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
…Crude extract of Salvia officinalis can reduce the minimum inhibitory concentration (MIC) of aminoglycoside antibiotics in vancomycin-resistant enterococci (VRE). …An effective compound was isolated from this extract and identified as salviaol. …Salviaol exhibits weak antibacterial activity but significantly reduces the MIC of various aminoglycoside antibiotics (enhancing the antibacterial activity of aminoglycosides) and some other antibacterial drugs against VRE. Salvia oxalic acid (a related compound) also shows similar activity. Salviaol and salvia oxalic acid have a synergistic effect when used in combination with gentamicin. …The protective effect of salviaol against rotenone-induced neurotoxicity in cultured dopaminergic cells was investigated. The results showed that salviaol significantly improved cell viability by downregulating caspase-3. Furthermore, carnosine significantly increased the expression of tyrosine hydroxylase, Nurr1, and extracellular signal-regulated kinase 1/2. These results suggest that carnosine may have the potential to develop new drugs for the treatment of Parkinson's disease. Male Sprague Dawley rats (n = 5) were treated with a single intraperitoneal injection of carnosine (5 mg/kg) after carbon tetrachloride (CCl₄, oral dose 4 g/kg body weight) injury. Twenty-four hours later, the rats were deeply anesthetized, and liver and blood were collected to assess biochemical and histological parameters of liver injury. Carnosine restored plasma bilirubin levels to normal, reduced hepatic malondialdehyde (MDA) content by 69%, reduced plasma alanine aminotransferase (ALT) activity by 50%, and partially prevented the decline in liver glycogen content and changes in liver parenchymal structure. The study concludes that carnosine may prevent acute liver injury by improving the structural integrity of hepatocytes. To achieve this goal, carnosine can scavenge carbon tetrachloride (CCl₄)-induced free radicals, thereby preventing the spread of lipid peroxides. Studies have shown that some of the beneficial properties of rosemary (Rosmarinus officinalis) may be attributed to carnosine. The study also investigated the effects of rosemary extract, caryophyllin, and ursolic acid on the inhibition of 7,12-dimethylbenzo[a]anthracene (DMBA)-DNA adduct formation and DMBA-induced mammary tumor development in female rats. Adding rosemary extract (0.5% wt) to the diet for two weeks significantly reduced the in vivo formation of DMBA-DNA adducts in rat mammary glands, showing a significant difference compared to the control group. Adding caryophyllin (1.0%) or ursolic acid (0.5%) did not have this effect. Intraperitoneal injection of rosemary and caryophyllin (at a dose of 200 mg/kg body weight) for 5 consecutive days significantly inhibited the formation of DMBA-DNA adducts in mammary glands, with inhibition rates of 44% and 40%, respectively, showing significant differences compared to the control group. Furthermore, injection of this dose of rosemary and caryophyllin significantly reduced the number of DMBA-induced mammary adenocarcinomas per rat by 74% and 65%, respectively, showing significant differences compared to the control group. Ursolic acid injection has no effect on breast tumor development…
For more complete data on interactions of CARNOSOL (6 in total), please visit the HSDB record page.

