scholarly journals Mitochondrial Protection and Against Glutamate Neurotoxicity via Shh/Ptch1 Signaling Pathway to Ameliorate Cognitive Dysfunction by Kaixin San in Multi-Infarct Dementia Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Xiaoqiong Li ◽  
Wen Wen ◽  
Ping Li ◽  
Ying Fu ◽  
Hao Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Brain Tissue ◽  
Energy Charge ◽  
Memory Loss ◽  
The Elderly ◽  
Protective Effects ◽  
Protein Levels ◽  
Glutamate Neurotoxicity ◽  
Mitochondrial Functions ◽  
The Brain

Multi-infarct dementia (MID), a prominent subtype of vascular dementia (VD), is responsible for at least 15 to 20 percent of dementia in the elderly. Mitochondrial dysfunctions and glutamate neurotoxicity due to chronic hypoperfusion and oxidative stress were regarded as the major risk factors in the pathogenesis. Kaixin San (KXS), a classic prescription of Beiji Qianjin Yaofang, was applied to treatment for “amnesia” and has been demonstrated to alleviate the cognitive deficit in a variety of dementias, including MID. However, little is known whether mitochondria and glutamate are associated with the protection of KXS in MID treatment. The aim of this study was to investigate the role of KXS in improving the cognitive function of MID rats through strengthening mitochondrial functions and antagonizing glutamate neurotoxicity via the Shh/Ptch1 signaling pathway. Our data showed that KXS significantly ameliorated memory impairment and hippocampal neuron damage in MID rats. Moreover, KXS improved hippocampal mitochondrial functions by reducing the degree of mitochondrial swelling, increasing the mitochondrial membrane potential (MMP), and elevating the energy charge (EC) and ATP content in MID rats. As expected, the concentration of glutamate and the expression of p-NMDAR1 were significantly reduced by KXS in the brain tissue of MID rats. Furthermore, our results showed that KXS noticeably activated the Shh/Ptch1 signaling pathway which was demonstrated by remarkable elevations of Ptch1, Smo, and Gli1 protein levels in the brain tissue of MID rats. Intriguingly, the inhibition of the Shh signaling pathway with cyclopamine significantly inhibited the protective effects of KXS on glutamate-induced neurotoxicity in PC12 cells. To sum up, these findings suggested that KXS protected MID rats from memory loss by rescuing mitochondrial functions as well as against glutamate neurotoxicity through activating Shh/Ptch1 signaling pathway.

scholarly journals Safety profile of the transcription factor EB (TFEB)-based gene therapy through intracranial injection in mice

2020 ◽  
Vol 11 (1) ◽  
pp. 241-250
Author(s):  
Zhenyu Li ◽  
Guangqian Ding ◽  
Yudi Wang ◽  
Zelong Zheng ◽  
Jianping Lv
Keyword(s):  
Gene Therapy ◽  
Transcription Factor ◽  
Neurodegenerative Diseases ◽  
Brain Tissue ◽  
Inflammatory Responses ◽  
Tissue Samples ◽  
Protein Levels ◽  
Virus Serotype ◽  
Transcription Factor Eb ◽  
The Brain

AbstractTranscription factor EB (TFEB)-based gene therapy is a promising therapeutic strategy in treating neurodegenerative diseases by promoting autophagy/lysosome-mediated degradation and clearance of misfolded proteins that contribute to the pathogenesis of these diseases. However, recent findings have shown that TFEB has proinflammatory properties, raising the safety concerns about its clinical application. To investigate whether TFEB induces significant inflammatory responses in the brain, male C57BL/6 mice were injected with phosphate-buffered saline (PBS), adeno-associated virus serotype 8 (AAV8) vectors overexpressing mouse TFEB (pAAV8-CMV-mTFEB), or AAV8 vectors expressing green fluorescent proteins (GFPs) in the barrel cortex. The brain tissue samples were collected at 2 months after injection. Western blotting and immunofluorescence staining showed that mTFEB protein levels were significantly increased in the brain tissue samples of mice injected with mTFEB-overexpressing vectors compared with those injected with PBS or GFP-overexpressing vectors. pAAV8-CMV-mTFEB injection resulted in significant elevations in the mRNA and protein levels of lysosomal biogenesis indicators in the brain tissue samples. No significant changes were observed in the expressions of GFAP, Iba1, and proinflammation mediators in the pAAV8-CMV-mTFEB-injected brain compared with those in the control groups. Collectively, our results suggest that AAV8 successfully mediates mTFEB overexpression in the mouse brain without inducing apparent local inflammation, supporting the safety of TFEB-based gene therapy in treating neurodegenerative diseases.

