generate a series of low molecular weight aromatic acids. Liver: Naringenin is highly conjugated to form naringenin-glucuronides, which allows it to pass into circulation. On the other hand, naringenin-glucuronides reach the liver from intestine and enter into hepatocytes via organic anion transporting protein-B (OATP), and then, they are transported by Mrp3 into the circulation.