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No significant toxicity was observed in PDX mice at a dose of 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 adequate decontamination has been performed. If the patient stops breathing, begin artificial respiration immediately, preferably using a valve resuscitator, bag-valve mask, or simple breathing mask, and follow the training instructions. Perform cardiopulmonary resuscitation if necessary. Immediately flush contaminated eyes with running water. Do not induce vomiting. If vomiting occurs, tilt the patient forward or to the left (head down if possible) to keep the airway open and prevent aspiration. Keep the patient calm and maintain normal body temperature. Seek medical assistance. /Class A and Class B Poisons/
/SRP:/ Basic Treatment: Establish a patent airway (using an oropharyngeal or nasopharyngeal airway if necessary). Suction as necessary. Observe for signs of respiratory failure and provide assisted ventilation if necessary. Administer oxygen via a non-invasive ventilation mask at a flow rate of 10 to 15 liters per minute. Monitor for pulmonary edema and treat as necessary… Monitor for shock and treat as necessary… Anticipate seizures and treat as necessary… If eyes are contaminated, flush with water immediately. During transport, continuously flush each eye with 0.9% normal saline (NS)… Do not use emetics. If swallowed, rinse mouth and dilute with 5 ml/kg body weight to 200 ml of water, provided the patient is able to swallow, has a strong gag reflex, and does not drool… After decontamination, cover skin burns with a dry, sterile dressing… /Class A and Class B Poisons/
/SRP:/ Advanced Treatment: For patients with altered mental status, severe pulmonary edema, or severe respiratory distress, consider oropharyngeal or nasopharyngeal endotracheal intubation to control the airway. Positive pressure ventilation with a bag-valve-mask may be effective. Consider medical treatment for pulmonary edema…. Consider the use of a beta-agonist (such as salbutamol) for severe bronchospasm…. Monitor heart rhythm and treat arrhythmias as needed…. Initiate intravenous infusion of 5% glucose solution (D5W) /SRP: "Keep patent", minimum flow rate/. If signs of hypovolemia appear, use 0.9% normal saline (NS) or lactated Ringer's solution. Administer fluids with caution in cases of hypotension with signs of hypovolemia. Be alert for signs of fluid overload…. Use diazepam or lorazepam for seizures…. Use promecaine hydrochloride as an adjunct to eye irrigation…. /Toxins A and B/

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Human Toxicity Excerpt
/Case Report/ A 56-year-old male working in a food processing plant developed contact dermatitis on his hands, forearms, and face after using a new herbal extract (Rosmanox) made from the leaves of rosemary (Rosmarinus officinalis). He reacted to caryophylloxel, the main component of Rosmanox. Results from a control group of 226 patients were all negative. To our knowledge, this is the first reported case of contact dermatitis caused by caryophylloxel.
/Genogenic Toxicity/ This study assessed antimutagenic activity using a micronucleus assay. The radioprotective effects of caryophyllic acid (CA), caryophylloxel (COL), and rosmarinic acid (RO) on γ-ray-induced chromosomal damage were compared by detecting the decrease in micronucleus (MN) frequency in human lymphocytes before and after γ-ray irradiation, and were compared with those of L-ascorbic acid (AA) and the sulfur-containing compound dimethyl sulfoxide (DMSO). When treated before gamma ray irradiation, the most effective compounds were, in descending order: CA > RO > or = COL > AA > DMSO. When treated after gamma ray irradiation, the radioprotective effect (anti-mutagenic effect) decreased, and the most effective compounds were CA and COL. RO and AA had weak radioprotective activity, while the sulfur-containing compound DMSO lacked gamma ray radioprotective ability. Therefore, CA and COL were the only compounds that showed significant anti-mutagenic activity both before and after gamma ray irradiation treatment…
/Substitution and In Vitro Experiments/…The mechanism by which rosemary components block the carcinogenic effect of the pre-carcinogen benzo[a]pyrene (B[a]P) in human bronchial epithelial cells (BEAS-2B) was investigated. The whole rosemary extract (6 μg/mL) or its most effective antioxidant components—sarsaparin or sarsaparin—at equivalent concentrations, after co-incubation with 1.5 μM B[a]P for 6 hours, inhibited 80% of DNA adduct formation. Under similar conditions, the presence of rosemary components reduced cytochrome P450 (CYP) 1A1 mRNA expression by 50% and inhibited CYP1A1 activity by 70-90%. The inhibitory effect of rosemary components on DNA adduct formation may primarily stem from the inhibition of benzo[a]pyrene activation to its final metabolite. Sagerol also affected the expression of the phase II enzyme glutathione S-transferase, known to detoxify the proximal oncogenic metabolite of benzo[a]pyrene. Treatment of BEAS-2B cells with sagerol (1 μg/ml) for 24 hours induced GST pi mRNA expression 3-4 times. Furthermore, sagerol induced the expression of another important phase II enzyme, NAD(P)H:quinone reductase, paralleling the induction of GST pi. Therefore, rosemary components possess the potential to reduce the activation of important human carcinogens and enhance their detoxification effects, making them potential candidate components for chemoprevention programs.
