scholarly journals Indigo Naturalis Suppresses Colonic Oxidative Stress and Th1/Th17 Responses of DSS-Induced Colitis in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Hai-tao Xiao ◽  
Jiao Peng ◽  
Bo Wen ◽  
Dong-dong Hu ◽  
Xiao-peng Hu ◽  
...  

Indigo naturalis (also known as Qing-dai, or QD), a traditional Chinese medicine, has been widely used as an anticolitis regimen in the clinical practice of Chinese medicine. However, the precise mechanisms behind its efficacy remain unknown. We investigated the protective effects and associated molecular mechanisms of QD in DSS-induced colitis in mice. We found that QD administration attenuated DSS-induced colon shortening, tissue damage, and the disease activity index during the onset of colitis. Moreover, QD administration significantly suppressed colonic MPO activity and increased the activities of colonic T-SOD, CAT, and GSH-Px, as well the expression of p-AMPK and Nrf-2 in colon tissues of colitic mice. In addition, QD was capable of reducing the colonic Th1 and Th17 cell cytokines, the frequencies of Th1 and Th17 cells, and the phosphorylation of p-STAT1 and p-STAT3 in the mesenteric lymph nodes of colitic mice. An in vitro assay showed that QD significantly suppressed the differentiation of Th1 and Th17 cells. These findings suggest that QD has the potential to alleviate experimental colitis by suppressing colonic oxidative stress and restraining colonic Th1/Th17 responses, which are associated with activating AMPK/Nrf-2 signals and inhibiting STAT1/STAT3 signals, respectively. These findings also support QD as an effective regimen in the treatment of IBD.

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Ana L. Colín-González ◽  
Ricardo A. Santana ◽  
Carlos A. Silva-Islas ◽  
Maria E. Chánez-Cárdenas ◽  
Abel Santamaría ◽  
...  

Aged garlic extract (AGE) is an odorless garlic preparation containing S-allylcysteine (SAC) as its most abundant compound. A large number of studies have demonstrated the antioxidant activity of AGE and SAC in bothin vivo—in diverse experimental animal models associated to oxidative stress—andin vitroconditions—using several methods to scavenge reactive oxygen species or to induce oxidative damage. Derived from these experiments, the protective effects of AGE and SAC have been associated with the prevention or amelioration of oxidative stress. In this work, we reviewed different antioxidant mechanisms (scavenging of free radicals and prooxidant species, induction of antioxidant enzymes, activation of Nrf2 factor, inhibition of prooxidant enzymes, and chelating effects) involved in the protective actions of AGE and SAC, thereby emphasizing their potential use as therapeutic agents. In addition, we highlight the ability of SAC to activate Nrf2 factor—a master regulator of the cellular redox state. Here, we include original data showing the ability of SAC to activate Nrf2 factor in cerebral cortex. Therefore, we conclude that the therapeutic properties of these molecules comprise cellular and molecular mechanisms at different levels.


2014 ◽  
Vol 37 (1) ◽  
pp. 1 ◽  
Author(s):  
Yunmin Lu ◽  
Meiying Zhu ◽  
Wei Chen ◽  
Li Yin ◽  
Jinshui Zhu ◽  
...  

Purpose: Tetramethylpyrazine (TMP) is an effective Chinese plant-derived medicine for colitis in the clinic, but the underlying molecular mechanisms of its use remain poorly understood. The purpose of this study was to investigate the mechanisms involved in its therapeutic action. Methods: A colitis mouse model was induced by oxazolone enema. TMP was administered at 80 mg/kg/day and sulphasalazine (SASP) was used as positive control and administered at 100 mg/kg/day for the treatment of colitis. On the fourth day after enema, mice were sacrificed. The inflammatory response was assessed by the disease activity index and histology. Colon mucosa was isolated and biochemically analyzed. In addition, in vitro studies were performed to evaluate the activity of TMP in Caco-2 cells. Results: Our results showed that TMP improved the colonic inflammatory status as evidenced by histological findings, as well as SASP. These effects were associated with a decrease in nucleus translocation of NF-κB. Paired with this inhibitive activity, there was a decrease in downstream signaling, such as C-MYC, iNOS and COX-2. In vitro assays revealed that TMP inhibited NF-κB translocation and its downstream production of inflammatory factors, such as TNF-α, IL-6 and IL-8, and that ROS production that was induced by LPS in Caco-2 cells. Conclusion: TMP improved the colitis induced by oxazoline, and its activity was associated with inhibition of NF-κB translocation, and subsequent inhibition of pro-inflammatory factor production and oxidative stress.


