Anti-diabetic Action of 7-<i>O</i>-Galloyl-d-sedoheptulose, a Polyphenol from Corni Fructus, through Ameliorating Inflammation and Inflammation-Related Oxidative Stress in the Pancreas of Type 2 Diabetics

Abstract

Compelling evidence indicates that polyphenolic antioxidants show protective effects against diabetic complications. We investigated the effects of a polyphenolic compound, 7-O-galloyl-d-sedoheptulose (GS), from Corni Fructus on a type 2 diabetic db/db mouse model. After 6 weeks of GS treatment, the effects of GS on serum and pancreatic biochemical factors were investigated. To define the underlying mechanism of these effects, we examined several key inflammatory markers, and inflammation-related oxidative stress markers. The results showed that levels of glucose, leptin, insulin, C-peptide, resistin, tumor necrosis factor-α, and interleukin-6 in serum were down-regulated, while adiponectin was augmented by GS treatment. In addition, GS suppressed reactive oxygen species and lipid peroxidation in the pancreas, but increased the pancreatic insulin and pancreatic C-peptide contents. Moreover, GS modulated protein expressions of pro-inflammatory nuclear factor-kappa Bp 65, cyclooxygenase-2, inducible nitric oxide synthase, c-Jun N-terminal kinase (JNK), phospho-JNK, activator protein-1, transforming growth factor-β 1 , and fibronectin. Based on these results, we conclude that a plausible mechanism of GS's anti-diabetic action may well be its anti-inflammatory property and anti-inflammatory-related anti-oxidative action. Thus, further investigation of GS as an effective anti-diabetic treatment for type 2 diabetes is warranted. Key words 7-O-galloyl-d-sedoheptulose; type 2 diabetes; pancreas; inflammation; oxidative stress; fibrosisInsulin resistance is a primary defect that is a characteristic feature of type 2 diabetes.1,2) The state of insulin resistance leads to increased insulin secretion by pancreatic β-cells and compensatory hyperinsulinemia. As long as compensatory hyperinsulinemia is sufficient to overcome the insulin resistance, fasting glycemia and glucose tolerance remain relatively normal. In patients predestined to progress to type 2 diabetes, β-cell compensation efficiency declines and relative insulin insufficiency develops, leading to impaired glucose tolerance and, eventually, type 2 diabetes. Consequently, type 2 diabetes results from the progressive failure of pancreatic β-cells in a setting of chronic insulin resistance. 3-5)Reactive oxygen species (ROS) play an important role in insulin resistance and pancreatic β-cell dysfunction, a highly prevalent condition implicated in the development of type 2 diabetes.6-10) Under a diabetic condition, chronic hyperglycemia may induce large amounts of ROS that are responsible for the progressive dysfunction of β-cells, worsening insulin resistance and further promoting relative insulin deficiency ROS.11) β-Cells, in particular, are particularly sensitive to ROS because they are low in free-radical quenching (antioxidant) enzymes such as catalase, glutathione peroxidase, and superoxide dismutase.12) The ROS formed may also indirectly damage cells by activating a variety of stress-sensitive intracellular signaling pathways, including nuclear factor-κB (NF-κB...

Go-sha-jinki-Gan (GJG) ameliorates allodynia in chronic constriction injury model mice via suppression of TNF-α expression in the spinal cord

“…45,46 GJG is composed of 10 crude drugs, each of which has several pharmacologic actions. For example, components of GJG such as Rehmanniae radix , 47,48 Corni fructus , 49,50 Plantaginis semen , 51 Moutan cortex , 52,53 and Cinnamomi cortex 54,55 have anti-inflammatory effects. Achyranthis radix 56,57 and Aconite tuber 58,59 have analgesic effects.…”

Cornus mas and Cornus Officinalis—Analogies and Differences of Two Medicinal Plants Traditionally Used

“…Ursolic acid ( 112 ) also present in both species is capable to stimulate the glucose uptake through the phosphorylation of insulin receptor (Zhang et al, 2006). Specific antidiabetic effects were reported for 7- O -galloyl-D-seduheptulose ( 120 ) and iridoids [e.g., loganin ( 1 ), morroniside ( 8 )] present in C. officinalis (Yamabe et al, 2009; Park et al, 2010, 2013; He et al, 2016) as well as for cyanidin 3- O -galactoside ( 58 ) and cyanidin 3- O -glucoside ( 59 ) present in C. mas (Jayaprakasam et al, 2005). On the other hand, loganin ( 1 ) and ursolic acid ( 112 ) were not able to affect an expression of phosphoenolpyruvate carboxykinase (PEPCK) in rat hepatoma H4IIE cell line on the contrary methanolic extract of C. officinalis fruit (50 μg/ml) which exerted insulin mimetic effect in this manner, and one of its fraction enhanced insulin secretion by rat insulin-secreting BRIN-BD11 cells in response to high glucose concentration (16.7 mM; Chen et al, 2008).…”

Quarter-Century Explorations of Bioactive Polyphenols: Diverse Health Benefits

“…In a clinical trial [42], grape resveratrol increases serum adiponectin and downregulates inflammatory genes (PAI-1, IL-6, AP-1, JUN, CREBP, etc.). In an animal model [43], 7-O-galloyl-D-sedoheptulose increases adiponectin level while downregulating leptin, insulin, C-peptide, resistin, TNFα, and IL-6 in serum and proinflammatory NFκB p65, COX-2, iNOS, JNK, phospho-JNK, AP-1, TGFβ1, and fibronectin.…”

“…[42]. 7-O-galloyl-D-sedoheptulose increases adiponectin level while downregulating leptin, insulin, C-peptide, resistin, TNFα, and IL-6 in serum and proinflammatory NFκB p65, COX-2, iNOS, JNK, phospho-JNK, AP-1, TGFβ1, and fibronectin [43]. Green tea extract upregulates adiponectin and its signaling, promoting BAT thermogenesis accompanied by decreasing final BW gain, adiposity index, adipocyte size and insulin resistance, induced energy expenditure, and promoted fat browning in animal models [166].…”