Caffeic Acid Phenethyl Ester Protects Kidney Mitochondria against Ischemia/Reperfusion Induced Injury in an In Vivo Rat Model

To improve ischemia/reperfusion tolerance, a lot of attention has been focused on natural antioxidants. Caffeic acid phenethyl ester (CAPE), an active component of the resinous exudates of the buds and young leaves of Populus nigra L., Baccharis sarothroides A., etc., and of propolis, possesses unique biological activities such as anti-inflammatory, antioxidant, immunomodulating, and cardioprotective effects, among others. There is a lack of studies showing a link between the antioxidant potential of CAPE and the mechanism of protective action of CAPE at the level of mitochondria, which produces the main energy for the basic functions of the cell. In the kidney, ischemia/reperfusion injury contributes to rapid kidney dysfunction and high mortality rates, and the search for biologically active protective compounds remains very actual. Therefore, the aim of this study was to identify the antioxidant potential of CAPE and to investigate whether CAPE can protect rat kidney mitochondria from in vivo kidney ischemia/reperfusion induced injury. We found that CAPE (1) possesses antioxidant activity (the reducing properties of CAPE are more pronounced than its antiradical properties); CAPE effectively reduces cytochrome c; (2) protects glutamate/malate oxidation and Complex I activity; (3) preserves the mitochondrial outer membrane from damage and from the release of cytochrome c; (4) inhibits reactive oxygen species (ROS) generation in the Complex II (SDH) F site; (5) diminishes ischemia/reperfusion-induced LDH release and protects from necrotic cell death; and (6) has no protective effects on succinate oxidation and on Complex II +III activity, but partially protects Complex II (SDH) from ischemia/reperfusion-induced damage. In summary, our study shows that caffeic acid phenethyl ester protects kidney mitochondrial oxidative phosphorylation and decreases ROS generation at Complex II in an in vivo ischemia/reperfusion model, and shows potential as a therapeutic agent for the development of pharmaceutical preparations against oxidative stress-related diseases.

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Increased Succinate Accumulation Induces ROS Generation in In Vivo Ischemia/Reperfusion-Affected Rat Kidney Mitochondria

BioMed Research International ◽

10.1155/2020/8855585 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Justina Kamarauskaite ◽

Rasa Baniene ◽

Darius Trumbeckas ◽

Arvydas Strazdauskas ◽

Sonata Trumbeckaite

Keyword(s):

Succinate Dehydrogenase ◽

Ischemia Reperfusion Injury ◽

Rat Kidney ◽

Ischemia Reperfusion ◽

Ros Generation ◽

Complex Ii ◽

Kidney Mitochondria ◽

New Findings ◽

Kidney Ischemia

Mitochondria are recognized as main reactive oxygen species (ROS) producers, involving ROS generation by mitochondrial complexes I and III. Lately, the focus has been shifting to the ROS generation by complex II. Contribution of complex II (SDH) to ROS generation still remains debatable, especially in in vivo settings. Moreover, it is not completely defined at what time of ischemia the first alterations in mitochondria and the cell begin, which is especially important with renal arterial clamping in vivo during kidney surgery, as it predicts the postischemic kidney function. The aim of this study on an in vivo rat kidney ischemia/reperfusion model was to determine if there is a connection among (a) duration of kidney ischemia and mitochondrial dysfunction and (b) succinate dehydrogenase activity, succinate accumulation, and ROS generation in mitochondria at low and saturating succinate concentrations. Our results point out that (1) mitochondrial disturbances can occur even after 30 min of kidney ischemia/reperfusion in vivo and increase progressively with the prolonged time of ischemia; (2) accumulation of succinate in cytosol after ischemia/reperfusion correlated with increased H2O2 generation mediated by complex II, which was most noticeable with physiological succinate concentrations; and (3) ischemia/reperfusion induced cell necrosis, indicated by the changes in LDH activity. In conclusion, our new findings on the accumulation of succinate in cytosol and changes in SDH activity during kidney ischemia/reperfusion may be important for energy production after reperfusion, when complex I activity is suppressed. On the other hand, an increased activity of succinate dehydrogenase is associated with the increased ROS generation, especially with physiological succinate concentrations. All these observations play an important role in understanding the mechanisms which occur in the early phase of ischemia/reperfusion injury in vivo and may provide new ideas for novel therapeutic approaches or injury prevention; therefore, more detailed studies are necessary in the future.

