Fullerene C60 protects against 7,12-dimethylbenz [a] anthracene (DMBA) induced-pancreatic damage via NF-κB and Nrf-2/HO-1 axis in rats.

The objective of this investigation was to investigate the protective effects of fullerene C60 nanoparticle against pancreatic damage experimentally induced by 7,12-dimethylbenz [a] anthracene (DMBA) in female rats. Fullerene C60 nanoparticle was administered to rats 5 times a week by oral gavage (o.g) at 1.7 mg/kg bw 7 days after DMBA administration. 60 Wistar albino female rats divided to four groups; Groups: (1) Control group: Fed with standard diet; (2) Fullerene C60 group: Fullerene C60 (1.7 mg/kg bw); (3) DMBA group: DMBA (45 mg/kg bw); (4) Fullerene C60 + DMBA group: Fullerene C60 (1.7 mg/kg bw) and DMBA (45 mg/kg bw). Lipid peroxidation malondialdehyde (MDA), catalase activity (CAT) and glutathione (GSH) levels in pancreatic tissue were determined by spectrophotometer. Protein expression levels of p53, HO-1, p38-α (MAPK), Nrf-2, NF-κB and COX-2 in pancreatic tissue were determined by western blotting technique. In our findings, compared to the group given DMBA, MDA levels and p38-α, NF-κB and COX-2 levels decreased, CAT activity, GSH level, total protein density and p53, HO-1, Nrf-2 levels in the groups given fullerene C60 nanoparticle an increase in expression levels was observed. Our results showed that fullerene C60 nanoparticle may be more beneficial in preventing pancreatic damage.

The effects of breast reduction with superomedial and inferior pedicle techniques on radiological breast imaging.

BACKGROUND: Several breast reduction techniques have been introduced, and the reliability of these techniques has been demonstrated in clinical practice. However, it is still controversial how patients should be evaluated radiologically both preoperative and postoperative. This study aims to compare the radiological findings seen following reduction mammoplasty with two different techniques (inferior pedicle and superomedial pedicle), in connection with the surgical steps. METHODS: Medical records of 141 patients and a total of 278 breasts who underwent breast reduction with the diagnosis of macromastia were retrospectively analyzed. Demographic and operative data such as age, type of pedicle, preoperative and postoperative nipple-areola complex (NAC) position, and NAC transfer distance were recorded. Radiological evaluation was performed by two radiologists experienced in breast imaging by reinterpreting preoperative and postoperative mammography images. RESULTS: The rate of postoperative structural distortion (p < 0.001), thickened areola (p = 0.011), and retroareolar fibrotic band (p < 0.001) were observed to be significantly higher in the superomedial group. The risk of fat necrosis increases as the NAC transfer distance increases and a value of >9.5 cm in the NAC transfer distance can be considered as the cutoff value in terms of fat necrosis development, especially in those using superomedial pedicle technique. CONCLUSION: Surgical technique-specific benign radiological changes occur following reduction mammoplasty. However, these changes do not significantly affect the Breast imaging, reporting, and data system category. The localization of fat necrosis differs depending on the surgical technique, and the risk of fat necrosis increases as the NAC transfer distance increases, especially in those who have undergone superomedial pedicle breast reduction surgery.

Fullerene C60 reduces acute lung injury by suppressing oxidative stress-mediated DMBA-induced apoptosis and autophagy by regulation of cytochrome-C/caspase-3/beclin-1/IL-1α/HO-1/p53 signaling pathways in rats.

