Keyword:Carnosic Acid,Anti-inflammatory,Anti-tumor
1. Anti-inflammatory activity
Kuhlmann and Peng et al found that the anti-inflammatory effect was related to the inhibition of N levels in the body. The carnosic acid was found by comparing the inflammatory effects of carnosic acid, carnosol, and rosmarinic acid on neonatal mouse glial cells by using NO as a parameter, The carnosic acid is the main component of anti-inflammatory. When the concentration of carnosic acid is 1.56-6.25 ug/mL, the inhibitory effect on NO is better. When the concentration is 12.5 or 25 ug/mL, the effect is more significant.
Kuo et al. compared the anti-inflammatory properties of rosemary extract and pure carnosic acid with lipopolysaccharide (LPS) pretreated mouse macrophage RAW264.7,It was found that carnosic acid was extracted from rosemary extract which the most abundant and anti-inflammatory phytochemicals, when the concentration of carnosic acid is 22.5 uM or 7.47 ug/mL, Its inhibitory effect on inflammation can reach 50% (ic50). Hadad et al. studied the combination of carotenoids and phenolic compounds such as carnosic acid in a mouse model of peritonitis to inhibit the release of inflammatory mediators from macrophages exposed to LPS. Experiments revealed low concentrations of carotenoids and The combination of phenolic compounds has a very significant inhibitory effect on the production of pro-inflammatory factors by LPS-induced macrophages.
Oh, et al. studied the inhibition of various skin inflammation reactions by carnosic acid and its mechanism. It was found that 20ug/mL of carnosic acid is not toxic to human body and can reduce various inflammations in the cortex; carnosic acid can prevent Gram-induced dermatitis the growth of positive and negative microorganisms such as Propionibacterium acnes, Pseudomonas aeruginosa, and Staphylococcus aureus, and it is predicted that carnosic acid is expected to be an anti-inflammatory drug that inhibits skin inflammation. Lin investigated whether carnosic acid can improve the inflammatory response induced by tumor necrosis factor (TNF-α). Western blot analysis showed that pretreatment with carnosic acid could reduce the activation of ERK and JNK by tumor necrosis factor (TNF-α). Studies have shown that in aliphatic cells, CA can attenuate the inflammatory response induced by tumor necrosis factor (TNF-β).
2. Antitumor Activity
Carnosic acid has anti-cancer and anti-tumor effects that can inhibit the proliferation of a variety of hematological tumors and solid tumor cells and can induce cell cycle arrest or even cell death. Research and analysis suggest that it is expected to become an anticancer drug. Yesil—Celiktas et al. compared the Soxhlet extract and supercritical carbon dioxide extract of rosemary leaves, and found that the latter has excellent anti-proliferative effect, and the inhibitory concentration IC50 of human cancer cell line chronic myeloid leukemia cell K562 is between 12.50 to 47.55 ug/mL. Shanmugam Manoharan et al. found that carnosic acid has potential chemopreventive ability against 7,12-dimethylaminobenzaldehyde (DMBA)-induced golden hamster cheek pouch carcinoma has the potential for chemical prevention by evaluating and investigating tumor incidence, tumor volume and load. It is suggested that the chemical prevention of oral cancer induced by DMBA may be due to its potential anti-lipid and regulating the detoxification enzyme activity of carcinogen. Suong et al. reviewed the research work from 1996 to 2010, inferring that the anti-cancer properties of carnosic acid in rosemary extract can prevent tumors in organs such as rectum, breast, liver, and stomach. Einbond et al believe that rosemary/carnosic acid can effectively inhibit the proliferation of endoplasmic reticulum (ER)-negative human breast cancer cells and induce cell cycle arrest in G1 phase; carnosic acid and turmeric/turmeric pigment have synergistic Inhibition effects on cancer cells; rosemary/carnosic acid alone or in combination with curcumin can be used to prevent and treat ER-negative breast cancer. Gomez-Garcia et al. compared the preventive effects of DMBA-induced hamster oral cancer by comparing 0.5% DMBA, 0.5% DMBA + apigenin (n=8) and 0.5% DMBA + carnosic acid (n=12). Think of carnosic acid and the apigenin has this preventive effect.
Carnosic acid has a partial differentiation effect on human promyelocytic leukemia cell line HL-60, which induces apoptosis and has little inhibitory effect on cell proliferation, but synergistic As2O3 and all-trans retinoic acid (ATAR) which ability to induce apoptosis and differentiate into mature granulocytes, this synergistic ability significantly exceeds the ability of As2O3 and ATAR to induce apoptosis and differentiation of cells; The combination of carnosic acid and Doxercalciferol l-D2 can enhance 1-D2 induces the differentiation of HL-60 and histiocytic lymphoma cells U937 cells and cell cycle arrest; carnosic acid can effectively reverse the resistance of promyelocytic leukemia cells MR-2 cells to ATRA. An et al.An et al. studied the effects of different concentrations of rat tail oxalic acid on hl-60 cells by measuring cell growth, cell cycle and cd14 expression of LPs receptor. It is believed that carnosic acid can enhance 1,25-dihydroxy vitamin D3 (1,25 (OH). 2D3) induces differentiation and inhibits proliferation of HL-60 cells, and has a significant time-effect relationship. That is, carnosic acid to cells for 48 hours and 72 hours, the G0/G1 phase cells increase, These results suggest that the inhibitory effect of leukemic cell proliferation may be related to cell cycle arrest. Ren et al. applied carnosic acid, 1,25(OH)2D3, alone or in combination to treat HL-60 cells, observed cell morphology by light microscopy, and detected by flow cytometry,the cell cycle and monocyte differentiation marker CD14 expression in different treatment groups showed that carnosic acid could enhance the differentiation of HL-60 cells induced by 1,25(OH)2D3 and inhibit the proliferation of HL-60 cells, the cells were blocked in G0／G1 phase.
Qu et al. observed the growth of the cells by tetrazolium blue method, observed the morphology of the cells by light microscopy, and measured the cell cycle, apoptosis rate and CD14 expression by flow cytometry. The induce effects of carnosic acid and 1,25 (OH)2D3 were observed alone and in combination on the growth, apoptosis and differentiation of acute promyelocytic leukemia cell line B4, it was found that carnosic acid and 1,25(OH)2D3 could inhibit the proliferation of NB4 cells, and carnosic acid on NB4 Cells have growth inhibition, can induce apoptosis of NB4 cells, and have a dose- and time-effect relationship; carnosic acid can enhance the differentiation of NB4 cells and inhibit cell proliferation by 1,25(OH)2D3. The reversal effect and mechanism of carnosic acid on human leukemia multidrug resistance (MDR) cell line K562/A02 cells were investigated. It is concluded that carnosic acid can effectively reverse the leukemia cell line K562/A02 against doxorubicin (ADM) and its multidrug resistance (MDR). Besides, the combination of carnosic acid and VD. has a synergistic inhibitory effect on acute myelogenous leukemia.
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