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Formulation development of folic acid conjugated PLGA nanoparticles for improved cytotoxicity of Caffeic acid phenethyl ester

Pharmaceutical Nanotechnology ◽

10.2174/2211738509666210111160528 ◽

2021 ◽

Vol 09 ◽

Author(s):

Harshad S Kapare ◽

Sathiyanarayanan L ◽

Arulmozhi S ◽

Kakasaheb Mahadik

Keyword(s):

Folic Acid ◽

Drug Release ◽

Caffeic Acid ◽

Caffeic Acid Phenethyl Ester ◽

Therapeutic Effects ◽

Formulation Development ◽

Sustained Drug Release ◽

Active Constituent

Background: Honey bee propolis is one of the natural product reported in various traditional systems of medicines including Ayurveda. Caffeic acid phenethyl ester (CAPE) is an active constituent of propolis which is well known for its anticancer potential. The therapeutic effects of CAPE are restricted owing to its less aqueous solubility and low bioavailability. Objective: In this study CAPE loaded folic acid conjugated nanoparticle system (CLFPN) was investigated to enhance solubility, achieve sustained drug release and improved cytotoxicity of CAPE. Methods: Formulation development, characterization and optimization were carried out by design of experiment approach. In vitro and in vivo cytotoxicity study was carried out for optimized formulations. Results: Developed nanoparticles showed particle size and encapsulation efficiency of 170 ± 2 - 195 ± 3 nm and 75.66 ± 1.52 - 78.80 ± 1.25 % respectively. Optimized formulation CLFPN showed sustained drug release over a period of 42 h. GI50 concentration was decreased by 46.09% for formulation as compared to CAPE in MCF-7 cells indicating targeting effect of CLFPN. An improved in vitro cytotoxic effect was reflected in in-vivo Daltons Ascites Lymphoma model by reducing tumor cells count. Conclusion: The desired nanoparticle characteristic with improved in vivo and in vitro cytotoxicity was shown by developed formulation. Thus it can be further investigated for biomedical applications.

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In Vivo and In Vitro Antıneoplastic Actions of Caffeic Acid Phenethyl Ester (CAPE): Therapeutic Perspectives

Nutrition and Cancer ◽

10.1080/01635581.2013.776693 ◽

2013 ◽

Vol 65 (4) ◽

pp. 515-526 ◽

Cited By ~ 56

Author(s):

Sumeyya Akyol ◽

Gulfer Ozturk ◽

Zeynep Ginis ◽

Ferah Armutcu ◽

M. Ramazan Yigitoglu ◽

...

Keyword(s):

Caffeic Acid ◽

Caffeic Acid Phenethyl Ester

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

Current Developments in Nutrition ◽

10.1093/cdn/nzz031.p06-089-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 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.

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Caffeic Acid Phenethyl Ester as a Protective Agent against Nephrotoxicity and/or Oxidative Kidney Damage: A Detailed Systematic Review

The Scientific World JOURNAL ◽

10.1155/2014/561971 ◽

2014 ◽

Vol 2014 ◽

pp. 1-16 ◽

Cited By ~ 14

Author(s):

Sumeyya Akyol ◽

Veli Ugurcu ◽

Aynur Altuntas ◽

Rukiye Hasgul ◽

Ozlem Cakmak ◽

...

Keyword(s):

Systematic Review ◽

Protective Effect ◽

Caffeic Acid ◽

Renal Injury ◽

Active Component ◽

Current Knowledge ◽

Ischemia Reperfusion ◽

Oxidative Injury ◽

Caffeic Acid Phenethyl Ester ◽

Protective Agent

Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been attracting the attention of different medical and pharmaceutical disciplines in recent years because of its antioxidant, anti-inflammatory, antiproliferative, cytotoxic, antiviral, antifungal, and antineoplastic properties. One of the most studied organs for the effects of CAPE is the kidney, particularly in the capacity of this ester to decrease the nephrotoxicity induced by several drugs and the oxidative injury after ischemia/reperfusion (I/R). In this review, we summarized and critically evaluated the current knowledge regarding the protective effect of CAPE in nephrotoxicity induced by several special medicines such as cisplatin, doxorubicin, cyclosporine, gentamycin, methotrexate, and other causes leading to oxidative renal injury, namely, I/R models and senility.

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