Antiulcerogenic and antioxidant activities of Plantago ovata ethanolic extract in rats / Atividade antiulcerogênica e antioxidante do extrato etanólico de Plantago ovata em ratos

This study aimed to determine the antiulcerogenic and antioxidant activities of Psyllium (Plantago ovata Forssk) seed ethanolic extract in rats. We assessed the antioxidant potential using free radical scavenging on DPPH, ß-carotene bleaching activity, ferric reducing power, and hydroxyl radical scavenging activity. In the antiulcerogenic study, pre-treatment with Plantago ovata seeds ethanolic extract (POE) (400 mg/kg b.wt) significantly protected against ethanol-induced gastric ulcer in rats by decreasing the ulcer index value and preserving the integrity of the gastric mucosa. The oxidative stress status in the stomach tissues showed a significant increase in the antioxidant enzyme levels of superoxide dismutase, catalase, and glutathione peroxidase with a significant decrease in lipid peroxidation during pre-treatment with POE. In conclusion, the POE protects against gastric ulcer due to its antioxidant potential and presence of bioactive molecules.

O presente estudo teve como objetivo determinar as atividades antiulcerogênica e antioxidante das sementes de Psyllium (Plantago ovata Forssk) em ratos. O potencial antioxidante foi avaliado utilizando o método do sequestro do radical livre DPPH, autooxidação do ß-caroteno, poder redutor de ferro e atividade de sequestro do radical hidroxila. No estudo antiulcerogênico, o pré-tratamento com o extrato etanólico das sementes de Plantago ovata (POE) (400 mg/Kg b.wt) reduziu a úlcera gástrica induzida pelo etanol em ratos, diminuindo o valor do índice de úlcera e preservando a integridade da mucosa gástrica. O estudo do estresse oxidativo nos tecidos estomacais mostrou um aumento significativo dos níveis das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase, com uma diminuição significativa da peroxidação lipídica enquanto pré-tratamento com POE. Em conclusão, o POE protege contra úlcera gástrica devido aos seus potenciais antioxidantes e à presença de moléculas bioativas.

Antiulcerogenic and antioxidant activities of Plantago ovata ethanolic extract in rats

Abstract This study aimed to determine the antiulcerogenic and antioxidant activities of Psyllium (Plantago ovata Forssk) seed ethanolic extract in rats. We assessed the antioxidant potential using free radical scavenging on DPPH, -carotene bleaching activity, ferric reducing power, and hydroxyl radical scavenging activity. In the antiulcerogenic study, pre-treatment with Plantago ovata seeds ethanolic extract (POE) (400 mg/kg b.wt) significantly protected against ethanol-induced gastric ulcer in rats by decreasing the ulcer index value and preserving the integrity of the gastric mucosa. The oxidative stress status in the stomach tissues showed a significant increase in the antioxidant enzyme levels of superoxide dismutase, catalase, and glutathione peroxidase with a significant decrease in lipid peroxidation during pre-treatment with POE. In conclusion, the POE protects against gastric ulcer due to its antioxidant potential and presence of bioactive molecules.

Resumo O presente estudo teve como objetivo determinar as atividades antiulcerogênica e antioxidante das sementes de Psyllium (Plantago ovata Forssk) em ratos. O potencial antioxidante foi avaliado utilizando o método do sequestro do radical livre DPPH, autooxidação do -caroteno, poder redutor de ferro e atividade de sequestro do radical hidroxila. No estudo antiulcerogênico, o pré-tratamento com o extrato etanólico das sementes de Plantago ovata (POE) (400 mg/Kg b.wt) reduziu a úlcera gástrica induzida pelo etanol em ratos, diminuindo o valor do índice de úlcera e preservando a integridade da mucosa gástrica. O estudo do estresse oxidativo nos tecidos estomacais mostrou um aumento significativo dos níveis das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase, com uma diminuição significativa da peroxidação lipídica enquanto pré-tratamento com POE. Em conclusão, o POE protege contra úlcera gástrica devido aos seus potenciais antioxidantes e à presença de moléculas bioativas.

Protective effect of loboob (a Persian traditional remedy) on sexual hormones, antioxidant activities and stereological changes of testis tissue on busulfan induced oligospermia in rats

Loboob as a traditional drug in Iranis known for its beneficial effects on busulfan-induced oligospermia. In this experimental study, protective effects of loboob (a Persian traditional remedy) on sexual hormones, antioxidant levels and stereological changes of testis tissue were evaluated in an oligospermia rat model induced by busulfan. Fifty male rats were randomly divided into five different groups: control, received no treatments; and the other groups administrated with a single dose of busulfan (10 mg/kg body weight). After 30 days, these groups were treated with 0, 35, 70 or 140 mg/kg/day of loboob for 60 days. Blood samples were collected for hormone and antioxidant enzyme assays. Unbiased stereology was performed on testis tissues to evaluate the volume of different parts of the testis and the number of various testis cells. Data indicated that FSH, LH and MDA were increased, and testosterone, catalase, SOD were decreased in the busulfan group, while treatment with loboob at 70 and 140 mg/kg significantly improved these parameters (P <0.05). Treatment with 70 and 140 mg/kg of loboob ameliorated the germinal epithelium volume, types A and B spermatogonia, spermatocytes, elongated and round spermatids, and Sertoli cells in the seminiferous tubules (P <0.05). High concentration of loboob also improved testis weight and volume, and leydig cell number (P <0.05). Thus, loboob is more effective for the recovery of seminiferous tubules and their cells than for the interstitial tissue. Loboob with various antioxidants, minerals and vitamins could overcome the side effects of busulfan.

