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Oxidative stress is a pivotal factor in the pathogenesis of various cardiovascular diseases. Rhodiola, a traditional Chinese medicine, is recognized for its potent antioxidant properties. Salidroside, a phenylpropanoid glycoside derived from Rhodiola rosea, has shown remarkable antioxidant capabilities. This study aimed to elucidate the potential protective mechanisms of Rhodiola and salidroside against H 2 O 2 -induced cardiac apoptosis in H9c2 cardiomyoblast cells. H9c2 cells were exposed to H 2 O 2 for 4 h, and subsequently treated with Rhodiola or salidroside for 24 h. Cell viability and apoptotic pathways were assessed. The involvement of insulin-like growth factor 1 receptor (IGF1R) and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) were investigated. H 2 O 2 (100 μM) exposure significantly induced cardiac apoptosis in H9c2 cells. However, treatment with Rhodiola (12.5, 25, and 50 μg/mL) and salidroside (0.1, 1, and 10 nM) effectively attenuated H 2 O 2 -induced cytotoxicity and apoptosis. This protective effect was associated with IGF1R-activated phosphorylation of ERK1/2, leading to the inhibition of Fas-dependent proteins, HIF-1α, Bax, and Bak expression in H9c2 cells. The images from hematoxylin and eosin staining and immunofluorescence assays also revealed the protective effects of Rhodiola and salidroside in H9c2 cells against oxidative damage. Our findings suggest that Rhodiola and salidroside possess antioxidative properties that mitigate H 2 O 2 -induced apoptosis in H9c2 cells. The protective mechanisms involve the activation of IGF1R and subsequent phosphorylation of ERK1/2. These results propose Rhodiola and salidroside as potential therapeutic agents for cardiomyocyte cytotoxicity and apoptosis induced by oxidative stress in heart diseases. Future studies may explore their clinical applications in cardiac health., (© 2024 Wiley Periodicals LLC.)

Background: Cardio-dysfunction is one of the complications in patients with diabetes mellitus (DM). This paper aimed to investigate if oral administration of green tea Epigallocatechin-3-gallate (EGCG, E) and transplantation of adipose-derived stem cells (ADSC) show cross effects on the treatment of cardiomyopathy in rats with type 1 DM., Materials and Methods: Wistar male rats were divided into four groups (each group contained 8 animals) including sham, DM (diabetic group), DM + ADSC (DM group with ADSC treatment) and DM + ADSC + E (DM + ADSC group with oral administration of EGCG)., Results: Pathological parameters including hypertrophy, inflammation, and fibrosis were activated in DM group. By contrast, all parameters were significantly improved in treatment group (DM + ADSC group). In addition, improvement of pathological parameters in DM + ADSC + E was significantly better than DM + ADSC., Conclusion: We found that EGCG can increase expression of survival marker in ADSC under high glucose environment and reduce serum oxidative stress in DM rats.

Doxorubicin (DOX) is a widely used antitumor drug that causes severe neurotoxicity in patients. Diallyl trisulfide (DATS) is an organosulfur compound with established potent antioxidant and anti-inflammatory properties. Herein, we investigated the neuroprotective efficacy of DATS in preventing DOX-induced neurotoxicity in a rat model. Specifically, DATS (40 mg/kg) was administered to rats 24 h after DOX treatment, once a week for 8 weeks. Our results showed that DATS treatment led to a decrease in plasma levels of tumor necrosis factor-alpha (TNF-α) induced by DOX. DATS restored cerebral cortex and hippocampus histopathological architecture and neuronal loss. Immunohistochemical staining indicated that DATS decreased the expression of glial fibrillar acidic protein (GFAP) in DOX treated rats. Components of stress-related inflammatory proteins (TNF-α, phospho nuclear factor kappa B (NF-κB), inducible nitricoxide synthase (iNOS) and cyclooxygenase-2 (COX-2)) were all significantly increased in the DOX group, in comparison with the control group, whereas they were decreased after DATS treatment. In addition, the mRNA of antioxidant enzymes (superoxide dismutase 2 (SOD2), catalase, glutathione peroxidase 1, 4 (GPx1 and GPx4)) and antioxidant proteins (heme oxygenase-1 (HO-1), superoxide dismutase 1, 2 (SOD1 and SOD2), Γ-glutamylcysteine synthase (Γ-GCSc)) were markedly increased in DOX group compared with the control group, which were significantly attenuated by DATS treatment. The upregulation of antioxidants enzymes in DOX group was probably a compensatory effect against elevated oxidative stress induced by DOX. DATS treatment could ameliorate this oxidative stress in brain. Our results suggested that DATS has potential clinical applications in the prevention of DOX-induced neurotoxicity by ameliorating inflammatory insults and oxidative stress., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aims: Luteolin is a common flavonoid that is abundantly present in various edible plants, it is known to exhibit beneficial effects on cardiovascular system. However, the mechanisms which underlie the protective effects of luteolin on endothelial cell damage caused by oxidative stress remains unclear. The purpose of this study is to test the hypothesis which states that luteolin protects against H 2 O 2 -induced oxidative stress via modulating ROS-mediated P38 MAPK/NF-κB and calcium-evoked mitochondrial apoptotic signalling pathways., Methods and Results: Human umbilical vein endothelial cells (HUVECs) were pretreated with luteolin prior to being stimulated by 600 μM H 2 O 2 for another 24 h. The expression of native and phosphorylated-P38, IκB, NF-κB, native eNOS, phosphorylated-eNOS, iNOS and several apoptosis-related proteins were analyzed by Western blot. In addition, intracellular calcium was determined by fura-2 AM and mitochondrial membrane potential was examined by using JC1. Using the data gathered, we found indications that H 2 O 2 induced P38 MAPK/NF-κB activation. H 2 O 2 downregulated the expression of eNOS and upregulated iNOS, which in turn contribute to an elevated NO generation and protein nitrosylation. However, pretreatment with luteolin markedly reversed all of these alterations dose-dependently. Additionally, an intracellular calcium rise and subsequent mitochondrial membrane potential collapse, P53 phosphorylation, reduced BcL-2/Bax ratio in the mitochondrial membrane, release cytochrome c from mitochondria, leading to the subsequent activation of caspase 3 activation by H 2 O 2 were all markedly suppressed in the presence of luteolin., Conclusion: Results from this study may provide the possible molecular mechanisms underlying cardiovascular protective effects of luteolin., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Doxorubicin (DOX) is an anthracycline antibiotic commonly employed for the treatment of various cancers. However, its therapeutic uses are hampered by side effects associated with cumulative doses during the course of treatment. Whereas deregulation of autophagy in the myocardium has been involved in a variety of cardiovascular diseases, the role of autophagy in DOX-induced cardiomyopathy remains debated. Our earlier studies have shown that DOX treatment in a rat animal model leads to increased expression of the novel stress-inducible protein insulin-like growth factor II receptor-α (IGF-IIRα) in cardiac tissues, which exacerbated the cardiac injury by enhancing oxidative stress and p53-mediated mitochondria-dependent cardiac apoptosis. Through this study, we investigated the contribution of IGF-IIRα to dysregulation of autophagy in heart using both in vitro H9c2 cells (DOX treated, 1 µM) and in vivo transgenic rat models (DOX treated, 5 mg/kg ip for 6 wk) overexpressing IGF-IIRα specifically in the heart. We found that IGF-IIRα primarily localized to mitochondria, causing increased mitochondrial oxidative stress that was severely aggravated by DOX treatment. This was accompanied by a significant perturbation in mitochondrial membrane potential and increased leakage of cytochrome c , causing increased cleaved caspase-3 activity. There were significant alterations in phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated Unc-51 like kinase-1 (p-ULK1), PARKIN, PTEN-induced kinase 1 (PINK1), microtubule-associated protein 1 light chain 3 (LC3), and p62 proteins, which were more severely disrupted under the combined effect of IGF-IIRα overexpression plus DOX. Finally, LysoTracker Red staining showed that IGF-IIRα overexpression causes lysosomal impairment, which was rescued by rapamycin treatment. Taken together, we found that IGF-IIRα leads to mitochondrial oxidative stress, decreased antioxidant levels, disrupted mitochondrial membrane potential, and perturbed mitochondrial autophagy contributing to DOX-induced cardiomyopathy.

