Protective Effects Of Scutellarin Research Articles

Protective effects of scutellarin in experimental colitis in rats

ABSTRACT Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology for which effective treatments are lacking. Scutellarin is a flavonoid with anti-apoptotic, antioxidant and anti-inflammatory effects. We investigated the possible protective effects of scutellarin on UC induced by acetic acid in rats. We used five groups of male rats: control, scutellarin, UC, UC + scutellarin, UC + sulfasalazine. Colonic mucosal inflammation was evaluated microscopically. Malondialdehyde (MDA), superoxide dismutase (SOD) activity, total antioxidant status (TAS), nitric oxide (NO), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and DNA fragmentation levels were measured. Colon tissue sections were evaluated using immunohistochemistry for Bcl-2 and Bax, TUNEL staining and histopathology. Pretreatment with scutellarin significantly reduced histological damage. Scutellarin significantly reduced serum and tissue levels of MDA, NO, IL-6 and TNF-α, and increased enzymatic activity of SOD and TAS. Scutellarin suppressed apoptosis by down-regulation of Bax, reduction of DNA fragmentation and increased expression of Bcl-2. Apoptosis was increased, while antioxidant enzymes were significantly decreased; some histopathologic disorders also were seen in the UC group. Administration of scutellarin ameliorated the pathological and biochemical alterations caused by UC in rats. We found that scutellarin might be protective against UC by down-regulating pro-inflammatory cytokines and suppressing apoptosis and oxidative stress.

Scutellarin Alleviates Ischemic Brain Injury in the Acute Phase by Affecting the Activity of Neurotransmitters in Neurons.

Cerebral ischemic stroke is a common neuron loss disease that is caused by the interruption of the blood supply to the brain. In order to enhance the CIS outcome, both identifying the treatment target of ischemic brain damage in the acute phase and developing effective therapies are urgently needed. Scutellarin had been found to be beneficial to ischemic injuries and has been shown to have potent effects in clinical application on both stroke and myocardial infarction. However, whether scutellarin improves ischemic brain damage in the acute phase remains unknown. In this study, the protective effects of scutellarin on ischemic brain damage in the acute phase (within 12 h) were illustrated. In middle cerebral artery occlusion and reperfusion (MCAO/R) modeling rats, the Z-Longa score was significantly down-regulated by 25% and 23.1%, and the brain infarct size was reduced by 26.95 ± 0.03% and 25.63 ± 0.02% when responding to high-dose and low-dose scutellarin treatments, respectively. H&E and TUNEL staining results indicated that the neuron loss of the ischemic region was improved under scutellarin treatment. In order to investigate the mechanism of scutellarin's effects on ischemic brain damage in the acute phase, changes in proteins and metabolites were analyzed. The suppression of scutellarin on the glutamate-inducing excitatory amino acid toxicity was strongly indicated in the study of both proteomics and metabolomics. A molecular docking experiment presented strong interactions between scutellarin and glutamate receptors, which score much higher than those of memantine. Further, by performing a parallel reaction monitoring-mass spectrometry (PRM-MS) study on both the cortex and hippocampus tissue of the ischemic region, we screened the scutellarin-regulating molecules that are involved in both the release and transportation of neurotransmitters. It was found that the aberrant levels of glutamate receptors, including EAAT2, GRIN1, GRIN2B, and GRM1, as well as of other glutamatergic pathway-involving proteins, including CAMKK2, PSD95, and nNOS, were significantly regulated in the ischemic cortex. In the hippocampus, EAAT2, GRIN1, nNOS, and CAM were significantly regulated. Taken together, scutellarin exerts potent effects on ischemic brain damage in the acute phase by regulating the activity of neurotransmitters and reducing the toxicity of excitatory amino acids in in neurons.

Protective effects of scutellarin on acute alcohol gastric injury

Protective effects of scutellarin on acute alcohol gastric injury

Protective Effects of Scutellarin on Acute Alcohol Intestinal Injury.

