Carnosic acid.
Birtić S, Dussort P, Pierre FX, Bily AC, Roller M
Phytochemistry. 2015 Jul;115:9-19. doi: 10.1016/j.phytochem.2014.12.026. Epub 2015 Jan 29.

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.
Choi SH, Jang GW, Choi SI, Jung TD, Cho BY, Sim WS, Han X, Lee JS, Kim DY, Kim DB, Lee OH.
Antioxidants (Basel). 2019 Mar 26;8(3). pii: E76. doi: 10.3390/antiox8030076.

Carnosic Acid Pretreatment Attenuates Mitochondrial Dysfunction in SH-SY5Y Cells in an Experimental Model of Glutamate-Induced Excitotoxicity.
de Oliveira MR, Duarte AR, Chenet AL, de Almeida FJS, Andrade CMB.
Neurotox Res. 2019 Apr 23. doi: 10.1007/s12640-019-00044-8.

The protective role of carnosic acid in ischemic/reperfusion injury through regulation of autophagy under T2DM.
Hu M, Li T, Bo Z, Xiang F.
Exp Biol Med (Maywood). 2019 Apr 4:1535370219840987. doi: 10.1177/1535370219840987.

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

Carnosic Acid Improves Outcome after Repetitive Mild Traumatic Brain Injury.
Maynard ME, Underwood EL, Redell JB, Zhao J, Kobori N, Hood KN, Moore AN, Dash PK.
J Neurotrauma. 2019 Mar 26. doi: 10.1089/neu.2018.6155.

Carnosic acid enhances the anti-lung cancer effect of cisplatin by inhibiting myeloid-derived suppressor cells.
Liu W, Wu TC, Hong DM, Hu Y, Fan T, Guo WJ, Xu Q.
Chin J Nat Med. 2018 Dec;16(12):907-915. doi: 10.1016/S1875-5364(18)30132-8.

Carnosic acid potentiates the anticancer effect of temozolomide by inducing apoptosis and autophagy in glioma.
Shao N, Mao J, Xue L, Wang R, Zhi F, Lan Q.
J Neurooncol. 2019 Jan;141(2):277-288. doi: 10.1007/s11060-018-03043-5. Epub 2018 Nov 20.

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.

Carnosic acid occurs naturally in rosemary (Rosmarinus officinalis) and sage (Salvia officinalis) has antibacterial, antiseptic, antioxidant functions. It belongs to the class of diterpenes.

The synthesis process takes place in several stages:

• Extraction from the leaves of the rosemary plant with various solvents, such as ethanol or acetone. The leaves are immersed in the solvent, which dissolves carnosic acid. The solution is then filtered to remove any solid plant material.
• Purification.  Carnosic acid is purified by the solvent with techniques such as column chromatography, where the solution is passed through a column filled with a material that selectively binds to carnosic acid. Carnosic acid can then be extracted from the column using a different solvent.
• Crystallization. The purified carnosic acid is crystallized by evaporating the solvent, which precipitates the carnosic acid from the crystal solution.

It appears as a yellow or brown powder.

What it is used for and where

Food

Antibacterial and antimicrobial activity: Carnosic acid has antimicrobial properties that make it effective against various bacteria, fungi and viruses. It has been studied for its potential application in food preservation and as an alternative to synthetic antimicrobial agents.

Medical

Anti-obesity effects. Carnosic acid has been studied for its potential to inhibit adipogenesis (the formation of fat cells) and promote fat breakdown. It may help regulate lipid metabolism and prevent weight gain.

Neuroprotector. The potential applications of carnosic acid for Alzheimer's disease, Parkinson's disease and COVID-19, through inhibition of the NLRP3 inflammasome are discussed in this study (1) In addition, carnosic acid reduced aberrant activation of microglia and astrocytes and decreased the production of mature IL-1β, TNFα and IL-6 in the APP/PS1 mouse brain (2).

Cosmetics

Antioxidant agent. Ingredient that counteracts oxidative stress and prevents cell damage. Free radicals, pathological inflammatory processes, reactive nitrogen species and reactive oxygen species are responsible for the ageing process and many diseases caused by oxidation.

Safety

It has no contraindications.