Oxidative stress has been implicated in the pathogenesis of atherosclerotic cardiovascular diseases. Dietary supplementation of anti-oxidants has been reported to have beneficial effects on the prevention of atherogenic diseases. Luteolin (a natural flavonoid) has been shown to possess antimutagenic, antitumorigenic, anti-oxidant and anti-inflammatory properties. However, the effects and underlying molecular mechanisms of luteolin on cardiovascular systems are poorly explored. Therefore, the aim of the present study was to test whether luteolin could protect against oxidative stress-induced endothelial cell injury and explore the underlying mechanisms. In this study, human umbilical vein endothelial cells (HUVECs) were pre-treated with luteolin followed by hydrogen peroxide induction (H 2 O 2 ). Our results showed that luteolin protected against H 2 O 2 -induced oxidative stress and ameliorated ROS and superoxide generation. In addition, we found that luteolin treatment inhibited the H 2 O 2 -induced membrane assembly of NADPH oxidase subunits, which was further confirmed by specifically inhibiting NADPH oxidase using DPI treatment. Furthermore, pAMPK protein expression was enhanced and p-PKC isoforms were significantly down-regulated by luteolin treatment in a dose-dependent manner, and a similar effect was observed upon DPI treatment. However, co-treatment with the specific inhibitor of AMPK (Compound C) restored p-PKC levels suggesting the role of AMPK signaling in regulating p-PKC expression under oxidative stress condition in HUVECs. Finally, we confirmed using siRNAs and specific inhibitor and/or activator of AMPK (AICAR) that luteolin treatment induced AMPK is a key player and regulator of activated expression of PKC isoforms and thereby confers protection against H 2 O 2 -induced oxidative stress in HUVECs.

