Flavonoid-Rich Sambucus nigra Berry Extract Enhances Nrf2/HO-1 Signaling Pathway Activation and Exerts Antiulcerative Effects In Vivo.

Sambucus nigra (SN) berry extract is characterized by high antioxidant and anti-inflammatory activity. The current study aimed to investigate the effect of SN berry extract against indomethacin (IND)-induced gastric ulcer in rats and the mechanism involved. SN berry extract alleviated IND-induced gastric ulcers, as shown by assessing pathological manifestations in the gastric mucosa. These protective effects are attributed to attenuated oxidative damage to the gastric mucosa, correlated to increased activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), enhanced glutathione (GSH) levels, total antioxidant capacity (TAC), and upregulation of the Nrf2/HO-1 cascade. Moreover, oxidative stress markers, including malondialdehyde (MDA) and total oxidant status (TOS), were downregulated in SN-extract-treated animals. Furthermore, SN berry extract suppressed gastric mucosal inflammation by downregulating interleukin (IL)-33, IL-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α) levels, and attenuating myeloperoxidase (MPO) activity. The protective effects of SN berry extract were similar to those exerted by esomeprazole (ESO), an acid-secretion-suppressive drug. In conclusion, SN berry extract has antiulcerative effects, alleviating oxidative stress and inflammation.

Chlorogenic Acid Attenuates Doxorubicin-Induced Oxidative Stress and Markers of Apoptosis in Cardiomyocytes via Nrf2/HO-1 and Dityrosine Signaling.

(1) Background: Doxorubicin (DOX) is extensively used for cancer treatments; however, its clinical application is limited because of its cardiotoxic adverse effects. A combination of DOX and agents with cardioprotective properties is an effective strategy to ameliorate DOX-related cardiotoxicity. Polyphenolic compounds are ideal for the investigation of novel cardioprotective agents. Chlorogenic acid (CGA), an essential dietary polyphenol found in plants, has been previously reported to exert antioxidant, cardioprotective, and antiapoptotic properties. The current research evaluated CGA's in vivo cardioprotective properties in DOX-induced cardiotoxicity and the probable mechanisms underlying this protection. (2) Methods: CGA's cardioprotective properties were investigated in rats that were treated with CGA (100 mg/kg, p.o.) for fourteen days. The experimental model of cardiotoxicity was induced with a single intraperitoneal (15 mg/kg i.p.) injection of DOX on the 10th day. (3) Results: Treatment with CGA significantly improved the DOX-caused altered cardiac damage markers (LDH, CK-MB, and cTn-T), and a marked improvement in cardiac histopathological features accompanied this. DOX downregulated the expression of Nrf2/HO-1 signaling pathways, and the CGA reversed this effect. Consistently, caspase-3, an apoptotic-related marker, and dityrosine expression were suppressed, while Nrf2 and HO-1 expressions were elevated in the cardiac tissues of DOX-treated rats after treatment with the CGA. Furthermore, the recovery was confirmed by the downregulation of 8-OHdG and dityrosine (DT) expressions in immunohistochemical findings. (4) Conclusions: CGA demonstrated a considerable cardioprotective effect against DOX-induced cardiotoxicity. One of the possible mechanisms for these protective properties was the upregulation of the Nrf2/HO-1-dependent pathway and the downregulation of DT, which may ameliorate oxidative stress and cardiomyocyte apoptosis. These findings suggest that CGA may be cardioprotective, particularly in patients receiving DOX-based chemotherapy.

Resveratrol in Neurodegeneration, in Neurodegenerative Diseases, and in the Redox Biology of the Mitochondria.