The objective of this study was to evaluate the effect of fullerene C60 nanoparticles against 7,12-dimethylbenz[a]anthracene (DMBA)-induced lung tissue damage in rats. 60 Wistar albino (8 weeks old) female rats were assigned into four groups: Control Group (C), Fullerene C60, DMBA, and Fullerene C60+DMBA. The rats in the DMBA and Fullerene C60+DMBA groups were administered DMBA (45 mg/kg bw, oral gavage). The rats in Fullerene C60, and Fullerene C60+DMBA groups were administered with Fullerene C60 (1.7 mg/kg bw, oral gavage). Expression levels of cytochrome-C, caspase-3, beclin-1, IL-1α, HO-1 and p53 proteins in lung tissue were determined by western blotting, lipid peroxidation malondialdehyde (MDA) analyzes, glutathione (GSH), glutathione peroxidase (GSH-Px), catalase activity (CAT) and total protein levels were determined by spectrophotometer. In addition, lung tissues were evaluated by histopathologically. Fullerene C60 reduced the increasing of MDA and IL-1α protein expression levels and attenuated histopathological changes in lung. Moreover, fullerene C60 enhanced the protein expression of cytochrome-C, caspase-3, beclin-1, HO-1, and p53, which were decreased in the DMBA group. Fullerene C60 has strong biological activity that it might be an effective approach for lung damage.

Activation of Nrf-2 Transcription Factor and Caspase Pathway with Royal Jelly Reduces Fluoride Induced Testicular Damage and Infertility in Rats.

This study was carried out to investigate the protective properties of royal jelly on the testicular tissue of rats with testicular damage by giving fluoride. Sperm motility, epididymal sperm density and abnormal sperm ratios were examined and visualized with a light microscope. Expression levels of Caspase-3, Bcl-2, Nrf-2, NF-κB, COX-2, TNF-α and IL1-α proteins in testis tissue were determined by western blot technique. As a result of the study, MDA level, expression level of Bcl-2, NFÒ¡B, COX-2, TNF-α and IL1-α proteins, abnormal sperm rates were found higher in Fluoride-50 and Fluoride100 groups compared to other groups. In addition GSH, Catalase enzyme levels, expression levels of Caspase-3 and Nrf-2 proteins were found to be higher in Fluoride + Royal Jelly groups compared to Fluoride-50 and Fluoride-100 groups. In addition, lower degeneration of testicular tissue was found in the histological evaluation in the Fluoride + Royal Jelly groups compared to the other groups. When the data are evaluated royal jelly provides effective protection against testicular damage. From this point of view, we hope that similar results will be obtained when royal jelly is tested on humans.

Royal jelly protects brain tissue against fluoride-induced damage by activating Bcl-2/NF-κB/caspase-3/caspase-6/Bax and Erk signaling pathways in rats.

This study is aimed at determining whether royal jelly (RJ) which has a powerful antioxidant property prevents fluoride-induced brain tissue damage and exploring whether Bcl-2/NF-κB/ and caspase-3/caspase-6/Bax/Erk pathways play a critical role in the neuroprotective effect of RJ. Wistar albino rats were chosen for the study, and they were randomly distributed into six groups: (i) control; (ii) royal jelly; (iii) fluoride-50; (iv) fluoride-100; (v) fluoride-50 + royal jelly; (vi) fluoride-100 + royal jelly. We established fluoride-induced brain tissue damage with 8-week-old male Wistar albino rats by administration of fluoride exposure (either 50 mg/kg or 100 mg/kg bw) through drinking water for 8 weeks. Then, the study duration is for 56 days where the rats were treated with or without RJ (100 mg/kg bw) through oral gavage. The effects of RJ on glutathione (GSH), catalase activity (CAT), and malondialdehyde (MDA) levels were determined via spectrophotometer. Western blot analysis was performed to investigate the effects of royal jelly on the protein expression levels of Bax, caspase-3, caspase-6, Bcl-2, NF-κB, COX-2, and Erk. It was also studied the effects of RJ on histopathological alterations in fluoride-induced damage to the rat brain. As a result, the Bcl-2, NF-κB, and COX-2 protein expression levels were increased in the fluoride-treated (50 and 100 mg/kg) groups but they were decreased significantly by RJ treatment in the brain tissue. Additionally, the protein expression of caspase-3, caspase-6, Bax, and Erk were decreased in fluoride-treated groups and they were significantly increased by RJ treatment compared to the un-treated rats. Our results suggested that RJ prevented fluoride-induced brain tissue damage through anti-antioxidant activities.

