Korean J Physiol Pharmacol.  2018 Jul;22(4):427-436. 10.4196/kjpp.2018.22.4.427.

Concurrent treatment with ursolic acid and low-intensity treadmill exercise improves muscle atrophy and related outcomes in rats

• Kim JC
• Kang YS
• Noh EB
• Seo BW
• Seo DY
• Park GD
• Kim SH

• KMID: 2414267
• DOI: http://doi.org/10.4196/kjpp.2018.22.4.427

Abstract

The objective of this study was to analyze the concurrent treatment effects of ursolic acid (UA) and low-intensity treadmill exercise and to confirm the effectiveness of UA as an exercise mimetic to safely improve muscle atrophy-related diseases using Sprague-Dawley (SD) rats with skeletal muscle atrophy. Significant muscle atrophy was induced in male SD rats through hind limb immobilization using casting for 10 days. The muscle atrophy-induced SD rats were group into four: SED, sedentary; UA, daily intraperitoneal UA injection, 5 mg/kg; EX, low-intensity (10-12 m/min, 0° grade) treadmill exercise; and UEX, daily intraperitoneal UA injection, 5 mg/kg, and low-intensity (10-12 m/min, 0° grade) treadmill exercise. After 8 weeks of treatment, endurance capacity was analyzed using a treadmill, and tissues were extracted for analysis of visceral fat mass, body weight, muscle mass, expression of muscle atrophy- and hypertrophy-related genes, and endurance capacity. Although the effects of body weight gain control, muscle mass increase, and endurance capacity improvement were inadequate in the UA group, significant results were confirmed in the UEX group. The UEX group had significantly reduced body weight and visceral fat, significantly improved mass of tibialis anterior and gastrocnemius muscles, and significantly decreased atrophy-related gene expression of MuRF1 and atrogin-1, but did not have significant change in hypertrophy-related gene expression of Akt and mTOR. The endurance capacity was significantly improved in the EX and UEX groups. These data suggest that concurrent treatment with low-intensity exercise and UA is effective for atrophy-related physical dysfunctions.

Keyword

Aging; Exercise; Muscle atrophy; Ursolic acid

MeSH Terms

Aging
Animals
Atrophy
Body Weight
Extremities
Gene Expression
Humans
Immobilization
Intra-Abdominal Fat
Male
Muscle, Skeletal
Muscles
Muscular Atrophy*
Rats*
Rats, Sprague-Dawley

Figure

• 

  Fig. 1 Muscle atrophy induced by 10-day hind limb IM.Data are presented as mean±SE. (A) TA. (B) SOL. (C) GAS. TA, tibialis anterior; SOL, soleus; GAS, gastrocnemius; IM, immobilization; IM, immobilization; CON, contralateral control. *p<0.05 vs. CON by two-sample t-test (n=3 rats).

• 

  Fig. 2 Reduction in final body weight and fat mass through UA supplementation with exercise.Rats were given UA and/or performed treadmill exercise for 8 weeks. Data are presented as mean±SE. (A, B) Initial and final body weights were measured before immobilization and before sacrifice (n=7 rats per group). (C, D) Weight of epididymal and retroperitoneal fat pads (n=6 rats per group). SED, sedentary; UA, ursolic acid; EX, exercise; UEX, ursolic acid plus exercise. *p<0.05, one-way analysis of variance.

• 

  Fig. 3 Improvement in atrophied hind limb muscle mass through UA supplementation with treadmill exercise.(A) Skeletal muscle atrophy of the TA, SOL, and GAS induced by IM is expressed in percentage of difference from the contralateral CON leg (non-immobilized). Data are presented as mean±SE. *p<0.05, one-way analysis of variance. (B) Micro-computed tomography (CT) scans of a rat hind limb. Lateral view of a whole limb (top) and mid-tibial transverse micro-CT scans of the same rat hind limb (bottom). TA, tibialis anterior; SOL, soleus; GAS, gastrocnemius; IM, immobilization; CON, control; SED, sedentary; UA, ursolic acid; EX, exercise; UEX, ursolic acid plus exercise.

• 

  Fig. 4 Reduction in atrophic gene expression through concurrent low-intensity treadmill exercise and UA treatment.Relative mRNA expression levels of atrophy- (A) and hypertrophy- (B) related genes and the content of atrophy- (C) and hypertrophy- (D) related protein after 8 weeks of treatment in the gastrocnemius muscle (n=6 rats per group). Signals were quantified and normalized against the contralateral CON leg (non-immobilized). Data are presented as mean±SE. *p<0.05, one-way analysis of variance. CON, control; SED, sedentary; UA, ursolic acid; EX, exercise; UEX, ursolic acid plus exercise.

• 

  Fig. 5 Increased endurance capacity from treadmill exercise, but not ursolic acid, after 8 weeks of treatment.Endurance capacity was me asured using a treadmill after 8 weeks. Data are presented as mean±SE (n=6 rats per group). *p<0.05, one-way analysis of variance.

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