Inhibits RSK2 kinase (IC₅₀ = 6.2 μM in kinase assay); Activates Nrf2 transcription factor. [1][3]

The findings demonstrated that whereas 10 μM carnosol significantly reduced RSK2 activity but had no effect on other kinases, it had no cytotoxic effect on GES1 cells. The phosphorylation of ATF1, the substrate of RSK2, and RSK2 autophosphorylation are both significantly and dose-dependently inhibited by carbosol [1].

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Carnosol (20-40 μM) suppressed proliferation of patient-derived gastric cancer cells with reduced phosphorylation of RSK2 downstream targets (Bad, YB-1).
Induced apoptosis in gastric cancer cells: Increased cleavage of caspase-3 and PARP, decreased anti-apoptotic protein Bcl-2.
Activated Nrf2 signaling in endothelial cells: At 10-30 μM, upregulated heme oxygenase-1 (HO-1) expression via PI3K/Akt pathway.
Enhanced endothelial barrier function: Increased transendothelial electrical resistance (TER) and reduced FITC-dextran permeability in HUVECs at 20 μM. [1][2][3]

In comparison to the vehicle-treated group, the results demonstrated that carnosol considerably decreased the weight and volume of the stomach tumor. Moreover, mice were able to withstand carnosol therapy without experiencing a discernible loss of weight, much as the group that was given the vehicle. While the expression of overall CREB remained mostly unaltered, the carnosol-treated group experienced a substantial inhibition of the phosphorylation of CREB, the direct downstream protein of RSK2 [1].

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In gastric cancer PDX (patient-derived xenograft) models, Carnosol (25 mg/kg, twice weekly) significantly reduced tumor volume by 65% after 4 weeks compared to controls.
Immunohistochemistry showed decreased Ki-67 proliferation index and increased cleaved caspase-3 in treated tumors. [1]

RSK2 kinase inhibition assay: Purified RSK2 protein incubated with ATP and substrate peptide, followed by detection of phosphorylation levels. Carnosol dose-dependently inhibited phosphorylation (IC₅₀ = 6.2 μM). [1]

Antiproliferative assay: Gastric cancer cells treated with Carnosol (0-80 μM) for 48-72 hrs, viability measured by MTT/WST-1.
Apoptosis assay: Annexin V/PI staining and flow cytometry after 24-48 hr treatment.
Western blot: Cell lysates probed for p-RSK2, p-Bad, HO-1, Nrf2, caspase-3, and PARP cleavage.
Transendothelial resistance: HUVEC monolayers treated with Carnosol (10-30 μM), TER measured using electrodes.
Endothelial permeability: FITC-dextran flux across HUVEC monolayers quantified by fluorescence. [1][2][3]

Gastric cancer PDX model: NOD/SCID mice implanted with patient-derived tumors. Carnosol dissolved in DMSO:corn oil (1:9), administered intraperitoneally at 25 mg/kg twice weekly for 4 weeks. Control group received vehicle. [1]

