Impact of protocatechuic acid on high fat diet-induced metabolic syndrome sequelae in rats.

The study aimed to assess the possible protective impact of protocatechuic acid (PCA) on high fat diet (HFD)-induced metabolic syndrome (Mets) sequelae in rats. Forty-two male Sprague-Dawley (SD) rats were randomly grouped as follows: CTR group; PCA group; HFD group; HFD-PCA group and HFD-MET group. Rats were fed on standard diet or HFD for 14 weeks. HFD-fed rats exhibited significant decreases in food intake and adiponectin (ADP) level; yet, body weight and anthropometrical parameters were significantly increased. Moreover, insulin sensitivity was impaired as indicated by significant elevation in glucose AUC during oral glucose tolerance test (OGTT), fasting serum glucose, fasting serum insulin and homeostasis model assessment of insulin resistance (HOMA-IR) index. Furthermore, chronic HFD feeding elicited significant increases in serum lipid profile and free fatty acids (FFAs) with concomitant hepatic steatosis. Additionally, serum C-reactive protein (CRP), interleukin 1b (Il-1b) and monocyte chemoattractant protein 1(MCP-1) levels were increased. Also, HFD-fed rats exhibited an increase in MDA level, while superoxide dismutase (SOD) and glutathione (GSH) activities were decreased. Moreover, the insulin-signaling pathway was markedly impaired in soleus muscles as indicated by a decrease in insulin-induced AKT phosphorylation. Histopathologically, adipose tissues showed significant increase in adipocyte size. Also, flow cytometry analysis of adipose tissue confirmed a significant increase in the percentage of number of CD68+ cells. PCA administration succeeded to attenuate HFD-induced obesity, insulin resistance, oxidative stress and inflammation. In conclusion, PCA administration could protect against HFD-induced Mets, possibly via its hypoglycemic, insulin-sensitizing, anti-oxidant and anti-inflammatory effects.

Nour OA ，Ghoniem HA ，Nader MA ，Suddek GM ... -  《-》

Preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed obese rats.

Maithilikarpagaselvi N ，Sridhar MG ，Swaminathan RP ，Sripradha R ... -  《-》

Protocatechuic acid improves hepatic insulin resistance and restores vascular oxidative status in type-2 diabetic rats.

This work explored influences of protocatechuic acid (PCA) on type 2 diabetes (T2D)-associated hepatic insulin resistance and other metabolic, hepatic and vascular irregularities using the rat model of high fat diet (HFD)+high fructose+low dose streptozotocin (STZ). Twenty-four male Wister rats were used. Twelve rats were ad libitum supplied with HFD and high fructose drinking water (25 % w/v) for 60 days. On day 30, they received a single injection of STZ (35 mg/kg, i.p). On day 32, they were divided into two subgroups (n = 6/each): T2D + PCA, received PCA (100 mg/kg/day, orally) and T2D, received PCA vehicle till the end of experiment. Rats provided with regular diet and fructose-free drinking water, with or without PCA treatment, served as PCA and control groups (n = 6/each), respectively. PCA treatment significantly reduced the elevated levels of fasting glycemia and insulin, AUCOGTT, AUCITT, and HOMA-IR index, while it boosted HOMA-β and insulinogenic index values in T2D rats. PCA ameliorated serum lipid levels and hepatic function parameters and mitigated hepatosteatosis in T2D rats. Mechanistically, PCA mitigated hepatic lipid peroxidation and restored reduced glutathione (GSH) and superoxide dismutase (SOD) to near-normal levels. Moreover, PCA enhanced hepatic protein levels of P-AKTser473 and hepatic mRNA expression of insulin receptor substrate 1 (IRS1), phosphatidylinositol 3 kinase (PI3K)-p85 and AKT2. Furthermore, PCA ameliorated aortic oxidative stress in T2D rats, possibly via reducing serum levels of advanced glycation end products (AGEs) and diminishing vascular expression of RAGE and NOX4 mRNA. Collectively, PCA may improve hepatic insulin resistance and vascular oxidative status by modulating IRS1/PI3K/AKT2 and AGE-RAGE-NOX4 pathways, respectively.

Abdelmageed ME ，Shehatou GSG ，Suddek GM ，Salem HA ... -  《-》

Athrixia phylicoides tea infusion (bushman tea) improves adipokine balance, glucose homeostasis and lipid parameters in a diet-induced metabolic syndrome rat model.

