Neuroprotection of retinal cells by Caffeic Acid Phenylethyl Ester（CAPE) is mediated by mitochondrial uncoupling protein UCP2

Zhang, Mingliang; Wang, Liming; Wen, Dejia; Ren, Changjie; Chen, Shuang; Zhang, Zhihui; Hu, Lanlan; Yu, Zihao; Tombran-Tink, Joyce; Zhang, Xiaomin; Li, Xiaorong; Barnstable, Colin J.

doi:10.1016/j.neuint.2021.105214

Cited by 12 publications

(15 citation statements)

References 35 publications

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“…Since a large component of the oxidative burden facing cells arises from ROS produced in mitochondria, this raises the interesting therapeutic possibility of enhancing these homeostatic mechanisms and providing cells with a greater tolerance of extrinsic oxidative stress. A strong case has been made for reducing mitochondrial stress and improving their function by using neuroprotective peptide factors, such as PEDF, and small molecules, such as CAPE [ 34 , 60 ]. There is now a growing body of literature to support the idea that UCPs, particularly UCP2, can modulate mitochondrial ROS generation and that they can provide significant protection in a variety of diseases.…”

Section: Ucps and Neural Degenerationmentioning

confidence: 99%

“…Recently, we took a different approach and looked for mimetics that have some structural similarity to the natural UCP2 activator 4-HNE but with less toxicity [ 60 ]. Among the compounds tested were caffeic acid and its phenyl ester, CAPE ( Figure 4 ).…”

Section: Ucp2 As a Target To Combat Retinal Degenerationmentioning

confidence: 99%

“… The molecular structures of 4-Hydroxynon-2-enal (4-HNE), caffeic acid phenyl ester and caffeic acid. Adapted from Reference [ 60 ]. …”

Section: Figurementioning

confidence: 99%

“…Error bars are only shown when they are larger than the data point symbols. Adapted from Reference [ 60 ].…”

Section: Figurementioning

confidence: 99%

“…The histogram shows the mean ± SD, n = 4; ** p < 0.01 *** p < 0.001, **** p < 0.0001. Adapted from Reference [ 60 ].…”

Section: Figurementioning

confidence: 99%

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Uncoupling Proteins as Therapeutic Targets for Neurodegenerative Diseases

Barnstable

Zhang

Tombran-Tink

2022

IJMS

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Most of the major retinal degenerative diseases are associated with significant levels of oxidative stress. One of the major sources contributing to the overall level of stress is the reactive oxygen species (ROS) generated by mitochondria. The driving force for ROS production is the proton gradient across the inner mitochondrial membrane. This gradient can be modulated by members of the uncoupling protein family, particularly the widely expressed UCP2. The overexpression and knockout studies of UCP2 in mice have established the ability of this protein to provide neuroprotection in a number of animal models of neurological disease, including retinal diseases. The expression and activity of UCP2 are controlled at the transcriptional, translational and post-translational levels, making it an ideal candidate for therapeutic intervention. In addition to regulation by a number of growth factors, including the neuroprotective factors LIF and PEDF, small molecule activators of UCP2 have been found to reduce mitochondrial ROS production and protect against cell death both in culture and animal models of retinal degeneration. Such studies point to the development of new therapeutics to combat a range of blinding retinal degenerative diseases and possibly other diseases in which oxidative stress plays a key role.

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Section: Ucps and Neural Degenerationmentioning

confidence: 99%

Section: Ucp2 As a Target To Combat Retinal Degenerationmentioning

confidence: 99%

“… The molecular structures of 4-Hydroxynon-2-enal (4-HNE), caffeic acid phenyl ester and caffeic acid. Adapted from Reference [ 60 ]. …”

Section: Figurementioning

confidence: 99%

“…Error bars are only shown when they are larger than the data point symbols. Adapted from Reference [ 60 ].…”

Section: Figurementioning

confidence: 99%

“…The histogram shows the mean ± SD, n = 4; ** p < 0.01 *** p < 0.001, **** p < 0.0001. Adapted from Reference [ 60 ].…”

Section: Figurementioning

confidence: 99%

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Uncoupling Proteins as Therapeutic Targets for Neurodegenerative Diseases

Barnstable

Zhang

Tombran-Tink

2022

IJMS

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Correlation between total phenolic and flavonoid contents and biological activities of 12 ethanolic extracts of Iranian propolis

Fathi Hafshejani

Lotfi

Rezvannejad

et al. 2023

Food Science & Nutrition

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Propolis is a resinous substance produced by honey bees that is very popular as a natural remedy in traditional medicine. The current research is the first study on the biological properties of ethanolic extracts of propolis (EEP) from several different regions (12) of Iran. Total phenolic and flavonoid contents (TPC and TFC) of Iranian EEPs were variable between 26.59-221.38 mg GAE/g EEP and 4.8-100.03 mg QE/g EEP. The DPPH scavenging assay showed all the studied EEP samples, except for the sample with the lowest TPC and TFC (P6), have suitable antioxidant activity. All the EEPs inhibited both cholinesterase enzymes (acetylcholinesterase: AChE, butyrylcholinesterase: BuChE) but most of them exhibited a distinct selectivity over BuChE.Evaluation of the antibacterial activity of the EEP samples using four pathogenic bacteria (B. cereus, S. aureus, A. baumannii, and P. aeruginosa) demonstrated that the antibacterial properties of propolis are more effective on the gram-positive bacterium.Spearman correlation analysis showed a strong positive correlation between TPC and TFC of the Iranian EEPs and their antioxidant, anticholinesterase, and antibacterial activities. Considering that there is ample evidence of anticholinesterase activity of flavonoids and a significant correlation between the anticholinesterase activity of the studied Iranian EEPs and their total flavonoid content was observed, the interaction of 17 well-known propolis flavonoids with AChE and BuChE was explored using molecular docking. The results indicated that all the flavonoids interact with the active site gorge of both enzymes with high affinity. Summing up, the obtained results suggest that Iranian propolis possesses great potential for further studies.

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Caffeic acid phenethyl ester attenuates indomethacin-induced gastric ulcer in rats

Neamatallah

2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Neuroprotection of retinal cells by Caffeic Acid Phenylethyl Ester（CAPE) is mediated by mitochondrial uncoupling protein UCP2

Cited by 12 publications

References 35 publications

Uncoupling Proteins as Therapeutic Targets for Neurodegenerative Diseases

Uncoupling Proteins as Therapeutic Targets for Neurodegenerative Diseases

Correlation between total phenolic and flavonoid contents and biological activities of 12 ethanolic extracts of Iranian propolis

Caffeic acid phenethyl ester attenuates indomethacin-induced gastric ulcer in rats

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