Further isolation of antioxidative (+)-1-hydroxypinoresinol-1-O-β-d-glucoside from the rhizome ofSalvia miltiorrhiza that acts on peroxynitrite, total ROS and 1,1-diphenyl-2-picrylhydrazyl radical

2003 ◽  
Vol 26 (1) ◽  
pp. 24-27 ◽  
Author(s):  
Hye Sook Kang ◽  
Hae Young Chung ◽  
Dae Seok Byun ◽  
Jae Sue Choi
Keyword(s):  
Total Ros

Phase Ib, international, dose-escalation study to evaluate the safety, pharmacokinetics (PK) and efficacy of ST-617 for the attenuation of oral mucositis (OM) in patients receiving chemoradiation (CRT) for head and neck (H&N) cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6075-6075
Author(s):  
Daniel Osei-Fofie ◽  
Julie Wetter ◽  
Greg A. Landers ◽  
Peter Alfred Kraus ◽  
Shawgi Sukumaran ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Critical Event ◽  
Tumor Control ◽  
Dose Escalation Study ◽  
Double Blind ◽  
Safety Issues ◽  
Treatment Interruptions ◽  
Treatment Safety ◽  
Historical Controls ◽  
Total Ros

6075 Background: OM is a common, painful, and costly toxicity associated with cytotoxic regimens used to treat H&N cancers, which may result in radiotherapy treatment interruptions to negatively impact tumor control. There are currently no approved interventions to successfully prevent or delay OM onset among patients being treated with radiation therapy, with or without concomitant chemotherapy (CRT). Oxidative stress is a critical event in OM’s pathogenesis. Through its effect on Nrf2, ST-617 has marked anti-oxidative activity/properties. Supportive Therapeutics is developing ST-617, a dithioethione, for the attenuation of OM onset, duration and severity. The objective of this trial was to assess the safety, tolerability, PK, PD and efficacy of ST-617 in patients at high risk of severe OM (SOM). Methods: A dose escalation trial in which ST-617 administered as an oral suspension, 1-2 hours before the administration of daily RT fractions was performed at 9 study sites in South Africa and Australia. Eighteen patients with diagnoses of oral or oropharyngeal CA were enrolled (up to 6 pts/dose). Patients received concomitant cisplatin either weekly or tri-weekly. ST-617 was administered 3 days prior to CRT, and then continuing daily until the end of treatment. Safety outcomes, using CTCAE criteria (v 4.03) were used. Dose escalation occurred in the absence of toxicity. OM occurrence and severity were assessed by trained and validated evaluators using WHO, NCI-CTC and RTOG criteria; scores were centrally assigned. The primary efficacy endpoints included the incidence and duration of SOM (WHO grades 3 or 4) vs historical controls. PD tracking measured total ROS/RNS, GSH/GSSG, regulation in plasma and buccal epithelial cells. Results: 17 pts completed the 50, 100 and 150mg/day with no safety issues. No early dose limiting toxicity (DLT) or serious Adverse Event linked to ST-617 were observed. AEs observed were mainly nausea which is usually associated with CRT as expected. The 100 mg/day dose has been well tolerated with no grade 4 OM. No CRT dose interruptions or delays due to OM has been observed. Total ROS/RNS levels in plasma and buccal samples show significant decrease with increased ST-617 dosing from 50 to 100 mg/day. Conclusions: ST-617 administration was safe at all doses tested. The course and severity of patients treated with ST-617 compared favorably with historical controls. Mechanistic correlation between ROS/RNS levels was seen. A randomized, controlled, double blind trial is planned with the recommended dose of 100mg/day. Clinical trial information: 20180138.

scholarly journals Ballodiolic Acid A and B: Two New ROS, (•OH), (ONOO−) Scavenging and Potent Antimicrobial Constituents Isolated from Ballota pseudodictamnus (L.) Benth.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 402
Author(s):  
Fozia ◽  
Asmat Shaheen ◽  
Ijaz Ahmad ◽  
Syed Badar Amin ◽  
Nisar Ahmad ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Inhibition Zone ◽  
2D Nmr ◽  
Scavenging Activity ◽  
Bacterial Strains ◽  
Activity Test ◽  
Ic50 Values ◽  
Chemical Studies ◽  
Antibacterial And Antifungal ◽  
Total Ros

