Identification and action mechanism of lipid regulating components from Rhei Radix et rhizoma

Rhei Radix et Rhizoma is widely used in Traditional Chinese Medicine to attack stagnation, clear damp heat, relieve fire, cool blood, remove blood stasis and detoxify recorded in Chinese Pharmacopoeia. Modern pharmacological research has showed the extract of Rhei Radix et Rhizoma has the effect of lowering blood lipids, but the main active components and their mechanisms are still not clear.

To reveal the lipid regulating components from Rhei Radix et Rhizoma and preliminarily explore their related action mechanisms.

A rat model of dyslipidemia was established by administration of a high-fat emulsion via gavage, and the intervention effect of different polar fractions of Rhei Radix et Rhizoma on rat blood lipids as well as their related action mechanisms were preliminarily investigated. The effective components were inferred based on the above tests and identified by high performance liquid chromatography in comparison with reference substances, their UV absorption and high resolution mass spectra characteristics.

The extract with dichloromethane fraction (DF) containing rhubarb free anthraquinones (aloe-emodin, rhein, emodin, chrysophanol and physcion) significantly regulated the disordered blood lipids, lowered TC and LDLC, reversed TG and increased HDLC level in dyslipidemic rats and also showed lipid-lowering effect on lipid abnormalities in HepG2 cells. DF could alter the signaling pathways such as PPARα and AMPK implicated in lipid metabolism, and it down-regulated the mRNA expression of liver APOA2, SCD-1, HMGCR, SREBP-2 and PCSK9, but up-regulated the expressions of liver APOE, LPL and intestinal ABCG8. Besides, it could change the composition of Firmicutes, Bacteroidetes and Proteobacteria in dyslipidemic rat feces samples.

Rhubarb free anthraquinones have a significant regulating effect on the levels of serum TC, LDLC and HDLC, and probably possess a bidirectional regulatory effect on TG level in dyslipidemic rats. These effects may be achieved by regulating the expressions of the liver PPARα and SREBP target genes, PCSK9 and the intestinal ABCG8 genes, which are involved in blood cholesterol transport, liver lipid metabolism and intestinal cholesterol excretion. Rhubarb free anthraquinones may also affect energy metabolism by changing the composition of gut microflora related to lipid metabolism in dyslipidemic rats.