scholarly journals Ophiopogonin A Alleviates Hemorrhagic Shock-Induced Renal Injury via Induction of Nrf2 Expression

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoming Sheng ◽  
Yang Yang ◽  
JiaJia Liu ◽  
Junbo Yu ◽  
Qingsong Guo ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Renal Injury ◽  
Cell Model ◽  
Tunel Staining ◽  
Related Factor ◽  
Tnf Α ◽  
Wide Range ◽  
Ophiopogon Japonicus

Ophiopogonin, including Ophiopogonin A, B, C, D, is an effective active component of traditional Chinese medicine Ophiopogon japonicus which has a wide range of pharmacological effects such as protecting myocardial ischemia, resisting myocardial infarction, immune regulation, lowering blood glucose, and anti-tumor. However, the functions of ophiopogonin A on hemorrhagic shock (HS)-induced renal injury remain unclear. First, this study constructed an HS rat model and hypoxia HK-2 cell model to assess the effects of ophiopogonin A in vivo and in vitro. In vivo, HE and TUNEL staining show that ophiopogonin A dose-dependently inhibits HS-induced tissue damage and apoptosis. Moreover, ophiopogonin A dose-dependently downregulates the levels of blood urea nitrogen (BUN), creatinine (Cr), KIM-1, NGAL, iNOS, TNF-α, IL-1β, and IL-6 in HS rats kidney tissues, and decreases the number of MPO-positive cells. In vitro, we get similar results that ophiopogonin A dose-dependently improves hypoxia-induced HK-2 cell apoptosis and damage. In addition, ophiopogonin A dose-dependently increases the expression of NF E2-related factor 2 (Nrf2), while knockdown of Nrf2 reverses the functions of ophiopogonin A in vivo and in vitro. Furthermore, ophiopogonin A dose-dependently promotes the phosphorylation of ERK in HS kidney tissues and hypoxia-treated HK-2 cells, suggesting that ophiopogonin A functions via the p-ERK/ERK signaling pathway.

scholarly journals MiR-22-3p suppresses sepsis-induced acute kidney injury by targeting PTEN

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xudong Wang ◽  
Yali Wang ◽  
Mingjian Kong ◽  
Jianping Yang
Keyword(s):  
Acute Kidney Injury ◽  
Inflammatory Response ◽  
Periodic Acid ◽  
Kidney Injury ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Tnf Α

Abstract Background: Septic acute kidney injury is considered as a severe and frequent complication that occurs during sepsis. The present study was performed to understand the role of miR-22-3p and its underlying mechanism in sepsis-induced acute kidney injury. Methods: Rats were injected with adenovirus carrying miR-22-3p or miR-NC in the caudal vein before cecal ligation. Meanwhile, HK-2 cells were transfected with the above adenovirus following LPS stimulation. We measured the markers of renal injury (blood urea nitrogen (BUN), serum creatinine (SCR)). Histological changes in kidney tissues were examined by hematoxylin and eosin (H&E), Masson staining, periodic acid Schiff staining and TUNEL staining. The levels of IL-1β, IL-6, TNF-α and NO were determined by ELISA assay. Using TargetScan prediction and luciferase reporter assay, we predicted and validated the association between PTEN and miR-22-3p. Results: Our data showed that miR-22-3p was significantly down-regulated in a rat model of sepsis-induced acute kidney injury, in vivo and LPS-induced sepsis model in HK-2 cells, in vitro. Overexpression of miR-22-3p remarkably suppressed the inflammatory response and apoptosis via down-regulating HMGB1, p-p65, TLR4 and pro-inflammatory factors (IL-1β, IL-6, TNF-α and NO), both in vivo and in vitro. Moreover, PTEN was identified as a target of miR-22-3p. Furthermore, PTEN knockdown augmented, while overexpression reversed the suppressive role of miR-22-3p in LPS-induced inflammatory response. Conclusions: Our results showed that miR-22-3p induced protective role in sepsis-induced acute kidney injury may rely on the repression of PTEN.

scholarly journals Protective Effect of Opuntia dillenii Haw Fruit against Lead Acetate-Induced Hepatotoxicity: In Vitro and In Vivo Studies

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Reza Shirazinia ◽  
Ali Akbar Golabchifar ◽  
Vafa Baradaran Rahimi ◽  
Abbas Jamshidian ◽  
Alireza Samzadeh-Kermani ◽  
...  
Keyword(s):  
Cell Viability ◽  
Lead Acetate ◽  
Male Rats ◽  
Tnf Α ◽  
Wide Range ◽  
Hepatoprotective Effects ◽  
Anti Inflammatory ◽  
Opuntia Dillenii