Bioassays guided phytochemical investigations on the ethyl acetate-soluble fraction of the root material of Ballota pseudodictamnus (L.) Benth. led to the isolation of two new compounds, ballodiolic acid A (1) and ballodiolic acid B (2), along with three known compounds ballodiolic acid (3), ballotenic acid (4), and β-amyrin (5), which were also isolated for the first time from this species by using multiple chromatographic techniques. The structures of the compounds (1–5) were determined by modern spectroscopic analysis including 1D and 2D NMR techniques and chemical studies. In three separate experiments, the isolated compounds (1–5) demonstrated potent antioxidant scavenging activity, with IC50 values ranging from 07.22–34.10 μM in the hydroxyl radical (•OH) inhibitory activity test, 58.10–148.55 μM in the total ROS (reactive oxygen species) inhibitory activity test, and 6.23–69.01 μM in the peroxynitrite (ONOO-) scavenging activity test. With IC50 values of (07.22 ± 0.03, 58.10 ± 0.07, 6.23 ± 0.04 μM) for •OH, total ROS, and scavenge ONOO-, respectively, ballodiolic acid B (2) showed the highest scavenging ability. Antibacterial and antifungal behaviors were also exposed to the pure compounds 1–5. In contrast to compound 5 and 4, compounds 1, 2, and 3 were active against all bacterial strains studied, with a good zone of inhibition proving these as a potent antibacterial agent. Similarly, compared to compounds 3–5, compounds 2 and 1 with a 47 percent and 45 percent respective inhibition zone were found to be more active against tested fungal strains.

scholarly journals Activation of Aflatoxin Biosynthesis Alleviates Total ROS in Aspergillus parasiticus

Toxins ◽  
2018 ◽  
Vol 10 (2) ◽  
pp. 57 ◽  
Author(s):  
Gabriel Kenne ◽  
Phani Gummadidala ◽  
Mayomi Omebeyinje ◽  
Ananda Mondal ◽  
Dominic Bett ◽  
...  
Keyword(s):  
Aspergillus Parasiticus ◽  
Aflatoxin Biosynthesis ◽  
Total Ros

scholarly journals Statin therapy lowers muscle sympathetic nerve activity and oxidative stress in patients with heart failure

2012 ◽  
Vol 303 (3) ◽  
pp. H377-H385 ◽  
Author(s):  
Shekhar H. Deo ◽  
James P. Fisher ◽  
Lauro C. Vianna ◽  
Areum Kim ◽  
Anand Chockalingam ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Statin Therapy ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Standard Drug ◽  
And Oxidative Stress ◽  
Total Ros

Despite standard drug therapy, sympathetic nerve activity (SNA) remains high in heart failure (HF) patients making the sympathetic nervous system a primary drug target in the treatment of HF. Studies in rabbits with pacing-induced HF have demonstrated that statins reduce resting SNA, in part, due to reductions in reactive oxygen species (ROS). Whether these findings can be extended to the clinical setting of human HF remains unclear. We first performed a study in seven statin-naïve HF patients (56 ± 2 yr; ejection fraction: 31 ± 4%) to determine if 1 mo of simvastatin (40 mg/day) reduces muscle SNA (MSNA). Next, to control for possible placebo effects and determine the effect of simvastatin on ROS, a double-blinded, placebo-controlled crossover design study was performed in six additional HF patients (51 ± 3 yr; ejection fraction: 22 ± 4%), and MSNA, ROS, and superoxide were measured. We tested the hypothesis that statin therapy decreases resting MSNA in HF patients and this would be associated with reductions in ROS. In study 1, simvastatin reduced resting MSNA (75 ± 5 baseline vs. 65 ± 5 statin bursts/100 heartbeats; P < 0.05). Likewise, in study 2, simvastatin also decreased resting MSNA (59 ± 5 placebo vs. 45 ± 6 statin bursts/100 heartbeats; P < 0.05). In addition, statin therapy significantly reduced total ROS and superoxide. As expected, cholesterol was reduced after simvastatin. Collectively, these findings indicate that short-term statin therapy concomitantly reduces resting MSNA and total ROS and superoxide in HF patients. Thus, in addition to lowering cholesterol, statins may also be beneficial in reducing sympathetic overactivity and oxidative stress in HF patients.

scholarly journals Baicalin ameliorates atherosclerosis by inhibiting NLRP3 inflammasome in apolipoprotein E-deficient mice

2020 ◽  
Vol 17 (6) ◽  
pp. 147916412097744
Author(s):  
Jingfei Zhao ◽  
Zhengtang Wang ◽  
Zhilu Yuan ◽  
Shuzhen Lv ◽  
Qingbo Su
Keyword(s):  
Apolipoprotein E ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Ros Production ◽  
Mice Model ◽  
Pyrin Domain ◽  
Plaque Area ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammation ◽  
Total Ros