Fullerene C60 Attenuates Heart Tissue Inflammation by Modulating COX-2 and TNF-Alpha Signaling Pathways in DMBA Induced Breast Cancer in Rats.

The present study aimed to investigate the therapeutic effect of fullerene C60 nanoparticle against heart tissue damage caused by 7,12-dimethylbenz [a] anthracene (DMBA) in female rats. Female Wistar albino rats, 8 weeks old (n = 60) weighing around (150 ± 10 g) were used for the study. These rats were divided into 4 groups and each group included 15 rats. Groups: (i) Control Group: Fed with standard diet; (ii) C60 Group: C60 (1.7 mg/kg bw, oral gavage); (iii) DMBA Group: DMBA (45 mg/kg bw, oral gavage); (iv) C60 and DMBA Group: C60 (1.7 mg/kg bw, oral gavage) and DMBA (45 mg/kg bw, oral gavage) group. Malondialdehyde (MDA) analysis, catalase activity (CAT), and glutathione (GSH) in heart tissue were determined by spectrophotometer. In addition, heart tissue DNA damage was investigated. Caspase-3, p53, HO-1, COX-2, and TNF-α protein expression levels in heart tissue were determined by western blotting. As a result, Caspase-3, p53, HO-1 protein expression, GSH levels and CAT activity increased, COX-2, TNF-α protein expression, and MDA levels were significantly decreased in the C60 + DMBA group compared to the DMBA group. Therefore, the fullerene C60 nanoparticle may be a promising and effective therapy for the treatment of heart diseases associated with inflammation.

Royal jelly arranges apoptotic and oxidative stress pathways and reduces damage to liver tissues of rats by down-regulation of Bcl-2, GSK3 and NF-κB and up-regulation of caspase and Nrf-2 protein signalling pathways.

IntroductionRoyal jelly (RJ) from the honey bee, Apis mellifera, is a traditional product that is widely used as a food supplement to support the medical treatment of various diseases.Material and methodsOur study continued for 8 weeks. 42 Wistar albino (8 weeks old) male rats were used in the study. The study included 6 groups; Group 1: Control group (fed with standard diet), Group 2: RJ (100 mg/kg, bw), Group 3: F-50 (50 mg/kg, bw), group 4: F-100 (100 mg/kg, bw) group 5: F-50 (50 mg/kg, bw) + RJ (100 mg/kg, bw) Group 6: F-100 (100 mg/kg, bw) + RJ (100 mg/kg, bw). Malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) activities in liver tissue were determined by spectrophotometer. Liver tissue samples were examined histopathologically and various protein levels were determined by Western blotting technique.ResultsRJ caused a significant decrease in MDA level, Bcl-2, GSK3 and NF-κB protein expression levels, whereas induced a significant increase in GSH level, CAT activities and Bax, BDNF, caspase-6, caspase-3, Nrf-2 protein expression levels.ConclusionOur findings suggest RJ to be used as a hepatoprotective agent in the clinic to modulate the toxic effects of fluoride and other chemicals in the future.

A new approach on the regulation of NF-κB and Bax protein signaling pathway activation by royal jelly in fluoride-induced pancreas damage in rats.