2021 ◽  
Author(s):  
Shouhai Wu ◽  
Tongxiang Lin ◽  
Yang Xu

Abstract BackgroundPaBing-II Formula (PB-II) is a traditional Chinese medicine developed to treat Parkinson's disease (PD). However, due to the complexity of PB-II and the difficulty of culturing human dopaminergic neurons (DAn) in vitro, the mechanism of PB-II to treat PD remains unclear. MethodsWe established the human induced pluripotent stem cells (iPSCs) and derived DAn from hiPSCs to study the protective effects of PB-II on DAn after oxidative stress, which plays an important role in PD pathogenesis. ResultsWe found that serum derived from rats that had ingested PB-II significantly protect hiPSC-derived DAn from reactive oxygen species (ROS). In addition, PB-II dependent serum can activate nuclear erythroid-derived factor 2 (Nrf2) responses, which are required for the neutralization of ROS. In addition, PB-II can activate the Nrf2/ARE signal pathway of midbrain dopaminergic neurons of PD rats induced with 6-hydroxydopamine (6-OHDA) injury, rescue DAn cells, and improve the symptoms of PD rats. ConclusionsPB-II significantly protects the DA neurons from oxidative stress by activating the Nrf2 pathway.


2018 ◽  
Vol 1 (1) ◽  
pp. 1-20 ◽  
Author(s):  
Sudeshna Paul ◽  
Shamreen Naaz ◽  
Arnab Kumar Ghosh ◽  
Sanatan Mishra ◽  
Aindrila Chattopadhyay ◽  
...  

Oxidative stress is an important causative factor for a number of diseases. Phenylhydrazine (PHZ) is a widely accepted model for studying hemolytic anemia by induction of oxidative stress. In the present study, goat red blood cells (RBCs) were incubated in vitro with PHZ (1mM) to generate oxidative stress. To test whether melatonin exhibits protective effects on PHZ induced RBC damage and to explore its potential molecular mechanisms, different concentrations of melatonin (5, 10, 20 and 40 nmoles/ml) were also included. PHZ caused altered profiles on biomarkers of oxidative stress and antioxidative as well as glucose metabolic enzymes in RBCs. These alterations indicated a development of oxidative stress. Melatonin at a concentration of 40 nmoles/ml provided optimal protection against all alterations induced by PHZ. The important cellular membrane proteins, including spectrin and actin, were also damaged by PHZ and this led to RBC deformation similar to that of observed in severe β-thalassaemia; the RBC deformation was also prevented by melatonin. Binding profiles of melatonin with PHZ and ferrous iron indicated favorable binding of melatonin with both of them, respectively. Thus, in addition to the direct antioxidant and free radical scavenging capability, melatonin also inhibited iron overloading by chelating iron and binding with the PHZ. This action of melatonin further reduces free radical generation. Based on the results, melatonin may provide therapeutic relevance to ß-thalassemia and other hemolytic RBC disorders involving oxidative stress. 


