Dataset Information

Identification of Caffeic Acid Phenethyl Ester (CAPE) as a Potent Neurodifferentiating Natural Compound That Improves Cognitive and Physiological Functions in Animal Models of Neurodegenerative Diseases.

ABSTRACT: Cell-based screening of bioactive compounds has served as an important gateway in drug discovery. In the present report, using human neuroblastoma cells and enrolling an extensive three-step screening of 57 phytochemicals, we have identified caffeic acid phenethyl ester (CAPE) as a potent neurodifferentiating natural compound. Analyses of control and CAPE-induced neurodifferentiated cells revealed: (i) modulation of several key proteins (NF200, MAP-2, NeuN, PSD95, Tuj1, GAP43, and GFAP) involved in neurodifferentiation process; and (ii) attenuation of neuronal stemness (HOXD13, WNT3, and Msh-2) and proliferation-promoting (CDC-20, CDK-7, and BubR1) proteins. We anticipated that the neurodifferentiation potential of CAPE may be beneficial for the treatment of neurodegenerative diseases and tested it using the Drosophila model of Alzheimer's disease (AD) and mice model of amnesia/loss of memory. In both models, CAPE exhibited improved disease symptoms and activation of physiological functions. Remarkably, CAPE-treated mice showed increased levels of neurotrophin-BDNF, neural progenitor marker-Nestin, and differentiation marker-NeuN, both in the cerebral cortex and hippocampus. Taken together, we demonstrate the differentiation-inducing and therapeutic potential of CAPE for neurodegenerative diseases.

SUBMITTER: Konar A

PROVIDER: S-EPMC7685006 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of Caffeic Acid Phenethyl Ester (CAPE) as a Potent Neurodifferentiating Natural Compound That Improves Cognitive and Physiological Functions in Animal Models of Neurodegenerative Diseases.

Konar Arpita A Kalra Rajkumar Singh RS Chaudhary Anupama A Nayak Aashika A Guruprasad Kanive P KP Satyamoorthy Kapaettu K Ishida Yoshiyuki Y Terao Keiji K Kaul Sunil C SC Wadhwa Renu R

Frontiers in aging neuroscience 20201110

Cell-based screening of bioactive compounds has served as an important gateway in drug discovery. In the present report, using human neuroblastoma cells and enrolling an extensive three-step screening of 57 phytochemicals, we have identified caffeic acid phenethyl ester (CAPE) as a potent neurodifferentiating natural compound. Analyses of control and CAPE-induced neurodifferentiated cells revealed: (i) modulation of several key proteins (NF200, MAP-2, NeuN, PSD95, Tuj1, GAP43, and GFAP) involved ...[more]

PMID: 33244299

Similar Datasets

Project description:Glutathione S-transferase (GST) and multidrug resistance-associated proteins (MRPs) play major roles in drug resistance in melanoma. In this study, we investigated caffeic acid phenethyl ester (CAPE) as a selective GST inhibitor in the presence of tyrosinase, which is abundant in melanoma cells. Tyrosinase bioactivates CAPE to an o-quinone, which reacts with glutathione to form CAPE-SG conjugate. Our findings indicate that 90% CAPE was metabolized by tyrosinase after a 60-min incubation. LC-MS/MS analyses identified a CAPE-SG conjugate as a major metabolite. In the presence of tyrosinase, CAPE (10-25?M) showed 70-84% GST inhibition; whereas in the absence of tyrosinase, CAPE did not inhibit GST. CAPE-SG conjugate and CAPE-quinone (25?M) demonstrated ?85% GST inhibition via reversible and irreversible mechanisms, respectively. Comparing with CDNB and GSH, the non-substrate CAPE acted as a weak, reversible GST inhibitor at concentrations >50?M. Furthermore, MK-571, a selective MRP inhibitor, and probenecid, a non-selective MRP inhibitor, decrease the IC(50) of CAPE (15?M) by 13% and 21%, apoptotic cell death by 3% and 13%, and mitochondrial membrane potential in human SK-MEL-28 melanoma cells by 10% and 56%, respectively. Moreover, computational docking analyses suggest that CAPE binds to the GST catalytic active site. Caffeic acid, a hydrolyzed product of CAPE, showed a similar GST inhibition in the presence of tyrosinase. Although, as controls, 4-hydroxyanisole and L-tyrosine were metabolized by tyrosinase to form quinones and glutathione conjugates, they exhibited no GST inhibition in the absence and presence of tyrosinase. In conclusion, both CAPE and caffeic acid selectively inhibited GST in the presence of tyrosinase. Our results suggest that intracellularly formed quinones and glutathione conjugates of caffeic acid and CAPE may play major roles in the selective inhibition of GST in SK-MEL-28 melanoma cells. Moreover, the inhibition of MRP enhances CAPE-induced toxicity in the SK-MEL-28 melanoma cells.

Project description:Liquid preservation of boar sperm is crucial for artificial insemination application in pig production. However, time-dependent oxidative damage to sperm is one of the major challenges during the liquid preservation period. Caffeic acid phenethyl ester (CAPE) possesses excellent antioxidant properties and has potential therapeutic use in reproductive organ injury linked to oxidative stress. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) involves in modulating the cellular redox state and exerts a beneficial effect on sperm preservation. In the present study, we firstly assessed different concentrations of CAPE that affect sperm quality during liquid storage to determine the appropriate addition. To further investigate whether CAPE exerts protective effects on boar sperm through modulation of AMPK activity, sperm quality parameters, antioxidant capacity, and marker protein expressions were evaluated under co-incubation with H2O2. The results showed that sperm treated with 210 μmol/L CAPE exhibited the highest motion parameters (total motility and progressive motility) and best functional integrity (mitochondrial activity, plasma membrane integrity, and acrosomal integrity). Even in the presence of H2O2, the addition of 210 μmol/L CAPE not only significantly improved sperm quality parameters, but also elevated CAT, SOD, and GSH-Px activities to enhance sperm antioxidant capacity. In addition, we found that CAPE could affect the protein activities of AMPK, phospho-AMPK α (p-AMPK), SOD, and Caspase-3 regardless of whether H2O2 is present or not. Our findings suggested that CAPE has potential application in liquid preservation of boar sperm and preliminary indicated that CAPE-induced improvement of sperm quality and antioxidant capacity should be mediated through conservation of AMPK activity. Further studies are required to illustrate the specific mechanism by which CAPE attenuates oxidative stress-mediated damages dependent on AMPK activity. Graphical Abstract The potential protective mechanism of CAPE on boar sperm. CAPE induces AMPK phosphorylation resulting in elevating the protein expression of SOD1 to eliminate ROS as well as inhibiting the protein expression of Caspase-3. Consequently, both the liquid preservation time and boar sperm quality are improved.

Dataset Information

Identification of Caffeic Acid Phenethyl Ester (CAPE) as a Potent Neurodifferentiating Natural Compound That Improves Cognitive and Physiological Functions in Animal Models of Neurodegenerative Diseases.

Publications

Identification of Caffeic Acid Phenethyl Ester (CAPE) as a Potent Neurodifferentiating Natural Compound That Improves Cognitive and Physiological Functions in Animal Models of Neurodegenerative Diseases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets