Search

Previous studies have shown that honokiol, a bioactive compound originated from the Magnolia, has beneficial effects on various chronic diseases. Although our previous study has demonstrated that honokiol effectively protects C2C12 myoblasts against hydrogen peroxide (H2O2)-induced oxidative stress and cytotoxicity, the antioxidant mechanism in human retinal pigment epithelial (RPE) cells has not been reported yet. Therefore, this study investigates whether honokiol attenuate cytotoxicity of H2O2 to human RPE ARPE-19 cells. Our results showed that H2O2-induced loss of cell viability and increase of reactive oxygen species production in ARPE-19 cells were significantly alleviated by honokiol, which was associated with increased phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulation of heme oxygenase-1 (HO-1). In addition, honokiol markedly attenuated DNA damage and G2/M phase cell cycle arrest and improved apoptosis in H2O2-treated ARPE-19 cells. Furthermore, mitochondrial dysfunction by H2O2 was reversed by honokiol through preservation of mitochondrial membrane potential, decrease of Bax/Bcl-2 expression ratio, and inhibition of cytochrome c release into the cytoplasm. However, zinc protoporphyrin, an inhibitor of HO-1, significantly abrogated these preventive effects, suggesting a critical role of Nrf2/HO-1 in the antioxidant activity of honokiol. Taken together, these results demonstrate that activation of Nrf2/HO-1 antioxidant signaling by honokiol could rescue ARPE-19 cells from oxidative damage. [ABSTRACT FROM AUTHOR]

Although the beneficial biological effects of Cornus officinalis fruit, Corni Fructus, are known to be correlated with antioxidant efficacy, the protective effect of muscle cells against oxidative damage is still unclear. In this study, we aimed to investigate the potential protective effect of Corni Fructus water extract (CFE) against cellular damage caused by oxidative stress in C2C12 murine myoblast cells. The results show that, in the non-cytotoxic range, CFE increased the expression of nuclear factor-erythroid-2 related factor 2 (Nrf2) and its phosphorylation. CFE also up-regulated heme oxygenase-1 (HO-1) expression, one of the representative downstream factors of Nrf2, indicating CFE activated the Nrf2/HO-1 signaling pathway. In addition, CFE pretreatment significantly ameliorated growth reduction and suppressed DNA damage and apoptosis in hydrogen peroxide (H2O2)-treated C2C12 myoblast, which was correlated with inhibition of reactive oxygen species generation. Furthermore, H2O2-induced mitochondrial dysfunction linked to apoptosis by increasing levels of cytoplasmic cytochrome c and Bax/Bcl-2 was restored by CFE in C2C12 cells. CFE also suppressed H2O2-induced activation of caspase-9 and -3 and cleavage of poly (ADP-ribose) polymerase. However, zinc protoporphyrin, a selective inhibitor of HO-1, markedly abolished the preventive effect of CFE, demonstrating that CFE protected C2C12 myoblasts from H2O2-induced damage via activation of the Nrf2/HO-1 antioxidant axis, and that CFE may be applicable as a therapeutic agent for oxidative stress-mediated muscle damage. [ABSTRACT FROM AUTHOR]

Although previous studies have shown anti-cancer activity of betulinic acid (BA), a pentacyclic triterpenoid, against various cancer lines, the underlying molecular mechanisms are not well elucidated. In this study, we evaluated the mechanisms involved in the anti-cancer efficacy of BA in U937 human myeloid leukemia cells. BA exerted a significant cytotoxic effect on U937 cells through blocking cell cycle arrest at the G2/M phase and inducing apoptosis, and that the intracellular reactive oxygen species (ROS) levels increased after treatment with BA. The down-regulation of cyclin A and cyclin B1, and up-regulation of cyclin-dependent kinase inhibitor p21WAF1/CIP1 revealed the G2/M phase arrest mechanism of BA. In addition, BA induced the cytosolic release of cytochrome c by reducing the mitochondrial membrane potential with an increasing Bax/Bcl-2 expression ratio. BA also increased the activity of caspase-9 and -3, and subsequent degradation of the poly (ADP-ribose) polymerase. However, quenching of ROS by N-acetyl-cysteine, an ROS scavenger, markedly abolished BA-induced G2/M arrest and apoptosis, indicating that the generation of ROS plays a key role in inhibiting the proliferation of U937 cells by BA treatment. Taken together, our results provide a mechanistic rationale that BA exhibits anti-cancer properties in U937 leukemia cells through ROS-dependent induction of cell cycle arrest at G2/M phase and apoptosis. [ABSTRACT FROM AUTHOR]