Interactions
... A crude extract from Salvia officinalis (sage) reduced the minimum inhibitory concentrations (MICs) of aminoglycosides in vancomycin-resistant enterococci (VRE). ... The effective compound /was isolated/ from the extract and identified ...as carnosol ... . Carnosol showed a weak antimicrobial activity, and greatly reduced the MICs of various aminoglycosides (potentiated the antimicrobial activity of aminoglycosides) and some other types of antimicrobial agents in VRE. Carnosic acid, a related compound, showed the similar activity. The effect of carnosol and carnosic acid with gentamicin was synergistic.
... The protective effects of carnosol on rotenone-induced neurotoxicity in cultured dopaminergic cells /were investigated/.. Results showed that cell viability was significantly improved with carnosol through downregulation of caspase-3. Furthermore, carnosol significantly increased the tyrosine hydroxylase, Nurr1, and extracellular signal-regulated kinase 1/2. These results suggest that carnosol may have potential as a possible compound for the development of new agents to treat Parkinson's disease.
... Male Sprague Dawley rats (n = 5) injured by CCl(4) (oral dose 4 g/kg of body weight) were treated with a single intraperitoneal dose (5 mg/kg) of carnosol. Twenty-four hours later, the rats were anaesthetized deeply to obtain the liver and blood, and biochemical and histological parameters of liver injury were evaluated. ... Carnosol normalized bilirubin plasma levels, reduced malondialdehyde (MDA) content in the liver by 69%, reduced alanine aminotransferase (ALT) activity in plasma by 50%, and partially prevented the fall of liver glycogen content and distortion of the liver parenchyma. /It was concluded that/ carnosol prevents acute liver damage, possibly by improving the structural integrity of the hepatocytes. To achieve this, carnosol could scavenge free radicals induced by CCl(4), consequently avoiding the propagation of lipid peroxides. It is suggested that at least some of the beneficial properties of Rosmarinus officinalis are due to carnosol.
... The activity of rosemary extract, carnosol and ursolic acid in inhibiting the in vivo formation of mammary 7,12-dimethylbenz[a]anthracene (DMBA)-DNA adducts and the initiation of DMBA-induced mammary tumorigenesis in female rats /was examined/. Supplementation of diets for 2 weeks with rosemary extract (0.5% by wt) but not carnosol (1.0%) or ursolic acid (0.5%) resulted in a significant decrease in the in vivo formation of rat mammary DMBA-DNA adducts, compared to controls. When injected intraperitoneally (ip) for 5 days at 200 mg/kg body wt, rosemary and carnosol, but not ursolic acid, significantly inhibited mammary adduct formation by 44% and 40%, respectively, compared to controls. Injection of this dose of rosemary and carnosol was associated with a significant 74% and 65% decrease, respectively, in the number of DMBA-induced mammary adenocarcinomas per rat, compared to controls. Ursolic acid injection had no effect on mammary tumorigenesis...
For more Interactions (Complete) data for CARNOSOL (6 total), please visit the HSDB record page.

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No significant toxicity observed in PDX mice at 25 mg/kg (twice weekly for 4 weeks) based on body weight and organ histology. [1]

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Antidote and Emergency Treatment
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

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Human Toxicity Excerpts
/CASE REPORTS/ A 56-year-old man, working in a food processing factory, developed contact dermatitis of his hands, forearms, and face after the introduction of a new herb extract (Rosmanox) made from the leaves of rosemary (Rosmarinus officinalis). He reacted to carnosol, the main constituent of Rosmanox. 226 controls were negative. To our knowledge, this is the 1st reported case of contact dermatitis from carnosol.

/GENOTOXICITY/ The radioprotective effects of carnosic acid (CA), carnosol (COL), and rosmarinic acid (RO) against chromosomal damage induced by gamma-rays, compared with those of L-ascorbic acid (AA) and the S-containing compound dimethyl sulfoxide (DMSO), were determined by use of the micronucleus test for antimutagenic activity, evaluating the reduction in the frequency of micronuclei (MN) in cytokinesis-blocked cells of human lymphocytes before and after gamma-ray irradiation. With treatment before gamma-irradiation, the most effective compounds were, in order, CA > RO > or = COL > AA > DMSO. The radioprotective effects (antimutagenic) with treatment after gamma-irradiation were lower, and the most effective compounds were CA and COL. RO and AA presented small radioprotective activity, and the sulfur-containing compound DMSO lacked gamma-ray radioprotection capacity. Therefore, CA and COL are the only compounds that showed a significant antimutagenic activity both before and after gamma-irradiation treatments...

