Total Ginsenosides from Panax ginseng Improve Exercise Tolerance in Rats with Spleen Qi Deficiency-like Features: Integrated Metabolomics of Serum and Hepatic Mitochondria-enriched Fractions.

Abstract

Ethnopharmacological relevance: Panax ginseng C.A.Mey. has traditionally been used to replenish Qi and strengthen the spleen, including for poor appetite and weakness associated with spleen deficiency. Ginsenosides are major constituents, but their metabolic effects under spleen Qi deficiency-like conditions remain to be clarified.

Aim of the study: To evaluate whether total ginsenosides (TGS) improve spleen Qi deficiency-like features in rats and characterize systemic and hepatic metabolic changes.

Materials and methods: A rat model was established using 50% food restriction combined with repeated weight-loaded swimming, and TGS (75, 150, or 300 mg·kg^-1) was administered for 21 days. Body weight, grip strength, swimming endurance, biochemical indices, and mitochondrial ultrastructure were evaluated. Untargeted metabolomic analyses of serum and hepatic mitochondria-enriched fractions were performed in the control (CON), model (MOD), and high-dose TGS (TGS-H) groups, and hepatic SIRT1 and PGC-1α protein expression was measured. Lipid accumulation, mitochondrial membrane potential, and SIRT1 and PGC-1α expression were also examined in oleic acid-treated HepG2 cells.

Results: TGS, particularly at 300 mg·kg^-1, attenuated the suppression of body-weight gain and improved grip strength and swimming endurance. These functional improvements were accompanied by increased ATP content and ATPase activities and attenuation of mitochondrial ultrastructural abnormalities. After TGS-H treatment, serum levels of several amino acids increased, and lipid profiles shifted toward the control pattern. In hepatic mitochondria-enriched fractions, accumulation of selected fatty acids decreased, and levels of selected organic acids increased. TGS increased hepatic PGC-1α protein expression at all three doses, whereas SIRT1 expression increased significantly only at the high dose. In oleic acid-treated HepG2 cells, increased expression of both proteins was accompanied by reduced lipid accumulation and partial recovery of mitochondrial membrane potential.

Conclusions: In rats with spleen Qi deficiency-like features induced by limited nutritional supply and repeated physical exertion, TGS attenuated the suppression of body-weight gain and improved exercise tolerance, accompanied by changes in energy-related indices. These findings provide experimental support for the traditional use of ginseng to replenish Qi and strengthen the spleen in relation to symptoms of weakness.