Carnosic Acid https://greenmedinfo.com/category/keywords/Carnosic%20Acid en Carnosic acid attenuates RANKL-induced oxidative stress and osteoclastogenesis. https://greenmedinfo.com/article/carnosic-acid-attenuates-rankl-induced-oxidative-stress-and-osteoclastogenesis n/a PMID:  J Mol Med (Berl). 2017 Oct ;95(10):1065-1076. Epub 2017 Jul 4. PMID: 28674855 Abstract Title:  Carnosic acid attenuates RANKL-induced oxidative stress and osteoclastogenesis via induction of Nrf2 and suppression of NF-κB and MAPK signalling. Abstract:  : Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor, which plays an important role in the cellular defense against oxidative stress by induction of anti-oxidant and cytoprotective enzymes. In the current study, we sought to investigate the osteoprotective effect of carnosic acid (CA), a phenolic (catecholic) diterpene. It is widely identified for its electrophilic nature under oxidative stress conditions and thus anticipated to counter osteoporosis by facilitation of Nrf2 signalling. Osteoclast differentiation was induced by incubation of RAW 264.7 (mouse macrophage) cells and mouse bone marrow macrophages (BMMs) in the presence of receptor activator of NF-κB ligand (RANKL) (100 ng/ml). After treatment, osteoclastogenesis was assessed using tartrate-resistant acid phosphatase (TRAP) assay. We observed that 6 h pretreatment with CA (1.25, 2.5, 5 μM) decreased RANKL-induced osteoclast formation and abolished RANKL-induced ROS generation by activating Nrf2 and its transcriptional targets. Further, CA also inhibited RANKL-induced activation of NF-κB and MAPK signalling. RANKL-induced mRNA expression of osteoclast related genes and transcription factors was also diminished by CA. In vivo osteolysis was developed in C57BL/6 male mice using lipopolysaccharide (LPS). Consistent with in vitro results, in vivo μ-CT analysis of femurs showed that bone mineral density (BMD), bone mineral content (BMC), and bone architecture parameters such as trabecular thickness (Tb.Th) and trabecular space (Tb.Sp) were positively modulated by CA in LPS-injected mice. The results obtained in this study support that CA inhibits RANKL-induced osteoclastogenesis by maintaining redox homeostasis through modulation of Nrf2 and NF-κB pathways. KEY MESSAGES: Carnosic acid (CA) inhibits RANKL-induced osteoclastogenesis. CA inhibits RANKL-induced oxidative stress by upregulating Nrf2 transcriptional targets. CA attenuates RANKL-induced NF-κB and MAPK signalling activation. CA decreases NFATc1 and c-Fos expression. In vivo μ-CT analysis reveals that CA prevents bone loss in LPS-injected mice. https://greenmedinfo.com/article/carnosic-acid-attenuates-rankl-induced-oxidative-stress-and-osteoclastogenesis#comments Bone Diseases Carnosic Acid Anti-Inflammatory Agents Antioxidants NF-kappaB Inhibitor Osteoprotective Anti-Inflammatory Agents Antioxidants Bone Diseases Carnosic Acid NF-kappaB Inhibitor Osteoprotective Animal Study In Vitro Study Fri, 25 May 2018 01:47:26 +0000 greenmedinfo 164771 at https://greenmedinfo.com Carnosic acid cooperates with tamoxifen to induce apoptosis in breast cancer cells. https://greenmedinfo.com/article/carnosic-acid-cooperates-tamoxifen-induce-apoptosis-breast-cancer-cells n/a PMID:  Biomed Pharmacother. 2017 May ;89:827-837. Epub 2017 Mar 6. PMID: 28282784 Abstract Title:  Carnosic acid cooperates with tamoxifen to induce apoptosis associated with Caspase-3 activation in breast cancer cells in vitro and in vivo. Abstract:  Tamoxifen is known as a standard therapeutic treatment for estrogen receptor-positive breast cancer, which down-regulates breast cancer mortality by 31% approximately. Carnosic acid is a phenolic diterpene, which has anti-cancer, anti-inflammation, anti-diabetic and anti-bacterial properties, generated by various species coming from Lamiaceae family. The breast cancer is reported as one of the most common tumors among women worldwide. In our study, the possible benefits of carnosic acid cooperation with tamoxifen for breast cancer treatment in vitro and in vivo were investigated. Carnosic acid and tamoxifen cooperation led to apoptosis in breast cancer cells. Caspase-3 signaling pathway was promoted for carnosic acid and tamoxifen co-treatment. Consistently, anti-apoptotic molecules Bcl-2 and Bcl-xl were down-regulated, while pro-apoptotic signals Bax and Bad were up-regulated. The elevation of decoy receptor 1 and 2 (DcR1 and DcR2) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were enhanced for carnosic acid and tamoxifen cooperation. Furthermore, the mouse xenograft model in vivo suggested that carnosic acid and tamoxifen combined therapy inhibited breast cancer growth in comparison to the carnosic acid or