Mass spectrometry molecular networking coupled with network pharmacology reveals cichoric acid as the potential ROS-associated antitumor constituent in Taraxacum mongolicum Hand.-Mazz.

ETHNOPHARMACOLOGICAL RELEVANCE: Triple negative breast cancer (TNBC) is the most aggressive subtype that results in the major death of woman cancer patients. Due to its high heterogeneity, there still lack of efficient therapy for TNBC. Taraxacum mongolicum Hand.-Mazz. (TM) has a long history as traditional Chinese medicine for its heat-clearing, detoxifying and nodule-dispersing properties. Although the promising anti-TNBC potential of TM has been demonstrated in various researches, its candidate bioactive constituents and underlying mechanisms of action remain incompletely elucidated.

AIM OF THE STUDY: The present study aimed to reveal the main active components of TM and underlying mechanism against TNBC through a combining strategy of mass spectrometry molecular networking, network pharmacology prediction and experimental validation.

MATERIALS AND METHODS: TM was analyzed by UPLC-Q-Exactive Orbitrap MS under negative and positive ion modes. Feature-based molecular network approach was applied to comprehensively identify the potential phenolic acids and flavonoids in TM extract and its absorbed components in rat plasma after administration. Network pharmacology analysis was performed based on these absorbed components to predict the mechanisms of TM extract and the potential active components. Then the efficacy of TM extract and the potential active components against TNBC were evaluated in vitro and in vivo.

RESULTS: As a result, a total of 31 phenolic acids and 17 flavonoids were identified in TM extract. And 22 absorbed components were used for network pharmacology analysis, which suggested to be highly correlated to ROS-related pathways. Low dose of TM extract significantly inhibited tumor growth in TNBC cell-derived xenograft mice with elevating ROS levels and cell apoptosis. The higher dose of TM extracts, however, showed no significant change compared with the model group. Similar phenomena were observed in cichoric acid-treated TNBC cell-derived xenograft mice.

CONCLUSION: This study demonstrated that cichoric acid represented a potential component of TM extract against TNBC, and its efficacy exhibited a non-monotonic dose-response profile, challenging the general assumption that higher doses always produced superior therapeutic effects.