Anti-obesity and hypolipidemic effects of Rheum undulatum in high-fat diet-fed C57BL/6 mice through protein tyrosine phosphatase 1B inhibition

Abstract

Protein tyrosine phosphatase 1B (PTP1B) is important in the regulation of metabolic diseases and has emerged as a promising signaling target. Previously, we reported the PTP1B inhibitory activity of Rheum undulatum (RU). In the present study, we investigated the metabolic regulatory effects of RU in a high-fat diet (HFD) model. RU treatment significantly blocked body weight gain, which was accompanied by a reduction of feed efficiency. In addition, it led to a reduction of liver weight mediated by overexpression of PPARα and CPT1 in the liver, and an increase in the expression of adiponectin, aP2, and UCP3 in adipose tissue responsible for the reduction of total and LDL-cholesterol levels. Chrysophanol and physcion from RU significantly inhibited PTP1B activity and strongly enhanced insulin sensitivity. Altogether, our findings strongly suggest that 2 compounds are novel PTP1B inhibitors and might be considered as anti-obesity agents that are effective for suppressing body weight gain and improving lipid homeostasis. [BMB reports 2012; 45(3): 141-146]

A Network Pharmacology Approach to Understanding the Mechanisms of Action of Traditional Medicine: Bushenhuoxue Formula for Treatment of Chronic Kidney Disease

“…Under severe insulin resistance, insulin secretion is significantly reduced and results in serious hyperglycemia. Chrysophanol, physcion and emodin showed moderated bioactivity against human protein tyrosine phosphatase in vitro [141], and they strongly enhanced insulin sensitivity [142]. Quercetin prevented the TNF alpha-mediated phosphorylation of insulin receptor substrate 1, protein tyrosine phosphatase kappa B gene expression and the suppression of insulin stimulated glucose uptake [139].…”

Chrysophanol: a review of its pharmacology, toxicity and pharmacokinetics

“…Chrysophanol increased glucose transport activity and elevated the tyrosine phosphorylation of insulin receptor via inhibiting tyrosine phosphatase 1B (PTP1B) activity and increasing the expression of Glut4 mRNA in L6 rat myoblasts . In‐vivo research showed that the combination of chrysophanol and emodin could inhibit PTP1B activity and strongly enhanced insulin sensitivity of HFD (high‐fat diet)‐fed mice . Subsequent research showed that chrysophanol was a competitive PTP1B inhibitor .…”

Antidiabetic potential of anthraquinones: A review

“…Chrysophanol isolated from S. obtusifolia and rhubarb rhizome inhibited PTP 1B activity (IC 50 : 5.8 μM) and stimulated glucose transport in insulin‐stimulated myotubes (Babu et al, ; Jung et al, ; Lee & Sohn, ; Lee, Yoon, Hwang, Kim, & Kim, ). Chrysophanol glucosides, chrysophanol‐8‐O‐β‐D‐glucopyranoside, chrysophanol triglucoside, and chrysophanol tetraglucoside from S. obtusifolia inhibited PTP 1B activity with IC 50 values of 8.8, 80.17, and 103.89 μM, respectively (Jung et al, ).…”