scholarly journals Caffeic Acid Phenylethyl Amide Protects against the Metabolic Consequences in Diabetes Mellitus Induced by Diet and Streptozocin

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Yi-Chun Weng ◽  
Sung-Ting Chuang ◽  
Yen-Chu Lin ◽  
Cheng-Fung Chuang ◽  
Tzong-Cherng Chi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Caffeic Acid ◽  
Ischemia Reperfusion ◽  
Cardiovascular Effects ◽  
Protective Effects ◽  
Phenyl Ester ◽  
Perfused Heart ◽  
Rapid Decomposition ◽  
Beneficial Effects

Caffeic acid phenyl ester is distributed wildly in nature and has antidiabetic and cardiovascular protective effects. However, rapid decomposition by esterase leads to its low bioavailability in vivo. In this study, chronic metabolic and cardiovascular effects of oral caffeic acid phenylethyl amide, whose structure is similar to caffeic acid phenyl ester and resveratrol, were investigated in ICR mice. We found that caffeic acid phenylethyl amide protected against diet or streptozocin-induced metabolic changes increased coronary flow and decreased infarct size after global ischemia-reperfusion in Langendorff perfused heart. Further study indicated that at least two pathways might be involved in such beneficial effects: the induction of the antioxidant protein MnSOD and the decrease of the proinflammatory cytokine TNFαand NFκB in the liver. However, the detailed mechanisms of caffeic acid phenylethyl amide need further studies. In summary, this study demonstrated the protective potential of chronic treatment of caffeic acid phenylethyl amide against the metabolic consequences in diabetes mellitus.

scholarly journals Cardiovascular Effects of Caffeic Acid and Its Derivatives: A Comprehensive Review

2020 ◽  
Vol 11 ◽  
Author(s):  
Henrique Silva ◽  
Nuno Miguel F. Lopes
Keyword(s):  
Cardiovascular System ◽  
Caffeic Acid ◽  
Current Knowledge ◽  
Biological Activities ◽  
Ischemia Reperfusion ◽  
Cardiovascular Effects ◽  
Vascular Effects ◽  
Vasorelaxant Activity ◽  
Anti Inflammatory

Caffeic acid (CA) and its phenethyl ester (CAPE) are naturally occurring hydroxycinnamic acids with an interesting array of biological activities; e.g., antioxidant, anti-inflammatory, antimicrobial and cytostatic. More recently, several synthetic analogs have also shown similar properties, and some with the advantage of added stability. The actions of these compounds on the cardiovascular system have not been thoroughly explored despite presenting an interesting potential. Indeed the mechanisms underlying the vascular effects of these compounds particularly need clarifying. The aim of this paper is to provide a comprehensive and up-to-date review on current knowledge about CA and its derivatives in the cardiovascular system. Caffeic acid, CAPE and the synthetic caffeic acid phenethyl amide (CAPA) exhibit vasorelaxant activity by acting on the endothelial and vascular smooth muscle cells. Vasorelaxant mechanisms include the increased endothelial NO secretion, modulation of calcium and potassium channels, and modulation of adrenergic receptors. Together with a negative chronotropic effect, vasorelaxant activity contributes to lower blood pressure, as several preclinical studies show. Their antioxidant, anti-inflammatory and anti-angiogenic properties contribute to an important anti-atherosclerotic effect, and protect tissues against ischemia/reperfusion injuries and the cellular dysfunction caused by different physico-chemical agents. There is an obvious shortage of in vivo studies to further explore these compounds’ potential in vascular physiology. Nevertheless, their favorable pharmacokinetic profile and overall lack of toxicity make these compounds suitable for clinical studies.

scholarly journals Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jian-Ping Zhang ◽  
Wei-Jing Zhang ◽  
Miao Yang ◽  
Hua Fang
Keyword(s):  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

Abstract P293: Endogenous Lats2 Plays an Important Role in Mediating Myocardial Injury Caused by Ischemia/Reperfusion Through Inhibition of FoxO3

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Dan Shao ◽  
Peiyong Zhai ◽  
Junichi Sadoshima
Keyword(s):  
Oxidative Stress ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Dominant Negative ◽  
Area At Risk ◽  
Perfused Heart ◽  
Developed Pressure