Lead is one of the most common environmental contaminants in the Earth’s crust, which induces a wide range of humans biochemical changes. Previous studies showed that Opuntia dillenii (OD) fruit possesses several antioxidant and anti-inflammatory properties. The present study evaluates OD fruit hydroalcoholic extract (OHAE) hepatoprotective effects against lead acetate- (Pb-) induced toxicity in both animal and cellular models. Male rats were grouped as follows: control, Pb (25 mg/kg/d i.p.), and groups 3 and 4 received OHAE at 100 and 200 mg/kg/d + Pb (25 mg/kg/d i.p.), for ten days of the experiment. Thereafter, we evaluated the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), catalase (CAT) activity and malondialdehyde (MDA) in serum, and liver histopathology. Additionally, the cell study was also done using the HepG2 cell line for measuring the direct effects of the extract on cell viability, oxidative stress MDA, and glutathione (GSH) and inflammation tumor necrosis factor-α (TNF-α) following the Pb-induced cytotoxicity. Pb significantly increased the serum levels of ALT, AST, ALP, and MDA and liver histopathological scores but notably decreased CAT activity compared to the control group ( p < 0.001 for all cases). OHAE (100 and 200 mg/kg) significantly reduced the levels of serum liver enzyme activities and MDA as well as histopathological scores while it significantly increased CAT activity compared to the Pb group ( p < 0.001 –0.05 for all cases). OHAE (20, 40, and 80 μg/ml) concentration dependently and significantly reduced the levels of MDA and TNF-α, while it increased the levels of GSH and cell viability in comparison to the Pb group ( p < 0.001 –0.05 for all cases). These data suggest that OHAE may have hepatoprotective effects against Pb-induced liver toxicity both in vitro and in vivo by its antioxidant and anti-inflammatory activities.

MDM2 inhibition improves cisplatin-induced renal injury in mice via inactivation of Notch/hes1 signaling pathway

2020 ◽  
pp. 096032712095215
Author(s):  
X Luo ◽  
L Zhang ◽  
G-D Han ◽  
P Lu ◽  
Y Zhang
Keyword(s):  
Signaling Pathway ◽  
Renal Injury ◽  
Cell Apoptosis ◽  
Renal Tissue ◽  
Tunel Staining ◽  
Acute Renal Injury ◽  
Renal Tubular ◽  
Injury Models

Objective: To explore the potential function of MDM2-mediated Notch/hes1 signaling pathway in cisplatin-induced renal injury. Methods: The acute renal injury models of mice after intraperitoneal injection of cisplatin in vivo, and the apoptotic models of human renal tubular epithelial (HK-2) cells induced by cisplatin in vitro, were conducted respectively. The renal function-related parameters were measured. The renal tissue pathological changes and apoptosis were observed by PAS staining and TUNEL staining, respectively. Cell viability and apoptosis were detected by MTT and flow cytometry. Notch/hes1 pathway-related proteins were tested by Western blotting. Results: After mice injected by cisplatin, the levels of Cr, BUN, urine cystatin C, urine NGAL and urine ACR were increased and GFR was decreased with the elevation of renal tubular injury scores, the upregulation of the expressions of MDM2, N1ICD, Hes1 and Cleaved caspase-3, as well as the enhancement of cell apoptosis accompanying decreased ratio of Bcl-2/Bax. However, these cisplatin-induced renal injuries of mice have been improved by MDM2 inhibition. Besides, the declined viability, increased cytotoxicity, and enhanced apoptosis were observed in cisplatin-induced HK-2 cells, with the activated Notch/hes1 pathway. Notably, the phenomenon was alleviated in cisplatin-induced HK-2 cells transfected with MDM2 shRNA, but was severer in those co-treated with AdMDM2. Moreover, Notch1 siRNA can reverse the injury of AdMDM2 on HK-2 cells. Conclusion: Inhibiting MDM2 could reduce cell apoptosis through blocking Notch/hes1 signaling pathway, thus alleviating the acute renal injury caused by cisplatin.

scholarly journals Dangshen Erling Decoction Ameliorates Myocardial Hypertrophy via Inhibiting Myocardial Inflammation

2022 ◽  
Vol 12 ◽  
Author(s):  
Yigang Zhong ◽  
Liuying Chen ◽  
Miaofu Li ◽  
Lian Chen ◽  
Yufeng Qian ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cardiac Tissue ◽  
Myocardial Hypertrophy ◽  
Cell Model ◽  
H9c2 Cell ◽  
Myocardial Inflammation ◽  
Cross Sectional ◽  
Tnf Α

