scholarly journals Alpinia oxyphylla Miq extract reduces cerebral infarction by downregulating JNK-mediated TLR4/T3JAM- and ASK1-related inflammatory signaling in the acute phase of transient focal cerebral ischemia in rats

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Chin-Yi Cheng ◽  
Su-yin Chiang ◽  
Shung-Te Kao ◽  
Shang-Chih Huang
Keyword(s):  
Cerebral Ischemia ◽  
Tumor Necrosis Factor ◽  
Cerebral Infarction ◽  
Calcium Binding ◽  
Tumor Necrosis ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Inflammatory Signaling ◽  
Alpinia Oxyphylla ◽  
Necrosis Factor

Abstract Background Post-ischemic inflammation is a crucial component in stroke pathology in the early phase of cerebral ischemia–reperfusion (I/R) injury. Inflammation caused by microglia, astrocytes, and necrotic cells, produces pro-inflammatory mediators and exacerbates cerebral I/R injury. This study evaluated the effects of the Alpinia oxyphylla Miq [Yi Zhi Ren (YZR)] extract on cerebral infarction at 1 day after 90 min of transient middle cerebral artery occlusion (MCAo) and investigated the molecular mechanisms underlying the regulation of c-Jun N-terminal kinase (JNK)-mediated inflammatory cascades in the penumbral cortex. Rats were intraperitoneally injected with the YZR extract at the doses of 0.2 g/kg (YZR-0.2 g), 0.4 g/kg (YZR-0.4 g), or 0.8 g/kg (YZR-0.8 g) at MCAo onset. Results YZR-0.4 g and YZR-0.8 g treatments markedly reduced cerebral infarction, attenuated neurological deficits, and significantly downregulated the expression of phospho-apoptosis signal-regulating kinase 1 (p-ASK1)/ASK1, tumor necrosis factor receptor-associated factor 3 (TRAF3), TRAF3-interacting JNK-activating modulator (T3JAM), ionized calcium-binding adapter molecule 1 (Iba1), p-JNK/JNK, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, toll-like receptor 4 (TLR4), glial fibrillary acidic protein (GFAP), nuclear factor-kappa B (NF-κB), and interleukin-6 in the penumbral cortex at 1 day after reperfusion. SP600125 (SP), a selective JNK inhibitor, had the same effects. Furthermore, Iba1- and GFAP-positive cells were colocalized with TLR4, and colocalization of GFAP-positive cells was found with NF-κB in the nuclei. Conclusion YZR-0.4 g and YZR-0.8 g treatments exerted beneficial effects on cerebral ischemic injury by downregulating JNK-mediated signaling in the peri-infarct cortex. Moreover, the anti-infarction effects of YZR extract treatments were partially attributed to the downregulation of JNK-mediated TLR4/T3JAM- and ASK1-related inflammatory signaling pathways in the penumbral cortex at 1 day after reperfusion.

scholarly journals A Novel Curcumin-Mycophenolic Acid Conjugate Inhibited Hyperproliferation of Tumor Necrosis Factor-Alpha-Induced Human Keratinocyte Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 956
Author(s):  
Yonelian Yuyun ◽  
Pahweenvaj Ratnatilaka Na Bhuket ◽  
Wiwat Supasena ◽  
Piyapan Suwattananuruk ◽  
Kemika Praengam ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Mycophenolic Acid ◽  
Tumor Necrosis ◽  
Molecular Mechanisms ◽  
Cellular Transport ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Curcumin (CUR) has been used as adjuvant therapy for therapeutic application in the treatment of psoriasis through several mechanisms of action. Due to the poor oral bioavailability of CUR, several approaches have been developed to overcome the limitations of CUR, including the prodrug strategy. In this study, CUR was esterified with mycophenolic acid (MPA) as a novel conjugate prodrug. The MPA-CUR conjugate was structurally elucidated using FT-IR, 1H-NMR, 13C-NMR, and MS techniques. Bioavailable fractions (BFs) across Caco-2 cells of CUR, MPA, and MPA-CUR were collected for further biological activity evaluation representing an in vitro cellular transport model for oral administration. The antipsoriatic effect of the BFs was determined using antiproliferation and anti-inflammation assays against hyperproliferation of tumor necrosis factor-alpha (TNF-α)-induced human keratinocytes (HaCaT). The BF of MPA-CUR provided better antiproliferation than that of CUR (p < 0.001). The enhanced hyperproliferation suppression of the BF of MPA-CUR resulted from the reduction of several inflammatory cytokines, including IL-6, IL-8, and IL-1β. The molecular mechanisms of anti-inflammatory activity were mediated by an attenuated signaling cascade of MAPKs protein, i.e., p38, ERK, and JNK. Our results present evidence for the MPA-CUR conjugate as a promising therapeutic agent for treating psoriasis by antiproliferative and anti-inflammatory actions.