Neferine, an alkaloid from N. nucifera has a broad range of pharmacological activity. Hypoxia mediated stress is involved in the generation of inflammatory responses and cell death. The present study evaluated the protective effect of neferine against hypoxia-induced cytotoxicity, oxidative stress and inflammatory response in human Peripheral Blood Mononuclear Cells (hPBMC). Cytotoxicity, as determined by MTT, LDH and NO assays revealed that 24h of hypoxic exposure results in 20% cell death (IC 20 ) and compromising of cellular integrity, which was restored to near control values by pretreatment with neferine. Oxidative stress parameters such as lipid peroxidation and antioxidant enzymes indicated that neferine exerted a protective effect on hypoxia-induced oxidative stress. Hypoxia-induced Tumor Necrosis Factor-α (TNF-α), Interleukin 6 (IL-6), and Interleukin 8 (IL-8) release were significantly reduced in the neferine pretreated samples indicating its anti-inflammatory role. Our results demonstrate for the first time that neferine exerts a cytoprotective effect against hypoxia-induced oxidative stress and inflammation in hPBMC., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objectives: Cell transplantation therapy of Schwann cells (SCs) is a promising therapeutic strategy after spinal cord injury. However, challenges such as oxidative stress hinder satisfactory cell viability and intervention for enhancing SCs survival is critical throughout the transplantation procedures. Ocimum gratissimum, widely used as a folk medicine in many countries, has therapeutic and anti-oxidative properties and may protect SCs survival. Methods: We examined the protective effects of aqueous O. gratissimum extract (OGE) against cell damage caused by H 2 O 2 -induced oxidative stress in RSC96 Schwann cells. Results: Our results showed that the RSC96 cells, damaged by H 2 O 2 oxidative stress, decreased their viability up to 32% after treatment with different concentrations of up to 300 μM H 2 O 2 , but OGE pretreatment (150 or 200 μg/mL) increased cell viability by approximately 62% or 66%, respectively. Cell cycle analysis indicated a high (43%) sub-G1 cell population in the H 2 O 2 -treated RSC96 cells compared with untreated cells (1%); whereas OGE pretreatment (150 and 200 μg/mL) of RSC96 cells significantly reduced the sub-G1 cells (7% and 8%, respectively). Furthermore, Western blot analysis revealed that OGE pretreatment inhibited H 2 O 2 -induced apoptotic protein caspase-3 activation and PARP cleavage, as well as it reversed Bax up-regulation and Bcl-2 down-regulation. The amelioration of OGE of cell stress and stress-induced apoptosis was proved by the HSP70 and HSP72 decrease. Conclusion: Our data suggest that OGE may minimize the cytotoxic effects of H 2 O 2 -induced SCs apoptosis by modulating the apoptotic pathway and could potentially supplement cell transplantation therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Persistence of cadmium (Cd) in the environment causes serious ecological problems. Tinospora cordifolia is a medicinal herb used in Ayurveda for treating various metabolic disorders and toxic conditions. The present study investigates the protective effect of T. cordifolia stem methanolic extract (TCME) on a heavy metal, Cd-induced cardiotoxicity in male Wistar rats. Male albino Wistar rats were divided into four groups (n=6). The animals after treatment for 28days with Cd and TCME were analysed for biochemical and histological changes in the serum and heart tissues. Cd induced lipid peroxidation and protein carbonylation was significantly reduced by TCME. TCME also reduced the histological alterations induced by Cd treatment in the heart tissues with diminished loss of myocardial fibers. Administration of TCME effectively prevented the altered levels of serum marker enzymes (creatine kinase and lactate dehydrogenase), antioxidants, such as superoxide dismutase, catalase, glutathione, glutathione peroxidase and glutathione-S-transferase, and glycoproteins contents such as hexose, hexoseamine, fucose, and sialic acid by Cd intoxication. TCME also offered protection against the change in levels of Na + K + ATPase, Mg 2+ ATPase and Ca 2+ ATPase activities against Cd toxicity. The study suggests TCME as a potent cardioprotective agent against Cd induced toxicity., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Neferine (Nef), a bisbenzylisoquinoline alkaloid from lotus seed embryo has a wide range of pharmacological activities. Possible molecular mechanism for the cytoprotective action of Nef during hypoxic stress has not been explored till now. Hence, this is an attempt to elucidate the molecular mechanism involved in the Nef mediated cytoprotection on hypoxia-induced cell injury. Cytoprotective dose of Nef in muscle cells (Human rhabdomyosarcoma cells) exposed to hypoxia was determined by MTT assay. Nef at 500 nM offered better cytoprotection and was used for all the experiments. ROS, intracellular calcium accumulation and mitochondrial membrane (ΔψM) potential were measured using fluorescent probes. Further, we evaluated the effect Nef on hypoxia induced inflammatory and apoptotic responses by FACS and analyzing the expression patterns of NF-κB, COX-2, HIF-1α, caspase-3, caspase-9, Bcl2, and Bax. The results of this study revealed that pretreatment of the cells with Nef significantly decreased the ΔψM and ROS in the cells subjected to hypoxia. Further, Nef inhibited NF-κB there by inhibiting the expression of its downstream regulator COX-2, while it induced the functional HIF-1α expression. The results also indicate that Nef significantly inhibited the ROS dependent mitochondrial mediated apoptosis induced during hypoxia. The cytoprotection elicited by Nef in a model of hypoxia induced cell death involves both anti-inflammatory and anti-apoptotic response. These results suggest that Nef may be used as prophylactic agent against the hypoxic challenge. © 2016 BioFactors, 42(4):407-417, 2016., (© 2016 International Union of Biochemistry and Molecular Biology.)

Background: Male Wistar rats were divided into seven groups as follows: group A, basal diet; group B, basal diet with Cholestin at 0.1667 g kg⁻¹ body weight (BW); groups C-F, oral feeding of ethanol at 7.9 g kg⁻¹ BW; groups D-F, Cholestin in diet at 0.1667, 0.3333 and 0.5 g kg⁻¹ BW respectively; group G, silymarin in diet at 200 mg kg⁻¹ BW., Results: The results showed that treatment with Cholestin for 8 weeks reduced the impact of ethanol toxicity on serum markers of liver damage: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). The antioxidant system was significantly enhanced: plasma and hepatic thiobarbituric acid-reactive substance (TBARS) levels were lowered while hepatic superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), ethanol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities and non-enzymatic antioxidants (vitamin E, vitamin C and GSH) were elevated., Conclusion: Cholestin shows a protective effect against hepatotoxicity indices in ethanol-fed rats comparable to that of silymarin, as supported by the evaluation of liver histopathology. The data suggest that Cholestin exerts its hepatoprotective effect by decreasing lipid peroxidation and improving antioxidants status, thus proving itself as an effective antioxidant in ethanol-induced oxidative damage in rats., (© 2014 Society of Chemical Industry.)

Ixora parviflora, a species of the Rubiaceae, is rich in polyphenols and flavonoids, and has been traditionally used as a folk medicine. An I. parviflora extract (IPE) has great antioxidant activity in vitro, including a scavenging effect on superoxide radicals, reducing power, and ferrous ion-chelating ability. However, whether IPE is efficacious against oxidative damage in vivo is not known. The purpose of this study was to determine the protective effects of IPE treatment on hepatic oxidative stress and antioxidant defenses after exhaustive exercise in mice. Fifty male C57BL/6 mice (6 week old) were randomly divided into five groups and designated a sedentary control with vehicle (C), and exhaustive exercise with vehicle (IPE0), low dosage (IPE10), medium dosage (IPE50) and high dosage (IPE100) of IPE at 0, 10, 50, and 100 mg/kg, respectively. After a single bout of exhaustive swimming exercise challenge, levels of blood ammonia and creatine kinase (CK), and hepatic superoxide dismutase (SOD) protein expression, thiobarbituric acid-reactive substance (TBARS), and gp91(phox), p22(phox), and p47(phox) subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expressions in the IPE0 group were significantly affected compared to those of the C group, but they were all significantly inhibited by the IPE treatments. Results of the present in vivo study in mice indicate that I. parviflora extract possesses antioxidative and hepatoprotective potential following exhaustive exercise.

