Role of Bile Acids and Nuclear Receptors in Acupuncture in Improving Crohn's Disease

Abstract

Nuclear receptors (NRs) are ligand-dependent transcription factors that regulate the transcription of target genes. Bile acids (BAs) can be used as effector molecules to regulate physiological processes in the gut, and NRs are important receptors for bile acid signaling. Relevant studies have shown that NRs are closely related to the occurrence of Crohn's disease (CD). Although the mechanism of NRs in CD has not been clarified completely, growing evidence shows that NRs play an important role in regulating intestinal immunity, mucosal barrier, and intestinal flora. NRs can participate in the progress of CD by mediating inflammation, immunity, and autophagy. As the important parts of traditional Chinese medicine (TCM) therapy, acupuncture and moxibustion in the treatment of CD curative mechanism can get a lot of research support. At the same time, acupuncture and moxibustion can regulate the changes of related NRs. Therefore, to explore whether acupuncture can regulate BA circulation and NRs expression and then participate in the disease progression of CD, a new theoretical basis for acupuncture treatment of CD is provided.

Figure 1

Schematic diagram of bile acid synthesis pathway and gut-liver circulation. The synthesis of BAs is mainly through classical and alternative pathways. The classical pathway is initiated by CYP7A1, and the alternative pathway is initiated by CYP27A1. CDCA is synthesized by cholesterol through a series of enzymatic reactions. CDCA forms conjugated CDCA by binding with glycine or taurine and are secreted into the intestine through bile duct. About 95% of BAs is transported into portal vein by intestinal epithelial cells and reabsorbed by hepatocytes and the remaining 5% will be excreted with feces. CYP7A1: cholesterol 7α-hydroxylase; HSD3B7: 3β-hydroxysteroid dehydrogenase; CYP8B1: sterol 12α-hydroxylase; CA: cholic acid; CDCA: chenodeoxycholic acid; CYP7B1: oxysterol 7α-hydroxylase; and CYP27A1: sterol 27-hydroxylase.

Figure 2

The general structure of nuclear receptors (a) and typical NR dimer (b). The main replication methods of NRs include direct repeat (DR), everted repeat (ER), and inverted repeat (IR). Nt: N-terminal; Ct: C-terminal; AF-1: activation domain 1; DBD: DNA-binding domain; AF-2: transcriptional activation domain; LBD: ligand-binding domain; and RXR: retinoid X receptor.

Figure 3

Effects of acupuncture and moxibustion on gut-liver circulation of BAs and the mechanism of regulating NRs.