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Carnosic acid
" Acido carnosico studi"
by A_Partyns (12455 pt)
2023-Jun-14 17:43

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Compendio degli studi più significativi con riferimento a proprietà, assunzione, effetti.

Birtić S, Dussort P, Pierre FX, Bily AC, Roller M. Carnosic acid. Phytochemistry. 2015 Jul;115:9-19. doi: 10.1016/j.phytochem.2014.12.026. 

Abstract. Carnosic acid (salvin), which possesses antioxidative and antimicrobial properties, is increasingly exploited within the food, nutritional health and cosmetics industries. Since its first extraction from a Salvia species (∼70 years ago) and its identification (∼50 years ago), numerous articles and patents (∼400) have been published on specific food and medicinal applications of Rosmarinus and Salvia plant extracts abundant in carnosic acid. In contrast, relevant biochemical, physiological or molecular studies in planta have remained rare. In this overview, recent advances in understanding of carnosic acid distribution, biosynthesis, accumulation and role in planta, and its applications are summarised. We also discuss the deficiencies in our understanding of the relevant biochemical processes, and suggest the molecular targets of carnosic acid. Finally, future perspectives and studies related to its potential roles are highlighted.

Choi SH, Jang GW, Choi SI, Jung TD, Cho BY, Sim WS, Han X, Lee JS, Kim DY, Kim DB, Lee OH. Development and Validation of an Analytical Method for Carnosol, Carnosic Acid and Rosmarinic Acid in Food Matrices and Evaluation of the Antioxidant Activity of Rosemary Extract as a Food Additive. Antioxidants (Basel). 2019 Mar 26;8(3):76. doi: 10.3390/antiox8030076.

Abstract. Antioxidants are used to prevent the oxidation of foods. When used for food additive purposes, the dosage should be regulated and the functionality evaluated to ensure stability. In this study, we performed a method validation for the quantitative analysis of rosemary extract residues and evaluated the antioxidant activity of rosemary extract in food matrices. The validated method was able to determine rosemary extract under the optimized high-performance liquid chromatography-photodiode array (HPLC-PDA) conditions. Furthermore, the antioxidant activity was evaluated by peroxide value, acid value, and in terms of the residual antioxidant levels in lard oil. For HPLC-PDA analysis, the limit of detection and quantification of rosemary extracts was ranged from 0.22 to 1.73 μg/mL, 0.66 to 5.23 μg/mL and the recoveries of the rosemary extracts ranged from 70.6 to 114.0%, with relative standard deviations of between 0.2% and 3.8%. In terms of antioxidant activity, carnosic acid performed better than carnosol. Furthermore, by evaluation of the residual antioxidant level using HPLC, we found that carnosic acid is more stable in lard oil than carnosol. These results indicate that rosemary extract can be used as an antioxidant and that the analytical method is suitable for the determination of rosemary extract in various food samples.

de Oliveira MR, Duarte AR, Chenet AL, de Almeida FJS, Andrade CMB. Carnosic Acid Pretreatment Attenuates Mitochondrial Dysfunction in SH-SY5Y Cells in an Experimental Model of Glutamate-Induced Excitotoxicity. Neurotox Res. 2019 Oct;36(3):551-562. doi: 10.1007/s12640-019-00044-8. 

Abstract. Mitochondria are the major site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, mitochondria produce most of the reactive oxygen species (ROS) in nucleated cells. Redox and bioenergetic abnormalities have been seen in mitochondria during the onset and progression of neurodegenerative diseases. In that context, excitotoxicity induced by glutamate (GLU) plays an important role in mediating neurotoxicity. Several drugs have been used in the treatment of diseases involving excitotoxicity. Nonetheless, some patients (20-30%) present drug resistance. Thus, it is necessary to find chemicals able to attenuate mitochondrial dysfunction in the case of excitotoxicity. In this work, we treated the human neuroblastoma SH-SY5Y cell line with the diterpene carnosic acid (CA) at 1 μM for 12 h prior to the exposure to GLU for further 24 h. We found that CA prevented the GLU-induced mitochondrion-related redox impairment and bioenergetic decline in SH-SY5Y cells. CA also downregulated the pro-apoptotic stimulus elicited by GLU in this experimental model. CA exerted mitochondrial protection by a mechanism associated with the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), since silencing of this protein with small interfering RNA (siRNA) suppressed the CA-induced protective effects. Future directions include investigating whether CA would be able to modulate mitochondrial function and/or dynamics in in vivo experimental models of excitotoxicity.

Hu M, Li T, Bo Z, Xiang F. The protective role of carnosic acid in ischemic/reperfusion injury through regulation of autophagy under T2DM. Exp Biol Med (Maywood). 2019 May;244(7):602-611. doi: 10.1177/1535370219840987. 

Abstract. We have provided, for the first time, evidence that carnosic acid (CA) attenuates ischemia-reperfusion injury of diabetic myocardium, i.e. diabetic myocardial ischemia/reperfusion (DMI/R) injury, via enhancement of autophagy. A greater understanding of the target molecule in CA-enhanced autophagy is necessary for the development of potential chemotherapy for DMI/R injury.

Teng L, Fan L, Peng Y, He X, Chen H, Duan H, Yang F, Lin D, Lin Z, Li H, Shao B. Carnosic Acid Mitigates Early Brain Injury After Subarachnoid Hemorrhage: Possible Involvement of the SIRT1/p66shc Signaling Pathway. Front Neurosci. 2019 Mar 5;13:26. doi: 10.3389/fnins.2019.00026. 