scholarly journals Protective Effects of 6,7,4′-Trihydroxyflavanone on Hypoxia-Induced Neurotoxicity by Enhancement of HO-1 through Nrf2 Signaling Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 341 ◽  
Author(s):  
Hyun-Su Lee ◽  
Gil-Saeng Jeong
Keyword(s):  
Signaling Pathway ◽  
Neurodegenerative Disorders ◽  
Nuclear Translocation ◽  
Protoporphyrin Ix ◽  
Protective Role ◽  
Osteoclast Formation ◽  
Protective Effects ◽  
Protein Levels ◽  
Nrf2 Signaling Pathway ◽  
Pre Treatment

Since hypoxia-induced neurotoxicity is one of the major causes of neurodegenerative disorders, including the Alzheimer’s disease, continuous efforts to find a novel antioxidant from natural products are required for public health. 6,7,4′-trihydroxyflavanone (THF), isolated from Dalbergia odorifera, has been shown to inhibit osteoclast formation and have an antibacterial activity. However, no evidence has reported whether THF has a protective role against hypoxia-induced neurotoxicity. In this study, we found that THF is not cytotoxic, but pre-treatment with THF has a cytoprotective effect on CoCl2-induced hypoxia by restoring the expression of anti-apoptotic proteins in SH-SY5y cells. In addition, pre-treatment with THF suppressed CoCl2-induced hypoxia-related genes including HIF1α, p53, VEGF, and GLUT1 at the mRNA and protein levels. Pre-treatment with THF also attenuated the oxidative stress occurred by CoCl2-induced hypoxia by preserving antioxidant proteins, including SOD and CAT. We revealed that treatment with THF promotes HO-1 expression through Nrf2 nuclear translocation. An inhibitor assay using tin protoporphyrin IX (SnPP) confirmed that the enhancement of HO-1 by pre-treatment with THF protects SH-SY5y cells from CoCl2-induced neurotoxicity under hypoxic conditions. Our results demonstrate the advantageous effects of THF against hypoxia-induced neurotoxicity through the HO-1/Nrf2 signaling pathway and provide a therapeutic insight for neurodegenerative disorders.

scholarly journals Low Protein Diet Induces Memory Loss and Anxiety Like Behavior via Decreases of Neurotransmitters in Aged Male Mice (P14-028-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Hideaki Sato ◽  
Masako Tsukamoto-Yasui ◽  
Satoko Ueno ◽  
Keiko Matsunaga ◽  
Akihiko Kitamura
Keyword(s):  
Cerebral Cortex ◽  
Memory Loss ◽  
The Elderly ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Avoidance Task ◽  
Maze Task ◽  
Low Protein ◽  
Plus Maze ◽  
The Brain

Abstract Objectives Increase of elderly people, dementia and cognitive decline has been already one of the social problems all over the world. There are a lot of risk factors including dietary composition. Several studies have reported the importance of protein for maintaining brain functions in the elderly, but the details are not well understood. To clarify the relationship between protein intake and brain function in the elderly, we evaluated the effect of low protein diet on cognitive function and psychiatric symptoms in aged mice. Methods Male mice at 60 weeks of age were fed a control diet (NPD; casein 20%) or a low protein diet (LPD; casein 5%). To evaluate neurobehavioral abnormality, we performed the elevated plus maze task (Day 64) and Passive avoidance task (conditioning: Day 66, evaluation: Day 67). Cerebral cortex tissues and plasma were measured for free amino acid concentration by LC-MSMS method, and monoamine concentration in cerebral cortex was measured by HPLC method. Results In the Passive avoidance task, LPD group decreased the time to keep staying in the light box and the rate of individuals entering the dark box during the test period. In the elevated plus maze task, LPD group significantly increased in the number of entry and staying times in open arm. In addition, total travel distance was significantly increased. Moreover, LPD decreased the concentration of not only amino acid in plasma and cerebral cortex but also neurotransmitter such as Glutamate, GABA, Aspartate, Glycine, Dopamine, Norepinephrine, Serotonin. Conclusions We found that long-term intake of low-protein diet occurred memory loss and anxiety like behavior in elderly mice. Intracerebral neurotransmitters are mainly synthesized from amino acids, which is transferred from blood, within the brain. Therefore, behavioral change observed in LPD group might be induced by the decrease of neurotransmitters in the brain. Funding Sources Ajinomoto Co., Inc.

