State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot 010070, China; Key Laboratory of Herbage & Endemic Crop Biology of Ministry of Education, School of Life Sciences, Inner Mongolia University, Hohhot 010070, China.
Inner Mongolia Academy of Agricultural & Animal Husbandry Sciences, Hohhot 010031, China.
Phytomedicine. 2021 Jul;87:153579. doi: 10.1016/j.phymed.2021.153579. Epub 2021 Apr 24.
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.
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.
The hepatoprotective activities were examined by acetaminophen (APAP)-induced zebrafish toxicity and carbon tetrachloride (CCl)-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.
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 µM) and their antithrombosis effects were more robust than aspirin (95.1% and 86.2% vs. 52.7% at 100 µM). 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 CCl-induced mouse liver injury and regulated the levels of HIF-1α, iNOS, TNF-α, α-SMA, and NFκB 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.
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.
红花中的羟基红花黄色素 A（HSYA）具有多种药理作用。然而，红花中其他化学成分的生物活性以及 HSYA 增强血液循环和保肝作用之间的关系知之甚少。
本研究旨在评价 HSYA 和 C 的抗血栓和保肝活性，研究其作用机制，包括对乙酰氨基酚排泄速度的影响，以及抗血栓、保肝和其他生物活性之间的关系。
通过对乙酰氨基酚（APAP）诱导的斑马鱼毒性和四氯化碳（CCl）诱导的小鼠肝损伤来检测保肝活性。通过 UHPLC-MS 定量测定斑马鱼中的 APAP 浓度和排泄到培养基中的 APAP 浓度。通过苯肼（PHZ）诱导的斑马鱼血栓来检测 HSYA 和 C 的抗血栓作用。
HSYA 和 HSYC 对 APAP 诱导的毒性和 PHZ 诱导的血栓形成有很强的保护作用。HSYA 和 C 的保肝作用强于阳性对照乙酰半胱氨酸（分别为 61.7%和 58.0%，在 100µM 时为 56.9%），其抗血栓作用强于阿司匹林（分别为 95.1%和 86.2%，在 100µM 时为 52.7%）。HSYA 和 C 促进血液循环，使形态异常的 APAP 处理斑马鱼恢复正常，并减轻肝特异性 RFP 表达转基因斑马鱼中 APAP 诱导的肝发育毒性。HSYC 减轻 CCl 诱导的小鼠肝损伤，并调节肝组织中 HIF-1α、iNOS、TNF-α、α-SMA 和 NFκB 的水平。HSYA 在双重血栓形成和肝毒性斑马鱼模型中也具有保护作用。通过 UHPLC-MS，HSYA 加速了 APAP 的排泄。
HSYA 和 C 是红花中的生物活性成分，负责红花草药传统上用于促进血液循环以祛瘀的作用。红花及其查尔酮成分可能通过增强毒素的排泄速度来保护免受外源性或疾病引起的内源性毒素的损害。