scholarly journals Tumor necrosis factor-α inhibition attenuates middle cerebral artery remodeling but increases cerebral ischemic damage in hypertensive rats

2014 ◽  
Vol 307 (5) ◽  
pp. H658-H669 ◽  
Author(s):  
Paulo W. Pires ◽  
Saavia S. Girgla ◽  
Guillermo Moreno ◽  
Jonathon L. McClain ◽  
Anne M. Dorrance
Keyword(s):  
Cerebral Ischemia ◽  
Tumor Necrosis Factor ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Tumor Necrosis ◽  
Myogenic Tone ◽  
Hypertensive Rats ◽  
Tnf Α ◽  
Necrosis Factor

Hypertension causes vascular inflammation evidenced by an increase in perivascular macrophages and proinflammatory cytokines in the arterial wall. Perivascular macrophage depletion reduced tumor necrosis factor (TNF)-α expression in cerebral arteries of hypertensive rats and attenuated inward remodeling, suggesting that TNF-α might play a role in the remodeling process. We hypothesized that TNF-α inhibition would improve middle cerebral artery (MCA) structure and reduce damage after cerebral ischemia in hypertensive rats. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with the TNF-α inhibitor etanercept (ETN; 1.25 mg·kg−1·day−1 ip daily) or PBS (equivolume) for 6 wk. The myogenic tone generation, postischemic dilation, and passive structure of MCAs were assessed by pressure myography. Cerebral ischemia was induced by MCA occlusion (MCAO). Myogenic tone was unchanged, but MCAs from SHRSP + ETN had larger passive lumen diameter and reduced wall thickness and wall-to-lumen ratio. Cerebral infarct size was increased in SHRSP + ETN after transient MCAO, despite an improvement in dilation of nonischemic MCA. The increase in infarct size was linked to a reduction in the number of microglia in the infarct core and upregulation of markers of classical macrophage/microglia polarization. There was no difference in infarct size after permanent MCAO or when untreated SHRSP subjected to transient MCAO were given ETN at reperfusion. Our data suggests that TNF-α inhibition attenuates hypertensive MCA remodeling but exacerbates cerebral damage following ischemia/reperfusion injury likely due to inhibition of the innate immune response of the brain.

Tumor necrosis factor-α in ischemia and reperfusion injury in rat lungs

1998 ◽  
Vol 85 (6) ◽  
pp. 2005-2011 ◽  
Author(s):  
Pavel L. Khimenko ◽  
G. J. Bagby ◽  
J. Fuseler ◽  
Aubrey E. Taylor
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Ischemia Reperfusion ◽  
Ischemia And Reperfusion Injury ◽  
Microvascular Damage ◽  
Rat Lungs ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

The effects of both recombinant rat tumor necrosis factor-α (TNF-α) and an anti-TNF-α antibody were studied in isolated buffer-perfused rat lungs subjected to either 45 min of nonventilated [ischemia-reperfusion (I/R)] or air-ventilated (V˙/R) ischemia followed by 90 min of reperfusion and ventilation. In the I/R group, the vascular permeability, as measured by the filtration coefficient ( K fc), increased three- and fivefold above baseline after 30 and 90 min of reperfusion, respectively ( P < 0.001). Over the same time intervals, the K fc for theV˙/R group increased five- and tenfold above baseline values, respectively ( P < 0.001). TNF-α measured in the perfusates of both ischemic models significantly increased after 30 min of reperfusion. Recombinant rat TNF-α (50,000 U), placed into perfusate after baseline measurements, produced no measurable change in microvascular permeability in control lungs perfused over the same time period (135 min), but I/R injury was significantly enhanced in the presence of TNF-α. An anti-TNF-α antibody (10 mg/rat) injected intraperitoneally into rats 2 h before the lung was isolated prevented the microvascular damage in lungs exposed to both I/R and V˙/R ( P < 0.001). These results indicate that TNF-α is an essential component at the cascade of events that cause lung endothelial injury in short-term I/R andV˙/R models of lung ischemia.

