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 ... -  《-》

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 ... -  《-》

Aqueous seed extract of Hunteria umbellata (K. Schum.) Hallier f. (Apocynaceae) palliates hyperglycemia, insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome in rats.

Hunteria umbellata is used in the management and treatment of diabetes and obesity in Nigeria. This study evaluates the effect of aqueous seed extract of Hunteria umbellata on insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome MATERIALS AND METHODS: Rats were randomized into seven groups (A-G). Control (group A) and group C rats received control diet for nine weeks while rats in groups B, D - G were placed on high-fructose diet for 9 weeks. In addition to the diets, groups C - F rats orally received 400, 100, 200 and 400mg/kg body weight aqueous seed extract of Hunteria umbellata for 3 weeks starting from 6th - 9th week. High-fructose diet (when compared to control rats) mediated a significant (p<0.05) increase in body weight, body mass index and abdominal circumference. Similarly, levels of blood glucose, insulin, leptin, adiponectin and insulin resistance were increased. It also caused a significant increase in the levels of cholesterol, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index, cardiac index and coronary artery index while high-density lipoprotein cholesterol was decreased significantly. Levels of proinflammatory factor, tumour necrosis factor-α, interleukin-6 and 8 were also increased by the high fructose diet. Moreover, it mediated decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase and level of glutathione reduced. Conversely, levels of malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl and fragmented DNA were elevated. Aqueous seed extract of Hunteria umbellata significantly ameliorated the high fructose diet-mediated alterations. From this study, it is concluded that aqueous seed extract of Hunteria umbellata possesses hypoglycemic, hypolipidemic and antioxidants abilities as evident from its capability to extenuate insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome rats.

Ajiboye TO ，Hussaini AA ，Nafiu BY ，Ibitoye OB ... -  《-》

Hypoglycemic and hepatoprotective effects of D-chiro-inositol-enriched tartary buckwheat extract in high fructose-fed mice.

Hu Y ，Zhao Y ，Ren D ，Guo J ，Luo Y ，Yang X ... -  《-》

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 ... -  《-》