/ALTERNATIVE and IN VITRO TESTS/ ... The mechanisms by which rosemary components block initiation of carcinogenesis by the procarcinogen benzo[a]pyrene (B[a]P) in human bronchial epithelial cells (BEAS-2B) /was studied/. Whole rosemary extract (6 ug/mL) or an equivalent concentration of its most potent antioxidant constituents, carnosol or carnosic acid, inhibited DNA adduct formation by 80% after 6 hr co-incubation with 1.5 uM B[a]P. Under similar conditions, cytochrome P450 (CYP) 1A1 mRNA expression was 50% lower in the presence of rosemary components, and CYP1A1 activity was inhibited 70-90%. The observed reduction of DNA adduct formation by rosemary components may mostly result from the inhibition of the activation of benzo[a]pyrene to its ultimate metabolites. Carnosol also affected expression of the phase II enzyme glutathione-S-transferase which is known to detoxify the proximate carcinogenic metabolite of B[a]P. Treatment of BEAS-2B cells with carnosol (1 microgram/ml) for 24 h resulted in a 3- to 4-fold induction of GST pi mRNA. Moreover, expression of a second important phase II enzyme, NAD(P)H: quinone reductase, was induced by carnosol in parallel with GST pi. Therefore, rosemary components have the potential to decrease activation and increase detoxification of an important human carcinogen, identifying them as promising candidates for chemopreventive programs.

/ALTERNATIVE and IN VITRO TESTS/ Carnosic acid (CA) and carnosol (CS) are phenolic diterpenes present in several labiate herbs like Rosmarinus officinalis (Rosemary) and Salvia officinalis (Sage). Extracts of these plants exhibit anti-inflammatory properties ... . CA and CS activate the peroxisome proliferator-activated receptor gamma, implying an anti-inflammatory potential on the level of gene regulation. ... Short-term effects of CA and CS on typical functions of human polymorphonuclear leukocytes (PMNL) /were/ ... (I), CA and CS inhibit the formation of pro-inflammatory leukotrienes in intact PMNL (IC(50)=15-20 uM [CA] and 7 uM [CS], respectively) as well as purified recombinant 5-lipoxygenase ..., IC(50)=1 uM [CA] and 0.1 uM [CS], respectively), (II) both CA and CS potently antagonize intracellular Ca(2+) mobilization induced by a chemotactic stimulus, and (III) CA and CS attenuate formation of reactive oxygen species and the secretion of human leukocyte elastase ... .. Together, /the/ findings provide a pharmacological basis for the anti-inflammatory properties reported for CS- and CA-containing extracts.

/ALTERNATIVE and IN VITRO TESTS/ The effects of 24 hr supplementation of Caco-2 cells with carnosic acid and carnosol, and their activities against 5 uM oleic acid hydroperoxide (OAHPx)-mediated oxidative stress, were investigated. At 24 hr of incubation, under nonstressed and stressed conditions, both compounds at 25, 50, and 100 uM supplement concentrations reduced catalase activity, whereas changes in glutathione peroxidase and superoxide dismutase activities varied depending upon the concentrations. Relative to control cultures, carnosic acid and carnosol reduced membrane damage by 40-50% when stressed by OAHPx. Carnosic acid and carnosol inhibited lipid peroxidation by 88-100% and 38-89%, respectively, under oxidative stress conditions. Both compounds significantly lowered DNA damage induced by OAHPx. Results of this study suggest that antioxidant activities of carnosic acid and carnosol could be partly due to their ability to increase or maintain glutathione peroxidase and superoxide dismutase activities.

