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Abstract: Ethnopharmacological relevance: Carthamus red isolated from safflower (Carthamus tinctorius L., a Chinese traditional medicine) is evaluated for antioxidant and hepatoprotective activity. Materials and methods: Carthamus red was isolated from a Na2CO3 extract of safflower and its analysis was carried out by HPLC/MS. Acute toxicity study was determined and the antioxidant activity was investigated using various established in vitro systems. An in vivo study against CCl4-induced liver injury was also conducted and compared with that of silymarin, a known hepatoprotective drug. Results: Carthamus red did not show any toxicity and mortality up to 2000mg/kg dose, and it showed strong antioxidant ability in vitro. In the in vivo study, carthamus red treatment lowered the serum levels of ALT, AST, ALP and total protein in liver damage rat models. Meanwhile, Nrf2, GSTα and NQO1 expressions were up-regulated at the protein level by carthamus red intervention. Additionally, the activities of antioxidant enzymes and level of GSH were elevated by carthamus red intervention, while the content of TBARS, which is an oxidative stress marker, was lessened. HE stain analysis showed that the condition of liver damage was mitigated. Conclusion: This study demonstrates that carthamus red may serve as a candidate with strong a hepatoprotective effect and antioxidant activity in liver damage. [Copyright &y& Elsevier]