Mitsuru Nomura

Dammarane-type triterpene extracts of Panax notoginseng root ameliorates hyperglycemia and insulin sensitivity by enhancing glucose uptake in skeletal muscle

Skeletal muscle is an important organ for controlling the development of type 2 diabetes. We discovered Panax notoginseng roots as a candidate to improve hyperglycemia through in vitro muscle cells screening test. Saponins are considered as the active ingredients of ginseng. However, in the body, saponins are converted to dammarane-type triterpenes, which may account for the anti-hyperglycemic activity. We developed a method for producing a dammarane-type triterpene extract (DTE) from Panax notoginseng roots and investigated the extract’s potential anti-hyperglycemic activity. We found that DTE had stronger suppressive activity on blood glucose levels than the saponin extract (SE) did in KK-Ay mice. Additionally, DTE improved oral glucose tolerance, insulin sensitivity, glucose uptake, and Akt phosphorylation in skeletal muscle. These results suggest that DTE is a promising agent for controlling hyperglycemia by enhancing glucose uptake in skeletal muscle. Graphical abstract DTM improved hyperglycemia.

Panaxatriol derived from ginseng augments resistance exercised–induced protein synthesis via mTORC1 signaling in rat skeletal muscle

Resistance exercise activates muscle protein synthesis via the mammalian target of rapamycin complex 1 (mTORC1) pathway and subsequent muscle hypertrophy. Upstream components of the mTORC1 pathway are widely known to be involved in Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. Previous studies have shown that ginseng stimulated Akt and ERK1/2 signaling. Therefore, we hypothesized that panaxatriol (PT) derived from ginseng triggers mTORC1 signaling and muscle protein synthesis by activating both the Akt and ERK1/2 signaling pathways, and that PT additively stimulates muscle protein synthesis when combined with resistance exercise. The study included male Sprague-Dawley rats. The legs of the rats were divided into control, PT-only, exercise-only, and exercise + PT groups. The right legs were subjected to isometric resistance exercise using percutaneous electrical stimulation, whereas the left legs were used as controls. PT (0.2 g/kg) was administered immediately after exercise. The Akt and ERK1/2 phosphorylation levels were significantly higher in the exercise + PT group than in the exercise-only group 0.5 hour after exercise. The phosphorylation of p70S6K was significantly increased at both 0.5 and 3 hours after exercise, and it was higher in the exercise + PT group than in the exercise-only group at both 0.5 and 3 hours after exercise. Muscle protein synthesis was significantly increased 3 hours after exercise, and it was higher in the exercise + PT group than in the exercise-only group 3 hours after exercise. Our results suggest that PT derived from ginseng enhances resistance exercise-induced protein synthesis via mTORC1 signaling in rat skeletal muscle.

Effects of Aerobic Exercise Combined with Panaxatriol Derived from Ginseng on Insulin Resistance and Skeletal Muscle Mass in Type 2 Diabetic Mice

Insulin resistance reduces insulin-induced muscle protein synthesis and accelerates muscle protein degradation. Ginseng ingestion has been reported to improve insulin resistance through the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. We hypothesized that panaxatriol (PT) derived from ginseng in combination with aerobic exercise (EX) may further promote protein synthesis and suppress protein degradation, and subsequently maintain muscle mass through the amelioration of insulin resistance. KKAy insulin-resistant mice were divided into control, panaxatriol only (PT), exercise only (EX), and EX+PT groups. EX and EX+PT ran on the treadmill for 45 min at 15 m/min 5 d/wk for 6 wk. PT and EX+PT groups were fed a standard diet containing 0.2% PT for 6 wk. Homeostasis model assessment for insulin resistance (HOMA-R) values was significantly improved after exercise for 6 wk. Moreover, EX+PT mice showed improved HOMA-R as compared to EX mice. p70S6K phosphorylation after a 4 h fast was significantly higher in EX than in the non-exercise control, and it was higher in EX+PT mice than in EX mice. Atrogin1 mRNA expression was significantly lower in EX than in the non-exercise control, and was significantly lowered further by PT treatment. EX and EX+PT mice showed higher soleus muscle mass and cross-sectional area (CSA) of the soleus myofibers than control animals, with higher values noted for both parameters in EX+PT than in EX. These results suggest that aerobic exercise and PT ingestion may contribute to maintain skeletal muscle mass through the amelioration of insulin resistance.