Carnosic acid protects normal mouse hepatocytes against H<sub>2</sub>O<sub>2</sub>‐induced cytotoxicity via sirtuin 1‐mediated signaling

Wang, Ting; Takikawa, Yasuhiro

doi:10.1111/hepr.12563

Cited by 11 publications

(6 citation statements)

References 45 publications

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“…33 It should be noted that although this study indicates that CA is absorbed into the bloodstream and is therefore bioavailable, the in vivo toxicity of such plasma levels is not known. In an in vitro study, CA at 10 μmol/L induced cytotoxicity in primary mouse hepatocytes but at lower concentrations (1 μmol/L) did not have any toxic effect 34 indicating that low CA concentrations, such as those used in the present study, should be preferred to avoid toxicity. More studies in animals and humans should be performed to find the oral doses of CA required for a beneficial effect without any observed toxicity.…”

Section: Discussionmentioning

confidence: 64%

Carnosic acid as a component of rosemary extract stimulates skeletal muscle cell glucose uptake via AMPK activation

Naimi

Vlavcheski

Murphy

et al. 2016

Clin Exp Pharma Physio

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Compounds that increase the activity of the energy sensor AMP-activated kinase (AMPK) have the potential to regulate blood glucose levels. Although rosemary extract (RE) has been reported to activate AMPK and reduce blood glucose levels in vivo, the chemical components responsible for these effects are not known. In the present study, we measured the levels of the polyphenol carnosic acid (CA) in RE and examined the effects and the mechanism of action of CA on glucose transport system in muscle cells. High performance liquid chromatography (HPLC) was used to measure the levels of CA in RE. Parental and GLUT4myc or GLUT1myc overexpressing L6 rat myotubes were used. Glucose uptake was assessed using [ H]-2-deoxy-d-glucose. Total and phosphorylated levels of Akt and AMPK were measured by immunoblotting. Plasma membrane GLUT4myc and GLUT1myc levels were examined using a GLUT translocation assay. Statistics included analysis of variance (ANOVA) followed by Tukey's post-hoc test. At concentrations found in rosemary extract, CA stimulated glucose uptake in L6 myotubes. At 2.0 μmol/L CA a response (226 ± 9.62% of control, P=.001), similar to maximum insulin (201 ± 7.86% of control, P=.001) and metformin (213 ± 10.74% of control, P=.001) was seen. Akt phosphorylation was not affected by CA while AMPK and ACC phosphorylation was increased and the CA-stimulated glucose uptake was significantly reduced by the AMPK inhibitor compound C. Plasma membrane GLUT4 or GLUT1 glucose transporter levels were not affected by CA. Our study shows increased muscle cell glucose uptake and AMPK activation by low CA concentrations, found in rosemary extract, indicating that CA may be responsible for the antihyperglycemic properties of rosemary extract seen in vivo.

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Section: Discussionmentioning

confidence: 64%

Carnosic acid as a component of rosemary extract stimulates skeletal muscle cell glucose uptake via AMPK activation

Naimi

Vlavcheski

Murphy

et al. 2016

Clin Exp Pharma Physio

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“…However, these pathological processes were significantly inhibited by carnosic acid. Many studies have shown that the compound induces apoptosis in cancer cells [54] However, some studies have revealed the anti-apoptotic effect of carnosic acid on normal cells in inflammatory conditions [55][56][57][58][59]. In animal models of several inflammatory diseases, carnosic acid inhibited apoptosis to ameliorate inflammation and tissue injury [48,59,60].…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Carnosic Acid on Lipopolysaccharide-Induced Acute Kidney Injury in Mice

et al. 2021

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Septic acute kidney injury (AKI) is an important medical problem worldwide, but current treatments are limited. During sepsis, lipopolysaccharide (LPS) activates various signaling pathways involved in multiorgan failure. Carnosic acid is a natural phenolic diterpene and has multiple bioactivities, such as anti-tumor, anti-inflammatory, and anti-oxidative effects. However, the effect of carnosic acid on septic AKI has not been explored. Therefore, this study aimed to determine whether carnosic acid has a therapeutic effect on LPS-induced kidney injury. Administration of carnosic acid after LPS injection ameliorated histological abnormalities and renal dysfunction. Cytokine production, immune cell infiltration, and nuclear factor-κB activation after LPS injection were also alleviated by carnosic acid. The compound suppressed oxidative stress with the modulation of pro-oxidant and antioxidant enzymes. Tubular cell apoptosis and caspase-3 activation were also inhibited by carnosic acid. These data suggest that carnosic acid ameliorates LPS-induced AKI via inhibition of inflammation, oxidative stress, and apoptosis and could serve as a useful treatment agent for septic AKI.

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“…In addition, CA (1 μM) enhanced the protein level of sirtuin (SIRT)1, and SIRT1 (siRNA) alleviated the protective role of CA against H 2 O 2 ‐induced cell death. Moreover, H 2 O 2 mediated phosphorylation of extracellular signal regulated kinase 1 and 2 (ERK1/2) in primary hepatocytes could be inhibited by CA . These data indicated that the protective role of CA against H 2 O 2 ‐induced cytotoxicity probably mediates by SIRT1 via regulating the activation of ERK1/2.…”

mentioning

confidence: 86%

Protective role of carnosic acid against liver injury

Lin

Di-sheng

2015

Hepatol Res

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Carnosic acid protects normal mouse hepatocytes against H₂O₂‐induced cytotoxicity via sirtuin 1‐mediated signaling

Abstract: Our data indicate that CA protects against oxidative stress-induced cytotoxicity via SIRT1 by regulating subsequent downstream factors such as ERK1/2.

Cited by 11 publications

References 45 publications

Carnosic acid as a component of rosemary extract stimulates skeletal muscle cell glucose uptake via AMPK activation

Carnosic acid as a component of rosemary extract stimulates skeletal muscle cell glucose uptake via AMPK activation

Protective Effects of Carnosic Acid on Lipopolysaccharide-Induced Acute Kidney Injury in Mice

Protective role of carnosic acid against liver injury

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Carnosic acid protects normal mouse hepatocytes against H2O2‐induced cytotoxicity via sirtuin 1‐mediated signaling

Abstract: Our data indicate that CA protects against oxidative stress-induced cytotoxicity via SIRT1 by regulating subsequent downstream factors such as ERK1/2.

Cited by 11 publications

References 45 publications

Carnosic acid as a component of rosemary extract stimulates skeletal muscle cell glucose uptake via AMPK activation

Carnosic acid as a component of rosemary extract stimulates skeletal muscle cell glucose uptake via AMPK activation

Protective Effects of Carnosic Acid on Lipopolysaccharide-Induced Acute Kidney Injury in Mice

Protective role of carnosic acid against liver injury

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Carnosic acid protects normal mouse hepatocytes against H₂O₂‐induced cytotoxicity via sirtuin 1‐mediated signaling