Central obesity and insulin resistance are associated with metabolic syndrome (MetS) which is aggravated by diet and sedentary lifestyle. Athrixia phylicoides (AP) is reported by rural communities to have medicinal benefits associated with MetS such as obesity and type 2 diabetes. This study was aimed to investigate the effects of AP on diet-induced MetS in Wistar rats to validate its ethnopharmacological use. AP was profiled for phytochemicals by LC-MS. After induction of MetS with high energy diet (HED), 30 male rats were divided into five treatment groups (n = 6): normal diet control, HED control, HED + AP 50 mg/Kg BW, HED + AP 100 mg/Kg BW and HED + 50 mg/Kg BW metformin. The rats were treated daily for 8 weeks orally after which weight gain, visceral fat, total cholesterol, free fatty acids (FFAs) and adipokine regulation; leptin: adiponectin ratio (LAR) were assessed. Also, glucose homeostatic parameters including fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glucose transporter 4 (GLUT 4), insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were determined. Findings showed that AP was rich in polyphenols. The HED control group showed derangements of the selected blood parameters of MetS. AP reversed diet-induced weight gain by reducing visceral fat, total blood cholesterol and circulating FFAs (p ≤ 0.05). Treatment with AP improved adipokine regulation depicted by reduced LAR (p<0.05). Treatment with AP improved parameters of glucose homeostasis as demonstrated by reduced FBG and HOMA-IR (p ≤ 0.05) and increased GLUT 4 (p<0.05). Athrixia phylicoides tea infusion was shown to possess anti-obesity and anti-inflammatory properties, improved glucose uptake and reduce insulin resistance in diet-induced MetS in rats which could be attributed to its richness in polyphenols. Therefore, AP could have potential benefits against type 2 diabetes and obesity which are components of MetS validating its ethnopharmacological use.

Mokwena MAM ，Engwa GA ，Nkeh-Chungag BN ，Sewani-Rusike CR ... -  《BMC Complementary Medicine and Therapies》

Protocatechuic acid exhibits hepatoprotective, vasculoprotective, antioxidant and insulin-like effects in dexamethasone-induced insulin-resistant rats.

Protocatechuic acid (PCA), the natural phenolic antioxidant, reportedly exhibited hypoglycemic and insulin-like effects. Recent studies have reported its cardioprotective effect in glucocorticoid (GC)-induced hypertensive rats. Nevertheless, its beneficial role has not been investigated in the setting of GCs excess-induced insulin resistance. This study aimed to investigate the possible protective potential and the plausible mechanisms of pretreatment with PCA against GCs-induced insulin resistance, liver steatosis and vascular dysfunction. Insulin resistance was induced in male Wistar rats by a 7-day treatment with dexamethasone (DEX) (1 mg/kg/day, i.p.). PCA (50, 100 mg/kg/day, orally) was started 7 days before DEX administration and continued during the test period. PCA significantly and dose-dependently attenuated DEX-induced a) glucose intolerance (↓ AUCOGTT), b) hyperglycemia (↓ fasting blood glucose), c) impaired insulin sensitivity [↓fasting plasma insulin and homeostasis model assessment of insulin resistance (HOMA-IR) index)] and d) dyslipidemia (↓total cholesterol, triglycerides, low-density lipoprotein-cholesterol and very low-density lipoprotein-cholesterol). PCA mitigated DEX-induced liver steatosis with associated reduction in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity. Moreover, PCA ameliorated DEX-induced vascular dysfunction and enhanced ACh-induced relaxation in aortic rings. The metabolic ameliorating effects of PCA might be attributed to the enhanced insulin signaling in soleus muscles (↑AKT phosphorylation) and mitigating gluconeogenesis (↓ hepatic mRNA expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). The vasculoprotective effect of PCA might be related to its ability to restore normal mRNA expression of [endothelial nitric oxide synthase (eNOS) and NADPH Oxidase 4 (NOX4)]. PCA restored normal oxidative balance [↓ oxidant species, malondialdehyde (MDA) and (↑ antioxidant superoxide dismutase (SOD)]. The findings herein reveal for the first time that PCA may be taken as a supplement with GCs to limit their metabolic and vascular side effects through its hypoglycemic, insulin-sensitizing, hypolipidemic and antioxidant effects.

El-Sonbaty YA ，Suddek GM ，Megahed N ，Gameil NM ... -  《-》