Effects of Iridoid Total Glycoside from Cornus officinalis on Prevention of Glomerular Overexpression of Transforming Growth Factor Beta 1 and Matrixes in an Experimental Diabetes Model

Corni Fructus (Cornus officinalis SIEB. et ZUCC.), a traditional medicine, is considered one of the 25 plant-based drugs most frequently used in China, Japan, and Korea. Recent studies have reported that Corni Fructus has a plasma glucose-lowering action in normal rats, along with anti neoplastic and anti-microbial effects.1-3) Moreover, Vareed et al. 4) reported that Corni Fructus has been used for improving liver and kidney functions. The components are total iridoid glycosides such as morroniside and loganin and also a few polyphenols such as cornusiin A, B, and C, monomeric and trimeric hydrolysable tannins, and so on. 5,6) Among them, the total iridoid glycosides are well-known as the main active constituents of Corni Fructus. The total iridoid glycosides of Corni Fructus containing loganin and morroniside inhibit oxidative stress 7) and prevent the renal overdeposition of fibronectin and laminin in an experimental diabetic rat model. 8) In particular, morroniside, one of the most abundant iridoid glycosides in Corni Fructus, has been proven effective in preventing diabetic complications such as diabetic angiopathy and the early stages of diabetic nephropathy by regulating renal mesangial cell growth through inhibiting oxidative stress.9,10) In addition, it exhibits a neuroprotective effect by providing cytoprotection against H 2 O 2 -toxicity in SH-SY5Y cells. 11)Diabetes mellitus is characterized by excessive glucose production. An abnormally elevated blood glucose level leads to oxidative stress and the formation of advanced glycation endproduct (AGE), which have been closely linked to diabetic complications such as neuropathy, retinopathy, and nephropathy.12,13) Especially, diabetics are at increased risk for several types of kidney disease, and the predominant cause of end-stage renal disease in this disorder is diabetic nephropathy.14,15) However, clinical trials suggest that there is no effective treatment for diabetic nephropathy.16) Therefore, prevention of the occurrence and progression of diabetic nephropathy has become a very important issue.Our previous investigations have demonstrated that Hachimi-jio-gan, a Chinese prescription consisting of eight crude drugs, owes it therapeutic potential to ameliorating functional and structural features associated with experimental types 1 and 2 diabetic nephropathy rat models. 17,18) Hachimi-jio-gan showed a preventive effect against kidney damage by reducing renal oxidative injury and the expression of fibronectin and transforming growth factor-b 1 (TGFb 1 ) protein, involved in the pathophysiology of diabetic nephropathy in diabetic rats, and effectively inhibited the progression of chronic renal failure through decreasing uremic toxins, elevating antioxidant enzymes such as superoxide dismutase and catalase activities, and ameliorating histopathological lesions in the kidney. 19,20) In addition, this traditional prescription also alleviated diabetic oxidative stress through the inhibition of lipid peroxidation. 21) Cornus Fructus, one of eight medicina...

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confidence: 99%

Protective Effects of Morroniside Isolated from Corni Fructus against Renal Damage in Streptozotocin-Induced Diabetic Rats

Yokozawa

Yamabe

Kim

et al. 2008

“…4,5) Several pharmacological actions such as anti-neoplasm, antiinflammation, hepatoprotection, and anti-diabetic nephropathy were elucidated from the crude extract of fruit of C. officinalis. 6,7) However, there is little information about the pharmacological action of cornuside. The present study, therefore, was designed to examine the effects of cornuside on the expression levels of cytokine-induced proinflammatory and adhesion molecules, which could account for its beneficial effect in the cardiovascular system.…”

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confidence: 99%

Cornuside Suppresses Cytokine-Induced Proinflammatory and Adhesion Molecules in the Human Umbilical Vein Endothelial Cells