Physiological and transcriptional responses to heat stress in a typical phenotype of Pinellia ternata / 中国天然药物

Pinellia ternata is an important medicinal plant, and its growth and development are easily threatened by high temperature. In this study, comprehensive research on physiological, cytological and transcriptional responses to different levels of heat stress were conducted on a typical phenotype of P. ternata. First, P. ternata exhibited tolerance to the increased temperature, which was supported by normal growing leaves, as well as decreased and sustained photosynthetic parameters. Severe stress aggravated the damages, and P. ternata displayed an obvious leaf senescence phenotype, with significantly increased SOD and POD activities (46% and 213%). In addition, mesophyll cells were seriously damaged, chloroplast thylakoid was fuzzy, grana lamellae and stroma lamellae were obviously broken, and grana thylakoids were stacked, resulting in a dramatically declined photosynthetic rate (74.6%). Moreover, a total of 16 808 genes were significantly differential expressed during this process, most of which were involved in photosynthesis, transmembrane transporter activity and plastid metabolism. The number of differentially expressed transcription factors in MYB and bHLH families was the largest, indicating that these genes might participate in heat stress response in P. ternata. These findings provide insight into the response to high temperature and facilitate the standardized cultivation of P. ternata.

In vivo antioxidant activity of rabbiteye blueberry (Vaccinium ashei cv. 'Brightwell') anthocyanin extracts / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Blueberries are rich in phenolic compounds including anthocyanins which are closely related to biological health functions. The purpose of this study was to investigate the antioxidant activity of blueberry anthocyanins extracted from 'Brightwell' rabbiteye blueberries in mice. After one week of adaptation, C57BL/6J healthy male mice were divided into different groups that were administered with 100, 400, or 800 mg/kg blueberry anthocyanin extract (BAE), and sacrificed at different time points (0.1, 0.5, 1, 2, 4, 8, or 12 h). The plasma, eyeball, intestine, liver, and adipose tissues were collected to compare their antioxidant activity, including total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity and glutathione-peroxidase (GSH-PX/GPX) content, and the oxidative stress marker malondialdehyde (MDA) level. The results showed that blueberry anthocyanins had positive concentration-dependent antioxidant activity in vivo. The greater the concentration of BAE, the higher the T-AOC value, but the lower the MDA level. The enzyme activity of SOD, the content of GSH-PX, and messenger RNA (mRNA) levels of Cu,Zn-SOD, Mn-SOD, and GPX all confirmed that BAE played an antioxidant role after digestion in mice by improving their antioxidant defense. The in vivo antioxidant activity of BAE indicated that blueberry anthocyanins could be developed into functional foods or nutraceuticals with the aim of preventing or treating oxidative stress-related diseases.

Cigarette Smoke Induces Gefitinib Resistance in NSCLC Cells via ROS/Sirt3/SOD2 Pathway / 中国肺癌杂志

BACKGROUND@#Epidermal growth factor receptor (EGFR) gene mutations are the most common driver mutations in non-small cell lung cancer (NSCLC). To prolong the survival of the patients, EGFR tyrosine kinase inhibitors (TKIs) resistance in NSCLC is a major challenge that needs to be addressed urgently, and this study focuses on investigating the mechanism of cigarette smoke (CS) induced Gefitinib resistance in NSCLC.@*METHODS@#PC-9 and A549 cells were cultured in vitro and treated with 1 µmol/L Gefitinib for 4 h and 10% cigarette smoke extract (CSE) for 48 h. Western blot was used to detect Sirtuin 3 (Sirt3) and superoxide dismutase 2 (SOD2) protein expressions; DCFH-DA probe was used to detect intracellular reactive oxygen species (ROS); CCK-8 kit was used to detect cell activity, and EdU was used to detect cell proliferation ability. Sirt3 overexpression plasmid (OV-Sirt3) was transfected in PC-9 and A549 cells and treated with 1 µmol/L Gefitinib for 4 h and 10% CSE for 48 h after N-acetylcysteine (NAC) action. The expressions of Sirt3 and SOD2 were detected by Western blot; the ROS level in the cells was detected by DCFH-DA probe, and the cell activity was detected by CCK-8.@*RESULTS@#CSE induced an increase in the 50% inhibitory concentration (IC50) of both PC-9 and A549 cells to Gefitinib (P<0.01) and enhanced the proliferation of PC-9 and A549 cells, suggesting that CS induced Gefitinib resistance in NSCLC. ROS was involved in CSE-induced Gefitinib resistance (P<0.05). CSE induced low expressions of Sirt3 and SOD2 (P<0.01), and Sirt3/SOD2 was associated with poor prognosis in lung cancer patients (P<0.05). OV-Sirt3 in PC-9 and A549 cells reversed CSE-induced Gefitinib resistance (P<0.05) and significantly reduced ROS production. NAC reversed CSE-induced Gefitinib resistance in PC-9 and A549 cells (P<0.05).@*CONCLUSIONS@#The ROS/Sirt3/SOD2 pathway is involved in CS-induced Gefitinib resistance in NSCLC.

