Cyclocarya paliurus (Batal.) Ijinskaja Aqueous Extract (CPAE) Ameliorates Obesity by Improving Insulin Signaling in the Hypothalamus of a Metabolic Syndrome Rat Model

Abstract

Background Antiobesity drugs may not be optimal for treating obesity. However novel antiobesity agents, especially those derived from natural products, may be suitable. Therefore, we investigated the effects and mechanisms of Cyclocarya paliurus (CP) aqueous extract (CPAE) on obesity. Methods SHR.Cg-Leprcp/NDmcr (SHR/cp) rats were used as a model of obesity and metabolic syndrome. Experimental animals were allocated into two groups—control and CPAE (0.5 g/kg)—for a 7-week treatment period. Examinations were performed, including general physiological characteristics, obesity-related biochemical parameters, and insulin-signaling pathway-related proteins in the hypothalamus. Results Treatment with CPAE reduced food intake, body weight, organ weight, fat mass, and body mass index (BMI) in SHR/cp rats. Meanwhile, CPAE also decreased the levels of fasting serum glucose, fasting serum insulin, HOMA-IR, serum free fatty acids, serum malondialdehyde, serum superoxide dismutase, and serum total-glutathione. The levels of phosphorylation of target proteins—including InsR, IRS1, PI3Kp85, Akt, and FoXO1 as well as protein expression of POMC—were significantly upregulated in the hypothalamus, but NPY expression remarkably decreased. Conclusions CPAE has antiobesity, antihypoglycemic, antihypolipidemic, and antioxidant properties. The mechanism responsible for the antiobesity effect of CPAE may be related to suppression of energy intake via regulation of insulin-signaling pathway in the hypothalamus.

Effect of Cyclocarya Paliurus on Hypoglycemic Effect in Type 2 Diabetic Mice

“…Blood glucose monitoring revealed that the blood glucose level of the mice remained at a high level in the DM group treated by solvent gavage. However, CPE intervention clearly reduced FBG and increased body weight in a dose-dependent manner, consistent with a previous study showing that treatment with CPAE (one of the main active components of CP) reduced food intake, body weight, organ weight, fat mass, and body mass index (BMI), as well as decreasing the levels of fasting serum glucose, fasting serum insulin, and serum-free fatty acids in SHR/cp rats [22]. Four weeks after the administration, the blood glucose of the high-dose CPE group significantly decreased.…”

Effects of Cyclocarya paliurus Aqueous and Ethanol Extracts on Glucolipid Metabolism and the Underlying Mechanisms: A Meta-Analysis and Systematic Review

“…Obstruction to insulin signaling pathways could lead to insulin resistance (47), causing hyperinsulinemia, which encourages other pathological changes associated with metabolic syndrome, including dyslipidemia, hypertension, as well as the progress of type 2 diabetes (42). CP was shown to decrease food intake in mice (10,11,31), this effect is probably due to its function in improving insulin signaling in the hypothalamus, and thus regulating the appetite regulating neuron neuropeptide Y (NPY) and proopiomelanocortin (POMC), leading to inhibition of food intake (10). In muscle tissues, CP also increases the activation of insulin receptor substrate-1(IRS-1), which further activates downstream proteins, such as phosphoinositide 3-kinases (PI3K), protein kinase B (Akt), and glucose transporter type 4 (GLUT4), and enhances glucose disposal in muscles (7).…”

“…Inflammatory cytokines like tumor necrosis factor-α (TNF-α) down-regulate the activation of insulin receptors (54), and eventually lead to insulin resistance, causing hypertriglyceridemia, low HDL levels and high LDL levels (55). In many current animal studies, CP administration successfully decreases the expression of TNFα, interleukin-6 (IL-6), malondialdehyde (MDA), and increases superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, showing its capacity for controlling inflammation and oxidative stress (8,10,11,16).…”

“…Recent scientific research shows that CP acts to reduce blood sugar levels and blood lipid levels, lowers body weight, and lowers blood pressure (8). Furthermore, a health tea made from CP leaves was approved by the United States Food and Drug Administration (FDA) in 1999, and was the first Chinese herbal tea approved by the institution (9,10). In short, as a dietary supplement, CP seems to be a potential candidate for assisting in the prevention and treatment of metabolic syndrome.…”

“…Among these studies, aqueous extract and ethanol extract have been the two most commonly studied CP preparations. Because of discrepancies in extraction processes, the components of the two extracts are different: polysaccharides are abundant in the aqueous extract (10), while the ethanol extract is enriched with flavonoids and triterpenoids (11). Polysaccharides (12), triterpenic acids (13,14), and flavonoids (15) were initially believed to be the active constituents of CP, however, there is also a study suggesting that polysaccharides may not be the anti-diabetic component of CP (16).…”