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; Kalra, Rajkumar S.; Chaudhary, Anupama; Nayak, Aashika; Guruprasad, Kanive Parashiva; Satyamoorthy, Kapaettu; Ishida, Yoshiyuki; Terao, Keiji; Kaul, Sunil C.; Wadhwa, Renu

doi:10.3389/fnagi.2020.561925

Cited by 15 publications

(9 citation statements)

References 57 publications

(69 reference statements)

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“…It is often quantitated as the level of ROS and offers a convenient assay to access antistress potential of natural and synthetic compounds. ROS homeostasis is achieved as a result of activities of several enzymes and natural antioxidants [ 40 ], and their imbalance has been connected to macromolecular damage leading to a variety of chronic illnesses including neurodegenerative disorders, metabolic disorder, and cancer [ 41 , 42 , 43 ]. Various kinds of traditional home medicine components have been shown to inhibit ROS production and impart protective role against neuronal injury [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Insights into the Antistress Potentials of Brazilian Green Propolis Extract and Its Constituent Artepillin C

Kaul

Kuthethur

Ishida³

et al. 2021

Molecules

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Propolis, also known as bee-glue, is a resinous substance produced by honeybees from materials collected from plants they visit. It contains mixtures of wax and bee enzymes and is used by bees as a building material in their hives and by humans for different purposes in traditional healthcare practices. Although the composition of propolis has been shown to depend on its geographic location, climatic zone, and local flora; two largely studied types of propolis: (i) New Zealand and (ii) Brazilian green propolis have been shown to possess Caffeic Acid Phenethyl Ester (CAPE) and Artepillin C (ARC) as the main bioactive constituents, respectively. We have earlier reported that CAPE and ARC possess anticancer activities, mediated by abrogation of mortalin-p53 complex and reactivation of p53 tumor suppressor function. Like CAPE, Artepillin C (ARC) and the supercritical extract of green propolis (GPSE) showed potent anticancer activity. In this study, we recruited low doses of GPSE and ARC (that did not affect either cancer cell proliferation or migration) to investigate their antistress potential using in vitro cell based assays. We report that both GPSE and ARC have the capability to disaggregate metal- and heat-induced aggregated proteins. Metal-induced aggregation of GFP was reduced by fourfold in GPSE- as well as ARC-treated cells. Similarly, whereas heat-induced misfolding of luciferase protein showed 80% loss of activity, the cells treated with either GPSE or ARC showed 60–80% recovery. Furthermore, we demonstrate their pro-hypoxia (marked by the upregulation of HIF-1α) and neuro-differentiation (marked by differentiation morphology and upregulation of expression of GFAP, β-tubulin III, and MAP2). Both GPSE and ARC also offered significant protection against oxidative stress and, hence, may be useful in the treatment of old age-related brain pathologies.

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Section: Discussionmentioning

confidence: 99%

Molecular Insights into the Antistress Potentials of Brazilian Green Propolis Extract and Its Constituent Artepillin C

Kaul

Kuthethur

Ishida³

et al. 2021

Molecules

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“…So far, according to the standard protocols, no specific treatment is managed for COVID-19-provoked neurologic manifestations. On the preventive side, several herbal formulations and natural compounds were found to support brain health, and also its homeostatic and nootropic function [86]. Severe systemic disease, hypoxia, hyperinflammation, hypercoagulation, and immune dysregulation are hypothesized to endorse neurologic manifestations in SARS-CoV-2-infected people.…”

