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. 2016 Nov 17;8(11):731. doi: 10.3390/nu8110731

Table 16.

Anticancer effects of Rosmarinic Acid (RA). In vivo studies.

Animal Model Dose and Duration Findings Mechanisms Reference
Seven-Nine week old male Balb/c mice 0.25, 0.5, 1.0 and 1.35 mg/mouse (30 months) before TPA treatment ↓ myeloperoxidase activity ↓ COX2 induction [107]
C57BL/6 mice implanted with Lewis lung carcinoma 1, 2 and 4 mg/kg RA (20 days) ↓ tumor growth [90]
Golden Syrian hamsters 100 mg/kg RA (14 weeks) Completely prevented tumor formation in DMBA-treated hamsters ↓ p53
↓ Bcl-2
[108]
C57BL/6J Min/+ (ApcMin) mice 360 mg/kg RA (8 weeks) ↓ the frequency of large adenomas ↑ levels of parent compound in plasma [109]
DMH induced colon cancer (Albino Wistar male rats) 2.5–10 mg/kg RA (16 weeks) through intragastric intubation ↓ DMH induced aberrant crypt foci ↓ DMH induced increase in bacterial enzymes [110]
DMBA induced skin cancer (Swiss albino mice) 100 mg/kg RA administered (1 weeks) before DMBA treatment ↓ skin tumors ↑ status of phase I (cyt p450) detoxification agents
↑ status of phase II (GST, GR, GSH) detoxification agents. Restored activity levels of casp 3, casp 9, p53 and Bcl-2.
[111]
DMH induced colon cancer (Male Wistar rats) 2.5, 5 and 10 mg/kg RA (4 weeks) ↓ DMH induced aberrant crypt foci, number of polyps, reversed the markers of oxidative stress, antioxidant status, CYP450 content and PNPH activity [112]
Five month old Syrian hamsters 1.3 mg/mL RA (2 weeks) pretreatment ↓ incidence of tumors
↑ differentiation
↓ scores in the tumor invasion front grading system.
[113]
5 week old male nude Balb/c mice incubated sub-cutaneously with MKN45 cells into their flanks. 2 mg/kg RA via celiac injection daily (14 days) ↓ Warburg effect ↓ glucose uptake [114]
DMH induced colon cancer (Male Wistar rats) 5 mg/kg RA orally (30 weeks) ↓ DMH induced colon tumor formation ↓ TNF-α
↓ IL-6
↓ COX2
[96]

TPA (12-O-tetradecanoylpheorbol-13-acetate), COX2 (cyclooxygenase 2), DMBA (7,12-dimethylbenz(a)anthracene), DMH (1,2-dimethylhydrazine), p53 (tumor protein p53), casp (caspase), Bcl-2 (B-cell CLL/lymphoma 2), CYP450 (cytochrome p450), GST (Glutathione S-transferase), GR (glucocorticoid receptor), GSH (glutathione), PNPH (p-nitrophenol hydroxylase), TNF-α (tumor necrosis factor alpha), IL-6 (interleukin-6).