Ginseng flower total saponin extract alleviates type 1 diabetes mellitus-associated liver injury via PI3K/AKT/HIF-1α signaling pathway

Abstract

Background

Type 1 diabetes mellitus (T1DM) induces liver complications via oxidative stress and inflammation, with limited therapeutic options targeting these mechanisms. Ginseng flower total saponin extract (GFTS), a multi-component natural product, shows metabolic regulatory potential but remains uncharacterized in T1DM-related hepatic injury.

Methods

Network pharmacology identified the PI3K/AKT/HIF-1α pathway as a key GFTS target axis in T1DM. Molecular docking validated ginsenoside binding to core proteins (PIK3CA, AKT, HIF-1α). In vitro, GFTS effects on high-glucose-exposed HepG2 cells (viability, MDA, IL-6/TNF-α) were assessed. In vivo, STZ-induced T1DM mice received GFTS (100–400 mg/kg/d) for 4 weeks, with evaluations including glucose metabolism, liver histology, and pathway activation via Western blot.

Results

GFTS improved HepG2 viability, reduced MDA (35–52 %), and suppressed cytokines (40–65 %) in vitro. In mice, it lowered fasting glucose (28–45 %), improved glucose tolerance, and alleviated hepatic vacuolisation/inflammation. Mechanistically, GFTS activated PI3K/AKT phosphorylation and inhibited HIF-1α in liver tissue.

Conclusion

GFTS protects against T1DM hepatic injury via PI3K/AKT/HIF-1α modulation and antioxidant effects, offering a novel adjuvant strategy for T1DM complications.