The effects of metformin, acetylsalicylic acid and ibuprofen on telomerase enzyme activity: inhibitory effect of ibuprofen

Abstract Telomerase enzyme is necessary for the elongation of telomeres while telomerase being critical for aging and cancer. Metformin, ibuprofen, and acetylsalicylic acid used in this research are drugs that millions of people already use and that many are likely to use in future. In this study, the effects of these drugs on telomerase activity of Mus musculus swiss albino mice in liver tissue were investigated and the telomerase activity was measured with a PCR-ELISA based kit. In the study a possible connection between telomerase enzyme activity and activities of antioxidant enzymes was also investigated by determining the activity of superoxide dismutase (SOD) and catalase enzymes. The data obtained show that metformin slightly decreased telomerase enzyme activity in low dose application; however, this change was not statistically significant. In ibuprofen application, there was a significant inhibitory effect when high doses were used; whereas, there was a slight inhibitory effect at low doses. In acetylsalicylic acid application, a slight activator effect was detected; it was not statistically significant, though. Metformin was observed to increase catalase and SOD activities in general while low and high doses of acetyl salicylic acid showed different effects. In addition, ibuprofen caused a statistically significant increase in liver SOD values. It is important to note that this study demonstrated a significant inhibitory effect of ibuprofen on telomerase enzyme activity in animal models..

Penetration ability and biological activity of fusion protein PTD4-Cu, Zn-SOD in human astrocytes in vitro by immunofluorescence test / 西安交通大学学报(医学版)

【Objective】 To observe the penetration and biological activity of PTD4-Cu, Zn-SOD into human astrocytes and whether it can mitigate hypoxia damages. 【Methods】 ①Immunohistochemistry and fluorescence test: We labeled the Cu, Zn-SOD by a monoclonal antibody, combined it with the fluorescent secondary antibody labeled with fluorescein isothiocyanate (FITC) to observe the effect of transduced PTD4-Cu, Zn-SOD on the viability of human astrocytes. ② The experimental group: After hypoxic damage model, the cells were divided into three groups: blank control, group Cu, Zn-SOD, and group PTD4-Cu, Zn-SOD. Group blank was added with DMEM medium (excluding serum) as control; DMEM medium was added to the other two for one hour (excluding serum) with its fusion proteins (Cu, Zn-SOD and PTD4 -Cu, Zn-SOD) with the final concentration of 2 μmoL/L. After the intervention, we used SOD and MDA test kits to observe PTD4-Cu, Zn-SOD and Cu, Zn-SOD in astrocytes after fusion protein intervention. 【Results】 The PTD4-Cu, Zn-SOD fusion protein could have aggregation distribution in the nucleus by FITC fluorescently labeled. After the intervention, it could increase the SOD activity in astrocytes in group PTD4-Cu, Zn-SOD and group Cu, Zn-SOD compared with control group, but the SOD activity was more obvious in the fusion proteins PTD4-Cu, Zn-SOD group. And the dose of MDA was reduced in group PTD4-Cu, Zn-SOD compared with group Cu, Zn-SOD and control group. 【Conclusion】 PTD4-Cu, Zn-SOD fusion protein can transcellular membrane of human astrocytes. The fusion protein PTD4-Cu, Zn-SOD can increase the SOD activity and reduce the content of MDA by human astrocytes from hypoxia injury.

TBN improves motor function and prolongs survival in SOD1G93A and TDP-43M337V mouse model of ALS / 中国药理学与毒理学杂志