The present study aims to investigate the roles of scutellarin (SCU) on acute alcohol intestinal injury. Mice were divided into six groups: alcohol, three administration, negative control and positive drug bifendate control. The administration group mice were intraperitoneally injected with SCU for 3 consecutive days followed by alcohol gavage at an interval of 1 h. After the mice were sacrificed, colon tissue damage was evaluated by histopathological examination; the activities of inducible nitric oxide synthase (iNOS) and catalase (CAT), as well as the content of malondialdehyde (MDA) were detected using biochemical kits; the levels of inflammatory cytokines mRNA were determined by real-time fluorescence quantitative PCR; the protein expression levels of hemeoxygenase-1 (HO-1) and phosphorylated nuclear factor-ĸB p65 were measured via western blotting. The results showed that alcohol induced severe colon morphological degradation, epithelia atrophy, and more inflammatory cells infiltration in the submucosa. SCU treatment prevented this process, especially in the middle and high dose groups. Alcohol treatment caused excessive lipid peroxidation product accumulation of MDA, restrained the activity of antioxidant enzyme CAT, induced HO-1 expression in the colon, whereas low dose SCU treatment significantly down-regulated the MDA level, enhanced the CAT level, and accelerated HO-1 signals. SCU prevented alcohol stimulation triggered inflammatory response in colon tissues through significantly downregulating the iNOS activity, transcript levels of Tnf-α, Il-1β and Il-6, and phosphorylation levels of NF-κB p65. These findings suggest that SCU protects the colon via antioxidant and anti-inflammatory mechanisms, making it a promising drug against alcohol-induced colon damage.

Pharmacological basis for application of scutellarin in Alzheimer's disease: Antioxidation and antiapoptosis.

Scutellarin (SC), mainly extracted from the Chinese herb Erigeron breviscapus (vant.), has been reported to possess various pharmacological activities; however, its effects on Alzheimer's disease (AD) have not been systemically reported. The protective effects of SC on AD were investigated using an L-glutamic acid (L-Glu)-damaged HT22 cell apoptosis model and an aluminum chloride plus D-galactose-induced AD mouse model. In L-Glu-damaged HT22 cells, SC significantly increased cell viability, inhibited lactate dehydrogenase release, reduced caspase-3 activity and suppressed apoptosis, which were determined via an MTT assay, an in vitro Toxicology Assay kit, a Caspase-3 activity assay kit, and propidium iodide and Annexin V staining. Furthermore, SC suppressed the accumulation of intracellular reactive oxygen species (ROS), restored the dissipation of mitochondrial membrane potential, enhanced the expression of antiapoptotic proteins and reduced the expression of pro-apoptotic proteins, as determined by immunofluorescence assays and western blotting. In AD mice, SC enhanced vertical and horizontal movements in an autonomic activity test, and reduced the escape latency time in the water maze test. SC reduced the deposition of amyloid β1–42 (Aβ1-42) and the expression of phosphorylated-Tau in the hippocampus as determined by immunohistochemistry analysis, but enhanced the serum levels of Aβ1–42 of AD mice as determined by ELISA. ELISA analyses also revealed that SC enhanced the levels of acetylcholine, and superoxide dismutase in serum and brain lysate, whereas reduced the levels of ROS in brain lysate of AD mice. The present study confirmed that the protective effects of SC in AD in vitro and in vivo are associated with its antioxidant and antiapoptotic properties.

Antiapoptotic effects of scutellarin on ultraviolet A-irradiated HaCaT human keratinocytes