Hemodialysis can remove uremic solutes but this treatment induces oxidative stress in uremic patients because of hemo-incompatibility. Therefore, we hypothesised that an antioxidant dialysate (a dialysate containing antioxidant(s)) would provide antioxidant defence in uremic patients during hemodialysis. Several herbal extracts were studied and measurements of antioxidant power and stability assays indicated that epigallocatechin gallate (EGCG) was the best of those tested for use as an antioxidant dialysate (EGCG dialysate). We observed that EGCG dialysate could provide the highest level of antioxidant defence at a dialysate flow rate of 500 ml/min and a blood flow rate of 200 ml/min. In addition, some important parameters for hemodialysis were calculated for supporting the protective role of EGCG dialysate. This is the first description of the preparation of an antioxidant dialysate. We suggest that EGCG dialysate will reduce the level of oxidative stress in hemodialysis patients, leading to a decrease of complications associated with oxidative damage., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Uremic patients with hyperlipidemia are classified at high atherogenic risk due to oxidative stress induced by regular hemodialysis process (hemoincompatibility) and a high level of oxidized low-density lipoprotein (ox-LDL). This study aimed to investigate whether LDL apheresis was capable of reducing oxidative and atherogenic markers in uremic patients with hyperlipidemia. We found that oxidative metabolites (methylquanidine, dityrosine, and ox-LDL) and atherogenic markers (lipoprotein (a), LDL, and LDL/HDL ratio) were significantly reduced (P < 0.05) after LDL apheresis. On the other hand, plasma total antioxidant status (TAS) was not influenced after LDL apheresis. Our results suggest that LDL apheresis reduces oxidative and atherogenic markers and do not influence plasma TAS in uremic patients with hyperlipidemia. This may lead to a decreased risk of atherosclerosis in these patients. However, supplementation of dietary proteins may be necessary because of the removal of some "useful" proteins (e.g., albumin and globulin) after LDL apheresis.

Recently, we showed that L-arginine (L-Arg) supplementation could attenuate acute exercise-induced oxidative and inflammatory stress in aging rats. In this study, we investigate whether L-Arg supplementation protects cellular oxidative stress, inflammation, or the mitochondrial DNA 4834-bp large deletion (mtDNA4834 deletion) in 14-week-old young rats tissues during exhaustive exercise. Rats were randomly divided into four groups: sedentary control (SC); SC with L-Arg treatment (SC+Arg); exhaustive exercise (E); and exhaustive exercise with L-Arg treatment (E+Arg). Rats in the SC+Arg and E+Arg groups received supplemental 2% L-Arg diet. Rats in groups E and E+Arg performed an exhaustive running test on a treadmill. The results showed a significant increase in xanthine oxidase (XO) and myeloperoxidase (MPO) activities and lipid peroxide (malondialdehyde; MDA) levels of muscular, hepatic, and renal tissues in exercised rats as compared with sedentary rats. The increased XO, MPO, and MDA levels of these tissues significantly decreased in exercised rats supplemented with L-Arg. However, exhaustive exercise had no effect on mtDNA4834 deletions of muscular and hepatic tissues. The activities of creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine (CRE), lactate, uric acid, non-esterified fatty acid (NEFA), and D-3-hydroxybutyrate in the plasma significantly increased in the exercised rats compared with the sedentary rats, while the CK, lactate and uric acid levels in the plasma significantly decreased in L-Arg-supplemented exercised rats. These findings suggest that L-Arg supplementation reduces the oxidative damage to and inflammatory response in skeletal muscles, the liver, and kidneys caused by exhaustive exercise in young rats.

This study examined the effects of beta-carotene on antioxidant status in rats with chronic alcohol consumption. At the beginning of experiment (week 0), according to both the plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, rats (n = 24) were divided into 3 groups and fed with a standard diet (group C), a diet containing ethanol (group E), or a diet containing ethanol and beta-carotene (group E+B). After 10 weeks, plasma AST and ALT, fat accumulation in the liver, antioxidant enzyme activities in erythrocytes and the liver, malondialdehyde (MDA), and alpha-tocopherol and retinol in plasma and hepatic samples were analyzed. The chronic alcohol diet significantly increased AST and ALT levels in plasma, and these changes were prevented by supplementing the diet with beta-carotene. Glutathione (GSH) in erythrocytes and in the liver was significantly elevated in rats fed with a diet containing beta-carotene. The results indicate that beta-carotene supplementation can prevent ethanol-induced liver damage and increase GSH concentrations in erythrocytes and the liver., ((c) 2009 John Wiley & Sons, Ltd.)