OBJECTIVE Amyotrophic lateral sclerosis(ALS)is a fetal neurodegenerative disease characterized by the progressive loss of upper and lower motor neu-rons,leading to skeletal muscle atrophy,weakness,and paralysis.Oxidative stress plays a crucial role in ALS pathogenesis,including the familial forms of the disease arising from mutations in the gene coding for superox-ide dismutase(SOD1).Additionally,the abnormal accu-mulation of TAR DNA-binding protein of 43 ku(TDP-43)is a pathological feature present in almost all patients,even though the pathogenesis of ALS is unclear.Current-ly,there is no drug that can cure ALS/FTLD.Tetramethyl-pyrazine nitrone(TBN)is a derivative of tetramethylapyr-azine,derived from traditional Chinese medicine Ligusti-cum chuanxiong,which has been extensively proven to have therapeutic effects on various models of neurode-generative diseases.METHODS We investigated the therapeutic effect of TBN in the SOD1G93A and TDP-43M337V ALS mouse models.In the SOD1G93A trans-genic mouse model,TBN was administered to mice via intraperitoneal or intragastric injection after the onset of motor deficits.We injected the TDP-43M337V virus into the striatum of mice unilaterally and bilaterally,and then administered TBN 30 mg·kg-1 intragastrically to observe changes in behavior and survival rate of mice.RESULTS TBN slowed the progression of motor neuron disease,as evidenced by improved motor performance,reduced spi-nal motor neuron loss and associated glial response,and decreased skeletal muscle fiber denervation and fibrosis.TBN treatment activated mitochondrial antioxidant activity through the PGC-1α/Nrf2/HO-1 pathway and decreased the expression of human SOD1.In the mice with unilateral injection of TDP-43M337V into the striatum,TBN improved motor deficits and cognitive impairment in the early stages of disease progression.In mice with bilateral injection of TDP-43M337V into the striatum,TBN not only improved motor function but also prolonged survival.Moreover,we demonstrate that its therapeutic effect may be through activation of the Akt/mTOR/GSK-3β and AMPK/PGC-1α/Nrf2 signaling pathways.CONCLUSION TBN shows promise as an agent for the treatment of ALS/FTLD.TBN is currently undergoing clinical investigation for several indications,including a Phase Ⅱ trial for ALS.

Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.

Hypolipidemic properties of the extracts of Belamcanda chinensis leaves (BCLE) in KK-A y mice

Abstract The extract of Belamcanda chinensis leaves (BCLE) is a traditional Chinese herbal medicine for the treatment of diabetes-related hyperlipidemia in Hainan province, South China. In this study, the lipid-decreasing effects of BCLE on obese diabetes were investigated on KK-Ay mice. The component F2 ameliorated lipid disorder, as indicated by decreased levels of body weight, liver index, levels of TC, TG and LDL-c in the serum and liver. The enhancement effect of F2 on liver SOD and the inhibitory effect of F2 on MDA demonstrated that F2 exhibited significant antioxidant activity on liver injury. F2 also prevented vacuolar degeneration and reduced pathological tissue injury in liver. In addition, the component F1 decreased the levels of TG, LDL-c and MDA in the liver. These findings suggest that F2 may have therapeutic potential in the prevention and therapy of hyperlipemia and liver disease associated with obesity-related diabetes.

Nicotinamide mononucleotide attenuates ischemia-reperfusion injury induced by donor liver from cardiac death through Sirt3 / 器官移植

Objective To evaluate the effect and mechanism of nicotinamide mononucleotide (NMN) on ischemia-reperfusion injury (IRI) induced by donor liver after cardiac death in rat models. Methods Rat models of orthotopic liver transplantation were established by "magnetic ring + double cuff" method. SD rats were randomly divided into the sham operation group (Sham group), orthotopic liver transplantation group (OLT group), NMN treatment + orthotopic liver transplantation group (NMN group), NMN+sirtuin-3 (Sirt3) inhibitor (3-TYP) + orthotopic liver transplantation group (NMN+3-TYP group), respectively. Pathological changes and hepatocyte apoptosis of the rats were observed in each group. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents in liver tissues were detected. The expression levels of Sirt3, microtubule-associated protein 1 light chain 3 (LC3)Ⅱ, PTEN-induced putative kinase 1 (PINK1), Parkin and translocase of the outer mitochondrial membrane 20 (TOMM20) in liver tissues were measured. Postoperative survival of the rats in each group was analyzed. Results Compared with the Sham group, serum ALT and AST levels were higher in the OLT group. Compared with the OLT group, the levels of ALT and AST were decreased in the NMN group. Compared with the NMN group, the levels of ALT and AST were increased in the NMN +3-TYP group (all P < 0.05). The liver tissue structure of rats in the Sham group was basically normal. In the OLT group, pathological changes, such as evident congestion, vacuolar degeneration and hepatocyte necrosis, were observed in the liver tissues. Compared with the Sham group, Suzuki score and apoptosis rate were higher in the OLT group. Suzuki score and apoptosis rate in the NMN group were lower than those in the OLT group. Suzuki score and apoptosis rate in the NMN+3-TYP group were higher compared with those in the NMN group (all P < 0.05). Compared with the Sham group, the SOD content was decreased, whereas the MDA content was increased in the OLT group. Compared with the OLT group, the SOD content was increased, whereas the MDA content was decreased in the NMN group. Compared with the NMN group, the SOD content was decreased, whereas the MDA content was increased in the NMN+3-TYP group (all P < 0.05). Compared with the Sham group, the relative expression levels of Sirt3 and TOMM20 proteins were down-regulated, whereas those of PINK1, Parkin and LC3Ⅱproteins were up-regulated in the OLT group. Compared with the OLT group, the relative expression levels of Sirt3, PINK1, Parkin and LC3Ⅱproteins were up-regulated, whereas that of TOMM20 protein was down-regulated in the NMN group. Compared with the NMN group, the relative expression levels of PINK1, Parkin and LC3Ⅱproteins were down-regulated, whereas that of TOMM20 protein was up-regulated in the NMN+3-TYP group (all P < 0.05). In the Sham group, the 7 d survival rate of rats was 100%, 50% in the OLT group, 75% in the NMN group and 58% in the NMN+3-TYP group, respectively. Conclusions NMN may enhance the antioxidative capacity of the liver, induce PINK1/Parkin-mediated mitochondrial autophagy, and alleviate IRI of the liver by up-regulating Sirt3, thereby playing a protective role in the donor liver after cardiac death.