Neurodegeneration is a process leading to the progressive loss of structure and functions of neurons. Many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease have shown many common points at the subcellular level. Neurons are metabolically active cells and need a high amount of energy. Mitochondria are known as the energy synthesis center for cells, involved in the synthesis of adenosine triphosphate by oxidative phosphorylation. Rather than just being an energy synthesis center, it has critical importance for many cellular functions such as calcium homeostasis, cell proliferation, cell growth, and apoptosis. In the process of mitochondrial dysfunction, cellular functions are disrupted and cells enter the apoptotic or necrotic pathway. Resveratrol (trans-3,5,4-trihydoxystilbene), a plant-derived polyphenol found in the seed of grapes, berries, peanuts, and wine, has many biological effects such as inhibition of lipid peroxidation, scavenging of free radicals, changes in eicosanoid synthesis, inhibition of platelet aggregation, anti-inflammatory and anticancer activity, and regulation of lipid metabolism. Through the reviewed literature, the current study investigated the protective role of resveratrol in neurodegenerative diseases. Studies show that resveratrol moderates mitochondrial function, redox status, and cellular dynamics in both in vivo and in vitro experimental models of neurodegeneration. Resveratrol suppresses reactive oxygen species production by reducing the activity of complex III due to its competition effect with coenzyme Q. In the present work, we discussed the protective effects of resveratrol on neurodegeneration, neurodegenerative diseases, and the redox biology of the mitochondria.

Effects of biotin deficiency on short term memory: The role of glutamate, glutamic acid, dopamine and protein kinase A.

Insufficient dietary biotin intake, biotinidase deficiency, drug-biotin interactions can cause biotin deficiency which may result in central nervous system dysfunctions. We hypothesized that biotin deficiency could disrupt learning and memory functions by altering glutamate, glutamine, dopamine levels and protein kinase A (PKA) activity in the hippocampus. Sixteen female and 4 male Wistar rats were mated and females were separated into 4 groups. Three pups were selected from each mother and a total of 48 pups were divided into the following experimental groups. NN group, normal diet in the prenatal and postnatal period. NB group, normal diet in the prenatal and a biotin-deficient diet in the postnatal period. BN group: biotin-deficient diet in the prenatal and a normal diet in the postnatal period, BB group: biotin-deficient diet in both the prenatal and postnatal period. Open Field, Y-Maze, Object Location, and Novel Object Recognition Tests were performed in all groups and rats were sacrificed. Glutamine, glutamate, dopamine levels and PKA activity were analyzed in the hippocampi. In the open field test, distance and velocity values of NB, BN and BB groups were decreased with respect to the NN group. Learning and memory functions of NB, BN and BB groups were found to be impaired in behavioral tests. Dopamine levels and PKA activity were also decreased in all rat pups fed with a biotin deficient diet. In conclusion, we demonstrated that biotin deficiency deteriorates short-term memory and locomotor activity. This impairment may relate to decreased dopamine levels and PKA activity in the hippocampus.

Effect of chronic L-carnitine supplementation on carnitine levels, oxidative stress and apoptotic markers in peripheral organs of adult Wistar rats.

This study investigated the effects of L-carnitine supplementation on carnitine levels, oxidative stress and apoptotic markers in the stomach, kidney, liver and testis tissues in adult rats. Rats were randomized to control and L-carnitine supplemented (LCAR) groups. Control group received distilled water for 7 months by intragastric gavage and the LCAR group was given 50 mg/kg/day L-carnitine via intragastric intubation for the same period. L-carnitine concentrations and caspase-3 activity were measured by fluorometric methods while cleaved caspase-3 was determined by Western blot analysis. Bcl-2 associated X protein (Bax) and B-cell lymphoma/leukemia-2 (Bcl-2) were quantified by enzyme immunoassay and Western blot analysis. Oxygen/nitrogen species (ROS/RNS) and total antioxidant capacity (TAC) were analyzed by colorimetric assay. Tissue L-carnitine concentrations were significantly increased in the LCAR group compared to controls. Anti-apoptotic Bcl-2 levels were significantly increased while pro-apoptotic Bax was significantly decreased in LCAR group rats compared to controls. Tissue caspase-3 was significantly alleviated in the LCAR group compared to controls. L-carnitine supplementation increased TAC and decreased ROS/RNS generation in the kidney, liver, stomach and testis tissues compared to controls. Obtained data suggests that L-carnitine supplementation can potentially be used to lessen both oxidative and apoptotic progression in peripheral organs.