Ohwia caudata (Thunb.) H. Ohashi (Leguminosae) also called as "Evergreen shrub" and Artemisia argyi H.Lév. and Vaniot (Compositae) also named as "Chinese mugwort" those two‐leaf extracts frequently used as herbal medicine, especially in south east Asia and eastern Asia. Anthracyclines such as doxorubicin (DOX) are commonly used as effective chemotherapeutic drugs in anticancer therapy around the world. However, chemotherapy‐induced cardiotoxicity, dilated cardiomyopathy, and congestive heart failure are seen in patients who receive DOX therapy, with the mechanisms underlying DOX‐induced cardiac toxicity remaining unclear. Mitochondrial dysfunction, oxidative stress, inflammatory response, and cardiomyocytes have been shown to play crucial roles in DOX‐induced cardiotoxicity. Isoliquiritigenin (ISL, 10 mg/kg) is a bioactive flavonoid compound with protective effects against inflammation, neurodegeneration, cancer, and diabetes. Here, in this study, our aim is to find out the Artemisia argyi (AA) and Ohwia caudata (OC) leaf extract combination with Isoliquiritigenin in potentiating and complementing effect against chemo drug side effect to ameliorate cardiac damage and improve the cardiac function. In this study, we showed that a combination of low (AA 300 mg/kg; OC 100 mg/kg) and high‐dose(AA 600 mg/kg; OC 300 mg/kg) AA and OC water extract with ISL activated the cell survival‐related AKT/PI3K signaling pathway in DOX‐treated cardiac tissue leading to the upregulation of the antioxidant markers SOD, HO‐1, and Keap‐1 and regulated mitochondrial dysfunction through the Nrf2 signaling pathway. Moreover, the water extract of AA and OC with ISL inhibited the inflammatory response genes IL‐6 and IL‐1β, possibly through the NFκB/AKT/PI3K/p38α/NRLP3 signaling pathways. The water extract of AA and OC with ISL could be a potential herbal drug treatment for cardiac hypertrophy, inflammatory disease, and apoptosis, which can lead to sudden heart failure. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases in post-menopausal women are on a rise. Oxidative stress is the main contributing factor to the etiology and pathogenesis of cardiovascular diseases. Diosgenin, a member of steroidal sapogenin, is structurally similar to estrogen and has been shown to have antioxidant effects. Therefore, we aimed to investigate the effects of diosgenin in preventing oxidation-induced cardiomyocyte apoptosis and assessed its potential as a substitute substance for estrogen in post-menopausal women. Apoptotic pathways and mitochondrial membrane potential were measured in H9c2 cardiomyoblast cells and neonatal cardiomyocytes treated with diosgenin for 1 h prior to hydrogen peroxide (H2O2) stimulation. H2O2-stimulated H9c2 cardiomyoblast cells displayed cytotoxicity and apoptosis via the activation of both Fas-dependent and mitochondria-dependent pathways. Additionally, it led to the instability of the mitochondrial membrane potential. However, the H2O2-induced H9c2 cell apoptosis was rescued by diosgenin through IGF1 survival pathway activation. This led to the recovery of the mitochondrial membrane potential by suppressing the Fas-dependent and mitochondria-dependent apoptosis. Diosgenin also inhibited H2O2-induced cytotoxicity and apoptosis through the estrogen receptor interaction with PI3K/Akt and extracellular regulated protein kinases 1/2 activation in myocardial cells. In this study, we confirmed that diosgenin attenuated H2O2-induced cytotoxicity and apoptosis through estrogen receptors-activated phosphorylation of PI3K/Akt and ERK signaling pathways in myocardial cells via estrogen receptor interaction. All results suggest that H2O2-induced myocardial damage is reduced by diosgenin due to its interaction with estrogen receptors to decrease the damage. Herein, we conclude that diosgenin might be a potential substitute substance for estrogen in post-menopausal women to prevent heart diseases. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disorder associated with striatal dopaminergic neuronal loss in the Substantia nigra. Oxidative stress plays a significant role in several neurodegenerative diseases. Paraquat (PQ) is considered a potential neurotoxin that affects the brain leading to the death of dopaminergic neurons mimicking the PD phenotype. Various scientific reports have proven that cryptotanshinone possesses antioxidant and anti‐inflammatory properties. We hypothesized that cryptotanshinone could extend its neuroprotective activity by exerting antioxidant effects. This study was designed to evaluate the effects of cryptotanshinone in both cellular and animal models of PQ‐induced PD. Annexin V‐PI double staining and immunoblotting were used to detect apoptosis and oxidative stress proteins, respectively. Reactive oxygen species kits were used to evaluate oxidative stress in cells. For in vivo studies, 18 B6 mice were divided into three groups. The rotarod data revealed the motor function and immunostaining showed the survival of TH+ neurons in SNpc region. Our study showed that cryptotanshinone attenuated paraquat‐induced oxidative stress by upregulating anti‐oxidant markers in vitro, and restored behavioral deficits and survival of dopaminergic neurons in vivo, demonstrating its therapeutic potential. [ABSTRACT FROM AUTHOR]

Hypertension is a common chronic cardiovascular disease reported among both men and women. Hypertension in males affects the testis and reproduction function; however, the pathogenesis is poorly understood. Rapamycin has been reported to have a variety of beneficial pharmacological effects; however, high‐doses rapamycin does have side effects such as immunosuppression. The present study investigates whether low‐dose rapamycin can reduce the damage caused by hypertension to the testis of spontaneously hypertensive rats (SHRs) and further examines molecular mechanism of low‐dose rapamycin in preventing testicular toxicity induced by angiotensin II (Ang II). Low rapamycin dose restores the testicle size, histological alterations, 3β‐hydroxysteroid dehydrogenase (3β‐HSD) expression, and prevents apoptosis in SHR rats. Ang II downregulates angiotensin‐converting enzyme‐2 (ACE2) expression through AT1R, p‐ERK, and MAS receptor in LC‐540 Leydig cells in a dose‐dependent manner. Low doses of rapamycin effectively upregulate steroidogenic enzymes, steroidogenic acute regulatory protein and 3β‐HSD expression in Leydig cells. Rapamycin upregulates ACE2 expression through p‐PKAc and p‐PI3k in Ang II‐treated cells. Further, rapamycin curbs mitochondrial superoxide generation and depleted mitochondrial membrane potential induced by Ang II through activation of Nrf2‐mediated Gpx4 and superoxide dismutase 2 expression. Our results revealed the involvement of ACE2, AT1R, AT2R, PKAc, and oxidative stress in Ang‐II‐induced testicular toxicity, suggesting low‐dose rapamycin could be a potential therapeutic candidate to attenuate testicular toxicity. [ABSTRACT FROM AUTHOR]

Oxidative stress‐induced brain cell damage is a crucial factor in the pathogenesis of reactive oxygen species (ROS)‐associated neurological diseases. Further, studies show that astrocytes are an important immunocompetent cell in the brain and play a potentially significant role in various neurological diseases. Therefore, elimination of ROS overproduction might be a potential strategy for preventing and treating neurological diseases. Accumulating evidence indicates that calycosin, a main active ingredient in the Chinese herbal medicine Huangqi (Radix Astragali Mongolici), is a potential therapeutic candidate with anti‐inflammation and/or anticancer effects. Here, we investigated the protective effect of calycosin in brain astrocytes by mimicking in vitro oxidative stress using H2O2. The results revealed that H2O2 significantly induced ROS and inflammatory factor (tumor necrosis factor [TNF]‐α and interleukin [IL]‐1β) production, whereas post‐treatment with calycosin dramatically and concentration‐dependently suppressed H2O2‐induced damage by enhancing cell viability, repressing ROS and inflammatory factor production, and increasing superoxide dismutase (SOD) expression. Additionally, we found that calycosin facilitated nuclear factor erythroid 2‐related factor 2 (Nrf2) expression and promoted its nuclear translocation, thereby inducing the expression of antioxidant molecules (heme oxygenase [HO]‐1 and SOD) following H2O2 treatment. Moreover, calycosin did not attenuated H2O2‐induced astrocyte damage and ROS production in the presence of the ML385 (a Nrf2‐specific inhibitor) and following Nrf2 silencing. Furthermore, calycosin failed to increase Akt phosphorylation and mitigate H2O2‐induced astrocyte damage in the presence of the LY294002 (a selective phosphatidylinositol 3‐kinase inhibitor), indicating that calycosin‐mediated regulation of oxidative‐stress homeostasis involved Akt/Nrf2/HO‐1 signaling. These findings demonstrated that calycosin protects against oxidative injury in brain astrocytes by regulating oxidative stress through the AKT/Nrf2/HO‐1 signaling pathway. [ABSTRACT FROM AUTHOR]