Section: Treatments Of Covid-19-induced Neurological Manifestationsmentioning

confidence: 99%

Emerging COVID-19 Neurological Manifestations: Present Outlook and Potential Neurological Challenges in COVID-19 Pandemic

et al. 2021

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The unremitting coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) marked a year-long phase of public health adversaries and has severely compromised healthcare globally. Early evidence of COVID-19 noted its impact on the pulmonary and cardiovascular functions, while multiple studies in recent time shed light on its substantial neurological complications, though a comprehensive understanding of the cause(s), the mechanism(s), and their neuropathological outcomes is scarce. In the present review, we conferred evidence of neurological complications in COVID-19 patients and shed light on the SARS-CoV-2 infection routes including the hematogenous, direct/neuronal, lymphatic tissue or cerebrospinal fluid, or infiltration through infected immune cells, while the underlying mechanism of SARS-CoV-2 invasion to the central nervous system (CNS) was also discussed. In an up-to-date manner, we further reviewed the impact of COVID-19 in developing diverse neurologic manifestations associated with CNS, peripheral nervous system (PNS), skeletal muscle, and also pre-existing neurological diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, and myasthenia gravis. Furthermore, we discussed the involvement of key factors including age, sex, comorbidity, and disease severity in exacerbating the neurologic manifestations in COVID-19 patients. An outlook of present therapeutic strategies and state of existing challenges in COVID-19 management was also accessed. Conclusively, the present report provides a comprehensive review of COVID-19-related neurological complications and emphasizes the need for their early clinical management in the ongoing COVID-19 pandemic. Keywords COVID-19 • SARS-CoV-2 • CNS • PNS • Neuroinvasion • COVID-19 pandemic • Neurological complications Highlights• Coronavirus disease 2019 (COVID-19)-associated complications involve substantial neurological manifestations.• SARS-CoV-2 infection routes include the hematogenous, neuronal, lymphatic tissue/cerebrospinal fluid, or infiltration through infected immune cells.• COVID-19 promotes neurologic manifestations associated with the central and peripheral nervous system and exacerbates the pre-existing neurological and neurodegenerative conditions. • Patient's age, sex, comorbidity, and severity of the infection are key factors that determine the extent of neurologic manifestations in COVID-19 patients.

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“…RAGE/NF-κB axis could be a potential therapeutic target in AD [170]. Some dietary nutraceuticals display inhibitory effects on the formation of advanced glycation end-products [171]. Resveratrol has been found to modulate levels of Aβ and certain inflammatory markers in AD patients [172].…”

Section: Potential Strategies Involving Cytokines For Management Of Admentioning

confidence: 99%

The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer’s Disease

Ogunmokun,

Dewanjee,

Chakraborty

et al. 2021

Cells

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Alzheimer’s disease (AD) is one of the most prominent neurodegenerative diseases, which impairs cognitive function in afflicted individuals. AD results in gradual decay of neuronal function as a consequence of diverse degenerating events. Several neuroimmune players (such as cytokines and growth factors that are key players in maintaining CNS homeostasis) turn aberrant during crosstalk between the innate and adaptive immunities. This aberrance underlies neuroinflammation and drives neuronal cells toward apoptotic decline. Neuroinflammation involves microglial activation and has been shown to exacerbate AD. This review attempted to elucidate the role of cytokines, growth factors, and associated mechanisms implicated in the course of AD, especially with neuroinflammation. We also evaluated the propensities and specific mechanism(s) of cytokines and growth factors impacting neuron upon apoptotic decline and further shed light on the availability and accessibility of cytokines across the blood-brain barrier and choroid plexus in AD pathophysiology. The pathogenic and the protective roles of macrophage migration and inhibitory factors, neurotrophic factors, hematopoietic-related growth factors, TAU phosphorylation, advanced glycation end products, complement system, and glial cells in AD and neuropsychiatric pathology were also discussed. Taken together, the emerging roles of these factors in AD pathology emphasize the importance of building novel strategies for an effective therapeutic/neuropsychiatric management of AD in clinics.

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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

Cited by 15 publications

References 57 publications

Molecular Insights into the Antistress Potentials of Brazilian Green Propolis Extract and Its Constituent Artepillin C

Molecular Insights into the Antistress Potentials of Brazilian Green Propolis Extract and Its Constituent Artepillin C

Emerging COVID-19 Neurological Manifestations: Present Outlook and Potential Neurological Challenges in COVID-19 Pandemic

The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer’s Disease

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