Carnosic acid studies

• Molecular Formula:  C₂₀H₂₈O₄
• Molecular Weight: 332.44 g/mol
• UNII: LI791SXT24
• CAS: 3650-09-7
• EC Number: 609-253-7
• PubChem Substance ID 329749247
• MDL number MFCD02259459
• Beilstein Registry Number 2707918

Synonyms:

• Salvin
• RoseOx
• 11,12-dihydroxy-13-isopropylpodocarpa-8,11,13-trien-17-oic acid
• (4aR,10aS)-5,6-dihydroxy-1,1-dimethyl-7-(propan-2-yl)-1,3,4,9,10,10a-hexahydrophenanthrene-4a(2H)-carboxylic acid
• (4aR,10aS)-5,6-Dihydroxy-7-isopropyl-1,1-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-4a-carboxylic Acid
• 4a(2H)-Phenanthrenecarboxylic acid, 1,3,4,9,10,10a-hexahydro-5,6-dihydroxy-1,1-dimethyl-7-(1-methylethyl)-, (4aR-trans)-

References_____________________________________________________________________

(1) Satoh, Takumi, Dorit Trudler, Chang-Ki Oh, and Stuart A. Lipton. 2022. "Potential Therapeutic Use of the Rosemary Diterpene Carnosic Acid for Alzheimer’s Disease, Parkinson’s Disease, and Long-COVID through NRF2 Activation to Counteract the NLRP3 Inflammasome" Antioxidants 11, no. 1: 124. https://doi.org/10.3390/antiox11010124

Abstract. Rosemary (Rosmarinus officinalis [family Lamiaceae]), an herb of economic and gustatory repute, is employed in traditional medicines in many countries. Rosemary contains carnosic acid (CA) and carnosol (CS), abietane-type phenolic diterpenes, which account for most of its biological and pharmacological actions, although claims have also been made for contributions of another constituent, rosmarinic acid. This review focuses on the potential applications of CA and CS for Alzheimer’s disease (AD), Parkinson’s disease (PD), and coronavirus disease 2019 (COVID-19), in part via inhibition of the NLRP3 inflammasome. CA exerts antioxidant, anti-inflammatory, and neuroprotective effects via phase 2 enzyme induction initiated by activation of the KEAP1/NRF2 transcriptional pathway, which in turn attenuates NLRP3 activation. In addition, we propose that CA-related compounds may serve as therapeutics against the brain-related after-effects of SARS-CoV-2 infection, termed “long-COVID.” One factor that contributes to COVID-19 is cytokine storm emanating from macrophages as a result of unregulated inflammation in and around lung epithelial and endovascular cells. Additionally, neurological aftereffects such as anxiety and “brain fog” are becoming a major issue for both the pandemic and post-pandemic period. Many reports hold that unregulated NLRP3 inflammasome activation may potentially contribute to the severity of COVID-19 and its aftermath. It is therefore possible that suppression of NLRP3 inflammasome activity may prove efficacious against both acute lung disease and chronic neurological after-effects. Because CA has been shown to not only act systemically but also to penetrate the blood–brain barrier and reach the brain parenchyma to exert neuroprotective effects, we discuss the evidence that CA or rosemary extracts containing CA may represent an effective countermeasure against both acute and chronic pathological events initiated by SARS-CoV-2 infection as well as other chronic neurodegenerative diseases including AD and PD.

(2) Yi-Bin, W., Xiang, L., Bing, Y. et al. Inhibition of the CEBPβ-NFκB interaction by nanocarrier-packaged Carnosic acid ameliorates glia-mediated neuroinflammation and improves cognitive function in an Alzheimer’s disease model. Cell Death Dis 13, 318 (2022). https://doi.org/10.1038/s41419-022-04765-1

Abstract. Neuroinflammation occurs early in Alzheimer’s disease (AD). The initial stage of AD is related to glial dysfunction, which contributes to impairment of Aβ clearance and disruption of synaptic connection. CEBPβ, a member of the CCAAT-enhancer-binding protein (CEBP) family, modulates the expression of inflammation-associated genes, and its expression is elevated in brains undergoing degeneration and injured brains. However, the mechanism underlying CEBPβ-mediated chronic inflammation in AD is unclear. In this study, we observed that increases in the levels of nuclear CEBPβ facilitated the interaction of CEBPβ with the NFκB p65 subunit, increasing the transcription of proinflammatory cytokines in the APP/PS1 mouse brain. Oral administration of nanocarrier-packaged carnosic acid (CA) reduced the aberrant activation of microglia and astrocytes and diminished mature IL-1β, TNFα and IL-6 production in the APP/PS1 mouse brain. CA administration reduced β-amyloid (Aβ) deposition and ameliorated cognitive impairment in APP/PS1 mice. We observed that CA blocked the interaction of CEBPβ with NFκB p65, and chromatin immunoprecipitation revealed that CA reduced the transcription of the NFκB target genes TNFα and IL-6. We confirmed that CA alleviated inflammatory mediator-induced neuronal degeneration and reduced Aβ secretion by inhibiting the CEBPβ-NFκB signalling pathway in vitro. Sulfobutyl ether-beta-cyclodextrin (SBEβCD) was used as the encapsulation agent for the CA-loaded nanocarrier to overcome the poor water solubility and enhance the brain bioavailability of CA. The CA nanoparticles (NPs) had no obvious toxicity. We demonstrated a feasible SBEβCD-based nanodelivery system targeting the brain. Our data provide experimental evidence that CA-loaded NPs are potential therapeutic agents for AD treatment.