Myocardial hypertrophy plays an essential role in the structural remodeling of the heart and the progression to heart failure (HF). There is an urgent need to understand the mechanisms underlying cardiac hypertrophy and to develop treatments for early intervention. Dangshen Erling decoction (DSELD) is a clinically used formula in Chinese medicine for treating coronary heart disease in patients with HF. However, the mechanism by which DSELD produces its cardioprotective effects remains largely unknown. This study explored the effects of DSELD on myocardial hypotrophy both in vitro and in vivo. In vitro studies indicated that DSELD significantly (p &lt; 0.05) reduced the cross-sectional area of the myocardium and reduced elevated lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels in the induced H9C2 cell model to study inflammation. In vivo experiments revealed that DSELD restores cardiac function and significantly reduces myocardial fibrosis in isoproterenol (ISO)-induced HF mouse model (p &lt; 0.05). In addition, DSELD downregulated the expression of several inflammatory cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), IL-1α, IL-1β, IL-3, IL-5, IL-7, IL-12, IL-13, and TNF-α in HF (p &lt; 0.05). Further analysis of the cardiac tissue demonstrated that DSELD produces its anti-inflammatory effects via the Toll-like receptor (TLR)4 signaling pathway. The expression of TLR4 downstream proteins such as matrix metalloproteinase-9 (MMP9) and myeloid differentiation factor-88 (MyD88) was among the regulated targets. In conclusion, these observations suggest that DSELD exerts antihypertrophic effects by alleviating the inflammatory injury via the TLR4 signaling pathway in HF and thus holds promising therapeutic potentials.

scholarly journals p38 MAP kinase inhibition ameliorates cisplatin nephrotoxicity in mice

2005 ◽  
Vol 289 (1) ◽  
pp. F166-F174 ◽  
Author(s):  
Ganesan Ramesh ◽  
W. Brian Reeves
Keyword(s):  
Renal Dysfunction ◽  
P38 Mapk ◽  
Renal Injury ◽  
Acute Renal Injury ◽  
Mapk Activation ◽  
Mapk Activity ◽  
Tnf Α

Cisplatin is an important chemotherapeutic agent but can cause acute renal injury. Part of this acute renal injury is mediated through tumor necrosis factor-α (TNF-α). The pathway through which cisplatin mediates the production of TNF-α and injury is not known. Cisplatin activates p38 MAPK and induces apoptosis in cancer cells. p38 MAPK activation leads to increased production of TNF-α in ischemic injury and in macrophages. However, little is known concerning the role of p38 MAPK in cisplatin-induced renal injury. Therefore, we examined the effect of cisplatin on p38 MAPK activity and the role of p38 MAPK in mediating cisplatin-induced TNF-α production and renal injury. In vitro, cisplatin caused a dose-dependent activation of p38 MAPK in proximal tubule cells. Inhibition of p38 MAPK activation led to inhibition of TNF-α production. In vivo, mice treated with a single dose of cisplatin (20 mg/kg body wt) developed severe renal dysfunction at 72 h [blood urea nitrogen (BUN): 154 ± 34 mg/dl, creatinine: 1.4 ± 0.4 mg/dl], which was accompanied by an increase in kidney p38 MAPK activity and an increase in infiltrating leukocytes. However, animals treated with the p38 MAPK inhibitor SKF-86002 along with cisplatin showed less renal dysfunction (BUN: 55 ± 14 mg/dl, creatinine: 0.3 ± 0.02 mg/dl, P < 0.05), less severe histological damage, and fewer leukocytes compared with cisplatin+vehicle-treated animals. Serum levels of TNF-α, sTNFRI, and sTNFRII also increased significantly in cisplatin-treated mice compared with SKF-86002-treated mice ( P < 0.05). Kidney mRNA levels of TNF-α were significantly increased in cisplatin-treated mice compared with either SKF-86002- or saline-treated animals. The hydroxyl radical scavenger DMTU (100 mg·kg body wt−1·day−1) prevented the activation of p38 MAPK by cisplatin both in vitro and in vivo. DMTU also completely prevented cisplatin-induced renal injury (BUN: 140 ± 27 vs. 22 ± 2 mg/dl, P < 0.005) and the increase in serum TNF-α (33 ± 7 vs. 4 ± 2 pg/ml, P < 0.005) and kidney TNF-α mRNA in vivo. We conclude that hydroxyl radicals, either directly or indirectly, activate p38 MAPK and that p38 MAPK plays an important role in mediating cisplatin-induced acute renal injury and inflammation, perhaps through production of TNF-α.