A well-known medicinal mushroom in the field of traditional Chinese medicine, Cordyceps sinensis, is a rare natural-occurring entomopathogenic fungus, and it typically grows at high altitudes on the plateau of the Himalayan. Previous studies indicated that cordycepin, the main bioactive chemical of Cordyceps sinensis, has very potent anticancer, anti-oxidant and anti-inflammatory activities. However, its protective effects against atherosclerotic changes in vascular endothelial cells have not been fully elucidated. In this study, we showed that pretreatment with cordycepin significantly attenuated palmitic acid (PA)-induced cytotoxicity, reactive oxygen species (ROS) generation, and inflammatory responses. We found that PA decreased phosphorylation of Akt, eNOS, and bioavailability of nitric oxide (NO), which in turn activated NF- κ B and the downstream inflammatory responses. All these detrimental events were markedly blocked by pretreatment with cordycepin. Moreover, cordycepin ameliorated destabilization of mitochondrial permeability, cytosolic calcium rises, and apoptotic features caused by PA. In addition, all these anti-inflammatory and anti-apoptosis effects of cordycepin were found to be inhibited by the PI3K and eNOS inhibitor, suggesting that its anti-atherosclerotic effects may partially be mediated by the PI3K/Akt/eNOS signaling pathway. [ABSTRACT FROM AUTHOR]

Heart failure (HF) and cardiac hypertrophy is an unfavorable outcome of pathological cardiac remodeling and represents the most important contributing factor for HF and cardiac hypertrophy. Amygdalin (AMG) is a cyanogenic glycoside derived from bitter almonds. Accumulating evidences have highlighted their pharmacological potentials against various diseases. However, there is no report delineating the potential of AMG against angiotensin (Ang II) induced cardiac injuries. Thus, the present study was performed to explore whether AMG could ameliorate Ang II induced cardiomyopathies and thereby ascertain the underlying mechanisms thereof. To this end, H9c2 cells were treated with Ang II and thereafter treated with various concentration of AMG and finally the cardio‐protective effects of AMG were analyzed through Western blotting, immunofluorescence, and insilico analysis. Our results showed that the cardiomyocyte cell size, inflammatory markers and cytokines(pNF‐κB, TNF‐α, iNOS and COX‐2) were markedly increased following Ang II treatment; nevertheless, treatment with AMG led to considerable decrement in the Ang II induced enlargement of the cardiomyocytes, and attenuate the expression of hypertrophic markers(ANP, BNP and MHC‐7), inflammatory markers and cytokines. Additionally, oxidative stress related proteins (Nrf2, catalase, SOD‐2, and GPX‐4) were markedly increased following AMG treatment. Molecular docking reveals the interaction of AMG with Nrf2 possessing good binding affinity. Cumulatively, our study highlights the cardio‐protective role of AMG against Ang II induced cardiomyopathies, including oxidative stress and inflammation effects. The intriguing in vitro results warrants the need of further animal studies to truly ascertain their potentialities. [ABSTRACT FROM AUTHOR]

Oxidative stress is a major cause of aging related skin injuries. Hydrogen peroxide related ROS accumulation triggers increase in matrix metalloproteinases and elevated collagen degradation, which is a characteristic of skin aging. In this study, we investigated the protective effect of Poria cocos, used widely in the treatment of inflammatory diseases, against H2O2 induced oxidative stress. The aqueous extract of dried P. cocos was obtained by heating 10 g in 500 ml of distilled water. The mixture was evaporated up to 400 ml and the remaining 100 ml was filtered through muslin cloth repeatedly to obtain a clear aqueous extract of the P. cocos. Hs68 human dermal fibroblast cells were challenged with 100 μM of H2O2 for 24 h. Following H2O2 challenge, the cells were treated with increasing concentration of P. cocos extract (100–400 μg/ml) for 24 h. P. cocos extract hindered the H2O2 induced cell death significantly that was correlated with reduction in ROS accumulation. Western blot analysis show that P. cocos extract suppressed the expression of metallomatrix proteinases, inflammatory markers and skin aging markers, but increased TGF‐β1 levels and antioxidant related proteins. These data suggest that P. cocos is effective in attenuating oxidative stress associated skin aging effects and may be a potential agent in cosmetics products. [ABSTRACT FROM AUTHOR]

The prevalence of chronic hyperglycemia and its complications, imposing a critical burden on the worldwide economy and the global healthcare system, is a pressing issue. Mounting evidence indicates that oxidative stress and hypoxia, two noticeable features of hyperglycemia, play a joint crucial role in mediating cellular apoptosis. However, the underlying detailed molecular mechanism remains elusive. Triggered by the observation that insulin‐like growth factor (IGF1)‐binding protein 3 (IGFBP3) can mediate, in renal cells, high‐glucose‐induced apoptosis by elevating oxidative stress, we wish to, in this study, know whether or not the similar scenario holds in cardiac cells and, if so, to find its relevant molecular key players, thereby dissecting the underlying molecular pathway. Specifically, we used a combination of three different cellular sources (H9c2 cells, diabetic rats, and neonatal rat ventricular cardiomyocytes) as our model systems of study. We made use of Co‐IP assay and western blot analysis in conjunction with loss‐of‐function reasoning, gain‐of‐function logic, and inhibitor treatment as our main analytical tools. As a result, briefly, our main findings are that hyperglycemia can induce cardiac IGFBP3 overexpression and secretion, that high levels of IGFBP3 can sequester IGF1 from IGF1 survival pathway, leading to apoptosis, and that IGFBP3 gene upregulation is hypoxia‐inducible factor (HIF)1α‐dependent and reactive oxygen species dependent. Piecing these findings together allows us to propose the improved molecular regulatory mechanism. In conclusion, we have established the molecular roles of IGFBP3, HIF1, and prolyl hydroxylase domain in connecting oxidative stress with hypoxia and in cellular apoptosis under hyperglycemia. [ABSTRACT FROM AUTHOR]

