Hydrophobic Compounds in the Paeonia suffruticosa Root Cortex Reduce Lipid Accumulation in Adipocytes and the Livers of Obese ob/ob Mice.

Insulin plays a critical role in the regulation of lipid and carbohydrate metabolism in the liver, muscle, and adipose tissue via its receptor. The root cortex of Paeonia suffruticosa (Paeoniaceae) has been used as a crude drug, Botanpi, in several formulae of traditional Japanese (Kampo) medicines, such as Hachimijiogan, to treat type 2 diabetes mellitus (DM). We previously isolated constituents from the P. suffruticosa root cortex and found that 1,2,3,4,6-pentagalloyl-β-d-glucose (β-PGG), methyl gallate, and paeonol, but not paeoniflorin, suppressed the production of the proinflammatory mediator nitric oxide in interleukin (IL)-1β-treated hepatocytes. Here, we selected three crude drugs that are often used for patients with obesity and DM (i.e., P. suffruticosa root cortex, P. lactiflora roots, and Alisma orientale roots). Among their extracts, P. suffruticosa root cortex extract and its ethyl acetate (EtOAc)-soluble fraction significantly decreased the triglyceride content in insulin-treated rat adipocytes. Additionally, β-PGG, a constituent of this fraction, efficiently reduced the triglyceride content. When the EtOAc-soluble fraction of the P. suffruticosa root cortex was administered to leptin-deficient (ob/ob) mice, a DM model, it markedly improved hepatic lipid accumulation compared with that in the non-treated mice. Furthermore, the blood glucose level and body weight of ob/ob mice administered the EtOAc-soluble fraction were significantly decreased. In hepatocytes, β-PGG reduced mRNA levels encoding glucose transporter 2, AMP-activated protein kinase, and forkhead box O1 transcription factor in the absence of IL-1β. Overall, hydrophobic constituents, including β-PGG and paeonol, may be involved in the antidiabetic effects of P. suffruticosa root cortex on ob/ob mice.