scholarly journals Ethyl Vanillin Protects against Kidney Injury in Diabetic Nephropathy by Inhibiting Oxidative Stress and Apoptosis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yuna Tong ◽  
Shan Liu ◽  
Rong Gong ◽  
Lei Zhong ◽  
Xingmei Duan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Cell Apoptosis ◽  
Cell Model ◽  
Critical Role ◽  
Kidney Injury ◽  
Related Factor ◽  
Ethyl Vanillin

Diabetes-induced oxidative stress and apoptosis is regarded as a critical role in the pathogenesis of diabetic nephropathy (DN). Treating diabetes-induced kidney damage and renal dysfunction has been thought a promising therapeutic option to attenuate the development and progression of DN. In this study, we investigated the renoprotective effect of ethyl vanillin (EVA), an active analogue of vanillin isolated from vanilla beans, on streptozotocin- (STZ-) induced rat renal injury model and high glucose-induced NRK-52E cell model. The EVA treatment could strongly improve the deterioration of renal function and kidney cell apoptosis in vivo and in vitro. Moreover, treating with EVA significantly decreased the level of MDA and reactive oxygen species (ROS) and stabilized antioxidant enzyme system in response to oxidative stress by enhancing the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in vivo and in vitro. Furthermore, EVA also markedly suppressed cleaved caspase-3, Bax, and nuclear transcription factor erythroid 2-related factor (Nrf2) expression in STZ-induced rats. Therefore, these results of our investigation provided that EVA might protect against kidney injury in DN by inhibiting oxidative stress and cell apoptosis.

scholarly journals Flavonoids as anti-inflammatory agents

2010 ◽  
Vol 69 (3) ◽  
pp. 273-278 ◽  
Author(s):  
Mauro Serafini ◽  
Ilaria Peluso ◽  
Anna Raguzzini
Keyword(s):  
Related Factor ◽  
Plant Foods ◽  
Reactive Protein ◽  
Cellular Models ◽  
Chemical Structures ◽  
Markers Of Inflammation ◽  
Wide Range ◽  
Anti Inflammatory

Epidemiological evidence suggests that a high intake of plant foods is associated with lower risk of chronic diseases. However, the mechanism of action and the components involved in this effect have not been identified clearly. In recent years, the scientific community has agreed to focus its attention on a class of secondary metabolites extensively present in a wide range of plant foods: the flavonoids, suggested as having different biological roles. The anti-inflammatory actions of flavonoids in vitro or in cellular models involve the inhibition of the synthesis and activities of different pro-inflammatory mediators such as eicosanoids, cytokines, adhesion molecules and C-reactive protein. Molecular activities of flavonoids include inhibition of transcription factors such as NF-κB and activating protein-1 (AP-1), as well as activation of nuclear factor-erythroid 2-related factor 2 (Nrf2). However, the in vitro evidence might be somehow of limited impact due to the non-physiological concentrations utilized and to the fact that in vivo flavonoids are extensively metabolized to molecules with different chemical structures and activities compared with the ones originally present in the food. Human studies investigating the effect of flavonoids on markers of inflammation are insufficient, and are mainly focused on flavonoid-rich foods but not on pure molecules. Most of the studies lack assessment of flavonoid absorption or fail to associate an effect on inflammation with a change in circulating levels of flavonoids. Human trials with appropriate placebo and pure flavonoid molecules are needed to clarify if flavonoids represent ancillary ingredients or key molecules involved in the anti-inflammatory properties of plant foods.

Ginkgetin inhibits proliferation of human leukemia cells via the TNF-α signaling pathway

2017 ◽  
Vol 72 (11-12) ◽  
pp. 441-447 ◽  
Author(s):  
Ling-Ling Pan ◽  
Wen-Jun Wu ◽  
Gao-Feng Zheng ◽  
Xiao-Yan Han ◽  
Jing-Song He ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
K562 Cell ◽  
Lymphoblastic Leukemia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Human Leukemia ◽  
Dependent Manner ◽  
Tnf Α