2020 ◽  
Vol 2020 ◽  
pp. 1-18 ◽  
Author(s):  
Zhao Deng ◽  
Qi Liu ◽  
Miaomiao Wang ◽  
Hong-Kui Wei ◽  
Jian Peng

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. Nur77, belongs to the NR4A subfamily of nuclear hormone receptors, plays a critical role in controlling the pathology of colitis. The aim of this study is to investigate the protection effect and mechanism of Gly-Pro-Ala (GPA) peptide, isolated from fish skin gelatin hydrolysate, in a mouse model of dextran sulfate sodium- (DSS-) induced colitis and intestinal epithelial cells (IECs) stimulated by lipopolysaccharide (LPS). In vivo, GPA treatment alleviates DSS-induced weight loss, disease activity index (DAI) increase, colon length shortening, and colonic pathological damage. Production of proinflammatory cytokines, ROS, and MDA is significantly decreased by GPA treatment. In vitro, GPA significantly inhibits proinflammatory cytokine production, cytotoxicity, ROS, and MDA in IECs. Furthermore, GPA induces autophagy to suppress inflammation and oxidative stress. GPA promotes Nur77 translocation from the nucleus to mitochondria where it facilitates Nur77 interaction with TRAF6 and p62, leading to the induction of autophagy. In addition, GPA contributed to the maintenance of tight junction architecture in vivo and in vitro. Taken together, GPA, as a Nur77 modulator, could exert anti-inflammatory and antioxidant effects by inducing autophagy in IECs, suggesting that GPA may be promising for the prevention of colitis.


2020 ◽  
Vol 1 (2) ◽  
pp. 51-74 ◽  
Author(s):  
Noel C. Salvoza ◽  
Pablo J. Giraudi ◽  
Claudio Tiribelli ◽  
Natalia Rosso

Non-alcoholic fatty liver disease (NAFLD) remains a major cause of chronic liver disease worldwide. Despite extensive studies, the heterogeneity of the risk factors as well as different disease mechanisms complicate the goals toward effective diagnosis and management. Recently, it has been shown that sex differences play a role in the prevalence and progression of NAFLD. In vitro, in vivo, and clinical studies revealed that the lower prevalence of NAFLD in premenopausal as compared to postmenopausal women and men is mainly due to the protective effects of estrogen and body fat distribution. It has been also described that males and females present differential pathogenic features in terms of biochemical profiles and histological characteristics. However, the exact molecular mechanisms for the gender differences that exist in the pathogenesis of NAFLD are still elusive. Lipogenesis, oxidative stress, and inflammation play a key role in the progression of NAFLD. For NAFLD, only a few studies characterized these mechanisms at the molecular level. Therefore, we aim to review the reported differential molecular mechanisms that trigger such different pathogenesis in both sexes. Differences in lipid metabolism, glucose homeostasis, oxidative stress, inflammation, and fibrosis were discussed based on the evidence reported in recent publications. In conclusion, with this review, we hope to provide a new perspective for the development of future practice guidelines as well as a new avenue for the management of the disease.


Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2748
Author(s):  
Kirti Parwani ◽  
Farhin Patel ◽  
Dhara Patel ◽  
Palash Mandal

Increased blood glucose in diabetic individuals results in the formation of advanced glycation end products (AGEs), causing various adverse effects on kidney cells, thereby leading to diabetic nephropathy (DN). In this study, the antiglycative potential of Swertiamarin (SM) isolated from the methanolic extract of E. littorale was explored. The effect of SM on protein glycation was studied by incubating bovine serum albumin with fructose at 60 °C in the presence and absence of different concentrations of swertiamarin for 24 h. For comparative analysis, metformin was also used at similar concentrations as SM. Further, to understand the role of SM in preventing DN, in vitro studies using NRK-52E cells were done by treating cells with methylglyoxal (MG) in the presence and absence of SM. SM showed better antiglycative potential as compared to metformin. In addition, SM could prevent the MG mediated pathogenesis in DN by reducing levels of argpyrimidine, oxidative stress and epithelial mesenchymal transition in kidney cells. SM also downregulated the expression of interleukin-6, tumor necrosis factor-α and interleukin-1β. This study, for the first time, reports the antiglycative potential of SM and also provides novel insights into the molecular mechanisms by which SM prevents toxicity of MG on rat kidney cells.