/Alternatives and In Vitro Testing/ Sagelic acid (CA) and sageol (CS) are phenolic diterpenoid compounds found in a variety of Lamiaceae plants, such as rosemary and sage. Extracts from these plants possess anti-inflammatory properties…CA and CS can activate peroxisome proliferator-activated receptor γ, suggesting their anti-inflammatory potential at the gene regulatory level. …Short-term effects of CA and CS on typical functions of human polymorphonuclear leukocytes (PMNL) /were /…(I) CA and CS inhibited the formation of pro-inflammatory leukotrienes in intact PMNLs (IC(50) 15-20 μM [CA] and 7 μM [CS], respectively), as well as the formation of purified recombinant 5-lipoxygenase (IC(50) 1 μM [CA] and 0.1 μM [CS], respectively);(II) Both CA and CS effectively antagonized chemotactic stimulation-induced intracellular Ca(2+) mobilization;(III) CA and CS attenuated the generation of reactive oxygen species and the secretion of human leukocyte elastase…In summary, these findings provide a pharmacological basis for the reported anti-inflammatory properties of extracts containing CS and CA.
/Effects of Substitution and In Vitro Assays/ This study investigated the inhibitory effects of oxalic acid and succinylcholine on 5 μM oleate hydroperoxide (OAHPx)-mediated oxidative stress in Caco-2 cells after 24 hours of incubation. Under both non-stressed and stressed conditions, after 24 hours of culture, concentrations of 25, 50, and 100 μM oxalic acid and succinylcholine all reduced catalase activity, while the activities of glutathione peroxidase and superoxide dismutase varied with concentration. Compared to the control group, oxalic acid and succinylcholine reduced cell membrane damage by 40-50% under OAHPx stress. Under oxidative stress conditions, oxalic acid and succinylcholine inhibited lipid peroxidation by 88-100% and 38-89%, respectively. Both compounds significantly reduced OAHPx-induced DNA damage. The results of this study suggest that the antioxidant activity of sarsaparillaric acid and sarsaparillaol may be partly attributed to their ability to enhance or maintain the activity of glutathione peroxidase and superoxide dismutase.

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Non-human toxicity excerpt
/Experimental animals: Chronic exposure or carcinogenicity/ This study evaluated the effects of methanol extracts of rosemary (Rosmarinus officinalis L.) leaves on the occurrence and development of skin tumors in mice. Application of rosemary to mouse skin inhibited the covalent binding of benzo[a]pyrene [B(a)P] to epidermal DNA and inhibited B(a)P and 7,12-dimethylbenzo[a]anthracene (DMBA)-induced tumorigenesis. Topical application of 20 nmol of benzo[a]pyrene (B(a)P) to the back of mice weekly for 10 weeks, followed by application of 15 nmol of 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 21 weeks resulted in an average of 7.1 tumors per mouse. In another group of mice, topical application of 1.2 mg or 3.6 mg of rosemary 5 minutes before each B(a)P treatment resulted in a 54% and 64% reduction in tumor number per mouse, respectively. Rosemary application to mouse skin also inhibited TPA-induced ornithine decarboxylase activity, TPA-induced inflammation, arachidonic acid-induced inflammation, TPA-induced hyperplasia, and TPA-induced tumor growth. Starting with 200 nmol dimethylbenzamide (DMBA), mice treated with 5 nmol TPA twice weekly for 19 weeks developed an average of 17.2 skin tumors per mouse. In DMBA-induced mice, treatment with 0.4, 1.2, or 3.6 mg of rosemary combined with 5 nmol TPA twice weekly for 19 weeks inhibited the number of TPA-induced skin tumors by 40%, 68%, and 99% per mouse, respectively. Topical application of caryophyllotoxin or ursolic acid isolated from rosemary inhibited TPA-induced ear inflammation, ornithine decarboxylase activity, and tumorigenesis. In mice previously induced by DMBA, topical application of 1, 3, or 10 μmol of caryophylloxera combined with 5 nmol TPA twice weekly for 20 weeks inhibited the number of skin tumors per mouse by 38%, 63%, and 78%, respectively. In a DMBA-induced mouse model, topical application of 0.1, 0.3, 1, or 2 μmol of ursolic acid and 5 nmol TPA twice weekly for 20 weeks reduced the number of tumors per mouse by 45-61%.