Association Between Tumor Necrosis Factor-α Gene Polymorphism and Sasang Constitution in Cerebral Infarction

2005 ◽  
Vol 33 (04) ◽  
pp. 547-557 ◽  
Author(s):  
Jae-Young Um ◽  
Jae-Heung Lee ◽  
Jong-Cheon Joo ◽  
Kyung-Yo Kim ◽  
Eun-Hee Lee ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cerebral Infarction ◽  
Promoter Region ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Sasang Constitution ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

During the last decade, a growing corpus of evidence has indicated an important role of cytokines in the development of brain damage following cerebral ischemia. Tumor necrosis factor-α (TNF-α), a potent immunomodulator and pro-inflammatory cytokine, has been implicated in many pathological processes. In this study, we examined whether promoter region polymorphism in the TNF-α gene at position –308 affects the odds of cerebral infarction (CI) and whether genetic risk is enhanced by Sasang constitutional classification. Two hundred and twelve CI patients and 610 healthy controls were genotyped and determined according to Sasang constitutional classification. A significant decrease was found for the TNF-α A allele in CI patients compared with controls ( p = 0.033, odds ratio, OR: 0.622). However, there was no significant association between TNF-α polymorphism and Sasang constitution in CI patients. Our finding suggests that TNF-α promoter region polymorphism is responsible for susceptibility to CI in Koreans.

Marked Difference in Tumor Necrosis Factor-α Expression in Warm Ischemia– and Cold Ischemia–Reperfusion of the Rat Liver

Cryobiology ◽  
2000 ◽  
Vol 41 (4) ◽  
pp. 301-314 ◽  
Author(s):  
Martina Lutterová ◽  
Zoltán Szatmáry ◽  
Marián Kukan ◽  
Daniel Kuba ◽  
Katarı́na Vajdová
Keyword(s):  
Tumor Necrosis Factor ◽  
Rat Liver ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Ischemia Reperfusion ◽  
Warm Ischemia ◽  
Cold Ischemia ◽  
Factor Α ◽  
Necrosis Factor

Effects of Prostacyclin on Hemodynamics after Intestinal Ischemia-Reperfusion

1997 ◽  
Vol 5 (1) ◽  
pp. 43-47
Author(s):  
S Fehmi Katircioğlu ◽  
Eser Özgencil ◽  
Birol Yamak ◽  
Tulga Ulus ◽  
Selime Ayaz ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Reperfusion Injury ◽  
Tumor Necrosis ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Venous Pressure ◽  
Control Group ◽  
Central Venous ◽  
Intestinal Ischemia Reperfusion ◽  
Necrosis Factor

Ten rabbits underwent 30 minutes of superior mesenteric artery occlusion to assess the release of tumor necrosis factor, subcellular damage, and hemodynamic changes after intestinal ischemia-reperfusion injury. Five were treated with prostacyclin 5 ng/kg/min 5 minutes before the arterial occlusion. It was increased to 25 ng/kg/min during occlusion, decreased to 5 ng/kg/min for the first 5 minutes of reperfusion, and then discontinued. A control group of 5 rabbits did not receive any pharmacological agent. Specimens were obtained from the small intestine for electron microscopy after 10 minutes and after 60 minutes of reperfusion, while simultaneous blood samples were collected for measurement of tumor necrosis factor. Minimal changes were seen in tissue from the prostacyclin group but severe mitochondrial damage and vacuolation occurred in the control group. The tumor necrosis factor level was 11.97 ± 3.17 U/mL in the control group and 5.06 ± 2.19 U/mL in the prostacyclin group, one hour after the end of mesenteric occlusion ( p < 0.05). Hemodynamic status, assessed by central venous and arterial pressures, was much more affected in the control group than in the prostacyclin group. Mean arterial pressure was 71 ± 5 mm Hg in the control group, and 91 ± 6 mm Hg in the prostacyclin group ( p < 0.05). Central venous pressure was 5.3 ± 0.9 mm Hg in the control group and 2.3 ± 0.7 mm Hg in the prostacyclin group ( p < 0.05). We conclude that intravenous prostacyclin reduced the severity of reperfusion injury occurring during the early period of reperfusion by inhibiting the release of the toxic mediator tumor necrosis factor, thus decreasing distant organ injury.

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