Cornuside

Biol Pharm Bull. 2007 Sep;30(9):1796-9.

Cornuside suppresses cytokine-induced proinflammatory and adhesion molecules in the human umbilical vein endothelial cells.[Pubmed: 17827743 ]

Cornuside is a bisiridoid glucoside compound isolated from the fruit of Cornus officinalis SIEB. et ZUCC.
METHODS AND RESULTS:
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-alpha (TNF-alpha)-induced nuclear factor-kappa B (NF-kappaB) 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-alpha. TNF-alpha-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.
CONCLUSIONS:
Taken together, the present study suggests that Cornuside suppresses expression levels of cytokine-induced proinflammatory and adhesion molecules in the human endothelial cells.

The FASEB Journal, 2006, 20(4):A668.

Cornuside exhibits vasodilatory and anti-inflammatory effects via a nitric oxide-cGMP pathway.[Reference: WebLink]

Vasorelaxant and anti-inflammatory effects of a Cornuside isolated from the fruits of Cornus officinalis and possible mechanisms responsible for this effect were investigated.
METHODS AND RESULTS:
Cornuside induced a concentration-dependent relaxation of the phenylephrine-precontracted rat aorta. This effect disappeared with the removal of functional endothelium. Pretreatment of the aortic tissues with either NG-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one (ODQ) inhibited the relaxation induced by Cornuside. Incubation of carotid arteries isolated from rats with Cornuside increased the production of cGMP in a dose-dependent manner, but this effect was blocked by pretreatment with L-NAME and ODQ, respectively. Cornuside suppressed the expression levels of adhesion molecules including intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) induced by TNF-α in HUVECs. TNF-α-induced monocyte chemoattractant protein-1 (MCP-1) expression was also attenuated by treatment of Cornuside.
CONCLUSIONS:
Taken together, the present study suggests that Cornuside dilates vascular smooth muscle and suppresses the vascular inflammatory process via endothelium-dependent nitric oxide (NO)/cGMP signaling.

Phytomedicine. 2011 Feb 15;18(4):266-71.

Protective roles of cornuside in acute myocardial ischemia and reperfusion injury in rats.[Pubmed: 20739159]

Cornuside is a secoiridoid glucoside isolated from the fruit of Cornus officinalis SIEB. et ZUCC. In this study, we investigated the anti-myocardial ischemia and reperfusion (I/R) injury effects of Cornuside in vivo and elucidated the potential mechanism.
METHODS AND RESULTS:
Rat models of myocardial I/R were induced by coronary occlusion followed by reperfusion or by Isoproterenol (ISO), treatment of rats with Cornuside (20 and 40 mg/kg, i.v.) protected the animals from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics and reduction of myocardial damage severity. Treatment with Cornuside also attenuated polymorphonuclear leukocytes (PMNs) infiltration, decreased myeloperoxidase (MPO) activity in the heart, lowered serum levels of pro-inflammatory factors and reduced phosphorylated IκB-α and nuclear factor kappa B (NF-κB) levels in the heart. Additionally, Cornuside was shown to have remarkable antioxidant activity and inhibited ISO-induced myocardial cell necrosis.
CONCLUSIONS:
Thus, Cornuside appeared to protect the rat from myocardial I/R injury by acting as an anti-inflammatory agent. These findings suggested that Cornuside may be used therapeutically in the setting of myocardial I/R where inflammation and oxidant injury are prominent.

Biosci Biotechnol Biochem. 2011;75(4):656-61.

Protective effect of cornuside against carbon tetrachloride-induced acute hepatic injury.[Pubmed: 21512227]

This study elucidated the effects of Cornuside on carbon tetrachloride (CCl₄)-induced hepatotoxicity.
METHODS AND RESULTS:
Rats were treated intraperitoneally with 0.5 mL/kg of CCl₄. Sixteen h after CCl₄ treatment, the levels of serum aminotransferases, tumor necrosis factor-α (TNF-α), and lipid peroxidation were significantly elevated, whereas the hepatic antioxidative enzyme activities were decreased. These changes were attenuated by Cornuside. Histological studies also indicated that Cornuside inhibited CCl₄-induced liver damage. Furthermore, the contents of hepatic nitrite, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were elevated after CCl₄ treatment, while cytochrome P450 2E1 (CYP2E1) expression was suppressed. Cornuside treatment inhibited the formation of liver nitrite, and reduced the overexpression of iNOS and COX-2 proteins, but restored the liver CYP2E1 content as compared with the CCl₄-treated rats.
CONCLUSIONS:
Our data indicate that Cornuside protects the liver from CCl₄-induced acute hepatotoxicity, perhaps due to its ability to restore the CYP2E1 function and suppress inflammatory responses, in combination with its capacity to reduce oxidative stress.