/Alternative and In Vitro Experiments/ Laboratory experiments investigated the antiplatelet activity of caryophylloxera, a phenolic diterpenoid isolated from rosemary. Caryophylloxera inhibited collagen- and arachidonic acid (AA)-induced platelet aggregation in washed rabbits in a concentration-dependent manner, with IC50 values of 5.5 ± 0.3 μM and 42.5 ± 0.9 μM, respectively, but had no inhibitory effect on ADP- and thrombin-induced platelet aggregation. Based on its inhibitory effect on collagen-induced platelet aggregation, carnosine revealed its blocking effect on collagen-mediated cytoplasmic calcium mobilization, serotonin secretion, and AA release. However, in contrast to its inhibition of AA-induced platelet aggregation, carnosine had no effect on AA-mediated TXA2 and PGD2 production, suggesting that carnosine may directly inhibit the TXA2 receptor. This conclusion is supported by the following finding: carnosine effectively inhibited U46619 (a TXA2 analog)-induced platelet aggregation with an IC50 value of 22.0 ± 2.5 μM. Furthermore, after application of carnosine at concentrations of 22 μM and 50 μM, the concentration-response curves induced by U46619 shifted downward, indicating that carnosine has a typical non-competitive antagonistic effect on the TXA2 receptor. In summary, these results suggest that the antiplatelet activity of carnosine may be mediated by inhibition of the TXA2 receptor and cytoplasmic calcium mobilization, and that carnosine has the potential to be developed into a novel antiplatelet drug.
/Other Toxicity Information/ Peroxisome proliferator-activated receptors (PPARs) play a crucial role in lipid and glucose homeostasis in metazoans. Therefore, PPARα (fibrates) and PPARγ (thiazide analogs) activators are widely used to treat dyslipidemia and diabetes, respectively. Increasing evidence suggests that herbal compounds can affect nuclear receptor signaling, such as PPARs. /Recently/ it has been reported that /scarpic acid and caryophyllene…/ are / activators of / PPARγ.

[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/ Known (+)-trans-ozic acid (1) and two novel latanane diterpenoids (2 and 3) were isolated from the ethanol extract of Orthosiphon labiatus. The structures of compounds 2 and 3 were determined primarily by one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy. Known apicranane diterpenoids, salviaol (4), rosmarinal (5), and salviaol (characterized by its derivative 6), were isolated from the ethanol extract of Salvia africana-lutea. Compounds 3 and 6 exhibited minimum inhibitory concentrations (MICs) of 157 μM and 28 μM against Mycobacterium tuberculosis, respectively, while compounds 2 and 6 showed cytotoxic activity against the human breast cancer (MCF-7) cancer cell line, with IC50 values of 82 μM and 69 μM, respectively. /EXPL/ Rosemary extracts were investigated… to identify bioactive compounds. ...Antibacterial activity was analyzed using disk diffusion and broth dilution methods. ...Although all rosemary extracts showed high free radical scavenging activity, their efficacy as antibacterial agents varied. The methanol extract containing 30% caryopsisic acid, 16% caryopsisol, and 5% rosmarinic acid exhibited the best antibacterial effect.

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Mechanism of Action
This study investigated the anticancer effect of caryopsisol on human prostate cancer PC3 cells and its role in regulating multiple oncogenic-related signaling pathways. ...Flow cytometry and biochemical analysis confirmed G2 phase cell cycle arrest. To establish a more precise mechanism of action, ...we performed a protein chip analysis containing 638 proteins related to cell signaling pathways. This protein chip analysis identified 5'-AMP-activated protein kinase (AMPK), a serine/threonine protein kinase involved in the regulation of cellular energy homeostasis, as a potential target. Downstream effects consistent with cancer suppression also included regulation of the mTOR/HSP70S6k/4E-BP1 pathway. Furthermore, ... sarcosinate targets the PI3K/Akt pathway in a dose-dependent manner. ... These results indicate that sarcosinate targets multiple signaling pathways, including the AMPK pathway... PMID: 18286356