Forty-two healthy adult male rats (Wistar albino, n = 42, 8 weeks old, starting weights 200-250 g) employed in this study were subdivided into six groups randomly with seven rats per group as follows: (i) Control group: received standard diet; (ii) RJ group: received standard diet supplemented with royal jelly; (iii) F50 group: received standard diet supplemented with fluoride (50 mg/kg BW); (iv) F100 group: received standard diet supplemented with fluoride (100 mg/kg BW); (v) F50 +RJ group: received standard diet supplemented with fluoride (50 mg/kg BW) and royal jelly; (iv) F100 +RJ group: received standard diet supplemented with fluoride (100 mg/kg BW) and royal jelly. The study continued for a total of eight weeks. Western blot analysis was conducted to determine the post-translational expression levels of NF-κB, Bax, Bcl-2, TNF-α, Caspase-3 and Caspase-6 proteins in pancreas tissue. The pancreatic tissue was subjected to histopathological evaluation. Furthermore, MDA, GSH and CAT activities were examined by spectrophotometric analyzes. Our findings demonstrate that, compared to the control and RJ groups, Bcl-2 protein expression was augmented and, conversely, Caspase-6, Caspase-3 and Bax protein levels were decreased upon fluoride treatment. A statistically significant increase in TNF-α and NF-κB protein expressions was observed in the groups with fluoride-induced damage compared to the control and RJ groups. The MDA levels were increased in all fluoride-treated rats compared to those in the control and RJ groups, whereas the CAT and GSH activities were reduced in all rats with fluoride- induced damage. Although there was not a great difference between the groups regarding histopathological findings, there was a tendency to decrease in the rate of damage upon royal jelly treatment.

Protective effect of royal jelly on fluoride-induced nephrotoxicity in rats via the some protein biomarkers signalling pathways: a new approach for kidney damage.

INTRODUCTION: Protective effect of royal jelly (RJ) on fluoride-induced nephrotoxicity was investigated in this study. METHODS: 42 healthy male Wistar rats (n = 42, 8 weeks of age) were divided equally into 6 groups with 7 rats in each; (1) Group-1: Controls fed with standard diet; (2) Group-2: RJ [100 mg/kg] bw (body weight), by oral gavage; (3) Group-3: Fluoride [50 mg/kg] bw, in drinking water; (4) Group-4: Fluoride [100 mg/kg] bw, in drinking water; (5) Group-5: RJ [100 mg/kg] bw, by oral gavage + Fluoride [50 mg/kg] bw, in drinking water; (6) Group-6: RJ [100 mg/kg] bw, by oral gavage + Fluoride [100 mg/kg] bw, in drinking water. After 8 weeks, all rats were decapitated and their kidney tissues were removed for further analysis. The protein expression levels of caspase-3, caspase-6, caspase-9, Bcl-2, Bax, VEGF, GSK-3, BDNF, COX-2 and TNF-α proteins in kidney tissue were analysed by western blotting technique. RESULTS: RJ increased Bcl-2, COX-2, GSK-3, TNF-α and VEGF protein levels and a decreased caspase-3, caspase -6, caspase-9, Bax and BDNF protein levels in fluoride-treated rats. CONCLUSION: RJ application may have a promising therapeutical potential in the treatment of many diseases in the future by reducing kidney damage.

Ellagic acid inhibits proinflammatory intermediary manufacture by suppressing NF-κB/Akt, VEGF and activating Nrf-2/Caspase-3 signaling pathways in rat testicular damage: a new way for testicular damage cure and in silico approach.

Ellagic acid (EA) has protective effect on testicular damage and this natural compound decreases oxidative damage. The present study aims to examine the preventive effect of ellagic acid (EA) against carbon tetrachloride (CCl4)-induced testicular tissue damage in rats. In testicular tissue, tumor necrosis factor-α (TNF-α), Nuclear factor erythroid-2 related factor 2 (Nrf-2), B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor (VEGF), Nuclear factor-kappa B (NF-κB), cysteine aspartic proteases (caspase-3) and protein kinase B (Akt) synthesis levels were analyzed by western blot method, reactive oxygen species (ROS) was measured by malondialdehyde (MDA) levels, Glutathione (GSH) level and catalase (CAT) by spectrophotometer. As a result, in comparison with the CCl4 group, caspase-3 and Nrf-2 protein synthesis levels increased in EA + CCl4 group, however, VEGF, Bcl-2, NF-κB, TNF-α and Akt protein synthesis levels decreased, EA application raised GSH levels and CAT activity, reduced MDA levels. In this study, in silico tools were applied to confirm the activity of EA against the cancer with macromolecules such as the above mentioned transcription factors. EA, turned out to show significant activity similarly to some cocrystal ligands, particularly against cancer. These results points out that EA can be used as a testicular damage cure drug in future.