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Non-Human Toxicity Excerpts
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ A methanol extract of the leaves of the plant Rosmarinus officinalis L. (rosemary) was evaluated for its effects on tumor initiation and promotion in mouse skin. Application of rosemary to mouse skin inhibited the covalent binding of benzo(a)pyrene [B(a)P] to epidermal DNA and inhibited tumor initiation by B(a)P and 7,12-dimethylbenz[a]anthracene (DMBA). Topical application of 20 nmol B(a)P to the backs of mice once weekly for 10 weeks, followed 1 week later by promotion with 15 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 21 weeks, resulted in the formation of 7.1 tumors per mouse. In a parallel group of animals that were treated topically with 1.2 or 3.6 mg of rosemary 5 min prior to each application of B(a)P, the number of tumors per mouse was decreased by 54 or 64%, respectively. Application of rosemary to mouse skin also inhibited TPA-induced ornithine decarboxylase activity, TPA-induced inflammation, arachidonic acid-induced inflammation, TPA-induced hyperplasia, and TPA-induced tumor promotion. Mice initiated with 200 nmol DMBA and promoted with 5 nmol TPA twice weekly for 19 weeks developed an average of 17.2 skin tumors per mouse. Treatment of the DMBA-initiated mice with 0.4, 1.2, or 3.6 mg of rosemary together with 5 nmol TPA twice weekly for 19 weeks inhibited the number of TPA-induced skin tumors per mouse by 40, 68, or 99%, respectively. Topical application of carnosol or ursolic acid isolated from rosemary inhibited TPA-induced ear inflammation, ornithine decarboxylase activity, and tumor promotion. Topical application of 1, 3, or 10 umol carnosol together with 5 nmol TPA twice weekly for 20 weeks to the backs of mice previously initiated with DMBA inhibited the number of skin tumors per mouse by 38, 63, or 78%, respectively. Topical application of 0.1, 0.3, 1, or 2 umol ursolic acid together with 5 nmol TPA twice weekly for 20 weeks to DMBA-initiated mice inhibited the number of tumors per mouse by 45-61%.

/ALTERNATIVE and IN VITRO TESTS/ Laboratory experiments were conducted to study the antiplatelet activity of carnosol, a phenolic diterpene isolated from rosemary. Carnosol concentration-dependently inhibited washed rabbit platelet aggregation induced by collagen and arachidonic acid (AA), with IC50 values of 5.5+or-0.3 and 42.5+or-0.9 uM, respectively, while it failed to inhibit that induced by ADP and thrombin. Based on the inhibition of collagen-induced platelet aggregation, carnosol revealed blocking of collagen-mediated cytosolic calcium mobilization, serotonin secretion and AA liberation. However, contrary to the inhibition of AA-induced platelet aggregation, carnosol had no effect on AA-mediated TXA2 and PGD2 formation, indicating that carnosol may directly inhibit the TXA2 receptor, which was supported by the finding that carnosol potently inhibited U46619 (a TXA2 mimic)-induced platelet aggregation, with an IC50 value of 22.0+or-2.5 uM. In addition, the U46619-induced concentration-response curve shifted downward by the application of carnosol at 22 and 50 uM, indicating a typical non-competitive antagonism on the TXA2 receptor. Taken together, these results suggest that the antiplatelet activity of carnosol may be mediated by the inhibition of the TXA2 receptor and cytosolic calcium mobilization and that carnosol has a potential to be developed as a novel-antiplatelet agent.

/OTHER TOXICITY INFORMATION/ The peroxisome proliferator-activated receptors play a pivotal role in metazoan lipid and glucose homeostasis. Synthetic activators of PPARalpha (fibrates) and PPARgamma (glitazones) are therefore widely used for treatment of dislipidemia and diabetes, respectively. There is growing evidence for herbal compounds to influence nuclear receptor signalling e.g. the PPARs. /It was/ recently reported /that/ carnosic acid and carnosol ... /are/ activators of PPARgamma.

[1]. Carnosol suppresses patient-derived gastric tumor growth by targeting RSK2. Oncotarget. 2018 Feb 6;9(76):34200-34212.

[2]. Carnosol as a Nrf2 Activator Improves Endothelial Barrier Function Through Antioxidative Mechanisms. Int J Mol Sci. 2019;20(4):880. Published 2019 Feb 18.

[3]. Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J Biol Chem. 2004;279(10):8919-8929.