AbstractGinkgetin is known to be an anticancer agent in many studies. However, its effectiveness in treating chronic lymphoblastic leukemia (CLL) remains unknown. The present study aimed to evaluate the effects of ginkgetin on the growth of the K562 cell line. The MTT assay was employed to examine the proliferation of K562, and a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining was conducted to detect the apoptotic rates. Furthermore, changes of tumor necrosis factor-α (TNF-α) were detected by Western blot analysis. Ginkgetin inhibited the proliferation of K562 cells in a dose- and time-dependent manner. Concentrations of ginkgetin required to induce 50% death of K562 at 24, 48 and 72 h were 38.9, 31.3 and 19.2 μM, respectively. Moreover, treatment of ginkgetin increased K562 apoptosis in vitro along with increased levels of TNF-α. Interestingly, anti-TNF-α antibody prevented ginkgetin-induced K562 cell apoptosis and growth inhibition via deactivation of caspase-8, caspase-9 and caspase-3. Concomitantly, downregulation of TNF-α by etanercept in vivo attenuated ginkgetin-induced inhibitory effects on the tumor growth in an xenograft mouse model. Our results indicate that ginkgetin effectively inhibits K562 cell proliferation, and TNF-α plays a key role in ginkgetin-induced cell apoptosis.

scholarly journals Enzyme Treatment Alters the Anti-Inflammatory Activity of the Water Extract of Wheat Germ In Vitro and In Vivo

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2490 ◽  
Author(s):  
Youngju Song ◽  
Hee-Young Jeong ◽  
Jae-Kang Lee ◽  
Yong-Seok Choi ◽  
Dae-Ok Kim ◽  
...  
Keyword(s):  
Wheat Germ ◽  
Water Extract ◽  
Inflammatory Activity ◽  
Enzyme Treatment ◽  
Related Factor ◽  
Nuclear Factor ◽  
Tnf Α ◽  
Anti Inflammatory

Wheat germ is rich in quinones that exist as glycosides. In this study, we used Celluclast 1.5L to release the hydroxyquinones, which turn into benzoquinone, and prepared the water extract from enzyme-treated wheat germ (EWG). We investigated whether enzyme treatment altered the anti-inflammatory activity compared to the water extract of untreated wheat germ (UWG). UWG inhibited the production of inducible nitric oxide synthase (iNOS) and interleukin (IL)-12 and induced the production of IL-10 and heme oxygenase (HO)-1 in lipopolysaccharide (LPS)-stimulated macrophages. Enzyme treatment resulted in greater inhibition of iNOS and IL-10 and induction of HO-1 compared to UWG, possibly involving the modulation of nuclear factor (NF)-κB, activator protein 1 (AP-1) and nuclear factor erythroid 2-related factor (Nrf2). Mice fed UWG or EWG had decreased serum tumor necrosis factor (TNF)-α and increased serum IL-10 levels after intraperitoneal injection of LPS, with UWG being more effective for IL-10 and EWG more effective for TNF-α. Hepatic HO-1 gene was only expressed in mice fed EWG. We provide evidence that enzyme treatment is a useful biotechnology tool for extracting active compounds from wheat germ.

The Potential Application of Pentacyclic Triterpenoids in the Prevention and Treatment of Retinal Diseases

Planta Medica ◽  
2021 ◽  
Author(s):  
Zhengqi Cheng ◽  
Yue Li ◽  
Xue Zhu ◽  
Ke Wang ◽  
Youmna Ali ◽  
...  
Keyword(s):  
High Mobility ◽  
Future Research ◽  
Related Factor ◽  
Retinal Diseases ◽  
Pentacyclic Triterpenoids ◽  
Wide Range ◽  
Prevention And Treatment ◽  
Pharmacological Potential

AbstractRetinal diseases are a leading cause of impaired vision and blindness but some lack effective treatments. New therapies are required urgently to better manage retinal diseases. Natural pentacyclic triterpenoids and their derivatives have a wide range of activities, including antioxidative, anti-inflammatory, cytoprotective, neuroprotective, and antiangiogenic properties. Pentacyclic triterpenoids have great potential in preventing and/or treating retinal pathologies. The pharmacological effects of pentacyclic triterpenoids are often mediated through the modulation of signalling pathways, including nuclear factor erythroid-2 related factor 2, high-mobility group box protein 1, 11β-hydroxysteroid dehydrogenase type 1, and Src homology region 2 domain-containing phosphatase-1. This review summarizes recent in vitro and in vivo evidence for the pharmacological potential of pentacyclic triterpenoids in the prevention and treatment of retinal diseases. The present literature supports the further development of pentacyclic triterpenoids. Future research should now attempt to improve the efficacy and pharmacokinetic behaviour of the agents, possibly by the use of medicinal chemistry and targeted drug delivery strategies.

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