Royal jelly regulates the caspase, Bax and COX-2, TNF-α protein pathways in the fluoride exposed lung damage in rats.

The study was carried out on 42 male rats divided into six groups with 7 rats in each group: two control groups, two injury groups and two treatment groups. One of the control groups received a basal diet while the other one was fed a basal diet supplemented with royal jelly (RJ) (100 mg/kg). The two injury groups were given 50 mg/kg and 100 mg/kg fluoride, respectively. The two treatment groups exposed to 50 mg/kg and 100 mg/kg fluoride were both fed basal diets with RJ (100 mg/kg). Lungs were taken for histopathological examination. Spectrophotometric analysis was utilized to determine Malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) activities, and Western blotting technique was used to evaluate the levels of specific proteins. On one hand, our experiments revealed that RJ caused decreased MDA levels, and downregulation of COX-2, Bcl-2, GSK3 and TNF-α protein expressions. On the other hand, rolay jelly caused augmented GSH and CAT activities, as well as upregulated Bax, BDNF, caspase-3, caspase-6, caspase-9 protein expressions in rats injuried by the fluoride exposure. The results suggest that the application of RJ was very likely to have a healing effect on the degenerative changes seen in the examined tissue.

In vivo, in vitro and in silico anticancer investigation of fullerene C60 on DMBA induced breast cancer in rats.

AIMS: The aim of the study was to determine the protective and therapeutic effect of fullerene C60 nanoparticle on DMBA-induced breast cancer in rats. MAIN METHODS: In vitro cell viability was determined by the WST-1 test. In vivo analysis was performed in female Wistar Albino rats. The expression of caspase-3, Bcl-2, Nrf-2, NF-κB, TNF-α, COX-2, p53, IL-6, IL-1α ve p38α (MAPK) proteins were assessed by western blotting. Furthermore, malondialdehyde (MDA), glutathione (GSH), catalase activity (CAT), total protein levels and DNA damage were investigated. In addition, tissues were evaluated by histopathologically. In in silico analysis, the binding affinities of the fullerene C60 nanoparticle to transcription factors such as caspase-3, Bcl-2, Nrf-2, NF-κB, TNF-α, COX-2, VEGF and Akt were demonstrated by molecular docking. KEY FINDINGS: Treatment of MCF-7 cells at various concentrations of fullerene C60 (0.1 to 100 mg/ml) inhibited cell viability in a dose dependent manner. Fullerene C60 treated rats exhibited considerable increase in the level of caspase-3 while decrease in the level of pro-survival protein Bcl-2. Bcl-2, NF-κB, TNF-α, COX-2, IL-6, IL-1α and p38α (MAPK) protein expression levels and malondialdehyde (MDA) levels were decreased in the C60 + DMBA groups compared to the DMBA group. It was observed that caspase-3, Nrf-2 and p53 protein expression levels, glutathione (GSH) level, catalase activities (CAT) and total protein levels increased significantly which was further confirmed through the resulting DNA fragmentation. SIGNIFICANCE: In silico assays, fullerene C60 has been observed to have similar affinity to some crystal ligands, especially against cancer.

The inducing of caspase and Bcl-2 pathway with royal jelly decreases the muscle tissue damage exposed with fluoride in rats.

