Cao Yongyi,Wang Yu,Li Yueyang,Liu Sihan,Wang Lizhe,Zhou Li,Zhu Ting
Ferroptosis is a unique programmed cell death driven by iron-dependent phospholipid peroxidation. Tumor cells that escape from the conventional therapies appear more sensitive to ferroptosis. Therefore, it is extremely urgent to find safe and efficient active ingredients that induce ferroptosis in tumor cells. Herein, we identified that angelic acid, as a potent anti-tumor active ingredient in Angelica sinensis , profoundly sensitizes CRC cells to ferroptosis via a natural compound library screen. We revealed that angelic acid treatment is sufficient to predispose CRC cells to ferroptosis phenotype, evidenced by malondialdehyde (MDA) accumulation, lipid peroxidation, and upregulation of ferroptosis-associated markers CHAC1 and PTGS2, which is abolished by ferroptosis inhibitor Fer-1. Moreover, the results of network pharmacology showed that NRF2 is critical for angelic acid-mediated CRC cell ferroptosis. Mechanistically, angelic acid exerted its ferroptosis induction via directly binding and facilitating the degradation of NRF2. In addition, the syngeneic mouse models revealed that angelic acid boosts CRC cell sensitivity to ferroptosis inducer sulfasalazine with essentially no toxicity in vivo. Collectively, our findings highlighted a previously unrecognized anti-tumor mechanism of angelic acid and represented an appealing therapeutic strategy for CRC treatment. Graphical abstract
As a traditional fermented soybean product in China, douchi is rich in diversity and varies from place to place. Because of the significance in food culture, the douchi from Sichuan, Hunan, and Guizhou are quite typical and distinctive. By analysing the volatile components of these three types of douchi, we can not only deconstruct the cause of aroma formation, but also lay the foundation for flavour adjustment. In this study, the key aroma-active compounds of the three types of douchi were identified by gas chromatography–olfactometry (GC–O) and gas chromatography–mass spectrometry (GC–MS) combined with sensory evaluation. 32 aroma compounds were identified in Tongchuan douchi (TC), and 16 of them with flavour dilution (FD) > 4 were determined. 14 substances were quantified, and 4 of them with OAV > 1. 30 aroma compounds were identified in TongRen douchi (TR), and 15 of them with flavour FD ≥ 4 were determined. 13 substances were quantified, and 11 of them with OAV > 1. 21 aroma compounds were identified in LiuYang douchi (LY), and 11 of them with FD ≥ 4 were determined, and all of them were quantified. 5 substances with OAV > 1 were determined. The sensory evaluation determined that the three types of douchi possessed sauce-like, sour, burnt, bean aroma, roasted, salty, fermented aroma, and rancid aroma.
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