Biol Pharm Bull. 2011;34(7):959-66.

Cornuside suppresses lipopolysaccharide-induced inflammatory mediators by inhibiting nuclear factor-kappa B activation in RAW 264.7 macrophages.[Pubmed: 21719998]

Cornuside, a secoiridoid glucoside compound, was isolated from the fruit of Cornus officinalis SIEB. et ZUCC. Cornuside has been reported to possess immunomodulatory and anti-inflammatory activities. However, the effects and mechanism of action of Cornuside in inflammation have not been fully characterized.
METHODS AND RESULTS:
The present study was therefore designed to examine whether Cornuside suppresses inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Cornuside significantly inhibited the LPS-induced production of nitric oxide, prostaglandin E(2), tumor necrosis factor-alpha, interleukin-6 (IL-6), and IL-1beta. The mRNA and protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were also decreased by Cornuside. Furthermore, Cornuside significantly attenuated the LPS-stimulated phosphorylation and degradation of inhibitory kappa B-alpha and the subsequent translocation of the p65 subunit of nuclear factor-kappa B (NF-κB) to the nucleus. Cornuside also reduced the phosphorylations of extracellular-signal-related kinase (ERK1/2), p38, and c-Jun N-terminal kinase (JNK1/2).
CONCLUSIONS:
These results suggest that the anti-inflammatory property of Cornuside is related to the downregulations of iNOS and COX-2 due to NF-κB inhibition as well as the negative regulation of ERK1/2, p38, and JNK1/2 phosphorylations in RAW 264.7 cells.

Pharmacology. 2009;84(3):162-70.

Cornuside attenuates apoptosis and ameliorates mitochondrial energy metabolism in rat cortical neurons.[Pubmed: 19696522]

Cornuside, a secoiridoid glucoside compound, was isolated from the fruit of Cornus officinalis Sieb. et Zucc.
METHODS AND RESULTS:
The present study elucidates the effects of Cornuside on cultured rat cortical neuron damage induced by oxygen-glucose deprivation. The results show that Cornuside treatment obviously attenuates apoptosis and ameliorates mitochondrial energy metabolism in rat cortical neurons by increasing the cell survival rate, mitochondrial antioxidant enzyme activities, mitochondrial respiratory enzyme activity, mitochondrial respiratory control ratio and the ATP content, and by decreasing the mitochondrial malondialdehyde content, lactate dehydrogenase leakage rate, intracellular Ca(2+) level and caspase-3 activity in a concentration-dependent manner.
CONCLUSIONS:
These findings indicate that Cornuside has protective potential against cerebral ischemic injury, and its protective effects may be due to the suppression of intracellular Ca(2+) elevation and caspase-3 activity, and improvements in mitochondrial energy metabolism and antioxidant properties.

Planta Med. 2009 May;75(6):614-9.

Effect of cornuside on experimental sepsis.[Pubmed: 19263342]

This study was conducted to investigate the efficacy of Cornuside, a secoiridoid glucoside compound, in cultured macrophages as well as in an experimental model of sepsis induced by cecal ligation and puncture (CLP) in rats.
METHODS AND RESULTS:
Cornuside was added to cultured macrophages at different concentrations, and all CLP rats were randomized to receive an intravenous injection of the corresponding drug followed by observation of its antisepsis effect. Our results showed that Cornuside downregulated the levels of TNF- alpha, IL-6, and NO production in a dose-dependent manner in activated macrophages, while it upregulated the level of IL-10. Intravenous injection of Cornuside or imipenem alone or in combination reduced CLP-induced lethality in rats after CLP. In addition, serum levels of TNF- alpha, IL-6, triggering receptor expressed on myeloid cells, and endotoxin were downregulated. On the other hand, the serum levels of IL-10 were upregulated. Decreased bacterial counts in blood, peritoneum, spleen, liver, and mesenteric lymph nodes and decreased myeloperoxidase in lung, liver, and small intestine also were found after Cornuside injection.
CONCLUSIONS:
These data indicate that the antisepsis therapeutic effect of Cornuside is mediated by decreased local and systemic levels of a wide spectrum of inflammatory mediators. This work provides first evidence for the clinic use of Cornuside as a new immunomodulatory drug that has the capacity to inhibit the inflammatory response in sepsis.