Superoxide Dismutase Expression in the Ovaries of Periodontitis Animal Models Induced by Porphyromonas gingivalis and Treated with Cassava Leaves Extract

@#The ovaries represent the female reproductive organs that determine the women's fertility status and their systemic and oral health, correlating to sex steroid hormone alteration. This study aimed to investigate the effect of cassava leaves extract treatment to SOD expression in the animal model-ovaries after Porphyromonas gingivalis injection. 15 female Sprague Dawley rats were used and divided into five groups: (1) control without cassava leaves extract treatment (C); (2) P. gingivalis without cassava leaves extract treatment (T1); (3) P. gingivalis and cassava leaves extract (T2); (4) P. gingivalis and vitamin C (T3); and (5) P. gingivalis and metronidazole (T4). Animal were euthanised at day seven after the initial treatment to collect ovaries. The ovaries sections were immunohistochemically stained to quantify SOD expression using light microscope while the Image J software was used to quantify the SOD expression. The results showed that all of the follicle types had the same intensity of SOD expression. Most of the follicles exhibited low intensity of SOD expression, except for atretic follicles. In conclusion, P. gingivalis and cassava leaves extract influenced SOD expression in the ovaries of animal models, which increased the SOD expression.

Effect of High-Fat Diet on SOD2, GPx, NeuN and BDNF Expression on Frontal Lobe of Obese Rats

@#Introduction: Obesity has been demonstrated to induce oxidative stress and inflammation processes that lead to senescence in brain cells. Obesity-induced cellular senescence in the brain is still widely investigated. This study aimed to investigate the expression of antioxidant and neuronal markers in the frontal lobes of obese rats. Methods: Eighteen adult rat Sprague Dawley divided into three groups: Control (SO), Obese-2 (DIO2), and Obese-4 (DIO4) were observed. Control rats were fed with a standard diet AIN 76A for two month. In contrast, DIO2 and DIO4 rats were fed with a high-fat diet daily for two and four months, respectively. After being sacrificed, the rats’ brains were dissected out then the frontal lobes were used for RNA extraction. Reverse transcriptase PCR of SOD2, GPx, BDNF, NeuN and beta-actin was performed to investigate the relative expression of the antioxidant and neuronal markers. Results: DIO2 and DIO4 groups had significantly increased body Weights, blood glucose level and triglyceride level after being fed with a high-fat diet for two and four months, respectively. The DIO4 group had the significantly lowest mRNA expressions of SOD2, GPx, BDNF and NeuN. Conclusion: Decreased antioxidant and neuronal markers in the rats frontal lobes were observed as the chronic effect of obesity.

Mild hypothermia alleviates renal ischemia-reperfusion injury by up-regulating the expression of cold-shock protein RBM3 / 器官移植

Objective To evaluate the effect of mild hypothermia on the renal ischemia-reperfusion injury (IRI), and the expression profile of RNA-binding motif protein 3(RBM3) and its downstream effector molecules during this process. Methods Eighteen healthy SD male rats were randomly divided into the normal control (NC) group, IRI group and mild hypothermia pretreat (MHP) group, with 6 rats in each group. Serum creatinine level was measured to evaluate the renal function. Hematoxylin-eosin (HE) staining was performed to assess the renal tissue injury. Western blot was used to determine the relative expression levels of RBM3, Yes-associated protein 1(YAP1), nuclear factor E2-related factor 2(Nrf2), B cell-lymphoma-2(Bcl-2) and Bcl-2-associated X protein (Bax) in the kidney tissues. Immunohistochemical staining was employed to further detect the expression levels of RBM3 and YAP1 proteins. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was adopted to detect the cell apoptosis of kidney tissues. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were evaluated to determine the oxidative stress level of kidney tissues. Results Compared with the NC group, the serum creatinine level, the pathological injury score of kidney tissues and the expression levels of RBM3, YAP1 and Nrf2 proteins were significantly up-regulated, the Bcl-2/Bax ratio was considerably lower, the apoptosis rate was remarkably elevated, the MDA content was significantly increased and the SOD activity was dramatically reduced in the IRI and MHP groups (all P < 0.05). Compared with the IRI group, the serum creatinine level and the pathological injury score of kidney tissues were significantly decreased, the expression levels of RBM3, YAP1 and Nrf2 proteins were significantly up-regulated, the Bcl-2/Bax ratio was considerably higher, the apoptosis rate was significantly decreased, the MDA content was significantly decreased and the SOD activity was considerably elevated in the MHP group (all P < 0.05). Conclusions Mild hypothermia may exert protective effect upon renal IRI and it could alleviate cell apoptosis and oxidative stress injury induced by IRI, probably by up-regulating the expression level of RBM3 and its downstream effector molecules of YAP1 and Nrf2.