Regular hemodialysis treatment induces an elevation in oxidative stress in patients with end-stage renal failure, resulting in oxidative damage of the most abundant serum protein, albumin. Oxidation of serum albumin causes depletion of albumin reactive thiols, leading to oxidative modification of serum albumin. The aim of this study was to screen the antioxidant capacity of albumins isolated from uremic patients (HD-ALB) or healthy volunteers (N-ALB). From high-performance liquid chromatography spectra, we observed that one uremic solute binds to HD-ALB via the formation of disulfide bonds between HD-ALB and the uremic solute. Furthermore, we found using chemiluminescent analysis that the antioxidant capacities for N-ALB to scavenge reactive oxygen species including singlet oxygen, hypochlorite and hydrogen peroxide were higher than HD-ALB. Our results suggest that protein-bound uremic solute binds to albumin via formation of disulfide bonds, resulting in the depletion of albumin reactive thiols. The depletion of albumin reactive thiols leads to a reduced antioxidant capacity of HD-ALB, implying postmodification of albumin. This situation may reduce the antioxidant capacity of albumin and increase oxidative stress, resulting in increase in complications related to oxidative damage in uremic patients. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Resveratrol is a Sirt-1-specific activator, which also exerts cardioprotective effects that regulate redox signalling during oxidative stress and autophagy during cardiovascular disease (CVD). Objective: This study investigated the protective effects of resveratrol against hydrogen peroxide-induced damage in cardiomyocytes. Design: In this article, hydrogen peroxide-induced autophagy and apoptosis in H9c2 cardiomyoblasts were studied at an increasing concentration from 0 to 100 µM. Results: Resveratrol pretreatment with concentrations of 10, 20, and 50 µM inhibits autophagic apoptosis by increasing p-Akt and Bcl-2 protein levels in H9c2 cells. Interestingly, resveratrol treatment activates the Beclin-1, LC3, p62, and the lysosome-associated protein LAMP2a within 24 h of administration. Conclusions: These results suggest that resveratrol-regulated autophagy may play a role in degrading damaged organelles in H9c2 cells rather than causing apoptosis, and this may be a possible mechanism by which resveratrol protects the heart during CVD. [ABSTRACT FROM AUTHOR]

Background: Previous studies reported divergent results on nutraceutical actions and free radical scavenging capability of ginseng extracts. Variations in ginsenoside profile of ginseng due to different soil and cultivating season may contribute to the inconsistency. To circumvent this drawback, we assessed the effect of major ginsenoside-Rg1 (Rg1) on skeletal muscle antioxidant defense system against exhaustive exercise-induced oxidative stress. Methods: Forty weight-matched rats were evenly divided into control (N = 20) and Rg1 (N = 20) groups. Rg1 was orally administered at the dose of 0.1 mg/kg bodyweight per day for 10-week. After this long-term Rg1 administration, ten rats from each group performed an exhaustive swimming, and remaining rats considered as non-exercise control. Tibialis anterior (TA) muscles were surgically collected immediately after exercise along with non-exercise rats. Results: Exhaustive exercise significantly (p<0.05) increased the lipid peroxidation of control group, as evidenced by elevated malondialdehyde (MDA) levels. The increased oxidative stress after exercise was also confirmed by decreased reduced glutathione to oxidized glutathione ratio (GSH/GSSG ratio) in control rats. However, these changes were completely eliminated in Rg1 group. Catalase (CAT) and glutathione peroxidase (GPx) activities were significantly (p<0.05) increased by Rg1 in non-exercise rats, while no significant change after exercise. Nevertheless, glutathione reductase (GR) and glutathione S-transferase (GST) activities were significantly increased after exercise in Rg1 group. Conclusions: This study provide compelling evidences that Rg1 supplementation can strengthen antioxidant defense system in skeletal muscle and completely attenuate the membrane lipid peroxidation induced by exhaustive exercise. Our findings suggest that Rg1 can use as a nutraceutical supplement to buffer the exhaustive exercise-induced oxidative stress. [ABSTRACT FROM AUTHOR]

Background: High levels circulating saturated fatty acids are associated with diabetes, obesity and hyperlipidemia. In heart, the accumulation of saturated fatty acids has been determined to play a role in the development of heart failure and diabetic cardiomyopathy. High-density lipoprotein (HDL) has been reported to possess key atheroprotective biological properties, including cellular cholesterol efflux capacity, anti-oxidative and anti-inflammatory activities. However, the underlying mechanisms are still largely unknown. Therefore, the aim of the present study is to test whether HDL could protect palmitic acid (PA)-induced cardiomyocyte injury and explore the possible mechanisms. Results: H9c2 cells were pretreated with HDL (50–100 μg/ml) for 2 h followed by PA (0.5 mM) for indicated time period. Our results showed that HDL inhibited PA-induced cell death in a dose-dependent manner. Moreover, HDL rescued PA-induced ROS generation and the phosphorylation of JNK which in turn activated NF-κB-mediated inflammatory proteins expressions. We also found that PA impaired the balance of BCL2 family proteins, destabilized mitochondrial membrane potential, and triggered subsequent cytochrome c release into the cytosol and activation of caspase 3. These detrimental effects were ameliorated by HDL treatment. Conclusion: PA-induced ROS accumulation and results in cardiomyocyte apoptosis and inflammation. However, HDL attenuated PA-induced lipotoxicity and oxidative dysfunction via ROS suppression. These results may provide insight into a possible molecular mechanism underlying HDL suppression of the free fatty acid-induced cardiomyocyte apoptosis. [ABSTRACT FROM AUTHOR]

