Anti-inflammatory effects of Rehmannia glutinosa polysaccharide on LPS-induced acute liver injury in mice and related underlying mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE

Rehmannia glutinosa (Gaertn.) DC., a perennial herb, has a rich cultivation history of over a thousand years across numerous Asian countries. This highly valued crop finds utility in both industrial and medicinal applications, providing promising clinical outcomes in enhancing immunity and mitigating inflammation in the body.

AIM OF THE STUDY

To investigate the protective effects of RGP against liver injury in mice and identify the underlying mechanisms.

MATERIALS AND METHODS

A mouse model of liver injury was established by treating mice with administered varying concentrations of RGP (50-200 mg/kg) for 14 days before the intraperitoneal administration of 5 mg/kg LPS. Additionally, a RAW264.7 macrophage cell injury model was established using LPS treatment. Comprehensive methodologies, including flow cytometry, Western blot, ELISA, and RT-PCR, were employed in combination with molecular docking and dynamic simulation techniques to simulate and examine the binding interactions between RGP and cell membrane proteins. The goal of this multifaceted approach was to gain deeper insights into the anti-inflammatory mechanisms of RGP against liver injury.

RESULTS

In cell-based experiments, RGP demonstrated the ability to reduce intracellular ROS levels, inhibit cell apoptosis, and decrease intracellular NO levels as well as iNOS mRNA expression. Furthermore, by modulating the TLR4/NF-κB signaling pathway, RGP could decrease the mRNA expression and serum levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Animal experiments further revealed that RGP could reduce MDA and CAT contents, improve the redox balance, and regulate the TLR4/MyD88/NF-κB signaling axis in mice. After RGP treatment, the gene and protein expression levels of pro-inflammatory factors such as TNF-α, IL-1β, IL-6, and caspase-1 were reduced in vivo, while the gene expression levels of the anti-inflammatory factor IL-10 were upregulated. Molecular docking and dynamic simulation analyses indicated that RGP could tightly bind to the TLR4 membrane protein and exert anti-inflammatory effects by directly regulating the TLR4/MyD88/NF-κB signaling axis.

CONCLUSIONS

These findings provide a theoretical foundation for the development of effective clinical agents that attenuate acute liver injury and enable its treatment.