Protective Effect of Xiangsha Yuyang Decoction on Oxidative Injury in Rats with Gastric Ulcer Based on p62/Keap1/Nrf2 Signal Pathway / 中国实验方剂学杂志

Objective:To confirm the protective effect of Xiangsha Yuyang decoction on acetic acid-induced gastric ulcer model rats and explore its mechanism， so as to provide experimental basis for clinical drug use. Method:The 60 SPF Wistar rats were randomly divided into 6 groups： group， model group， high， middle and low dose groups of Xiangsha Yuyang decoction and omeprazole control group. The rat model of gastric ulcer was induced by acetic acid. The rats in the high， middle and low dose groups of Xiangsha Yuyang decoction were intragastrically administered at the dose of 28，14，7 g·kg^-1， and with omeprazole at the dose of 4.17 g·kg^-1in normal saline， respectively. The rats in the blank group and model group were intragastrically infused with the same volume of normal saline once a day. After 14 days of continuous treatment， the rats were killed， the blood was collected， the area and inhibition rate of gastric ulcer were measured and calculated， the histopathological sections of gastric mucosa were made and the state of gastric mucosal injury was observed， and the changes of gastric mucosal repair factor， gastric tissue related protein， oxidative stress factor and inflammatory factor in serum were detected by enzyme-linked immunosorbent assay（ELISA）. Detected the expression of p62 Kelch-like epichlorohydrin-related protein 1 （Keap1）， nuclear transcription factor E2 related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） signal pathway-related proteins in gastric mucosa by Western blot. Result:Compared with control group， the gastric mucosa of the model group showed obvious pathological changes and a large number of leukocytes infiltrated. In model group， the ulcer area was significantly increased（<italic>P</italic><0.01）， the contents of mucin mucoprotein 5AC （MUC5AC）， epidermal growth factor （EGF）， superoxide dismutase （SOD） and increased prostaglandin E₂ （PGE₂） were significantly decreased（<italic>P</italic><0.01）， the gastrin （GAS）， 8-hydroxydeoxyguanosine （8-OHdG）， malondialdehyde （MDA）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， cyclooxygenase-2 （COX-2） were significantly increased. The expression of HO-1 and Nrf2 protein decreased significantly（<italic>P</italic><0.01）， the content of Keap1 increased significantly （<italic>P</italic><0.05）， and the expression of p62 protein decreased. Compared with model group， the hierarchical structure of cells in Xiangsha Yuyang decoction high dose group and omeprazole group were clearer and regular， middle and low dose groups could also repair gastric mucosa to a certain extent. The high and middle dose groups of Xiangsha Yuyang decoction could significantly reduce the gastric ulcer area of acetic acid-induced gastric ulcer rat model （<italic>P</italic><0.01） and increase the ulcer inhibition rate. It can effectively promote the expression of MUC5AC and EGF in gastric mucosa， decrease the level of GAS（<italic>P</italic><0.05，<italic>P</italic><0.01）， decrease the level of 8-OHdG and MDA， increase the activity of SOD（<italic>P</italic><0.01）， decrease the expression level of TNF-<italic>α</italic> and COX-2， increase the content of PGE₂， and significantly increase the amount of Nrf2 and HO-1 protein in gastric mucosa（<italic>P</italic><0.01）. The high dose group of Xiangsha Yuyang decoction could decrease the protein expression of Keap1（<italic>P</italic><0.05） and increase the expression of p62 protein. Conclusion:Xiangsha Yuyang decoction is effective in the treatment of acetic acid-induced gastric ulcer model rats， which can effectively reduce the ulcer area， increase the ulcer inhibition rate and protect the ulcer tissue. Its mechanism may be related to activating p62/Keap1/Nrf2 signal pathway and regulating the expression of related genes so as to improve inflammatory response and regulate oxidative stress response.

