Hydroxysafflor yellows alleviate thrombosis and acetaminophen-induced toxicity in vivo by enhancing blood circulation and poison excretion

文献类型： 外文期刊

第一作者： Wang, Li-Wei

作者： Wang, Li-Wei;Cui, Xue-Ying;Duan, Shen;Liu, Chun-Rui;Shan, Cheng-Bin;Wang, Yu;Ma, Chao-Mei;Wang, Li-Wei;Cui, Xue-Ying;Duan, Shen;Liu, Chun-Rui;Shan, Cheng-Bin;Wang, Yu;Ma, Chao-Mei;He, Jiang-Feng

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关键词： Carthamus tinctorius; Safflower; Hydroxysafflor yellow; Antithrombosis; Hepatoprotection; Poison excretion

期刊名称：PHYTOMEDICINE （ 影响因子：5.34； 五年影响因子：5.161 ）

ISSN： 0944-7113

年卷期： 2021 年 87 卷

页码：

收录情况： SCI

摘要： Background: Hydroxysafflor yellow A (HSYA) from the flower of Carthamus tinctorius (Safflower) has been reported to have various pharmacological effects. However, little is known about the bioactivities of other chemical constituents in Safflower and the relationship between enhancement of blood circulation and hepatoprotection by HSYA. Purpose: The present research was to evaluate the antithrombotic and hepatoprotective activities of HSYA and C, examine their mechanisms of actions, including influence on the excretion velocity of acetaminophen, and the relationship between the antithrombotic, hepatoprotective, and other bioactivities. Methods: The hepatoprotective activities were examined by acetaminophen (APAP)-induced zebrafish toxicity and carbon tetrachloride (CCl4)-induced mouse liver injury. The concentrations of APAP in zebrafish and APAP that was excreted to the culture media were quantified by UHPLC-MS. The anti-thrombosis effect of HSYA and C were examined by the phenylhydrazine (PHZ)-induced zebrafish thrombosis. Results: HSYA and HSYC showed robust protection on APAP-induced toxicity and PHZ-induced thrombosis. The hepatoprotective effects of HSYA and C were more potent than that of the positive control, acetylcysteine (61.7% and 58.0%, respectively, vs. 56.9% at 100 mu M) and their antithrombosis effects were more robust than aspirin (95.1% and 86.2% vs. 52.7% at 100 mu M). HSYA and C enhanced blood circulation, rescued APAP-treated zebrafish from morphological abnormalities, and mitigated APAP-induced toxicity in liver development in liver-specific RFP-expressing transgenic zebrafish. HSYC attenuated CCl4-induced mouse liver injury and regulated the levels of HIF-1 alpha, iNOS, TNF-alpha, alpha-SMA, and NF kappa B in liver tissues. HSYA was also protective in a dual thrombotic and liver toxicity zebrafish model. By UHPLC-MS, HSYA accelerated the excretion of APAP. Conclusion: HSYA and C are the bioactive constituents of Safflower that are responsible for the herbal drug's traditional use in promoting blood circulation to remove blood stasis. Safflower and its chalcone constituents may protect from damage due to exogenous or disease-induced endogenous toxins by enhancing the excretion velocity of toxins.

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