Kang

Moon

Lee

et al. 2007

Cornuside is a bisiridoid glucoside compound isolated from the fruit of Cornus officinalis SIEB. et ZUCC. The present study was designed to examine the effects of cornuside on expression levels of cytokine-induced proinflammatory and adhesion molecules in the human umbilical vein endothelial cells (HUVECs). Cornuside treatment attenuated tumor necrosis factor-a a (TNF-a a)-induced nuclear factor-kappa B (NF-k kB) p65 translocation in HUVECs. In addition, cornuside suppressed the expression levels of endothelial cell adhesion molecules including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) induced by TNF-a a. TNF-a a-induced monocyte chemoattractant protein 1 (MCP-1) expression was also attenuated by treatment of cornuside. These inhibitory effects of cornuside on proinflammatory and adhesion molecules were not due to decreased HUVEC viability as assessed by MTT test. Taken together, the present study suggests that cornuside suppresses expression levels of cytokine-induced proinflammatory and adhesion molecules in the human endothelial cells.

“…24,25) Furthermore, several reports of its use including traditional medicine have been made, e.g., Vareed et al 26) reported that Corni Fructus has been used for improving liver and kidney functions, and iridoid total glycoside has the effect of preventing the overexpression of transforming growth factor-b 1 and matrixes in glomeruli with a diabetic model. 27) Moreover, we have previously reported that not only Hachimi-jiogan, containing Corni Fructus, could prevent the development of type 1 and 2 diabetic nephropathy, 3,4) and also that Corni Fructus led to a better AGE clearance due to improving the renal function than aminoguanidine, the prototype AGE inhibitor, suggesting that Corni Fructus might become an effective remedy against diabetic AGE accumulation.…”

Section: Discussionmentioning

confidence: 99%

Identification of Antidiabetic Effect of Iridoid Glycosides and Low Molecular Weight Polyphenol Fractions of Corni Fructus, a Constituent of Hachimi-jio-gan, in Streptozotocin-Induced Diabetic Rats

Yamabe

Kang

Matsuo

et al. 2007

Diabetes mellitus is a leading cause of many complications, such as atherosclerosis, cardiac dysfunction, retinopathy, neuropathy, and nephropathy. In longitudinal hyperglycemia, advanced glycation end-product (AGE) formation, resulting from the non-enzymatic reactions of carbohydrates and oxidized lipids with proteins, is increased and is also stimulated by oxidative stress which is closely linked with the pathogenesis of diabetic complications as well as the polyol pathway and protein kinase C pathway.1,2) Therefore, interference with AGE formation has the therapeutic potential to prevent the progression of diabetic complications.Traditional medicines are recently being focused on to treat diabetes and its complications because of their absence of toxic-and/or side-effects. In our previous study, we reported that Hachimi-jio-gan ameliorated functional and structural features associated with experimental type 1 and 2 diabetic nephropathy rat models, 3,4) and according to the three-dimensional HPLC profile of Hachimi-jio-gan, morroniside and loganin obtained from Corni Fructus (Cornus officinalis SIEB. et ZUCC.) are the major compounds. It was previously discovered that Corni Fructus could ameliorate glucose-associated metabolic disorders, and its mechanisms were intimately related to the formation of AGEs, as well as those of Hachimi-jio-gan. 5) To add to these findings, we evaluated the major active components in Corni Fructus. As the first step, we prepared five fractions from Corni Fructus extract, that is, one sugar with organic acid fraction (S1D1), one iridoid glycoside fraction (S1D2), and three polyphenol fractions (from low to high molecular weights: S2, S3, and S4) as shown in Fig. 1A. Next, we examined the effect of Corni Fructus and its five fractions on hydroxyl radical scavenging activity associated with the glycation reaction, because this reaction is, in part, mediated by hydrogen peroxide and transition metal ions, called the Fenton reaction.6) As a result, only the fraction of S1D1 was weaker than Corni Fructus and S1D2 was similar to Corni Fructus; that is, the relation of these activities was as follows, "S1D1