In this study, 42 Wistar albino male rats (n = 42, 8 weeks old) were used. Rats were divided into 6 groups and 7 rats included each group. Groups: (i) Control group: Standard diet; (ii) RJ (royal jelly) group: Standard diet + royal jelly; (iii) F50 group: Standard diet + 50 mg/kg fluoride; (iv): F100 group: Standard diet + 100 mg/kg fluoride; (v) F50+RJ group: Standard diet + 50 mg/kg fluoride + royal jelly; (vi): F100+RJ group: Standard diet + 100 mg/kg fluoride + royal jelly. After 8 weeks, the rats were decapitated, and their muscle tissues were removed. Expression levels of Caspase-3, Caspase-6, Bax, tumor necrosis factor-α (TNF-α), interleukin 1 alpha (IL1-α) and Bcl-2 proteins in muscle tissue were determined by western blotting method. Histopathological analyses were also performed on the muscle tissue. Malondialdehyde (MDA), glutathione (GSH) and catalase (CAT) analyses were determined by a spectrophotometer. According to the obtained results, Bcl-2, TNF-α and IL1-α protein expression was increased in damage groups compared to the control and royal jelly groups, while Caspase-3, Caspase-6 and Bax protein expression levels decreased in damage groups. MDA level increased in damage groups compared to the control and royal jelly groups, while CAT and GSH levels increased with royal jelly application in royal jelly-given group in comparison to the flouride-exposed group. According to histopathological analysis results, edema and inflammatory cell formations were found in the injury groups, a tendency to decrease in these injuries was observed in the treatment groups. Based on these results, we can say that royal jelly has protective effects on muscle tissue against fluoride damage.

Royal jelly abrogates flouride-induced oxidative damage in rat heart tissue by activating of the nrf-2/NF-κB and bcl-2/bax pathway.

Royal jelly is known to strengthen memory, provide antioxidative, antidiabetic, antitumor, anticancer, antibacterial, antiinflammatory, antihypertensive. In this study, 42 rats (n = 42) were used, and these rats were divided into 6 groups of 7 rats each. Groups: (i) Control Group: Group fed with standard diet; (ii) Royal Jelly (RJ) Group: RJ (100 mg/kg bw, gavage); (iii) F50 Group: Fluoride (50 mg/kg bw, drinking water); (iv) F100 Group: F (100 mg/kg bw, drinking water); (v) F50 + RJ Group: F (50 mg/kg bw, drinking water) + RJ (100 mg/kg bw, gavage); (vi) F100 + RJ Group: F (100 mg/kg bw, drinking water) + RJ (100 mg/kg bw, gavage). The rats were decapitated after 8 weeks, and their heart tissues were taken and examined. Lipid peroxidation by MDA (malondialdehyde) analyzes, GSH (glutathione) level and catalase activity were determined by spectrophotometer. Protein expression levels of caspase-3, caspase-6, caspase-9, Bcl-2, Bax, BDNF, Gsk-3, Nrf-2 and NF-κB proteins in heart tissue were determined by western blotting technique and hearth tissue evaluated by histopathologically. As a result, MDA levels, Bcl-2, Gsk-3 and NF-κB protein expression levels were reduced, whereas GSH levels, caspase-3, caspase-9, caspase-6, Bax, BDNF and Nrf-2 protein levels were increased in the F50 + RJ and F100 + RJ groups compared to the F50 and F100 groups. According to the results of this study, it has been concluded that Royal jelly has the potential to be developed in to a drug for treatment of heart diseases in addition to providing protection against heart damage.

The impact of ellagic acid on some apoptotic gene expressions: a new perspective for the regulation of pancreatic Nrf-2/NF-κB and Akt/VEGF signaling in CCl4-induced pancreas damage in rats.

OBJECTIVE: The aim of this study was to evaluate the potential effect of ellagic acid (EA) in the treatment of pancreatic injury. EA has been found to have strong anti-inflammatory, antioxidative, and anticancer properties. The effects of EA on pancreati˜c star cell (PSC) activation and cell functions have been evaluated and it has been shown that it inhibits the activation of basic cell functions and PSCs and. it has antidiabetic activity through its effect on ß-pancreas cells. MATERIALS AND METHODS: In this work, 36 Wistar albino rats (n = 36, 8 weeks old) were used. Rats were divided to 4 groups and 9 rats were each group. Groups: Group 1: control group; Group 2: EA group; Group 3: carbon tetrachloride (CCl4) group; Group 4: EA + CCl4 group. Animals were decapitated after 8 weeks and their pancreas tissue samples were taken and researched. In pancreas tissue, NF-κB, TNF-α, Nrf-2, VEGF, Bcl-2, caspase-3, and Akt proteins expression ratios were analyzed by western blotting method, CAT activity and GSH levels were determined by spectrophotometer and ROS production was detected by MDA. RESULTS: In our results, the Nrf-2 and caspase-3 protein expressions, catalase activities and GSH levels increased, TNF-α, NF-κB, Bcl-2, VEGF, and Akt protein expressions and MDA levels reduced in EA + CCl4 group comparable to the CCl4 group. CONCLUSIONS: These findings reveal that EA decreases pancreas tissue injury in rats and that EA may also be used as a drug against pancreas tissue injury in the future.