Myocardial infarction due to ischemia accounts for majority of deaths among cardiovascular disorders. Isoproterenol (ISO) induced myocardial infarction and the protection offered by piperine was investigated in the present report. Lipid profile analysis by determining the levels of cholesterol, phospholipids, triglycerides and lipoproteins in serum and heart tissues showed anti-dyslipidemic action of piperine against ISO induced myocardial injury by modulating the ISO induced altered lipid profiles, maintaining to near control values. ISO treatment increased TBARS levels, PCC, serum markers of heart, depleted antioxidant status (GSH, SOD, CAT, GPx and GST) in tissues and, total, protein- and non-protein-sulfhydryl levels in serum and heart tissues. Piperine pre-treatment decreased the levels of serum markers, lipid peroxidation and PCC with increased antioxidant status in the heart tissues of ISO administered rats. Increased levels of the glycoprotein components in serum and decreased levels in heart tissues upon ISO administration were restored to near normal levels by piperine pre-treatment. Our present reports also showed the modulatory effect of piperine on membrane bound ATPase’s showing protection against ISO induced changes in membrane fluidity. The present study proved piperine as a potent therapeutic agent with its antioxidant and anti-dyslipidemic action against ISO induced myocardial infarction. [ABSTRACT FROM AUTHOR]

We have previously reported the prevention of Hypoxia mediated apoptosis by Neferine, an alkaloid from Nelumbo nucifera . The present study was designed to assess the role of neferine in modulation of hypoxia induced autophagy in muscle cells. Cytoprotective dose of neferine in muscle cells (Rhabdomyosarcoma cells) exposed to hypoxia was determined by MTT assay. Hypoxia induced oxidative stress in muscle cells by enhancing lipid peroxidation and depleting cellular antioxidant enzymes. The inhibition of PI3K/Akt/mTOR cell survival signaling acts as a trigger for the hypoxia induced Autophagy. Hypoxia exposure in muscle cells resulted in acidic vesicular formation, as studied by acridine orange staining which serves as an indicator of autophagosome formation. Pretreatment with neferine inhibited autophagy induction by activating Akt/mTOR pathway and down regulating Beclin 1, PI3KCIII and LC3B-II in cells exposed to hypoxia. Further, Neferine also modulated hypoxia mediated changes in the cellular antioxidant levels by Nrf2 nuclear translocation. Collectively, results of the study suggest the role of neferine in preventing hypoxia induced autophagy in muscle cells. [ABSTRACT FROM AUTHOR]

Abstract: Polyphenols, such as (−)-epigallocatechin gallate (EGCG), have pro-oxidant properties that lead to activation of the cellular apoptotic pathway; however, the mechanism underlying the induction of this pro-oxidant activity is unclear. We found intensive chemiluminescence for EGCG and hydroquinone (HQ) in the presence of amino acids with basic amino side-chains, such as arginine or lysine. In addition, the chemiluminescence of EGCG and arginine or lysine was totally suppressed by the addition of superoxide dismutase; whereas the chemiluminescence of HQ and arginine or lysine was totally suppressed by the addition of catalase. Furthermore, we found that polyphenols are capable of inducing oxidative stress, including depletion of albumin thiol content, elevation of plasma oxidized low-density lipoprotein and acceleration of cell death in the presence of arginine. Taking the results together, we suggest that amino acids with basic amino side-chain accelerate the production of reactive oxygen species in the presence of polyphenols. [Copyright &y& Elsevier]

Toll-like receptor 4 (TLR4) is an important mediator of hypertension and AngII induced cardiac inflammation and remodelling. In this study, the potential of nerolidol to ameliorate hypertension induced cardiac injuries and the underlying mechanism of action was explored by using in vitro and in vivo models. The in vitro analysis was performed on AngII challenged H9c2 cells and their ability to overcome cardiac inflammation and cardiac remodelling effects was determined by evaluating TLR4/NF-κB signalling cascade using Western blot analysis and immunofluorescence. The results were further ascertained using in vivo experiments. Eighteen week old male rats were randomly allocated into different groups i.e. Wistar Kyoto (WKY) rats, hypertensive SHRs, SHRs treated with a low-dose (75 mg/kg b.w) and high-dose of nerolidol (150 mg/kg b.w) and SHRs treated with captopril (50 mg/kg b.w) through oral gauge and finally analysed through echocardiography, histopathological techniques and molecular analysis. The results show that nerilodol target TLR4/NF-κB signalling and thereby attenuate hypertension associated inflammation and oxidative stress thereby provides effective cardioprotection. Echocardiography analysis showed that nerolidol improved cardiac functional characteristics including Ejection Fraction and Fractional Shortening in the SHRs. Collectively, the data of the study demonstrates nerolidol as a cardio-protective agent against hypertension induced cardiac remodelling. Image 1 [ABSTRACT FROM AUTHOR]

• Hypertension-associated renal damage is ameliorated by the bioactive peptide IF. • IF activates the antioxidant pathway via the upregulation of Nrf2 in hypertensive kidneys. • The bioactive peptide IF improves the survival of renal cells via the DJ-I and AKT axes. • IF might be an alternative therapy for reducing hypertension-associated renal damage. Hypertension, which is known as a silent killer, is the second leading cause of kidney failure worldwide. Elevated blood pressure causes approximately 7.6 million deaths, which account for ~13.5% of the total deaths and will continue to rise. High blood pressure is the prime risk factor associated with complications in major organs, including the heart, brain and kidney. High blood pressure accelerates oxidative stress and thereby causes organ dysfunction through the production of reactive oxygen species. In this study, we investigated the renal-protective effects of the bioactive peptide IF from alcalase potato protein hydrolysate in spontaneously hypertensive rat kidney. Sixteen-week-old spontaneously hypertensive rats were divided into three groups (n = 6), and Sixteen-week-old Wistar Kyoto rats (n = 6) served as the control group. The rats were administered IF and captopril via oral gavage for 8 weeks and then sacrificed, and their kidneys were harvested. The kidney sections from the rats treated with IF showed restoration of the structure of the glomerulus and Bowman's capsule. The expression levels of Nrf2-mediated antioxidants were also increased, as confirmed by 4-hydroxynonenal immunohistochemical staining. The TUNEL assay revealed a significant reduction in the number of apoptotic cells in the IF-treated groups, which was consistent with the western blot results. Thus, the bioactive peptide IF exerts potential protective effects against hypertension-associated ROS-mediated renal damage via the Nrf2-dependent antioxidant pathway along the DJ-1 and AKT axes. Hence, we speculate that IF might have promising therapeutic effects on renal damage associated with hypertension. [ABSTRACT FROM AUTHOR]