scholarly journals Luteolin Alleviates AflatoxinB1-Induced Apoptosis and Oxidative Stress in the Liver of Mice through Activation of Nrf2 Signaling Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1268
Author(s):  
Shahid Ali Rajput ◽  
Aftab Shaukat ◽  
Kuntan Wu ◽  
Imran Rashid Rajput ◽  
Dost Muhammad Baloch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Aflatoxin B1 ◽  
Physiological Saline ◽  
Protective Effects ◽  
Biochemical Alterations ◽  
Protein Levels ◽  
Nrf2 Signaling Pathway ◽  
Induced Apoptosis

Aflatoxin B1 (AFB1), a threatening mycotoxin, usually provokes oxidative stress and causes hepatotoxicity in animals and humans. Luteolin (LUTN), well-known as an active phytochemical agent, acts as a strong antioxidant. This research was designed to investigate whether LUTN exerts protective effects against AFB1-induced hepatotoxicity and explore the possible molecular mechanism in mice. A total of forty-eight mice were randomly allocated following four treatment groups (n = 12): Group 1, physiological saline (CON). Group 2, treated with 0.75 mg/kg BW aflatoxin B1 (AFB1). Group 3, treated with 50 mg/kg BW luteolin (LUTN), and Group 4, treated with 0.75 mg/kg BW aflatoxin B1 + 50 mg/kg BW luteolin (AFB1 + LUTN). Our findings revealed that LUTN treatment significantly alleviated growth retardation and rescued liver injury by relieving the pathological and serum biochemical alterations (ALT, AST, ALP, and GGT) under AFB1 exposure. LUTN ameliorated AFB1-induced oxidative stress by scavenging ROS and MDA accumulation and boosting the capacity of the antioxidant enzyme (CAT, T-SOD, GSH-Px and T-AOC). Moreover, LUTN treatment considerably attenuates the AFB1-induced apoptosis in mouse liver, as demonstrated by declined apoptotic cells percentage, decreased Bax, Cyt-c, caspase-3 and caspase-9 transcription and protein with increased Bcl-2 expression. Notably, administration of LUTN up-regulated the Nrf2 and its associated downstream molecules (HO-1, NQO1, GCLC, SOD1) at mRNA and protein levels under AFB1 exposure. Our results indicated that LUTN effectively alleviated AFB1-induced liver injury, and the underlying mechanisms were associated with the activation of the Nrf2 signaling pathway. Taken together, LUTN may serve as a potential mitigator against AFB1-induced liver injury and could be helpful for the development of novel treatment to combat liver diseases in humans and/or animals.

scholarly journals Neuroinflammatory Reactions in the Brain of 1,2-DCE-Intoxicated Mice during Brain Edema

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 987 ◽  
Author(s):  
Xiaoxia Jin ◽  
Tong Wang ◽  
Yingjun Liao ◽  
Jingjing Guo ◽  
Gaoyang Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Brain Edema ◽  
P38 Mapk ◽  
Adhesion Molecule ◽  
Calcium Binding ◽  
Mapk Signaling ◽  
Intercellular Adhesion Molecule ◽  
Inflammatory Reactions ◽  
Protein Levels ◽  
The Brain