Lats2 is a tumor suppressor and a serine/threonine kinase, acting downstream of mammalian sterile 20 like kinase1 (Mst1), which stimulates apoptosis and inhibits hypertrophy in cardiomyocytes (CM). We investigated the role of Lats2 in mediating myocardial injury after ischemia/reperfusion (IR). Phosphorylation of YAP, an in vivo substrate of Lats2, was increased after 45 minutes ischemia followed by 24 hours reperfusion in control mouse hearts compared with sham, but not in dominant negative (DN) Lats2 transgenic mouse (Tg) hearts, suggesting that Lats2 is activated by IR. The size of myocardial infarction (MI)/area at risk was significantly smaller in Tg mice than in NTg mice (19% and 49%, p<0.01). And there were fewer TUNEL positive cells in Tg than in NTg mice (0.04% and 0.11%, p<0.05). Following 30 min of global ischemia and 60 min of reperfusion in Langendorff perfused heart preparations, left ventricular (LV) systolic pressure (100 vs 71mmHg, p<0.05) and LV developed pressure (79 vs 47 mmHg, p<0.05) were significantly greater in Tg than in NTg mice, indicating that suppression of Lats2 induces better functional recovery after IR. Oxidative stress, as evaluated by 8-OHdG staining, was attenuated in Tg mice. In cultured CMs, DN-Lats2 significantly decreased H 2 O 2 -induced cell death. Overexpression of Lats2 significantly downregulated (51% and 75%, p<0.05), whereas that of DN-Last2 upregulated (100 and 70%, p<0.05), MnSOD and catalase, suggesting that Lats2 negatively regulates expression of antioxidants. Reporter gene assays showed that overexpression of Lats2 significantly inhibits (−70%), whereas knocking down Lats2 by sh-Lats2 increases (+60%), FoxO3-mediated transcriptional activity. Overexpression of Lats2 in CMs inhibited FoxO3 expression, whereas that of DN-Lats2 significantly inhibited FoxO3 downregulation after IR in vivo, suggesting that Lats2 negatively regulates FoxO3 protein expression, which may lead to the downregulation of MnSOD and catalase. Taken together, these results suggest that endogenous Lats2 plays an important role in mediating myocardial injury in response to IR, In part through downregulation of FoxO3 and consequent downregulation of antioxidants and increased oxidative stress in the heart.

scholarly journals Protective effects of ginsenoside Rg1 on intestinal ischemia/reperfusion injury-induced oxidative stress and apoptosis via activation of the Wnt/β-catenin pathway

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Guo Zu ◽  
Jing Guo ◽  
Ningwei Che ◽  
Tingting Zhou ◽  
Xiangwen Zhang
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Ginsenoside Rg1 ◽  
Intestinal Ischemia Reperfusion

Abstract Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients in Panax ginseng, and it attenuates inflammation and apoptosis. The aims of our study were to explore the potential of Rg1 for the treatment of intestinal I/R injury and to determine whether the protective effects of Rg1 were exerted through the Wnt/β-catenin signaling pathway. In this study, Rg1 treatment ameliorated inflammatory factors, ROS and apoptosis that were induced by intestinal I/R injury. Cell viability was increased and cell apoptosis was decreased with Rg1 pretreatment following hypoxia/reoxygenation (H/R) in the in vitro study. Rg1 activated the Wnt/β-catenin signaling pathway in both the in vivo and in vitro models, and in the in vitro study, the activation was blocked by DKK1. Our study provides evidence that pretreatment with Rg1 significantly reduces ROS and apoptosis induced by intestinal I/R injury via activation of the Wnt/β-catenin pathway. Taken together, our results suggest that Rg1 could exert its therapeutic effects on intestinal I/R injury through the Wnt/β-catenin signaling pathway and provide a novel treatment modality for intestinal I/R injury.