Biological and Oxidative Effect of Ellagic Acid on Saccharomyces cerevisiae: A New Way for Culture Developing

Abstract In this study, the effects of Ellagic acid (EA) on protein expression in yeasts and cellular development were investigated. Four groups were formed. Groups: 1) Control group; yeast only cultivated group; 2) Ellagic Acid (EA) group: EA (10%) given group; 3) Hydrogen peroxide (H2O2) Group: The group given H2O2 (15 mM); 4) EA + H2O2 group: EA (10%) + H2O2 (15 mM) group. After sterilization, EA (10%) and H2O2 (15 mM) were added to the Saccharomyces cerevisiae (S. cerevisiae) cultures and the cultures were grown at 30 °C for 1 hour, 3 hours, 5 hours and 24 hours (overnight). S. cerevisiae cell growth, lipid peroxidation MDA (malondialdehyde) analysis and GSH (glutathione) level were analyzed by spectrophotometer. Total protein changes were determined by SDS-PAGE electrophoresis and measured by the Bradford method. According to the obtained results, compared with the H2O2 group, cell development (1, 3, 5 and 24 hours), GSH level and total protein synthesis (24 hours) were increased with EA, while MDA level (24 hours) decreased. These results show that EA reduces oxidative damage, increases cell growth and it has a protective effect to promote protein synthesis in S. cerevisiae culture.

Ellagic acid prevents kidney injury and oxidative damage via regulation of Nrf-2/NF-κB signaling in carbon tetrachloride induced rats.

Phytochemicals, bioactive food compounds, found in plants have been described as protective agents against renal injury. This work was planned to evaluate the effects of EA on anti-oxidative and anti-inflammation pathways in kidney damage induced with carbon tetrachloride. In this study, experimental animals (n = 36, 8 weeks old rats) were divided into 4 groups as follows: 1) Control group 2) EA group (10 mg/kg body weight) 3) CCl4 group (1.5 ml/kg, body weight) 4) EA + CCl4 group. The potentially protective effect of EA on kidney damage exposed by CCl4 in rats were evaluated. EA administration protects CCl4 induced kidney damage against oxidative stress through its antioxidant protection. Treatment of EA significantly reduced lipid peroxidation and improved glutathione and catalase enzyme activity. Recently studies showed that EA activated caspase-3 and nuclear transcription factor erythroid 2 related factor driven antioxidant signal pathway and protected the kidney against damage induced by oxidative stress. Furthermore, EA also markedly decreased the level of cyclooxygenase-2, the vascular endothelial growth factor and tumor necrosis factor-alpha and suppressed the protein synthesis of nuclear factor-kappa-B. This study reveals that EA has kidney protective effect against CCl4 induced oxidative damage and inflammation.

The preventive effect of ellagic acid on brain damage in rats via regulating of Nrf-2, NF-kB and apoptotic pathway.

