Sesquiterpenoids from the Florets of Carthamus tinctorius (Safflower) and Their Anti-Atherosclerotic Activity.

(1) Background: The florets of Carthamus tinctorius L. are traditionally used as a blood-activating drug and can be used for the treatment of atherosclerosis, but no compounds with anti-atherosclerotic activity have been reported. (2) Methods: This study investigated the chemical compounds from the florets of C. tinctorius . Comprehensive spectroscopic techniques revealed their structures, and ECD calculations established their absolute configurations. Nile Red staining, Oil Red O staining, and cholesterol assessment were performed on these compounds and their aglycones for the inhibitory activity against the formation of foam cells induced by oxidized low-density lipoprotein (ox-LDL) in RAW264.7 macrophages. In addition, RAW264.7 macrophages were tested for their anti-inflammatory activity by measuring the inhibition of NO production caused by LPS. (3) Results: Five new sesquiterpenoids ( 1 - 5 ) isolated from the florets of C. tinctorius were identified as (-)-(1 R ,4 S ,9 S ,11 R )-caryophyll-8(13)-en-14-ol-5-one ( 1 ), (+)-(1 R ,4 R ,9 S ,11 R )-caryophyll-8(13)-en-14-ol-5-one ( 2 ), (-)-(3 Z ,1 R ,5 S ,8 S ,9 S ,11 R )-5,8-epoxycaryophyll-3-en-14- O - β -D-glucopyranoside ( 3 ), (+)-(1 S ,7 R ,10 S )-guai-4-en-3-one-11- O - β -D-fucopyranoside ( 4 ), and (-)-(2 R ,5 R ,10 R )-vetispir-6-en-8-one-11- O - β -D-fucopyranoside ( 5 ). All compounds except for compound 3 reduced the lipid content in ox-LDL-treated RAW264.7 cells. Compounds 3 and 4 and their aglycones were found to reduce the level of total cholesterol (TC) and free cholesterol (FC) in ox-LDL-treated RAW264.7 cells. However, no compounds showed anti-inflammatory activity. (4) Conclusion: Sesquiterpenoids from C. tinctorius help to decrease the content of lipids, TC and FC in RAW264.7 cells, but they cannot inhibit NO production, which implies that their anti-atherogenic effects do not involve the inhibition of inflammation.