Persimmon tannin promoted macrophage reverse cholesterol transport through inhibiting ERK1/2 and activating PPARγ both in vitro and in vivo

- Persimmon tannin promoted cholesterol efflux by ERK1/2-PPARγ pathway in vitro.
- Persimmon tannin facilitated RCT in high-cholesterol diet fed C57BL/6J mice.
- Inhibition of persimmon tannin on ERK1/2 contributed to macrophage RCT in vivo.

The purpose of this study was to investigate whether persimmon tannin is associated with cholesterol efflux and macrophage-reverse cholesterol transport (RCT). In J774A.1 macrophage cells, persimmon tannin could inhibit cellular cholesterol accumulation and promote 22-NBD-cholesterol efflux through inhibiting the phosphorylation of ERK1/2 and up-regulating the protein levels of PPARγ. Macrophage RCT in vivo was evaluated by injecting 22-NBD-cholesterol-loaded J774A.1 macrophages intraperitoneally into C57BL/6J mice. Administration of persimmon tannin significantly (P < 0.05) decreased the cholesterol concentration in both serum and liver, and increased faecal cholesterol excretion compared with the high-cholesterol group. In transcriptional levels, persimmon tannin enhanced the expression of cholesterol transport-related genes (ABCA1, LCAT, ABCG5/G8, NPC1L1 and CYP7A1) and their upstream nuclear receptors (PPARγ, PPARα and LXRα). Moreover, the regulation of persimmon tannin on RCT-related genes might be mediated by its inhibition on ERK1/2 in mice. Therefore, persimmon tannin promoted macrophage reverse cholesterol transport through the regulation on ERK1/2-PPARγ signaling pathway both in vitro and in vivo.