The aim of this study was to investigate the neuroprotective role of ellagic acid (EA) on CCl4 -induced brain injury in rats. In this study, the rats were divided into four groups. Groups: (1) Control group; (2) EA group; (3) CCl4 group; (4) EA + CCl4 group. In brain tissue, tumor necrosis factor-α (TNF-α), nuclear factor kappa b (NF-kB), cyclooxygenase-2 (COX-2), nuclear erythroid related factor 2 (Nrf-2), cysteine-aspartic acid protease (caspase-3), VEGF (vascular endothelial growth factor) and B-cell lymphoma-2 (bcl-2) protein expression levels were analyzed by western blotting. MDA (malondialdehyde), catalase enzyme activity (CAT) and glutathione (GSH) analysis were determined by spectrophotometer. In our findings, EA ameliorated Nrf-2 and caspase-3 protein expression levels, GSH and catalase activities, NF-kB, TNF-α, VEGF, Bcl-2, COX-2 protein expression levels and MDA levels in CCl4 intoxicated rats. These results suggest that EA demonstrated the neuroprotective effect on CCl4 -induced brain damage in rats. PRACTICAL APPLICATIONS: Ellagic acid has different biological activities, these are; antioxidant, anti-inflammatory, antidepressant, antifibrosis, anticancer, neuroprotective and hepatoprotective. For example it was reported that EA protects the cells against DNA injury induced by free radicals and it can prevent the traumatic brain injury. These results obtained from this study reveals that EA has a protective effect against rat brain damage and it may be used as an alternative drugs for the brain injury treatment in future.

The effect of ellagic acid on caspase-3/bcl-2/Nrf-2/NF-kB/TNF-α /COX-2 gene expression product apoptosis pathway: a new approach for muscle damage therapy.

The goal of this study was to determine the protective role of ellagic acid (EA) against CCl4-induced muscle injury in rats. In this study, 36 Wistar albino rats (n = 36, 8 weeks old) were used. The rats were divided into 4 groups and 9 rats were included each group. Groups: (i) control Group: standard diet; (ii) EA Group: standard diet + EA group; (iii) CCl4 group: standard diet + CCl4 group; (iv) EA + CCl4 group: standard diet + EA + CCl4. The animals were decapitated after 8 weeks, and their muscle tissues were received and investigated. In the muscle tissue, TNF-α, COX-2, Nrf-2, NF-kB, caspase-3 and bcl-2 expression levels were analyzed by the western blotting technique, lipid peroxidation was detected by MDA (malondialdehyde), and catalase and GSH levels were determined by a spectrophotometer. In our findings, in comparison to the CCl4 group, in the EA + CCl4 group, the Nrf-2 and caspase-3 protein expression levels, GSH and catalase activities increased, while the NF-kB, bcl-2, TNF-α and COX-2 protein expression levels and MDA levels decreased. These results suggest that EA reduces muscle tissue damage rate in rats and that EA may also be used as a potential drug to protect against muscle tissue damage in the future.

Ellagic acid ameliorates lung damage in rats via modulating antioxidant activities, inhibitory effects on inflammatory mediators and apoptosis-inducing activities.

Phytochemicals is considered one of the most effective and safe alternative therapy against oxidative linked lung diseases. Ellagic acid (EA), an important component of fruits, nuts, and vegetables, are partly responsible for their beneficial health effects against oxidation-related diseases. In the present study, we investigated the ameliorative effect of EA on lung damage induced by carbon tetrachloride (CCl4) in Wistar male albino rats. Thirty-six male rats (n = 36, 8-week old) were divided into 4 groups, each with 9 rats. The groups were: Control group: received standard diet; EA group: administered with EA (10 mg/kg body weight, intraperitoneal); CCl4 group: administered with CCl4 (1.5 mg/kg body weight, intraperitoneal); EA+CCl4 group: administered with EA and CCl4. . The rats were decapitated at the end of experimental period of 8 weeks and the lung tissues were examined. CCl4-induced rats showed elevation in the expressions of inflammatory proteins, nuclear factor kappa b (NF-κB), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α); and the indicator of lipid peroxidation, malondialdehyde (MDA). Intraperitoneal administration of EA significantly reduced the levels of these markers. EA administration increased the protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf-2) and enhanced the activity of glutathione (GSH) and catalase enzyme (CAT). In addition, EA administration increased the expression levels of the executioner protein of apoptosis, caspase-3, and decreasing pro-survival protein, B cell lymphoma-2 (Bcl-2). In conclusion, these results establishes the protective role of EA in the treatment of lung damage and that in the future, this may have the potential to be used as a medication for the prevention or attenuation of lung diseases. Graphical abstract.