Role of micronize purified flavonoid fraction and ethanol Graptophyllum pictum extract on experimental anal ulcer healing. Study on Wistar rat / Papel da fração flavonoica purificada micronizada e do extrato etanólico de Graptophyllum Pictum em experimento de cicatrização de úlcera anal. Estudo com ratos Wistar

ABSTRACT Aim of the study To evaluate the role of micronized purified flavanoid fraction and ethanol Graptophyllum pictum extract in the treatment of anal ulcer. Method Twenty-eight Wistar rats were randomly allocated into four groups. Groups 2, 3 and 4 the anus were induced with croton oil, but was not induced on group 1. Groups 1 and 2 were treated with normal saline, while groups 3 and 4 were treated with micronized purified flavanoid fraction, and ethanol G. pictum extract, respectively. On 9th days blood sample were taken from the retro-orbital region, and Wistar was killed by cervical dislocation under ether anesthesia. The anal canal was resected up 2 cm from anal opening, weighted, photographically taken to measure the percentage of residual ulcer, and then prepared for microscopic examination. Elisa methods were done for superoxide dismutase and malondialdedhyde. The total leukocyte in the anal specimen was counted under 400 magnification power. superoxide dismutase, anal coefficient, and total leukocyte for statistical analysis were using ANOVA and LSD, while malondialdedhyde and percentage of ulcers were using Kruskal-Wallis and Mann-Whitney. Result Treatment with ethanol G. pictum extract dose of 100 mg/kg BW significantly reduces the percentage of anal ulcer, the edema, leukocyte infiltration, and malondialdedhyde, and increase the superoxide dismutase in comparison without treatment. Treatment with micronized purified flavanoid fraction did not reduce the leukocyte, anal coefficient, and percentage of anal ulcer, only increase malondialdedhyde and decrease superoxide dismutase significantly.

RESUMO Objetivo do estudo Avaliar o papel da Fração Flavonoica Purificada Micronizada e do Extrato Etanólico de Graptophyllum pictum no tratamento de úlcera anal. Método Vinte e oito ratos Wistar foram randomicamente alocados em quatro grupos. Nos grupos 2, 3 e 4, indução com óleo de cróton foi realizada no ânus, excetuando-se o Grupo 1. Os grupos 1 e 2 foram tratados com solução salina normal, enquanto os grupos 3 e 4 foram tratados com fração flavonoica purificada micronizada e extrato etanólico de Graptophyllum pictum, respectivamente. No nono dia, amostras de sangue foram colhidas da região retroorbital, e o rato Wistar sofreu eutanásia por deslocamento cervical sob anestesia com éter. O canal anal foi ressecado até 2 cm da abertura anal, ponderado e fotografado para medir a porcentagem de úlcera residual e, em seguida, preparado para exame microscópico. Os métodos superoxide dismutase e malondialdedhyde do ensaio Elisa foram realizados. A contagem total de leucócitos foi realizada na amostra anal com ampliação de 400 vezes. ANOVA e LSD foram utilizados para a análise estatística de superoxide dismutase, coeficiente anal e número total de leucócitos, enquanto os testes de Kruskal-Wallis e Mann-Whitney foram utilizados para a análise de malondialdedhyde e porcentagem de úlceras. Resultado O tratamento com o extrato etanólico de Graptophyllum pictum (100 mg/kg de peso corporal) reduz de modo significativo a porcentagem de úlceras anais, o edema, a infiltração de leucócitos e o malondialdedhyde e aumenta a superoxide dismutase, comparado ao não tratamento. O tratamento com a fração flavonoica purificada micronizada não reduziu os leucócitos, o coeficiente anal e a porcentagem de úlceras anais, apenas aumentou o malondialdedhyde e diminuiu significativamente a superoxide dismutase.

Effects of TAT-SOD at Acupoints on Essential Hypertension by Monitoring Meridians Electrical Potential / 中国结合医学杂志

OBJECTIVES@#To investigate the effect on essential hypertension of the topical application of TAT-Cu, Zn-superoxide dismutase (TAT-SOD) at left acupoint Zusanli (ST 36), and to observe whether the change of electrical potential difference (EPD) can be related to the change of blood pressure.@*METHODS@#Sixteen patients with essential hypertension and 16 healthy subjects were included in the study. EPD between the left acupoints of Yanglingquan (GB 34) and Qiuxu (GB 40) was firstly screened out for the EPD detection. An intracellular superoxide quenching enzyme, TAT-SOD, was topically applied to the acupoint ST 36 within an area of 1 cm once a day, and the influence on EPD was investigated. The dosage applied to TAT-SOD group (n=8) was 0.2 mL of 3000 U/mL TAT-SOD cream prepared by adding purified TAT-SOD to a vehicle cream, while placebo group (n=8) used the vehicle cream instead. The left acupoints of Yanglingquan (GB 34) and Qiuxu (GB 40) were selected for EPD measurement after comparing EPD readings between 5 acupoints on each of all 12 meridians.@*RESULTS@#EPDs between the left acupoints of GB 34 and GB 40 for 16 patients of essential hypertension and 16 healthy subjects were 44.9±6.4 and 5.6±0.9 mV, respectively. Daily application of TAT-SOD for 15 days at ST 36 of essential hypertension patients significantly decreased systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 179.6 and 81.5 mm Hg to 153.1 and 74.1 mm Hg, respectively. Responding to the change in blood pressure, EPD between the left acupoints of GB 34 and GB 40 also declined from 44.4 to 22.8 mV with the same trend. No change was observed with SBP, DBP and EPD between the left acupoints of GB 34 and GB 40 with the daily application of the placebo cream.@*CONCLUSION@#Enzymatic scavenging of the intracellular superoxide at ST 36 proved to be effective in decreasing SBP and DBP. The results reconfirm the involvement of superoxide anions and its transportation along the meridians, and demonstrate that EPD between acupoints may be an indicator to reflect its functioning status. Moreover, preliminary results suggest a close correlation between EPD and blood pressure readings, implying a possibility of using EPD as a sensitive parameter for blood pressure and to monitor the effect of antihypertensive treatment.