BackgroundThis study examines the cellular protective effects of scutellarin on HaCaT cells in which oxidative stress was induced by ultraviolet A (UVA).MethodsCell viability and lipid peroxidation were measured using WST-1 and MDA assays, respectively. The changes in cell number in the sub-G1 phase were assessed using cell cycle analysis, and tailed DNA levels were measured using the comet assay to examine the degree of DNA damage. The difference in the mitochondrial membrane potential was examined using JC-1 staining, and the regulation of BAX mRNA expression levels was examined using quantitative real-time polymerase chain reaction.ResultsAlthough UVA-irradiated cells resulted in a 3.63-fold increase in lipid peroxide, scutellarin-treated cells showed concentration-dependent decreases of 2.06, 1.39, and 0.97 times at scutellarin concentrations of 1, 5, and 10 μM, respectively. The cell number in the sub-G1 phase increased by 227% when irradiated by UVA but decreased to 187, 139, and 120% when cells were treated with scutellarin at concentrations of 1, 5, and 10 μM, respectively. Tailed DNA also showed a protective effect. The mitochondrial membrane potential difference decreased up to 36% when irradiated by UVA but recovered up to 58, 82, and 92% when cells were treated with scutellarin at concentrations of 1, 5, and 10 μM, respectively. BAX gene expression levels increased 9.7-fold by UVA but was downregulated to 7.4-, 4.71-, and 2.49-fold when cells were treated with scutellarin at concentrations of 1, 5, and 10 μM, respectively.ConclusionsThis study revealed the cellular protective effects of scutellarin on HaCaT cells. Further studies are warranted to determine the use of scutellarin as a cosmeceutical ingredient.

Protective effect of scutellarin on myocardial infarction induced by isoprenaline in rats.

Objective(s):Scutellarin (Scu) is the main effective constituent of Erigeron breviscapus which has anti-oxidant, anti-apoptotic, anti-inflammatory and other therapeutic properties. The purpose of this study was to investigate the protective effect of Scu on myocardial infarction (MI) induced by isoprenaline (ISO).Materials and Methods:The rats were subcutaneously injected with ISO (45 mg/kg) on the first day, then single tail-intravenously injected with different doses of Scu (10 mg/kg, 20 mg/kg, 40 mg/kg) for 7 consecutive days. The protective effect of Scu on ISO-induced MI was evaluated by measuring markers of heart injury in serum, levels of lipid peroxidation, and antioxidants in heart tissue, observing pathological changes of tissue, and detecting quantified expression of apoptotic-related family members and inflammation.Results:Compared with the model group, the concentration of troponin T (CTn-T) and troponin I (CTn-I), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in the serum all decreased in the Scu high dose group. The activities of superoxide dismutase (SOD), catalase (CAT), and the content of reduced glutathione (GSH) in heart increased, and the content of malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS) decreased. In addition, the histopathologic aspects showed that pathological heart change was found in the model group, and was reduced to varying degrees in the Scu group. Moreover, the expression of Bax, P53, Caspase3, Caspase9, cytochrome C, NGAL, NFκB, IL-1β and IL-6 in the heart decreased, while the expression of Bcl2 increased.Conclusion:Scu could reduce the degree of MI induced by ISO by improving the antioxidant, anti-apoptotic, and anti-inflammatory capacities of the body.

Protective Effects of Scutellarin on Human Cardiac Microvascular Endothelial Cells against Hypoxia-Reoxygenation Injury and Its Possible Target-Related Proteins.

Scutellarin (SCU) is one of the main components of traditional Chinese medicine plant Erigeron breviscapus (Vant.) Hand.-Mazz. In this paper, we studied the protective effects of SCU on human cardiac microvascular endothelial cells (HCMECs) against hypoxia-reoxygenation (HR) injury and its possible target-related proteins. Results of MTT assay showed that pretreatment of SCU at doses of 1, 5, and 10 μM for 2 h could significantly inhibit the decrease in cell viability of HCMECs induced by HR injury. Subcellular fractions of cells treated with vehicle control, 1 μM SCU, HR injury, or 1 μM SCU + HR injury were separated by ultracentrifugation. The protein expression profiles of cytoplasm and membrane/nuclei fractions were checked using protein two-dimensional electrophoresis (2-DE). Proteins differentially expressed between control and SCU-treated group, control and HR group, or HR and SCU + HR group were identified using mass spectrometry (MS/MS). Possible interaction network of these target-related proteins was predicted using bioinformatic analysis. The influence of SCU on the expression levels of these proteins was confirmed using Western blotting assay. The results indicated that proteins such as p27BBP protein (EIF6), heat shock 60 kDa protein 1 (HSPD1), and chaperonin containing TCP1 subunit 6A isoform (CCT6A) might play important roles in the effects of SCU.

