Nutr Res Pract.  2025 Feb;19(1):30-40. 10.4162/nrp.2025.19.1.30.

Combination of ferulic acid and exercise alleviates menopause symptoms and skin remodeling in ovariectomized rats

• Lee W
• Cho J
• Yoo SY
• Park E

• KMID: 2565394
• DOI: http://doi.org/10.4162/nrp.2025.19.1.30

Abstract

BACKGROUND/OBJECTIVES
Estrogen regulates certain biological functions, including bone health, maintenance of skin components, and cardiovascular and brain protection. Estrogen deficiency manifests as hot flashes, wrinkles, skin dryness, reduced bone mineral density (BMD), sleep disorders, and cardiovascular diseases. This study aimed to investigate the effects of aerobic exercise combined with ferulic acid (FA) in ovariectomized rats.
MATERIALS/METHODS
Female Sprague–Dawley rats were classified into control (N), ovariectomy (OV), ovariectomy and exercise (OV+EX), and ovariectomy and exercise with ferulic acid (OV+EX+F) groups. Following ovariectomy at 22 weeks of age, the rats were tower climbing exercise at gradually increase the load (3 days/week for 12 weeks) with or without FA (5 g/kg diet) administration.
RESULTS
Estrogen deficiency in female rats (OV group) resulted in increased body weight, increased blood triglyceride (TG) levels, and decreased BMD following ovariectomy. Interestingly, compared with the rats in the OV group, the rats in the OV+EX+F group exhibited reduced body weight and blood TG levels and maintained BMD following ovariectomy, similar to those in the N group. Histological analysis of the skin of estrogen-deficient rats (OV group) revealed significantly decreased skin thickness with fewer dermal cells and distorted subcutaneous fat layers, similar to the aging phenotype. Interestingly, the rats in the OV+EX+F group exhibited rescued skin phenotypes compared with those in the OV and OV+EX groups. The skin of rats from all groups was analyzed for the expression of DNA damage and repair proteins. The OV+EX+F and OV+EX groups exhibited enhanced protein levels of pCHK1 (S345), an initiator of DNA repair signaling, and p53, indicating increased cellular DNA damage because of ovariectomy and ultimately an underlying DNA repair process.
CONCLUSION
Exercise with FA had beneficial effects on lipid profiles, BMD, and skin remodeling during menopause.

Keyword

Ferulic acid; exercise; ovariectomy; p53; skin

Figure

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  Fig. 1 Schematic overview of study design. Rats underwent ovariectomy at week 15, followed by a 2-week recovery period. Exercise and dietary interventions were performed for 12-week, and the rats were sacrificed at week 30.N, control (normal); OV, ovariectomized rats that were fed a control diet; OV+EX, a control diet with exercise training; OV+EX+F, a diet including ferulic acid with exercise training; FA, ferulic acid.

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  Fig. 2 Tower climbing exercise program.1RM, one-repetition maximum.

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  Fig. 3 Final body weight (A), total cholesterol (B), TG (C), and insulin (D) levels. All values are presented as the mean ± SD. Data were statistically analyzed using one-way analysis of variance, followed by a Tukey’s multiple range test.N, control (normal); OV, ovariectomized rats that were fed a control diet; OV+EX, a control diet with exercise training; OV+EX+F, a diet including ferulic acid with exercise training.a,bDifferent letters indicate statistically significant differences.

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  Fig. 4 (A) The representative femur bone head and shaft tissues stained by hematoxylin and eosin (magnification 10×, scale bar 100 μm). Graph presenting adipocytes count in (B) bone head and (C) shaft. All values are presented as the mean ± SD. Data were statistically analyzed using one-way analysis of variance, followed by a Tukey’s multiple range test.N, control (normal); OV, ovariectomized rats that were fed a control diet; OV+EX, a control diet with exercise training; OV+EX+F, a diet including ferulic acid with exercise training.a,b,cDifferent letters indicate statistically significant differences.

• 

  Fig. 5 (A) The representative skin tissue stained by hematoxylin and eosin (magnification 4×, scale bar 50 μm). Graphs presenting changes in (B) skin size, (C), dermis length, (D) percent of dermis length, and (E) area of subcutaneous fat. All values are presented as the mean ± SD. Data were statistically analyzed using one-way analysis of variance, followed by a Tukey’s multiple range test.N, control (normal); OV, ovariectomized rats that were fed a control diet; OV+EX, a control diet with exercise training; OV+EX+F, a diet including ferulic acid with exercise training.a,b,cDifferent letters indicate statistically significant differences.

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  Fig. 6 (A) The protein levels of pCHK1 and p53 analyzed by western blotting. (B, C) The relative band intensities were normalized by β-actin. All values are presented as the mean ± SD. Data were statistically analyzed using one-way analysis of variance, followed by a Tukey’s multiple range test.N, control (normal); OV, ovariectomized rats that were fed a control diet; OV+EX, a control diet with exercise training; OV+EX+F, a diet including ferulic acid with exercise training.a,b,cDifferent letters indicate statistically significant differences.

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