We previously reported that expression of matrix metalloproteinase-9 (MMP-9) mRNA and protein was upregulated during 1,2-dichloroethane (1,2-DCE) induced brain edema in mice. We also found that the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway resulted in MMP-9 overexpression and nuclear factor-κB (NF-κB) activation in mice treated with 1,2-DCE. In this study, we further hypothesized that inflammatory reactions mediated by the p38 MAPK/ NF-κB signaling pathway might be involved in MMP-9 overexpression, blood–brain barrier (BBB) disruption and edema formation in the brain of 1,2-DCE-intoxicated mice. Our results revealed that subacute poisoning by 1,2-DCE upregulates protein levels of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), interleukin-1β (IL-1β), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and p-p65 in mouse brains. Pretreatment with an inhibitor against p38 MAPK attenuates these changes. Moreover, pretreatment with an inhibitor against NF-κB attenuates alterations in brain water content, pathological indications notable in brain edema, as well as mRNA and protein expression on levels of MMP-9, VCAM-1, ICAM-1, iNOS, and IL-1β, tight junction proteins (TJs), GFAP and Iba-1 in the brain of 1,2-DCE-intoxicated mice. Furthermore, pretreatment with an inhibitor against MMP-9 obstructs the decrease of TJs in the brain of 1,2-DCE-intoxicated mice. Lastly, pretreatment with an antagonist against the IL-1β receptor also attenuates changes in protein levels of p-p38 MAPK, p-p65, p-IκB, VCAM -1, ICAM-1, IL-1β, and Iba-1 in the brain of 1,2-DCE-intoxicated-mice. Taken together, findings from the current study indicate that the p38 MAPK/ NF-κB signaling pathway might be involved in the activation of glial cells, and the overproduction of proinflammatory factors, which might induce inflammatory reactions in the brain of 1,2-DCE-intoxicated mice that leads to brain edema.

scholarly journals Pilose Antler Peptide-3.2KD Ameliorates Adriamycin-Induced Myocardial Injury Through TGF-β/SMAD Signaling Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Yan Xu ◽  
Xiaobo Qu ◽  
Jia Zhou ◽  
Guangfu Lv ◽  
Dong Han ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Myocardial Fibrosis ◽  
Myocardial Injury ◽  
Pathological Examination ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Expression Levels ◽  
Smad Signaling ◽  
Protein Levels ◽  
Smad Signaling Pathway

Adriamycin (ADR)-based combination chemotherapy is the standard treatment for some patients with tumors in clinical, however, long-term application can cause dose-dependent cardiotoxicity. Pilose Antler, as a traditional Chinese medicine, first appeared in the Han Dynasty and has been used to treat heart disease for nearly a thousand years. Previous data revealed pilose antler polypeptide (PAP, 3.2KD) was one of its main active components with multiple biological activities for cardiomyopathy. PAP-3.2KD exerts protective effects againt myocardial fibrosis. The present study demonstrated the protective mechanism of PAP-3.2KD against Adriamycin (ADR)-induced myocardial injury through using animal model with ADR-induced myocardial injury. PAP-3.2KD markedly improved the weight increase and decreased the HW/BW index, heart rate, and ST height in ADR-induced groups. Additionally, PAP-3.2KD reversed histopathological changes (such as disordered muscle bundles, myocardial fibrosis and diffuse myocardial cellular edema) and scores of the heart tissue, ameliorated the myocardial fibrosis and collagen volume fraction through pathological examination, significantly increased the protein level of Bcl-2, and decreased the expression levels of Bax and caspase-3 in myocardial tissue by ELISA, compared to those in ADR-induced group. Furthermore, ADR stimulation induced the increased protein levels of TGF-β1 and SMAD2/3/4, the increased phosphorylation levels of SMAD2/3 and the reduced protein levels of SMAD7. The expression levels of protein above in ADR-induced group were remarkably reversed in PAP-3.2KD-treated groups. PAP-3.2KD ameliorated ADR-induced myocardial injury by regulating the TGF-β/SMAD signaling pathway. Thus, these results provide a strong rationale for the protective effects of PAP against ADR-induced myocardial injury, when ADR is used to treat cancer.

scholarly journals CSF and Plasma Cholinergic Markers in Patients With Cognitive Impairment