Therapeutic Uses
/EXPL/ The known (+)-trans-ozic acid (1) and two new labdane diterpenoids (2 and 3) have been isolated from an ethanol extract of Orthosiphon labiatus. The structures of 2 and 3 were established mainly by 1D and 2D NMR spectroscopic means. The ethanolic extract of Salvia africana-lutea afforded the known abietane diterpenoids carnosol (4), rosmadial (5), and carnosic acid (characterized as its derivative 6). Compounds 3 and 6 exhibited MICs of 157 and 28 uM, respectively, against Mycobacterium tuberculosis, while 2 and 6 showed cytotoxic activity with IC50 82 and 69 uM, respectively, against a breast (MCF-7) human cancer cell line.
/EXPL/ Rosmarinus officinalis extracts were investigated ... to identify bioactive compounds. ... Antimicrobial activity analysis was carried out using the disk diffusion and broth dilution techniques. ... Although all rosemary extracts showed a high radical scavenging activity, a different efficacy as antimicrobial agent was observed. Methanol extract containing 30% of carnosic acid, 16% of carnosol and 5% of rosmarinic acid was the most effective antimicrobial.

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Mechanism of Action
This study examines the anti-cancer effect of carnosol in human prostate cancer PC3 cells and its role in modulating multiple signaling pathways associated with carcinogenesis. ... Analysis using flow cytometry as well as biochemical analysis identified G2-phase cell cycle arrest. To establish a more precise mechanism, ... a protein array that evaluated 638 proteins involved in cell signaling pathways /was performed/. The protein array identified 5'-AMP-activated protein kinase (AMPK), a serine/threonine protein kinase involved in the regulation of cellular energy balance as a potential target. Further downstream effects consistent with cancer inhibition included the modulation of the mTOR/HSP70S6k/4E-BP1 pathway. Additionally, ... carnosol targeted the PI3K/Akt pathway in a dose dependent manner. ... These results suggest that carnosol targets multiple signaling pathways that include the AMPK pathway... PMID:18286356

Carnosol and carnosic acid, two antioxidant polyphenols present in Rosmarinus officinalis (rosemary), were investigated for their antiproliferative properties toward Caco-2 cells. Twenty hours of treatment with both carnosol and carnosic acid inhibited 3H-thymidine incorporation in a dose-dependent manner, with a 50% inhibitory concentration of 23 uM and significantly increased the doubling time of Caco-2 cells from 29.5 to 140 and 120 hr, respectively. These effects were associated with accumulation of treated cells in the G2/M phase of the cell cycle. Carnosol was found to exert its major cell cycle effect after prometaphase, and caused an increase in cyclin B1 protein levels whereas carnosic acid arrested cells prior to prometaphase, and caused a reduction in cyclin A levels. These structurally related phytochemicals, therefore, appear to arrest cells at different phases of the cell cycle possibly through influencing the levels of different cyclin proteins. PMID:16019137

...The antioxidant activity of carnosol and other compounds extracted from rosemary. Carnosol showed potent antioxidative activity in alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) free radicals scavenge and DNA protection from Fenton reaction. High concentrations of nitric oxide (NO) are produced by inducible NO synthase (iNOS) in inflammation and multiple stages of carcinogenesis. Treatment of mouse macrophage RAW 264.7 cell line with carnosol markly reduced lipopolysaccharide (LPS)-stimulated NO production in a concentration-related manner with an IC50 of 9.4 uM; but other tested compounds had slight effects. Western blot, reverse transcription-polymerase chain reaction, and northern blot analyses demonstrated that carnosol decreased LPS-induced iNOS mRNA and protein expression. Carnosol treatment showed reduction of nuclear factor-kappaB (NF-kappaB) subunits translocation and NF-kappaB DNA binding activity in activated macrophages. Carnosol also showed inhibition of iNOS and NF-kappaB promoter activity in transient transfection assay. These activities were referred to down-regulation of inhibitor kappaB (IkappaB) kinase (IKK) activity by carnosol (5 microM), thus inhibited LPS-induced phosphorylation as well as degradation of IkappaBalpha. Carnosol also inhibited LPS-induced p38 and p44/42 mitogen-activated protein kinase (MAPK) activation at a higher concentration (20 microM). These results suggest that carnosol suppresses the NO production and iNOS gene expression by inhibiting NF-kappaB activation, and provide possible mechanisms for its anti-inflammatory and chemopreventive action. PMID:12082020

