The Beneficial Effects of Morroniside on the Inflammatory Response and Lipid Metabolism in the Liver of <i>db</i>/<i>db</i> Mice

Abstract

Diabetes mellitus is a major cause of mortality and morbidity worldwide, and its prevalence is increasing at an alarming rate. Hyperglycemia and dyslipidemia lead to complications associated with diabetes mellitus, and, also, the attenuation of oxidative stress and regulation of stress-sensitive signaling pathways have been considered as ways to alleviate diabetes. [1][2][3][4] Hyperglycemia causes oxidative stress by two mechanisms: first, by decreasing the regeneration of the important cellular antioxidant, reduced glutathione (GSH) from oxidized glutathione (GSSG), and second, by decreasing the availability of reduced nicotinamide adenine dinucleotide phosphate (NADPH). Furthermore, hyperglycemia-induced reactive oxygen species (ROS) stimulate the activation of protein kinase C (PKC), formation of advanced glycation endproducts (AGE), and sorbitol accumulation. Also, increased ROS lead to the activation of nuclear factor-kappa B (NF-kB), and activated NF-kB can enhance the expression of proinflammatory cytokines, chemokines, adhesion molecules, inflammatory receptors, and inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). 5-7)Dyslipidemia is the abnormal state of elevated cholesterol, triglyceride, and low-density lipoprotein or decreased highdensity lipoprotein in the plasma level that contribute to the development of atherosclerosis. Dyslipidemia is a risk factor for coronary artery disease, a leading cause of mortality in patients with diabetes mellitus. [8][9][10] Triglyceride is involved in the ectopic accumulation of lipid stores in the liver and are associated with a number of diseases such as metabolic syndrome and type 2 diabetes. Critical players in potentiating the promoting effect of hyperinsulinemia on hepatic lipid accumulation are the anabolic transcription factor peroxisome proliferator activated receptor a (PPARa) and sterol regulatory element binding proteins (SREBPs), which upregulate genes such as those for fatty acid synthase and cholesterol levels. [11][12][13] Corni Fructus (Cornus officinalis SIEB. et ZUCC.) is a rich source of iridoid glycosides in traditional medicine.14) Iridoids are a group of natural products belonging to the terpenoids, which are ubiquitous in plants. However, only a limited number of taxa possess the enzymes that give rise to the cyclopentane ring that is characteristic of the carbocyclic iridoids.15) Morroniside is a carbocyclic iridoid glycoside which has been reported to exhibit marked antioxidant activity. 16) In our previous studies, we reported the beneficial effect of morroniside on streptozotocin-induced type 1 diabetic renal damage. The administration of morroniside could ameliorate hyperglycemia, renal oxidative stress, and inflammation in diabetic rats. 17) However, the effect of morroniside on the type 2 diabetic liver, especially in dyslipidemia, has not yet been determined. The liver is an important organ for maintaining glucose metabolism and lipid homeostasis, since it can store (via glycogen synthes...

Evaluation of Morroniside, Iridoid Glycoside from Corni Fructus, on Diabetes-Induced Alterations such as Oxidative Stress, Inflammation, and Apoptosis in the Liver of Type 2 Diabetic db/db Mice

“…17,18) Among them, morroniside has been reported as the main active constituent of Corni Fructus, with several bioactivities such as antioxidant, 11,19) neuroprotective, 20) and anti-inflammatory effects. 19) Furthermore, morroniside has been proven effective in preventing diabetic complications such as diabetic angiopathy and the early stage of diabetic nephropathy by regulating renal mesangial cell growth through inhibiting oxidative stress. 21) Our previous studies showed that Corni Fructus exerted protective effects against hyperglycemia and its related renal damage in streptozotocin-induced diabetic rats.…”

Effect of ambrex (a herbal formulation) on oxidative stress in hyperlipidemic rats and differentiation of 3T3-L1 preadipocytes

“…[30] PPARγ and SREBP are the major players in adipogenesis. Our in vitro experimental reports demonstrate that ambrex may be a potential drug against hyperlipidemia by repressing PPARγ and SREBP regulated adipogenesis pathway.…”

Vinegar-Baked Radix Bupleuri Regulates Lipid Disorders via a Pathway Dependent on Peroxisome-Proliferator-Activated Receptor-αin High-Fat-Diet-Induced Obese Rats

“…The SREBP-2 isoform activates genes of the cholesterogenic pathway, whereas the SREBP-1 isoforms are more active in regulating the synthesis of fatty acids [30]. It has been documented that SREBPs were the upregulated genes related to fatty acid synthase and cholesterol levels [20]. In the current study, the elevated expressions of SREBP-1 and SREBP-2 in HFD-fed rats were significantly decreased by the VBRB (1.0 g kg −1 per day) treatment.…”

“…Hepatic fractions were prepared as described previously [20]. To prepare nuclear fractions, hepatic tissue was homogenized with ice-cold lysis buffer containing 5 mmol L −1 Tris-HCl (pH 7.5), 2 mmol L −1 MgCl 2 , 15 mmol L −1  L CaCl 2 , 1.5 mol L −1 sucrose, 0.1 mol L −1 dithiothreitol (DTT), and protease inhibitor cocktail.…”