2021 ◽  
Vol 13 ◽  
Author(s):  
Azadeh Karami ◽  
Taher Darreh-Shori ◽  
Marianne Schultzberg ◽  
Maria Eriksdotter
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Performance ◽  
Protein Concentration ◽  
Memory Loss ◽  
Chat Activity ◽  
Protein Levels ◽  
Cholinergic Signaling ◽  
Hydrolysis Of ◽  
The Brain ◽  
Prevalent Form

IntroductionAlzheimer’s disease (AD) is the most prevalent form of dementia with symptoms of deteriorating cognitive functions and memory loss, partially as a result of a decrease in cholinergic neurotransmission. The disease is incurable and treatment with cholinesterase inhibitors (ChEIs) is symptomatic. Choline acetyltransferase (ChAT), the enzyme that synthesizes acetylcholine (ACh), has been proven recently to be present in both cerebrospinal fluid (CSF) and plasma. As ChAT plays a role in regulating the extracellular ACh levels, it may have an impact on prognosis and cognitive performance in AD patients.ObjectivesTo measure ChAT activity and its protein concentration in CSF and plasma from patients with AD, mild cognitive impairment (MCI), or Subjective cognitive impairment (SCI).MethodsPlasma and CSF samples were obtained from 21 AD, 32 MCI, and 30 SCI patients. The activity and protein levels of ChAT and acetylcholinesterase (AChE), the enzyme catalyzing the hydrolysis of ACh, were analyzed using an integrated activity and protein concentration ELISA-like assay. A Cholinergic Index was calculated as the ratio of ChAT to AChE activities in CSF. The data were analyzed in relation to dementia biomarkers and cognitive performance of the patients.ResultsThe CSF ChAT activity was significantly higher (55–67%) in MCI patients compared to AD and SCI cases. The CSF Cholinergic Index was 41 and 22% lower in AD patients than in MCI and SCI subjects, respectively. This index correlated positively with the Aβ42/p-tau ratio in CSF in SCI but negatively with that in AD and MCI. The ChAT activity and protein levels in plasma exhibited significant differences with the pattern of AD>>MCI>SCI.ConclusionThis is the first study investigating soluble levels of the key cholinergic enzyme, ChAT, in both plasma and CSF of individuals at different clinical stages of dementia. Although further validation is needed, the overall pattern of the results suggests that in the continuum of AD, the cholinergic signaling exhibits an inverse U-shape dynamic of changes in the brain that greatly differs from the changes observed in the plasma compartment.

scholarly journals Protective Effects of Colivelin Against Alzheimer's Disease in a PDAPP Mouse Model

2016 ◽  
Vol 38 (3) ◽  
pp. 1138-1146 ◽  
Author(s):  
Rong Yin ◽  
Kai Yin ◽  
ZhiQiang Guo ◽  
ZhiQiang Zhang ◽  
LiPin Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Impairment ◽  
Memory Loss ◽  
The Elderly ◽  
Morris Water Maze Test ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Western Blot Assay ◽  
P38 Inhibitor

Background: Alzheimer's disease (AD) is characterized with progressive memory loss and severe cognitive impairments, which affect everyday life and human health in the elderly. It is required that an effective and safe protective reagent against AD should be developed. It has been reported that humanin (HN) exerts neuroprotective effects against AD. In this study, we investigated the effect of a novel and more effective HN derivative, Colivelin (CLN) on AD. Methods: PDAPPV717I transgenic AD model mice (derived from parental C57/BL6 mice) were used in our study as AD model. Morris water maze test was used to test the memory impairment of AD mice and the levels of Aβ40 and Aβ42 were determined by an Elisa assay. We used an Immunohistochemistry and Immunofluorescence staining method to check the GFAP and MAP2 positive cells, and TUNEL to assess the apoptotic cells. Western blot assay was used to check the expression and phosphorylation level of p38. Results: We found that CLN improved the memory impairment induced by AD and reduced the deposit of Aβ40 and Aβ42. CLN also inhibited cell apoptosis and activation of caspase 3 in brain tissues of AD mice. Inflammation in AD mice was alleviated by CLN treatment, including the accumulation of GFAP positive cells and the inflammatory cytokines. With both structure of AGA-HNG and ANDF, CLN exhibited significantly stronger effects than synchronously administration of AGA-HNG and ADNF, suggesting CLN as a novel potential effective therapeutic reagent for AD patients. Finally, we found that CLN inhibited phosphorylation of p38 in AD mice and p38 inhibitor, SB203580 weakened the therapeutic effect of CLN. Conclusion: CLN effectively improved the memory dysfunction in PDAPP mice, and our data suggests CLN as a novel and effective reagent which may have great potentials in AD therapy.