2018 ◽  
Vol 15 (4) ◽  
pp. 345-354 ◽  
Author(s):  
Barbara D'Orio ◽  
Anna Fracassi ◽  
Maria Paola Cerù ◽  
Sandra Moreno

Background: The molecular mechanisms underlying Alzheimer's disease (AD) are yet to be fully elucidated. The so-called “amyloid cascade hypothesis” has long been the prevailing paradigm for causation of disease, and is today being revisited in relation to other pathogenic pathways, such as oxidative stress, neuroinflammation and energy dysmetabolism. The peroxisome proliferator-activated receptors (PPARs) are expressed in the central nervous system (CNS) and regulate many physiological processes, such as energy metabolism, neurotransmission, redox homeostasis, autophagy and cell cycle. Among the three isotypes (α, β/δ, γ), PPARγ role is the most extensively studied, while information on α and β/δ are still scanty. However, recent in vitro and in vivo evidence point to PPARα as a promising therapeutic target in AD. Conclusion: This review provides an update on this topic, focussing on the effects of natural or synthetic agonists in modulating pathogenetic mechanisms at AD onset and during its progression. Ligandactivated PPARα inihibits amyloidogenic pathway, Tau hyperphosphorylation and neuroinflammation. Concomitantly, the receptor elicits an enzymatic antioxidant response to oxidative stress, ameliorates glucose and lipid dysmetabolism, and stimulates autophagy.


2021 ◽  
Vol 11 (8) ◽  
pp. 3637
Author(s):  
Jun-Ho Chang ◽  
Dae-Won Kim ◽  
Seong-Gon Kim ◽  
Tae-Woo Kim

Damaged dental pulp undergoes oxidative stress and 4-hexylresorcinol (4HR) is a well-known antioxidant. In this study, we aimed to evaluate the therapeutic effects of a 4HR ointment on damaged dental pulp. Pulp cells from rat mandibular incisor were cultured and treated with 4HR or resveratrol (1–100 μM). These treatments (10–100 μM) exerted a protective effect during subsequent hydrogen peroxide treatments. The total antioxidant capacity and glutathione peroxidase activity were significantly increased following 4HR or resveratrol treatment (p < 0.05), while the expression levels of TNF-α and IL1β were decreased following the exposure to 4HR pre-treatment in an in vitro model. Additionally, the application of 4HR ointment in an exposed dental pulp model significantly reduced the expression of TNF-α and IL1β (p < 0.05). Conclusively, 4HR exerted protective effects against oxidative stress in dental pulp tissues through downregulating TNF-α and IL1β.


2021 ◽  
pp. 153537022110091
Author(s):  
Yanhong Si ◽  
Hua Tian ◽  
Bingqing Dong ◽  
Ying Zhang ◽  
Yuanyuan Wen ◽  
...  

Oxidative stress and inflammation are closely related to atherosclerotic cardiovascular disease. It is established that hydrogen has significant protective effects on many diseases as a potential antioxidative and anti-inflammatory agent. The purpose of this study is to evaluate the effect of hydrogen on unstable angina in vitro and in vivo. An atherosclerosis model in vitro was constructed by ox-LDL-induced injury of human umbilical vein endothelial cells and in vitro testing indicated hydrogen inhibited ox-LDL-induced oxidative stress and inflammatory response by down-regulating LOX-1/NF-kB signaling pathway. Subsequently, the attenuating effect of hydrogen-rich water intake on unstable angina was further confirmed in clinic. Forty hospitalized subjects with unstable angina were enrolled and consumed either 1000–1200 mL/d hydrogen-rich water or the same amount of placebo pure water in addition to conventional drugs for three months. Clinical analysis showed hydrogen-rich water intake relieved angina symptoms in unstable angina patients. Serum analysis showed that hydrogen-rich water addition resulted in more effective reductions of total-cholesterol, low-density lipoprotein-cholesterol, and apolipoprotein B levels compared with conventional treatment. These results support that hydrogen as adjuvant treatment has a beneficial effect on unstable angina.


Sign in / Sign up

Export Citation Format

Share Document