Background: NLR family pyrin domain containing 3 (NLRP3) inflammasome has been implicated in the development of atherosclerosis and several studies have suggested that inhibiting NLRP3 inflammasome could be a potential therapeutic approach to treat atherosclerosis. Baicalin is a flavone glycoside with anti-inflammation, anti-oxidative activities. The inhibition of NLRP3 inflammasome activation by baicalin has also been described. Therefore, the effects of baicalin on NLRP3 inflammasome activation and atherosclerosis were evaluated in present study. Methods: We established the apolipoprotein E-deficient atherosclerosis mice model. After baicalin treatment, the IL-1, IL-18, and reactive oxygen species (ROS) production, and the plaque area was monitored. We also measured the NLRP3, ASC, caspase-1, ICAM-1, and VCAM-1 expression in atherosclerosis mice after baicalin treatment. We silenced NLRP3 by administration of lentivirus expressing NLRP3 shRNA to atherosclerosis mice and monitored the IL-1, IL-18, and ROS production, and NLRP3 inflammasome activation. Results: Baicalin remarkably inhibited the production of IL-1, IL-18, mitochondria ROS, total ROS, ICAM-1, and VCAM-1. Baicalin reduced the expression of NLRP3 inflammasome and suppressed its activation. Baicalin significantly reduced the plaque area. Silencing NLRP3 resulted in decreased production of IL-1, IL-18, mitochondria ROS, total ROS, ICAM-1, and VCAM-1, and inhibition of NLRP3 inflammasome activation. Conclusion: Baicalin ameliorated atherosclerosis by inhibiting NLRP3 inflammasome.

scholarly journals The 26S Proteasome Regulatory Subunit GmPSMD Promotes Resistance to Phytophthora sojae in Soybean

2021 ◽  
Vol 12 ◽  
Author(s):  
Tengfei Liu ◽  
Huiyu Wang ◽  
Zhanyu Liu ◽  
Ze Pang ◽  
Chuanzhong Zhang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Antioxidant Enzymes ◽  
Hairy Roots ◽  
Phytophthora Sojae ◽  
26S Proteasome ◽  
Regulatory Subunit ◽  
Bhlh Transcription Factor ◽  
Transgenic Soybean ◽  
Ros Scavenging ◽  
Total Ros

Phytophthora root rot, caused by Phytophthora sojae is a destructive disease of soybean (Glycine max) worldwide. We previously confirmed that the bHLH transcription factor GmPIB1 (P. sojae-inducible bHLH transcription factor) reduces accumulation of reactive oxygen species (ROS) in cells by inhibiting expression of the peroxidase-related gene GmSPOD thus improving the resistance of hairy roots to P. sojae. To identify proteins interacting with GmPIB1 and assess their participation in the defense response to P. sojae, we obtained transgenic soybean hairy roots overexpressing GmPIB1 by Agrobacterium rhizogenes mediated transformation and examined GmPIB1 protein–protein interactions using immunoprecipitation combined with mass spectrometry. We identified 392 proteins likely interacting with GmPIB1 and selected 20 candidate genes, and only 26S proteasome regulatory subunit GmPSMD (Genbank accession no. XP_014631720) interacted with GmPIB1 in luciferase complementation and pull-down experiments and yeast two-hybrid assays. Overexpression of GmPSMD (GmPSMD-OE) in soybean hairy roots remarkably improved resistance to P. sojae and RNA interference of GmPSMD (GmPSMD -RNAi) increased susceptibility. In addition, accumulation of total ROS and hydrogen peroxide (H2O2) in GmPSMD-OE transgenic soybean hairy roots were remarkably lower than those of the control after P. sojae infection. Moreover, in GmPSMD-RNAi transgenic soybean hairy roots, H2O2 and the accumulation of total ROS exceeded those of the control. There was no obvious difference in superoxide anion (O2–) content between control and transgenic hairy roots. Antioxidant enzymes include peroxidase (POD), glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT) are responsible for ROS scavenging in soybean. The activities of these antioxidant enzymes were remarkably higher in GmPSMD-OE transgenic soybean hairy roots than those in control, but were reduced in GmPSMD-RNAi transgenic soybean hairy roots. Moreover, the activity of 26S proteasome in GmPSMD-OE and GmPIB1-OE transgenic soybean hairy roots was significantly higher than that in control and was significantly lower in PSMD-RNAi soybean hairy roots after P. sojae infection. These data suggest that GmPSMD might reduce the production of ROS by improving the activity of antioxidant enzymes such as POD, SOD, GPX, CAT, and GmPSMD plays a significant role in the response of soybean to P. sojae. Our study reveals a valuable mechanism for regulation of the pathogen response by the 26S proteasome in soybean.