Aging of Brain Related with Mitochondrial Dysfunctions

2020 ◽  
Vol 21 ◽  
Author(s):  
Vipin Dhote ◽  
Prem Samundre ◽  
Aditya Ganeshpurkar ◽  
Aman Upaganlawar
Keyword(s):  
Neurodegenerative Diseases ◽  
Psychiatric Symptoms ◽  
Neuronal Damage ◽  
The Elderly ◽  
Environmental Chemicals ◽  
Aging Brain ◽  
Mitochondrial Dysfunctions ◽  
Mitochondrial Functions ◽  
Key Issues ◽  
The Brain

Abstract:: Advancing age presents a major challenge for the elderly population in terms of quality of life. The risk of cognitive impairment, motor in-coordination, and behavioral inconsistency due to neuronal damage is relatively higher in aging individuals of society. The brain, through its structural and functional integrity, regulates vital physiological events; however, the susceptibility of the brain to aging-related disturbances signal the onset of neurodegenerative diseases. Mitochondrial dysfunctions impair bioenergetic mechanism, synaptic plasticity, and calcium homeostasis in the brain, thus sufficiently implying mitochondria as a prime causal factor in accelerating aging-related neurodegeneration. We reviewed the fundamental functions of mitochondria in a healthy brain and aimed to address the key issues in aging-related diseases by asking: 1) What goes wrong with mitochondria in the aging brain? 2) What are the implications of mitochondrial damage on motor functions and psychiatric symptoms? 3) How environmental chemicals and metabolic morbidities affect mitochondrial functions? Further, we share insight on opportunities and pitfalls in drug discovery approaches targeting mitochondria to slow down the progression of aging and related neurodegenerative diseases.

scholarly journals Cucurbitacin I Protects H9c2 Cardiomyoblasts against H2O2-Induced Oxidative Stress via Protection of Mitochondrial Dysfunction

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Dong Kwon Yang ◽  
Shang-Jin Kim
Keyword(s):  
Oxidative Stress ◽  
Cardiac Injury ◽  
Cardiac Cells ◽  
Ros Production ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Protein Levels ◽  
Mitochondrial Functions ◽  
H9c2 Cardiomyoblasts ◽  
Antioxidant Effects

Cucurbitacin I, a triterpenoid natural compound, exhibits various pharmacological properties, including anticancer, anti-inflammatory, and hepatoprotective properties. However, antioxidant effects of cucurbitacin I in cardiac cells are currently unknown. In the present study, we assessed the preventive effects of cucurbitacin I against the oxidative stress in H9c2 cardiomyoblasts. To evaluate antioxidant effects of cucurbitacin I in H9c2 cardiomyoblasts, H2O2-treated H9c2 cells were pretreated with various concentrations of the cucurbitacin I. Cell viability, reactive oxygen species (ROS) production, and apoptosis were determined to elucidate the protective effects of cucurbitacin I against H2O2-induced oxidative stress in H9c2 cells. In addition, we assessed the mitochondrial functions and protein expression levels of mitogen-activated protein kinases (MAPKs). Cucurbitacin I prevented the cells against cell death and ROS production and elevated the antioxidant protein levels upon oxidative stress. Furthermore, cucurbitacin I preserved the mitochondrial functions and inhibited the apoptotic responses in H2O2-treated cells. Cucurbitacin I also suppressed the activation of MAPK proteins (extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38). Collectively, cucurbitacin I potentially protects the H9c2 cardiomyoblasts against oxidative stress and further suggests that it can be utilized as a therapeutic agent for the prevention of oxidative stress in cardiac injury.

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