Abstract. Carnosic acid (CA) has been reported to exhibit a variety of bioactivities including antioxidation, neuroprotection, and anti-inflammation; however, the impact of CA on subarachnoid hemorrhage (SAH) has never been elucidated. The current study was undertaken to explore the role of CA in early brain injury (EBI) secondary to SAH and the underlying mechanisms. Adult male Sprague-Dawley rats were perforated to mimic a clinical aneurysm with SAH. CA or vehicle was administered intravenously immediately after the SAH occurred. Mortality, SAH grade, neurologic function scores, brain water content, Evans blue extravasation, and the levels of reactive oxygen species (ROS) levels in the ipsilateral cortex were determined 24 h after the SAH occurred. Western blot, immunofluorescence, Fluoro-Jade C (FJC) and TUNEL staining were also performed. Our results showed that CA decreased ROS levels, alleviated brain edema and blood-brain barrier permeability, reduced neuronal cell death, and promoted neurologic function improvement. To probe into the potential mechanisms. We showed that CA increased SIRT1, MnSOD, and Bcl-2 expression, as well as decreased p66shc, Bax, and cleaved caspase-3 expression. Interestingly, sirtinol, a selective inhibitor of SIRT1, abolished the anti-apoptotic effects of CA. Taken together, these data revealed that CA has a neuroprotective role in EBI secondary to SAH. The potential mechanism may involve suppression of neuronal apoptosis through the SIRT1/p66shc signaling pathway. CA may provide a promising therapeutic regimen for management of SAH.

Maynard ME, Underwood EL, Redell JB, Zhao J, Kobori N, Hood KN, Moore AN, Dash PK. Carnosic Acid Improves Outcome after Repetitive Mild Traumatic Brain Injury. J Neurotrauma. 2019 Jul 1;36(13):2147-2152. doi: 10.1089/neu.2018.6155. 

Abstract. In the majority of cases, the cognitive and behavioral impairments resulting from a mild traumatic brain injury (TBI) (also referred to as concussion) wane within days to weeks. In contrast, these impairments can persist for months to years after repetitive mild TBI (rmTBI). The cellular and molecular mechanisms underlying these impairments are not well understood. In the present study, we examined the consequences of rmTBI (three weight drops each separated by 72 h) on brain tissue respiration, pathology, and cognitive performance in mice. The transcription factor nuclear factor-erythroid 2-realted factor 2 (Nrf2) has been demonstrated to enhance the expression of numerous cytoprotective genes. Carnosic acid (CA) has been shown to activate Nrf2 and suppress the proinflammatory transcription factor nuclear factor kappa B (NF-κB). Because contemporaneous activation of cytoprotective genes and inhibition of proinflammatory genes can be beneficial, we questioned whether CA can be used to mitigate the pathobiology of rmTBI. The rmTBI increased hippocampal adenosine triphosphate-linked tissue respiration and proton leak that were unaffected by CA treatment. The rmTBI also caused significant motor and cognitive dysfunction, as tested using the foot fault, Barnes maze, and novel object recognition tasks. These impairments occurred in the absence of visible neuronal or dendritic loss. Post-rmTBI administration of CA significantly improved motor and cognitive function, and decreased Gfap and Iba1 immunoreactivities within white matter tracks. Taken together, these results show that rmTBI can cause cognitive impairments in the absence of overt neuronal pathologies, and post-injury treatment with CA can lessen some of these impairments.

Shao N, Mao J, Xue L, Wang R, Zhi F, Lan Q. Carnosic acid potentiates the anticancer effect of temozolomide by inducing apoptosis and autophagy in glioma. J Neurooncol. 2019 Jan;141(2):277-288. doi: 10.1007/s11060-018-03043-5. 

Abstract. 

Neuroprotection Comparison of Rosmarinic Acid and Carnosic Acid in Primary Cultures of Cerebellar Granule Neurons.
Taram F, Ignowski E, Duval N, Linseman DA.
Molecules. 2018 Nov 13;23(11). pii: E2956. doi: 10.3390/molecules23112956.

Carnosic acid improves diabetic nephropathy by activating Nrf2/ARE and inhibition of NF-κB pathway.
Xie Z, Zhong L, Wu Y, Wan X, Yang H, Xu X, Li P.
Phytomedicine. 2018 Aug 1;47:161-173. doi: 10.1016/j.phymed.2018.04.031. Epub 2018 Apr 17.

Carnosic acid impedes cell growth and enhances anticancer effects of carmustine and lomustine in melanoma.
Lin KI, Lin CC, Kuo SM, Lai JC, Wang YQ, You HL, Hsu ML, Chen CH, Shiu LY.
Biosci Rep. 2018 Jul 2;38(4). pii: BSR20180005. doi: 10.1042/BSR20180005. Print 2018 Aug 31.

An Integrated Proteomics and Bioinformatics Approach Reveals the Anti-inflammatory Mechanism of Carnosic Acid.
Wang LC, Wei WH, Zhang XW, Liu D, Zeng KW, Tu PF.
Front Pharmacol. 2018 Apr 16;9:370. doi: 10.3389/fphar.2018.00370. eCollection 2018.

Carnosic Acid as a Promising Agent in Protecting Mitochondria of Brain Cells.
de Oliveira MR.
Mol Neurobiol. 2018 Aug;55(8):6687-6699. doi: 10.1007/s12035-017-0842-6. Epub 2018 Jan 15.

Protective effect of carnosic acid against acrylamide-induced toxicity in RPE cells.
Albalawi A, Alhasani RHA, Biswas L, Reilly J, Shu X.
Food Chem Toxicol. 2017 Oct;108(Pt B):543-553. doi: 10.1016/j.fct.2017.01.026. Epub 2017 Feb 1.

 

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