Abstract 327: NADPH Oxidase-dependent Signaling Involved In Endothelial Cell Survival And Proliferation: Role Of Nox2 And Nox4

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Hitesh Peshavariya ◽  
Stavros Selemidis ◽  
Grant Drummond ◽  
Fan Jiang ◽  
Gregory J Dusting
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Nadph Oxidase ◽  
Therapeutic Angiogenesis ◽  
Trypan Blue Exclusion ◽  
Catalytic Subunits ◽  
Akt Phosphorylation ◽  
Oxidase Enzyme ◽  
Total Ros

Objective: Endothelial cells (EC) produce a variety of reactive oxygen species (ROS) which act as mediators of signaling for proliferation, migration, differentiation and cell death. The major source of ROS in EC at rest is the NADPH oxidase enzyme complex. We aimed to determine the roles of the Nox2 and Nox4 catalytic subunits of NADPH oxidase in proliferation and survival of human microvascular endothelial cells (HMEC-1). Methods: Intracellular superoxide was measured by dihydroethidium fluorescence and lucigenin chemiluminescence, and total ROS by dichlorodihydrofluorescein-diacetate assay. Nox4 and Nox2 protein expression was measured by Western blot, and cell proliferation was quantitated by trypan blue exclusion and a tetrazolium-based MTS assay. EC survival was measured by caspase3/7 activity. Results: The expression of Nox4 (but not Nox2) protein, superoxide and total ROS, were all significantly higher (P < 0.05, N = 4) under proliferative conditions (sparse culture or serum addition) than in quiescent (dense culture or serum-starved) cells. Suppression of NADPH oxidase-derived ROS with specific siRNA significantly reduced cell proliferation as shown below. Under proliferative conditions phosphorylation of ERK and Akt were increased. Suppression of Nox4-derived ROS production reduced the phosphorylation of both ERK and Akt, whereas suppression of Nox2 reduced only Akt phosphorylation. Further, suppression of Nox2, but not Nox4, significantly activated caspase3/7 (P < 0.05, N = 4). Thus Nox4-derived ROS act to promote proliferation of EC via ERK and Akt signaling, whereas Nox2 prevents apoptotic signaling via Akt and caspase3/7. Conclusion: Nox isoform-derived ROS act via distinct signaling pathways to promote EC proliferation and survival. Selective modulation of Nox-type NADPH oxidase could be a useful approach for blocking angiogenesis or for therapeutic angiogenesis in chronic ischemia or tissue engineering.

Neutrophil Hyper-responsiveness in Periodontitis

2007 ◽  
Vol 86 (8) ◽  
pp. 718-722 ◽  
Author(s):  
J.B. Matthews ◽  
H.J. Wright ◽  
A. Roberts ◽  
N. Ling-Mountford ◽  
P.R. Cooper ◽  
...  
Keyword(s):  
Matched Control ◽  
Ros Generation ◽  
Ros Production ◽  
Fcγ Receptor ◽  
Blood Neutrophils ◽  
And Control ◽  
Reduced Activity ◽  
Peripheral Neutrophil ◽  
Post Therapy ◽  
Total Ros

Peripheral neutrophil hyper-responsiveness in chronic periodontitis leads to excessive reactive oxygen species (ROS) production. We aimed to determine whether neutrophil hyper-responsiveness was constitutive or reactive, and to discover the effect of non-surgical therapy. Peripheral blood neutrophils from patients (n = 19), before and 3 months after therapy, and matched control individuals were Fcγ-receptor-stimulated with/without priming with P. gingivalis and F. nucleatum. Total and extracellular ROS were determined by luminol/isoluminol chemiluminescence. The high total ROS generation of patients’ neutrophils compared with that of control individuals ( P = 0.016) continued at a reduced level post-therapy ( P = 0.059). Reduced activity post-therapy was also seen with priming. Unstimulated total ROS levels did not differ between patients and control individuals before or after therapy. However, the high unstimulated, extracellular ROS production by patients’ neutrophils compared with control individuals ( P < 0.05) continued post-therapy and was unaffected by priming. Therapy reduced Fcγ-receptor-stimulated total ROS production, but not unstimulated extracellular radical release, suggesting that constitutive and reactive mechanisms underlie neutrophil hyper-responsiveness.

Inhibitory activity of flavonoids fromPrunus davidiana and other flavonoids on total ROS and hydroxyl radical generation

2003 ◽  
Vol 26 (10) ◽  
pp. 809-815 ◽  
Author(s):  
Hyun Ah Jung ◽  
Mee Jung Jung ◽  
Ji Young Kim ◽  
Hae Young Chung ◽  
Jae Sue Choi
Keyword(s):  
Hydroxyl Radical ◽  
Inhibitory Activity ◽  
Radical Generation ◽  
Total Ros
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