Objective To investigate the effects of Niuxi (Achyranthis Bidentatae Radix, ABR) on tissue distribution, plasma protein binding rate and receptor expression of marker components (amygdalin, hydroxysafflor yellow A, ferulic acid, paeoniflorin, naringin) from Xuefu Zhuyu Decoction (血府逐瘀汤, XFZYD) in rats with metabolic-associated fatty liver disease (MAFLD) of qi stagnation and blood stasis syndrome (QS-BSS), and to further clarify the mechanism underlying its meridian-guiding effect. Methods A rat model of MAFLD with QS-BSS was established by high-fat diet combined with adrenaline injection. After successful modeling, rats were stratified and grouped by body weight, followed by intragastric administration of XFZYD (full formula), XFZYD without Jiegeng (Platycodonis Radix, PR), XFZYD without ABR, and XFZYD without both PR and ABR. For the plasma protein binding rate and receptor expression experiments, abdominal aortic blood was collected at 10, 30 min after a single administration, after which rats were euthanized for the collection of brain, heart, lung, liver, and kidney tissues. For the tissue distribution experiment, rats were euthanized at 10, 30, 60 min after a single administration, with the same tissues collected as above. The concentrations of marker components in tissues were determined by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Qualitative and quantitative analyses of these components in plasma were performed to determine their plasma protein binding rates. The expression levels of platelet-activating factor (PAF) and receptors including adenosine A1 receptor (A1R), P2Y12 receptor, and endothelin A receptor (ETAR) in tissues were measured by ELISA. Results ABR decreased the plasma protein binding rates of amygdalin, hydroxysafflor yellow A, ferulic acid, and naringin in model rats. Meanwhile, ABR increased the distribution of amygdalin and paeoniflorin in the brain and liver, hydroxysafflor yellow A in the liver and kidney, ferulic acid in the brain, heart, liver, and kidney, and naringin in the liver and kidney. Furthermore, ABR upregulated the expression levels of A1R in brain, heart, and liver as well as P2Y12 receptor in the brain, heart, and kidney, while downregulating the expression level of PAF in brain, heart, liver, and kidney and the expression level of ETAR in brain, heart and lung. Conclusion ABR could reduce the plasma protein binding rates of amygdalin, hydroxysafflor yellow A, ferulic acid and naringin in MAFLD-QS-BSS rats, thereby increasing the distribution of these components in the corresponding tissues, enhancing the effect of each component on the related receptors, and ultimately regulating the upregulation or downregulation of receptor expression in various tissues, which synergistically exerts the therapeutic effect against QS-BSS. This may be one of the mechanisms by which ABR exerts its meridian-guiding effect in XFZYD.

Achyranthis Bidentatae Radix  /  Xuefu Zhuyu Decoction  /  tissue distribution  /  plasma protein binding  /  receptor expression  /  qi stagnation and blood stasis syndrome  /  metabolic-associated fatty liver disease  /  amygdalin  /  hydroxysafflor yellow A  /  ferulic acid  /  paeoniflorin  /  naringin