Atractylodes macrocephala Rhizoma alleviates blood hyperviscosity induced by high-fat, high-sugar, and high-salt diet via inhibition of gut-liver inflammatory activation and fibrinogen synthesis.

Abstract

Ethnopharmacological relevance: 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.

Aim of the study: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.