Lin Qiwei, Chen Yigong, Yu Bingqing, Chen Ziyan, Zhou Hengpu, Su Jie, Yu Jingjing, Yan Meiqiu, Chen Suhong, Lv Guiyuan
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Zhejiang, Hangzhou, 310053, China.
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Zhejiang, Hangzhou, 310053, China.
J Ethnopharmacol. 2025 Feb 10;338(Pt 1):119034. doi: 10.1016/j.jep.2024.119034. Epub 2024 Nov 4.
Unhealthy dietary patterns and lifestyle changes have been linked to increased blood viscosity, which is recognized as an important pathogenic factor in cardiovascular and cerebrovascular diseases. The underlying mechanism may involve chronic inflammation resulting from intestinal barrier disruption induced by unhealthy diets. The rhizome of Atractylodes macrocephala Koidz. (Called Baizhu in China), is a well-used "spleen-reinforcing" traditional Chinese medicinal herb used for thousands of years. Previous research has demonstrated its multiple gastrointestinal health benefits and its ability to regulate metabolic disorders. However, the effects of Baizhu on blood hyperviscosity induced by long-term unhealthy diets remain unclear.
This study aimed to investigate the effects of the aqueous extract of Baizhu on blood hyperviscosity induced by unhealthy diet and to explore the possible mechanisms.
The blood hyperviscosity model in SD rats was established utilizing a high-fat, high-sugar, and high-salt diet (HFSSD). Subsequently, the rats underwent a twelve-week intervention with varying doses of Baizhu and a positive control. To evaluate the efficacy of Baizhu on blood hyperviscosity in model rats, we measured behavioral index, hemorheological parameters, inflammatory cytokines, hematology, adhesion molecules, as well as biochemical indicators in serum and liver. We also assessed the pathological states of the colon and liver. Furthermore, Western blotting, ELISA, IHC, and qRT-PCR were used to determine the effect of Baizhu on the IL-6/STAT3/ESRRG signaling pathway and FIB synthesis.
The intervention of Baizhu showed evident attenuating effects on blood viscosity and microcirculation disorders, and exhibit the capacity to moderately modulate parameters including grip, autonomous activities, vertigo time, TC, TG, LDL-c, inflammatory factors, adhesion factors, hematological indicators, etc. At the same time, it reduces liver lipid droplet deposition, restores intestinal integrity, and lowers LPS level in the serum. Subsequent experimental results showed that Baizhu downregulated the expression of TLR4 and NF-κB in colon tissue, as well as the expression of IL-6, TLR4, p-JAK2, p-STAT3, and ESRRG in liver tissue. Finally, we also found that Baizhu could regulate the levels of FIB in plasma and liver.
Baizhu protects HFSSD-induced rats from blood hyperviscosity, likely through repairing the intestinal barrier and inhibiting LPS/TLR4-associated liver inflammatory activation, thus suppressing FIB synthesis through the downregulation of IL-6/STAT3/ESRRG pathway.
不健康的饮食模式和生活方式改变与血液粘度增加有关，血液粘度增加被认为是心脑血管疾病的一个重要致病因素。潜在机制可能涉及不健康饮食引起的肠道屏障破坏导致的慢性炎症。白术根茎（在中国称为白术）是一种使用了数千年的常用“健脾”传统草药。先前的研究已经证明了它对胃肠道健康的多种益处以及调节代谢紊乱的能力。然而，白术对长期不健康饮食诱导的血液高粘度的影响仍不清楚。
本研究旨在探讨白术水提取物对不健康饮食诱导的血液高粘度的影响，并探索其可能的机制。
利用高脂、高糖、高盐饮食（HFSSD）建立SD大鼠血液高粘度模型。随后，大鼠接受为期十二周的不同剂量白术和阳性对照干预。为了评估白术对模型大鼠血液高粘度的疗效，我们测量了行为指标、血液流变学参数、炎症细胞因子、血液学指标、黏附分子以及血清和肝脏中的生化指标。我们还评估了结肠和肝脏的病理状态。此外，采用蛋白质免疫印迹法、酶联免疫吸附测定法、免疫组织化学法和定量逆转录聚合酶链反应法来确定白术对IL-6/STAT3/ESRRG信号通路和纤维蛋白原（FIB）合成的影响。
白术干预对血液粘度和微循环障碍有明显的减轻作用，并具有适度调节包括握力、自主活动、眩晕时间、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-c）、炎症因子、黏附因子、血液学指标等参数的能力。同时，它减少肝脏脂质滴沉积，恢复肠道完整性，并降低血清中脂多糖（LPS）水平。后续实验结果表明，白术下调结肠组织中Toll样受体4（TLR4）和核因子κB（NF-κB）的表达，以及肝脏组织中白细胞介素-6（IL-6）、TLR4、磷酸化的Janus激酶2（p-JAK2）、磷酸化的信号转导和转录激活因子3（p-STAT3）和雌激素相关受体γ（ESRRG）的表达。最后，我们还发现白术可以调节血浆和肝脏中FIB的水平。
白术可能通过修复肠道屏障和抑制LPS/TLR4相关的肝脏炎症激活，从而通过下调IL-6/STAT3/ESRRG通路抑制FIB合成，保护HFSSD诱导的大鼠免受血液高粘度的影响。