In a previous study, ... carnosic acid (CA) protected cortical neurons by activating the Keap1/Nrf2 pathway, which activation was initiated by S-alkylation of the critical cysteine thiol of the Keap1 protein by the "electrophilic"quinone-type of CA ... . Carnosic acid, a catechol-type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1 ... . The present study ... used HT22 cells, a neuronal cell line, to test CA derivatives that might be more suitable for in vivo use, as an electrophile like CA might react with other molecules prior to reaching its intended target. CA and carnosol protected the HT22 cells against oxidative glutamate toxicity. CA activated the transcriptional antioxidant-responsive element of phase-2 genes including hemeoxygenase-1, NADPH-dependent quinone oxidoreductase, and gamma-glutamyl cysteine ligase, all of which provide neuroprotection by regulating cellular redox. This finding was confirmed by the result that CA significantly increased the level of glutathione. We synthesized a series of its analogues in which CA was esterified at its catechol hydroxyl moieties to prevent the oxidation from the catechol to quinone form or esterified at those moieties and its carbonic acid to stop the conversion from CA to carnosol. In both cases, the conversion and oxidation cannot occur until the alkyl groups are removed by an intracellular esterase. Thus, the most potent active form as the activator of the Keap1/Nrf2 pathway, the quinone-type CA, will be produced inside the cells. However, neither chemical modulation potentiated the neuroprotective effects, possibly because of increased lipophilicity. These results suggest that the neuroprotective effects of CA critically require both free carboxylic acid and catechol hydroxyl moieties. Thus, the hydrophilicity of CA might be a critical feature for its neuroprotective effects.

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Carnosol is a rosemary-derived diterpene with antioxidant properties. Mechanisms include: 1) Direct binding to RSK2 to inhibit pro-survival signaling; 2) Nrf2-mediated HO-1 induction for endothelial protection.
Potential therapeutic applications: Gastric cancer (via RSK2 inhibition) and vascular barrier dysfunction (via Nrf2 activation). [1][2][3]

C20H26O4

330.4180

330.183

C, 72.70; H, 7.93; O, 19.37

5957-80-2

442009

White to off-white solid powder

1.3±0.1 g/cm3

524.8±50.0 °C at 760 mmHg

187.0±23.6 °C

0.0±1.4 mmHg at 25°C

1.607

3.71

2

4

1

24

542

3

CC(C)C1=C(C(=C2C(=C1)[C@@H]3C[C@@H]4[C@@]2(CCCC4(C)C)C(=O)O3)O)O

XUSYGBPHQBWGAD-PJSUUKDQSA-N

InChI=1S/C20H26O4/c1-10(2)11-8-12-13-9-14-19(3,4)6-5-7-20(14,18(23)24-13)15(12)17(22)16(11)21/h8,10,13-14,21-22H,5-7,9H2,1-4H3/t13-,14-,20+/m0/s1

(1R,8S,10S)-3,4-dihydroxy-11,11-dimethyl-5-propan-2-yl-16-oxatetracyclo[6.6.2.01,10.02,7]hexadeca-2,4,6-trien-15-one

carnosol; 5957-80-2; 483O455CKD; DTXSID80904451; NSC-39143; (1R,8S,10S)-3,4-dihydroxy-11,11-dimethyl-5-propan-2-yl-16-oxatetracyclo[6.6.2.01,10.02,7]hexadeca-2,4,6-trien-15-one; 2H-9,4a-(Epoxymethano)phenanthren-12-one, 1,3,4,9,10,10a-hexahydro-5,6-dihydroxy-1,1-dimethyl-7-(1-methylethyl)-, (4aR-(4aalpha,9alpha,10abeta))-; (1R,8S,10S)-3,4-dihydroxy-11,11-dimethyl-5-(propan-2-yl)-16-oxatetracyclo[6.6.2.0^{1,10}.0^{2,7}]hexadeca-2,4,6-trien-15-one;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product is not stable in solution, please use freshly prepared working solution for optimal results.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~151.32 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (6.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (6.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)