Honokiol is one of the main active components of Magnolia officinalis, and has been demonstrated to have multiple pharmacological activities against a variety of diseases. Recently, this phenolic compound is known to have antioxidant activity, but its mechanism of action remains unclear. The purpose of the current study was to evaluate the preventive effects of honokiol against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts. The present study found that honokiol inhibited hydrogen peroxide (H2O2)-induced DNA damage and mitochondrial dysfunction, while reducing reactive oxygen species (ROS) formation. The inhibitory effect of honokiol on H2O2-induced apoptosis was associated with the up-regulation of Bcl-2 and down-regulation of Bax, thus reducing the Bax/Bcl-2 ratio that in turn protected the activation of caspase-9 and -3, and inhibition of poly (ADP-ribose) polymerase cleavage, which was associated with the blocking of cytochrome c release to the cytoplasm. Collectively, these results demonstrate that honokiol defends C2C12 myoblasts against H2O2-induced DNA damage and apoptosis, at least in part, by preventing mitochondrial-dependent pathway through scavenging excessive ROS. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to explore the efficacy of fermented extract of sea tangle (Laminaria japonica Aresch, FST) with Lactobacillus brevis on DNA damage and apoptosis in hydrogen peroxide (H2O2)-stimulated osteoblastic MC3T3-E1 cells and clarify related signaling pathways. Our results showed that exposure to FST significantly improved cell viability, inhibited apoptosis, and suppressed the generation of reactive oxygen species (ROS) in H2O2-stimulated cells. In addition, H2O2 triggered DNA damage in MC3T3-E1 cells was markedly attenuated by FST pretreatment. Moreover, H2O2-induced mitochondrial dysfunctions associated with apoptotic events, including loss of mitochondrial membrane potential (MMP), decreased Bcl-2/Bcl-2 associated x-protein (Bax) ratio, and cytosolic release of cytochrome c, were reduced in the presence of FST. FST also diminished H2O2-induced activation of caspase-3, which was associated with the ability of FST to protect the degradation of poly (ADP-ribose) polymerase. Furthermore, FST notably enhanced nuclear translocation and phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) in the presence of H2O2 with concomitant upregulation of heme oxygenase-1 (HO-1) expression. However, artificial blockade of this pathway by the HO-1 inhibitor, zinc protoporphyrin IX, greatly abolished the protective effect of FST against H2O2-induced MC3T3-E1 cell injury. Taken together, these results demonstrate that FST could protect MC3T3-E1 cells from H2O2-induced damage by maintaining mitochondrial function while eliminating ROS along with activation of the Nrf2/HO-1 antioxidant pathway. [ABSTRACT FROM AUTHOR]

Mori Ramulus, the dried twigs of Morus alba L., has been attracting attention for its potent antioxidant activity, but its role in muscle cells has not yet been elucidated. The purpose of this study was to evaluate the protective effect of aqueous extracts of Mori Ramulus (AEMR) against oxidative stress caused by hydrogen peroxide (H2O2) in C2C12 mouse myoblasts, and in dexamethasone (DEX)-induced muscle atrophied models. Our results showed that AEMR rescued H2O2-induced cell viability loss and the collapse of the mitochondria membrane potential. AEMR was also able to activate AMP-activated protein kinase (AMPK) in H2O2-treated C2C12 cells, whereas compound C, a pharmacological inhibitor of AMPK, blocked the protective effects of AEMR. In addition, H2O2-triggered DNA damage was markedly attenuated in the presence of AEMR, which was associated with the inhibition of reactive oxygen species (ROS) generation. Further studies showed that AEMR inhibited cytochrome c release from mitochondria into the cytoplasm, and Bcl-2 suppression and Bax activation induced by H2O2. Furthermore, AEMR diminished H2O2-induced activation of caspase-3, which was associated with the ability of AEMR to block the degradation of poly (ADP-ribose) polymerase, thereby attenuating H2O2-induced apoptosis. However, compound C greatly abolished the protective effect of AEMR against H2O2-induced C2C12 cell apoptosis, including the restoration of mitochondrial dysfunction. Taken together, these results demonstrate that AEMR could protect C2C12 myoblasts from oxidative damage by maintaining mitochondrial function while eliminating ROS, at least with activation of the AMPK signaling pathway. In addition, oral administration of AEMR alleviated gastrocnemius and soleus muscle loss in DEX-induced muscle atrophied rats. Our findings support that AEMR might be a promising therapeutic candidate for treating oxidative stress-mediated myoblast injury and muscle atrophy. [ABSTRACT FROM AUTHOR]