tamoxifen monotherapy. Our study supplies a novel therapeutic strategy to induce apoptosis for suppressing breast cancer, which was relied on Caspase-3/TRAIL activation. https://greenmedinfo.com/article/carnosic-acid-cooperates-tamoxifen-induce-apoptosis-breast-cancer-cells#comments Breast Cancer Carnosic Acid Apoptotic Bcl-2 protein down-regulation Bcl-xL down-regulation Tamoxifen Apoptotic Bcl-2 protein down-regulation Bcl-xL down-regulation Breast Cancer Carnosic Acid Synergy with Tamoxifen Animal Study In Vitro Study Tue, 23 May 2017 12:42:51 +0000 greenmedinfo 148116 at https://greenmedinfo.com Carnosic acid induces apoptosis of hepatocellular carcinoma cells. https://greenmedinfo.com/article/carnosic-acid-induces-apoptosis-hepatocellular-carcinoma-cells n/a PMID:  Chem Biol Interact. 2017 Nov 1 ;277:91-100. Epub 2017 Sep 13. PMID: 28918123 Abstract Title:  Carnosic acid induces apoptosis of hepatocellular carcinoma cells via ROS-mediated mitochondrial pathway. Abstract:  Carnosic acid (CA), an important bioactive phenolic diterpene mainly found in labiate plants, exerts various biological functions, including antioxidant, anti-inflammatory, antitumor, and neuroprotective activities. In the present study, we proved the deleterious effects of CA against hepatocellular carcinoma (HCC) in both in vitro and in vivo models. In vitro, CA significantly decreased cell viability, inhibited cell proliferation and migration, enhanced apoptosis, and increased caspase-3, -8, and -9 activities in HepG2 and SMMC-7721 cells. Specifically, CA led to a decreased mitochondrial membrane potential (MMP)and increases in intracellular reactive oxygen species (ROS) levels and apoptosis-related protein expression. Pre-incubation of HCC cells with N-Acetyl-l-cysteine (NAC), a ROS inhibitor, strongly suppressed CA-induced apoptotic phenomena, including reduced cell viability, excessive ROS levels, MMP decreases, and abnormal protein expression, suggesting an association of CA-induced apoptosis with oxidative stress-mediated mitochondrial pathways. In HepG2-and SMMC-7721-xenograft tumor mouse models, treatment with CA inhibited tumor growth and modulated apoptosis-related protein expression, confirming the anti-HCC effects of this chemical. Moreover, the CA-mediated anti-HCC effects associated with oxidative stress provide experimental evidence to support the potential use of CA as a drug therapy for HCC. https://greenmedinfo.com/article/carnosic-acid-induces-apoptosis-hepatocellular-carcinoma-cells#comments Carnosic Acid Liver Cancer Antineoplastic Agents Apoptotic Antineoplastic Agents Apoptotic Carnosic Acid liver cancer Animal Study In Vitro Study Fri, 25 May 2018 00:38:13 +0000 greenmedinfo 164766 at https://greenmedinfo.com Carnosic acid prevents dextran sulfate sodium-induced acute colitis. https://greenmedinfo.com/article/carnosic-acid-prevents-dextran-sulfate-sodium-induced-acute-colitis n/a PMID:  Sci Rep. 2017 Sep 8 ;7(1):11036. Epub 2017 Sep 8. PMID: 28887507 Abstract Title:  Carnosic acid prevents dextran sulfate sodium-induced acute colitis associated with the regulation of the Keap1/Nrf2 pathway. Abstract:  Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBDs) with high prevalence in humans. Carnosic acid (CA) has been reported to possess antioxidative properties; however, its role in IBDs has not been determined. In the present study, we found that CA significantly prevented the loss of body weight and shortening of colon length in acute colitis induced by dextran sodium sulfate (DSS). Pronounced infiltration of immune cells and a loss of crypt architecture and goblet cells were ameliorated by CA. CA significantly decreased the activity of MPO and infiltration of F4/80macrophages in the colon. DSS-induced pro-inflammatory cytokine mRNA and protein levels in the colon were also attenuated by CA. CA decreased the activation of p65 and c-Jun signalling. CA inhibited DSS-induced NLRP3 inflammasome activation by reducing caspase 1 activity. In addition, CA increased the level of Nrf2 and prevented the degradation of Nrf2 via ubiquitination by blocking the interaction between Cullin3 and Keap1, which resulted in the decrease of Nrf2 target genes. Finally, GSH levels and SOD activity were increased after CA treatment, while MDA and iNOS levels were significantly reduced. Taken together, our data showed that CA may be useful as a potential therapeutic candidate for IBDs. https://greenmedinfo.com/article/carnosic-acid-prevents-dextran-sulfate-sodium-induced-acute-colitis#comments Carnosic Acid Colitis Antioxidants Nrf2 activation Antioxidants Carnosic Acid Colitis Nrf2 activation In Vitro Study Fri, 25 May 2018 01:13:29 +0000 greenmedinfo 164768 at https://greenmedinfo.com Carnosic acid protected retinal pigment epithelium cells from acrylamide-induced toxicity. https://greenmedinfo.com/article/carnosic-acid-protected-retinal-pigment-epithelium-cells-acrylamide-induced-to n/a PMID:  Food Chem Toxicol. 