Abstract 144: Post-myocardial Infarction Therapeutics Using Cardiovascular Progenitor Cells (PC) Derived from Induced Pluripotent Stem Cells (iPSC)

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Yigang Wang
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Vessel Density ◽  
Protective Effects ◽  
Paracrine Factors ◽  
Beneficial Effects ◽  
The Third ◽  
Simplex Virus ◽  
Patch Group

Objective: We sought to assess the cardiac protective effects after MI of (1) PC differentiated directly into cardiomyocytes (CM) and endothelial cells (EC) to the site of injury, or (2) paracrine factors released from PC. Methods: These concepts were evaluated by using iPSC-derived PC genetically modified to express the herpes simplex virus thymidine kinase (TK) under the control of cardiomyocyte (NCX1) or endothelial cell (VE-cadherin) specific promoters. PC expressing the TK permitted ablation at the first week or the third week by iv ganciclovir (GCV). If GCV applied at the first week, but not at the third week, altered cardiac function, we would conclude that myocardial contractile recovery depends on CM and EC-derived from iPSC. If the beneficial effects on cardiac function persisted after GCV was given at the third week, we would surmise that the PC effect was via by a paracrine action. MI created by ligation of LAD, the cell patch with PC was applied to the scarred myocardium. Rats were treated with GCV at 1 or 3 weeks to ablate implanted PC. Echocardiography, vessel density, and histological analysis were used to obtain endpoints for this study. Result: In vivo : The levels of IGF-1α and VEGF released from ischemic tissues were significant higher in the cell patch group. Heart function, infarction size, and vessel density were significantly improved after cell patch treatment. However, this beneficial effect on cardiac function was completely abolished in the group given GCV at week 1, but only partially abolished in the group given GCV at week 3 compared to the untreated cell patch group. Conclusions: Taken together, these data support our conclusion that iPSC-derived cardiovascular lineages (CM and EC) contribute directly to an improved cardiac performance and attenuated remodeling, and that paracrine factors also play a supporting role in the restoration of heart function after MI.

The Indispensable Value of Clinical Trials in the Modernization of Traditional Chinese Medicine: 12 Years' Experience at CUHK and Future Perspectives

2014 ◽  
Vol 42 (03) ◽  
pp. 587-604 ◽  
Author(s):  
Willmann Liang ◽  
David T. Yew ◽  
Kam Lun Hon ◽  
Chun Kwok Wong ◽  
Timothy C. Y. Kwok ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chinese Medicine ◽  
Herbal Medicines ◽  
Chinese Herbs ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Artery Disease ◽  
The Many

The last decade has seen a wealth of information reporting the beneficial effects of Chinese herbal medicines. While a lot more studies were done using in vitro and in vivo research platforms, much fewer investigations were conducted according to evidence-based requirements in clinical settings. The Institute of Chinese Medicine at the Chinese University of Hong Kong (CUHK) has had the opportunity to collaborate with clinicians over the years to initiate and conduct dozens of clinical trials investigating and verifying the therapeutic values of Chinese herbs in selected disease conditions. Of the many disorders, we chose to focus on those that are known for their difficulties achieving perfect results with conventional treatment methods. Examples include non-healing ulcers, allergic conditions, degenerative diseases and cancer. Protective effects of the herbs in such chronic diseases as coronary artery disease and osteoporosis were also part of our focus. Even in healthy individuals and those recovering from chemotherapy, Chinese herbs could help with the immune system and were studied in our clinical trials as well. This paper aims to highlight the important findings from these clinical studies while at the same time, stressing the indispensable value of clinical trials in modernizing the use of Chinese herbs in present-day medicine.

scholarly journals Ticagrelor Conditioning Effects Are Not Additive to Cardioprotection Induced by Direct NLRP3 Inflammasome Inhibition: Role of RISK, NLRP3, and Redox Cascades

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Claudia Penna ◽  
Manuela Aragno ◽  
Alessia Sofia Cento ◽  
Saveria Femminò ◽  
Isabella Russo ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Ex Vivo ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Oral Treatment ◽  
P2y12 Receptor ◽  
Protective Effects ◽  
Area At Risk ◽  
Beneficial Effects ◽  
Pyrin Domain