Isoalantolactone (IALT) is one of the isomeric sesquiterpene lactones isolated from the roots of Inula helenium L. IALT is known to possess various biological and pharmacological activities, but its anti-cancer mechanisms are not well understood. The aim of the present study was to investigate the anti-proliferative effects of IALT in human hepatocellular carcinoma (HCC) cells and to evaluate the potential anti-cancer mechanisms. Our results demonstrated that IALT treatment concentration-dependently suppressed the cell survival of HCC Hep3B cells, which was associated with the induction of apoptosis. IALT increased the expression of death-receptor-related proteins, activated caspases, and induced Bid truncation, subsequently leading to cleavage of poly (ADP-ribose) polymerase. In addition, IALT contributed to the cytosolic release of cytochrome c by destroying mitochondrial integrity, following an increase in the Bax/Bcl-2 expression ratio. However, IALT-mediated growth inhibition and apoptosis were significantly attenuated in the presence of a pan-caspase inhibitor, suggesting that IALT induced caspase-dependent apoptosis in Hep3B cells. Moreover, IALT activated the mitogen-activated protein kinases signaling pathway, and the anti-cancer effect of IALT was significantly diminished in the presence of a potent c-Jun N-terminal kinase (JNK) inhibitor. IALT also improved the generation of intracellular reactive oxygen species (ROS), whereas the ROS inhibitor significantly abrogated IALT-induced growth reduction, apoptosis, and JNK activation. Furthermore, ROS-dependent apoptosis was revealed as a mechanism involved in the anti-cancer activity of IALT in a 3D multicellular tumor spheroid model of Hep3B cells. Taken together, our findings indicate that IALT exhibited anti-cancer activity in HCC Hep3B cells by inducing ROS-dependent activation of the JNK signaling pathway. [ABSTRACT FROM AUTHOR]

Hemistepsin A, a sesquiterpene lactone compound isolated from Hemistepta lyrata , has been identified a variety of pharmacological actions including anti-hepatotoxic, anti-inflammatory and anti-cancer activities. Nevertheless, the antioxidant effects of hemistepsin A and the underlying mechanisms have not been investigated properly. Therefore, in the present study, we investigated the protective effect of hemistepsin A against oxidative stress in HaCaT human keratinocytes. The results demonstrated that hemistepsin A suppressed 500 μM hydrogen peroxide (H 2 O 2)-induced cytotoxicity and DNA damage by blocking ROS accumulation. 10 μM Hemistepsin A also prevented apoptosis by preventing the mitochondrial dysfunction and the cytosolic release of cytochrome c , reducing the rate of Bax/Bcl-2 expression, and decreasing the activation of caspase-9 and caspase-3, suggesting that hemistepsin A protected cells from H 2 O 2 -induced mitochondria-mediated apoptosis. In addition, hemistepsin A markedly promoted the activation of nuclear factor-erythroid-2-related factor 2 (Nrf2), which was associated with the enhanced expression and activity of heme oxygenase-1 (HO-1) in the presence of 500 μM H 2 O 2. However, inhibiting the expression of HO-1 by artificially blocking the expression of Nrf2 or HO-1 using siRNA significantly eliminated the protective effect of hemistepsin A, indicating that hemistepsin A activates the Nrf2/HO-1 signaling pathway in HaCaT cells to protect against oxidative stress. Therefore, these results suggest that hemistepsin A may be useful as a potential therapeutic agent against various oxidative stress-related skin diseases. Image 1 • Hemistepsin A has an antioxidant effect in HaCaT human keratinocytes. • Hemistepsin A suppress H 2 O 2 -induced cytotoxicity and DNA damage by blocking ROS accumulation. • Hemistepsin A protects against H 2 O 2 -induced mitochondria-mediated apoptosis. • Hemistepsin A activates the Nrf2/HO-1 signaling pathway to protect against oxidative stress. [ABSTRACT FROM AUTHOR]

Licochalcone A (LCA) is a chalcone that is predominantly found in the root of Glycyrrhiza species, which is widely used as an herbal medicine. Although previous studies have reported that LCA has a wide range of pharmacological effects, evidence for the underlying molecular mechanism of its anti-cancer efficacy is still lacking. In this study, we investigated the anti-proliferative effect of LCA on human bladder cancer cells, and found that LCA induced cell cycle arrest at G2/M phase and apoptotic cell death. Our data showed that LCA inhibited the expression of cyclin A, cyclin B1, and Wee1, but increased the expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1, and increased p21 was bound to Cdc2 and Cdk2. LCA activated caspase-8 and -9, which are involved in the initiation of extrinsic and intrinsic apoptosis pathways, respectively, and also increased caspase-3 activity, a typical effect caspase, subsequently leading to poly (ADP-ribose) polymerase cleavage. Additionally, LCA increased the Bax/Bcl-2 ratio, and reduced the integrity of mitochondria, which contributed to the discharge of cytochrome c from the mitochondria to the cytoplasm. Moreover, LCA enhanced the intracellular levels of reactive oxygen species (ROS); however, the interruption of ROS generation using ROS scavenger led to escape from LCA-mediated G2/M arrest and apoptosis. Collectively, the present data indicate that LCA can inhibit the proliferation of human bladder cancer cells by inducing ROS-dependent G2/M phase arrest and apoptosis. [ABSTRACT FROM AUTHOR]