Study on the Antioxidation and Anti-hypoxia Effects of Yuanshen Granule in Normal Mice / 中国药房

OBJECTIVE：To study the anti-oxidation and an ti-hypoxia effect of Yuanshen granule on normal mice. METHODS ： Totally 800 mice were randomly divided into blank control group ，Yuanshen granule low-dose ，middle-dose and high-dose groups （10，20，40 g/kg）and Hongjingtian oral liquid group （positive control ，2 mL/kg），with 160 mice in each group. Administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 30 d. Blank control group was given constant volume of normal saline by the same method. At 1st，3rd，7th，14th and 30th day after administration ，8 mice in each group at each time point were randomly selected for anoxia tolerance test under normobaric pressure and decompression ；the contents of MDA and SOD in myocardium and cerebral tissue were measured ；the hemolysis effect of red blood cell induced by H 2O2 was investigated. RESULTS ：Compared with blank control group ，the survival time of anoxia tolerance under normobaric pressure and under decompression （after 7 days of administration ）were prolonged significantly in Yuanshen granule groups （P＜0.05）. The contents of MDA in myocardium and cerebral tissue （after 3 or 7 days of administration ；after 3，7 or 14 days of administration ） were significantly decreased （P＜0.05），and the contents of SOD （after 7，14 or 30 days of administration ；after 7 days of administration）were increased significantly （P＜0.05）；the erythrocyte hemolysis rate （after 3 or 7 days of administration ）was significantly decreased （P＜0.05）. At some time points ，the improvement effect of the above indexes in the Yuanshen granule middle-dose and high-dose groups was significantly better than that of Hongjingtian oral liquid group （P＜0.05）. CONCLUSIONS ： Yuanshen granule can effectively prolong the hypoxia tolerance survival time of normal mice ，it has anti-oxidant and anti-hypoxia effects on normal mice ，and the effect of Yuanshen granule middle-dose and high-dose groups is better than that of Hongjingtian oral liquid group.

Growth and antioxidant response of juvenile oysters Crassostrea sikamea and Crassostrea corteziensis treated with Streptomyces strains / Crescimento e resposta oxidative de ostras jovens Crassostrea sikamea e Crassostrea corteziensis tratadas com cultura Streptomyces

The effect of three Streptomyces strains (N7, RL8 and V4) and a mixture of Bacillus (BMix) on the growth (Weight, Size) and superoxide dismutase activity (SOD) in hatchery-reared juvenile oysters Crassostrea corteziensis and Crassostrea sikamea was investigated to determine their probiotic potential. Microorganisms were added to culture water at 1×106 CFU/ml once a day during 30 days and all oysters fed daily a microalgae mix. Juveniles of C. sikamea treated with strains N7, RL8 and V4 had a significant weight gain compared to the control group. C. corteziensis juveniles treated with strains RL8 and BMix showed a significantly higher weight gain than the control group. No significant size increase was observed in any treated group for both oyster species. SOD activity significantly increased in C. sikamea treated with RL8 and with RL8, N7 and BMix in C. corteziensis. Streptomyces strains RL8 and N7 emerge as promising probiotic agents to cultivate C. sikamea and C. corteziensis and may also be useful to other molluscs and marine invertebrates .(AU)

O efeito de três culturas Streptomyces (N7, RL8 e V4) e uma mistura de Bacillus (BMix) sobre o cresimento (Peso, Tamanho) e atividade superóxido dismutase (SOD) em ostras jovens Crassostrea corteziensis e Crassostrea sikamea cultivadas artificalmente foi investigado para determinar seu potencial probiótico. Microorganismos foram adicionados à água de cultura a 1×10 6 CFU/ml uma vez por dia durante 30 dias e todas as ostras foram alimentadas diariamente com uma mistura de microalgas. Jovens C. sikamea tratados com culturas N7, RL8 e V4 tiveram ganho de peso significativo quando comparado ao grupo de controle. Jovens C. corteziensis tratados com culturas RL8 e BMix demonstraram peso significativamente mais algo que o grupo de controle. Nenhum aumento em tamanho foi observado em grupos tratados em ambas espécies. A atividade SOD foi significamente aumentada em C. sikamea treatado com RL8 e com RL8, N7 e BMix em C. corteziensis. Culturas Streptomyces RL8 e N7 surgem como agentes probióticos promissores para o cultivo de C. sikamea e C. corteziensis e podem ser úteis para outros moluscos animais marinhos invertebrados.(AU)