Inhibition of either P2Y12 receptor or the nucleotide-binding oligomerization domain- (NOD-) like receptor pyrin domain containing 3 (NLRP3) inflammasome provides cardioprotective effects. Here, we investigate whether direct NLRP3 inflammasome inhibition exerts additive effects on myocardial protection induced by the P2Y12 receptor antagonist Ticagrelor. Ticagrelor (150 mg/kg) was orally administered to rats for three consecutive days. Then, isolated hearts underwent an ischemia/reperfusion (30 min ischemia/60 min reperfusion; IR) protocol. The selective NLRP3 inflammasome inhibitor INF (50 μM) was infused before the IR protocol to the hearts from untreated animals or pretreated with Ticagrelor. In parallel experiments, the hearts isolated from untreated animals were perfused with Ticagrelor (3.70 μM) before ischemia and subjected to IR. The hearts of animals pretreated with Ticagrelor showed a significantly reduced infarct size (IS, 49±3% of area at risk, AAR) when compared to control IR group (69±2% of AAR). Similarly, ex vivo administration of INF before the IR injury resulted in significant IS reduction (38±3% of AAR). Myocardial IR induced the NLRP3 inflammasome complex formation, which was attenuated by either INF pretreatment ex vivo, or by repeated oral treatment with Ticagrelor. The beneficial effects induced by either treatment were associated with the protective Reperfusion Injury Salvage Kinase (RISK) pathway activation and redox defence upregulation. In contrast, no protective effects nor NLRP3/RISK modulation were recorded when Ticagrelor was administered before ischemia in isolated heart, indicating that Ticagrelor direct target is not in the myocardium. Our results confirm that Ticagrelor conditioning effects are likely mediated through platelets, but are not additives to the ones achieved by directly inhibiting NLRP3.

scholarly journals Caffeic Acid Phenethyl Ester and Its Fluorinated Derivative as Natural Anti-obesity Agents (P06-089-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Srujana Rayalam ◽  
Devin Mills ◽  
Yusra Azhar ◽  
Ebony Miller ◽  
Xinyu Wang
Keyword(s):  
Life Cycle ◽  
Caffeic Acid ◽  
Lipid Content ◽  
Dose Range ◽  
Caffeic Acid Phenethyl Ester ◽  
Beneficial Effects ◽  
Funding Sources ◽  
Treatment Of Obesity ◽  
Methyl Xanthine

Abstract Objectives Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, is well studied for its beneficial effects on cancer, inflammation and diabetes. There are however limited studies investigating the effects of CAPE on obesity. Currently, several natural products are under investigation for their effects on adipocyte life cycle. A multi-targeted approach for prevention and treatment of obesity includes targeting adipocytes at all the stages of life cycle by decreasing adipocyte differentiation, inducing lipolysis and/or by inducing adipocyte apoptosis. In this study, we examined the effects of CAPE on preadipocyte viability, adipogenesis and lipolysis. Earlier reports on CAPE indicate that CAPE is liable to enzymatic hydrolysis in vivo making this compound unstable for therapeutic applications. In the current study, we compared the anti-adipogenic effects of CAPE with its novel fluorinated derivative (FCAPE), a more stable compound. Methods 3T3-L1 pre-adipocytes were differentiated using a cocktail consisting of insulin, dexamethasone, and isobutyl methyl xanthine in DMEM supplemented with 10% FBS following adipogeneic differentiation. Pre- and mature adipocytes were incubated with CAPE or FCAPE for 24–48 hours and their effects on viability, lipolysis, and adipogenesis was tested using Prestoblue, Lipolysis assay (Zen-Bio) and AdipoRed assay respectively. Results Our results indicate that neither CAPE nor FCAPE significantly altered preadipocyte viability within the tested dose range. Although both CAPE and FCAPE significantly decreased adipogenesis compared to control, FCAPE decreased lipid content by 73.6 ± 1.6% while CAPE reduced lipid content by only 36.8 ± 9.1% at 25 μM concentration. In contrast to adipogenesis data, our preliminary results with lipolysis assay indicate that only CAPE, but not FCAPE induces lipolysis in mature adipocytes. Conclusions These findings suggest that both CAPE and FCAPE possess anti-adipogenic properties. Further studies are needed to elucidate their differential effects on adipogenesis and lipolysis. Funding Sources This study was funded by the Department of Research, PCOM.