2017 Oct ;108(Pt B):543-553. Epub 2017 Feb 1. PMID: 28159594 Abstract Title:  Protective effect of carnosic acid against acrylamide-induced toxicity in RPE cells. Abstract:  Acrylamide is a substance that can be neurotoxic in humans and experimental animals. It is formed at different rates in starchy foods cooked at temperatures above 120 °C as a result of interaction between monosaccharides and the amino acid asparagine. Carnosic acid accounts for over 90% of the antioxidant properties of rosemary extract and is a powerful inhibitor of lipid peroxidation in microsomal and liposomal systems. Carnosic acid has been shown to protectagainst oxidative and inflammatory effects. In order to investigate the protective properties of carnosic acid against acrylamide-induced toxicity in human retinal pigment epithelium (RPE) cells, ARPE-19 cells were pre-treated with 10 μM carnosic acid for 24 h followed by treatment with acrylamide (0.7 or 1 mM) for 24 h. ARPE-19 cells pre-treated with 10 μM carnosic acid showed significantly increased cell viability and decreased cell death rate when compared to ARPE-19 cells treated with acrylamide alone. Activities of SOD and catalase and the level of GSH and expression of NRF2 and a number of anti-oxidant genes were significantly decreased in ARPE-19 cells, while there were significant increases in ROS and MDA; pre-treatment with carnosic acid significantly counteracted these changes. Our results suggest that carnosic acid protected RPE cells from acrylamide-induced toxicity. https://greenmedinfo.com/article/carnosic-acid-protected-retinal-pigment-epithelium-cells-acrylamide-induced-to#comments Acrylamide-induced toxicity Carnosic Acid Acrylamide Antioxidants Acrylamide-induced toxicity Antioxidants Carnosic Acid In Vitro Study Fri, 25 May 2018 01:55:02 +0000 greenmedinfo 164773 at https://greenmedinfo.com Protective effects of carnosic acid against mitochondria-mediated injury in H9c2 cardiomyocytes induced by hypoxia/reoxygenation. https://greenmedinfo.com/article/protective-effects-carnosic-acid-against-mitochondria-mediated-injury-h9c2-car n/a PMID:  Exp Ther Med. 2017 Dec ;14(6):5629-5634. Epub 2017 Oct 2. PMID: 29285102 Abstract Title:  Protective effects of carnosic acid against mitochondria-mediated injury in H9c2 cardiomyocytes induced by hypoxia/reoxygenation. Abstract:  Myocardial ischemia and reperfusion occurs in myocardial infarction. Timely reperfusion will exacerbate the injury through the mitochondria-mediated apoptosis in cardiomyocytes due to the accumulation of excessive reactive oxygen species (ROS). In order to identify novel therapeutic approaches, the cardioprotective effects of carnosic acid and the underlying mechanisms were investigated in the present study in H9c2 cardiomyocytes injured by hypoxia/reoxygenation in vitro. The viability of H9c2 cardiomyocytes was detected by MTT assay and further confirmed by the detection of intracellular lactate dehydrogenase (LDH) release. The mitochondrial function in H9c2 cardiomyocytes was evaluated using fluorescence methods. The proteins related to apoptosis, including caspase-3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were analyzed by western blot analysis, and the activity of caspase-3 was determined using a colorimetric method. As a result, carnosic acid was demonstrated to improve the viability of H9c2 cardiomyocytes and suppress the leakage of cytosolic lactate dehydrogenase under hypoxia/reoxygenation. In addition, the overproduction of intracellular ROS and intracellular calcium overload were ameliorated in the presence of carnosic acid. The dysfunction of mitochondria in H9c2 cardiomyocytes was also attenuated by carnosic acid through blocking the collapse of mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) opening. Furthermore, the apoptosis of H9c2 cardiomyocytes resulted from hypoxia/reoxygenation was inhibited by carnosic acid through the upregulation of Bcl-2 and the downregulation of Bax and caspase-3 levels. These results provided evidence for further investigation that would assist in the development of novel therapeutic approaches for myocardial infarction. https://greenmedinfo.com/article/protective-effects-carnosic-acid-against-mitochondria-mediated-injury-h9c2-car#comments Carnosic Acid Hypoxia Ischemia: Myocardial Cardioprotective Cardioprotective Carnosic Acid Hypoxia Ischemia: Myocardial In Vitro Study Tue, 09 Jan 2018 21:45:15 +0000 greenmedinfo 158267 at https://greenmedinfo.com