Protective effects of scutellarin on type II diabetes mellitus-induced testicular damages related to reactive oxygen species/Bcl-2/Bax and reactive oxygen species/microcirculation/staving pathway in diabetic rat.

The goal of our study is to evaluate the effect of Scutellarin on type II diabetes-induced testicular disorder and show the mechanism of Scutellarin's action. We used streptozotocin and high-fat diet to establish type II diabetic rat model. TUNEL and haematoxylin and eosin staining were used to evaluate the testicular apoptotic cells and morphologic changes. Immunohistochemical staining was used to measure the expression level of vascular endothelial growth factor and blood vessel density in testes. Oxidative stress in testes and epididymis was tested by fluorescence spectrophotometer and ELISA. The expression of Bcl-2/Bax and blood flow rate in testicular vessels were measured by western blot and Doppler. Our results for the first time showed that hyperglycemia induced apoptotic cells and morphologic impairments in testes of rats, while administration of Scutellarin can significantly inhibit these damages. This effect of Scutellarin is controlled by two apoptotic triggers: ROS/Bcl-2/Bax and ROS/microcirculation/starving pathway.

Protective Effects of Scutellarin and Breviscapine on Brain and Heart Ischemia in Rats

Scutellarin is an active molecule existing in Erigeron breviscapus (vant.) Hand-Mazz. The present work was designed to study the antiischemic effects of scutellarin and its mixture with another substance, breviscapine, in male Sprague-Dawley (SD) rats. Ligature of left anterior descending arteries was performed to induce acute myocardial infarction (MI), and the middle cerebral artery occlusion was created to induce focal cerebral ischemia. The MI size was significantly reduced by scutellarin (15 and 50 mg/kg) but not by breviscapine (5 to 50 mg/kg); the effect of scutellarin on the anti-MI was dose-dependent. Compared with control group, scutellarin (50 mg/kg) reduced the myocardium cell apoptosis in MI rats. The two drugs together (5 to 50 mg/kg) significantly reduced infarction size in focal brain ischemic rats (P < 0.05). There were no significant differences among the 3 dosages in breviscapine-treated rats, and the effect of scutellarin on the anticerebral ischemia was dose-dependent. The results demonstrate that the protective effects of scutellarin on cardiovascular and cerebrovascular ischemia were better than its mixture, breviscapine, in rats.

Scutellarin attenuates oxidative glutamate toxicity in PC12 cells.

The present study investigated the protective effects of the antioxidant scutellarin against oxidative toxicity induced by glutamate in PC12 cells. Vitamin E, a classical antioxidant was employed as a comparative agent. Incubation of PC12 cells with 10 mM glutamate resulted in significant cytotoxity as evaluated by the MTT and lactate dehydrogenase (LDH) assays, decreases of GSSG reductase activity, disturbance of the cell redox state as indicated by the GSH/GSSG ratio, and accumulation of intracellular reactive oxygen species (ROS) and lipid peroxidation products. Scutellarin at 0.1, 1 and 10 microM significantly protected against the cytoxicity and production of ROS and lipid peroxidation induced by glutamate. Scutellarin did not prevent the reduction of cellular GSH levels, but it up-regulated GSSG reductase activity, thus preventing an increase in cellular GSSG levels, and concomitantly improved the cell redox status. Our data also show that the protective effects of scutellarin against glutamate-induced oxidative toxicity are more potent than that of vitamin E. These results demonstrate that scutellarin can protect PC12 cells from oxidative glutamate toxicity by scavenging ROS, inhibiting lipid peroxidation and improving the cell redox status, and may reduce the cellular damage in pathological conditions associated with excessive glutamate release.