scholarly journals Polyphenol Microbial Metabolites Exhibit Gut and Blood–Brain Barrier Permeability and Protect Murine Microglia against LPS-Induced Inflammation

Metabolites ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 78 ◽  
Author(s):  
Shelby L. Johnson ◽  
Riley D. Kirk ◽  
Nicholas A. DaSilva ◽  
Hang Ma ◽  
Navindra P. Seeram ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Systemic Circulation ◽  
Brain Barrier ◽  
Protective Effects ◽  
Microbial Metabolites ◽  
Dietary Polyphenols ◽  
Beneficial Effects ◽  
Blood Brain ◽  
Traditional Mediterranean Diet

Increasing evidence supports the beneficial effects of polyphenol-rich diets, including the traditional Mediterranean diet, for the management of cardiovascular disease, obesity and neurodegenerative diseases. However, a common concern when discussing the protective effects of polyphenol-rich diets against diseases is whether these compounds are present in systemic circulation in their intact/parent forms in order to exert their beneficial effects in vivo. Here, we explore two common classes of dietary polyphenols, namely isoflavones and lignans, and their gut microbial-derived metabolites for gut and blood–brain barrier predicted permeability, as well as protection against neuroinflammatory stimuli in murine BV-2 microglia. Polyphenol microbial metabolites (PMMs) generally showed greater permeability through artificial gut and blood–brain barriers compared to their parent compounds. The parent polyphenols and their corresponding PMMs were evaluated for protective effects against lipopolysaccharide-induced inflammation in BV-2 microglia. The lignan-derived PMMs, equol and enterolactone, exhibited protective effects against nitric oxide production, as well as against pro-inflammatory cytokines (IL-6 and TNF-α) in BV-2 microglia. Therefore, PMMs may contribute, in large part, to the beneficial effects attributed to polyphenol-rich diets, further supporting the important role of gut microbiota in human health and disease prevention.

Intravenous bilirubin provides incomplete protection against renal ischemia-reperfusion injury in vivo

2007 ◽  
Vol 292 (2) ◽  
pp. F888-F894 ◽  
Author(s):  
Kristin Kirkby ◽  
Chris Baylis ◽  
Anupam Agarwal ◽  
Byron Croker ◽  
Linda Archer ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Rat Kidney ◽  
Ischemia Reperfusion ◽  
Renal Plasma Flow ◽  
In Vivo Model ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Organ Systems

Exogenous bilirubin (BR) substitutes for the protective effects of heme oxygenase (HO) in several organ systems. Our objective was to investigate the effects of exogenous BR in an in vivo model of ischemia-reperfusion injury (IRI) in the rat kidney. Four groups of male Sprague-Dawley rats were anesthetized using isoflurane in oxygen and treated with 1) 5 mg/kg intravenous (iv) BR, 1 h before ischemia and 6-h reperfusion; 2) vehicle 1 h before ischemia and 6-h reperfusion; 3) 20 mg/kg iv BR, 1 h before and during ischemia; and 4) vehicle 1 h before and during ischemia. Bilateral renal clamping (30 min) was followed by 6-h reperfusion. Infusion of 5 mg/kg iv BR achieved target levels in the serum at 6 h postischemia (31 ± 9 μmol/l). Infusion of 20 mg/kg BR reached 50 ± 22 μmol/l at the end of ischemia, and a significant improvement was seen in serum creatinine at 6 h (1.07 ± 28 vs. 1.38 ± 0.18 mg/dl, P = 0.043). Glomerular filtration rate, estimated renal plasma flow, fractional excretion of electrolytes, and renal vascular resistance were not significantly improved in BR-treated groups. Histological grading demonstrated a trend toward preservation of cortical proximal tubules in rats receiving 20 mg/kg iv BR compared with control; however, neither BR dose provided protection against injury to the renal medulla. At the doses administered, iv BR did not provide complete protection against IRI in vivo. Combined supplementation of both BR and carbon monoxide may be required to preserve renal blood flow and adequately substitute for the protective effects of HO in vivo.

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