This study investigated the antiproliferative properties of two antioxidant polyphenols found in rosemary (Rosmarinus officinalis)—sarcosinate and sarcosinate—on Caco-2 cells. Treatment with sarcosinate and sarcosinate for 20 hours both inhibited the incorporation of 3H-thymidine in a dose-dependent manner, with a 50% inhibitory concentration of 23 μM, and significantly prolonged the doubling time of Caco-2 cells from 29.5 hours to 140 hours and 120 hours, respectively. These effects are related to the accumulation of cells in the G2/M phase of the cell cycle after treatment. The study found that sarcosinate plays a major role after the prophase of the cell cycle, leading to an increase in cyclin B1 levels; while sarcosinate arrests cells before the prophase of the cell cycle, leading to a decrease in cyclin A levels. Therefore, these structure-associated phytochemicals appear to arrest cells at different stages of the cell cycle by affecting the levels of various cyclins. PMID:16019137
…Antioxidant activity of caryophylloxera and other compounds extracted from rosemary. Caryophylloxera exhibits potent antioxidant activity in scavenging α,α-diphenyl-β-picrylhydrazine (DPPH) radicals and protecting DNA from Fenton reaction damage. Inflammation and various carcinogenic processes, inducible nitric oxide synthase (iNOS) produces high concentrations of nitric oxide (NO). Treatment of mouse macrophage cell line RAW 264.7 with inosine significantly reduced lipopolysaccharide (LPS)-stimulated NO production in a concentration-dependent manner, with an IC50 value of 9.4 μM; while other tested compounds had weaker effects. Western blot, reverse transcription-polymerase chain reaction (RT-PCR), and Northern blot analyses showed that inosine reduced LPS-induced iNOS mRNA and protein expression. Inosine treatment reduced the translocation of the nuclear factor-κB (NF-κB) subunit and NF-κB DNA-binding activity in activated macrophages. Transient transfection assays showed that inosine also inhibited the activity of the iNOS and NF-κB promoters. These changes in activity were associated with the downregulation of inhibitory κB kinase (IKK) activity by inosine (5 μM), thereby inhibiting LPS-induced IκBα phosphorylation and degradation. Higher concentrations (20 μM) of sarsine also inhibited LPS-induced activation of p38 and p44/42 mitogen-activated protein kinases (MAPK). These results suggest that sarsine inhibits NO production and iNOS gene expression by suppressing NF-κB activation, providing a possible mechanism for its anti-inflammatory and chemopreventive effects. PMID:12082020
In previous studies, ...caryopic acid (CA) protects cortical neurons by activating the Keap1/Nrf2 pathway, which is initiated by the S-alkylation of a key cysteine thiol on the Keap1 protein by CA's electrophilic quinone-type compounds...Caryopic acid is a catechol-type electrophilic compound that activates the Keap1/Nrf2 pathway by targeting cysteine residues on the Keap1 protein, thereby protecting neurons in vitro and in vivo... This study used HT22 cells (a neuronal cell line) to test CA derivatives in order to find derivatives more suitable for in vivo application. This is because electrophilic agents such as CA may react with other molecules before reaching the target molecule. Both CA and caryopic acid can protect HT22 cells from glutamate oxidative toxicity. CA activates transcriptional antioxidant response elements in phase II genes, including heme oxygenase-1, NADPH-dependent quinone oxidoreductase, and γ-glutamylcysteine ligase, all of which exert neuroprotective effects by regulating cellular redox state. This finding is confirmed by the significant increase in glutathione levels resulting from CA. We synthesized a series of CA analogs in which the catechol hydroxyl group of CA was esterified to prevent its oxidation to quinone, or the catechol hydroxyl group and its carbonate group of CA were esterified to prevent its conversion to caryophyllene. In both cases, conversion and oxidation only occurred after the alkyl group was removed by an intracellular esterase. Therefore, the most active form of Keap1/Nrf2 pathway activator—quinone-type catecholamine (CA)—was produced intracellularly. However, neither of these chemical modifications enhanced its neuroprotective effect, likely due to increased lipophilicity. These results indicate that the neuroprotective effect of CA is critically dependent on the free carboxylic acid and catechol hydroxyl group. Therefore, the hydrophilicity of CA may be a key characteristic of its neuroprotective activity.

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Rosemaryol is a rosemary-derived diterpenoid compound with antioxidant properties. Its mechanisms of action include: 1) directly binding to RSK2 to inhibit pro-survival signals; 2) protecting endothelial cells by inducing HO-1 through Nrf2-mediated inhibition.
Potential therapeutic applications: gastric cancer (by inhibiting RSK2) and vascular barrier dysfunction (by activating Nrf2). [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.)