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. 2018 Sep 13;19(9):2746.
doi: 10.3390/ijms19092746.

The Beneficial Effect of Proanthocyanidins and Icariin on Biochemical Markers of Bone Turnover in Rats

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Free PMC article

The Beneficial Effect of Proanthocyanidins and Icariin on Biochemical Markers of Bone Turnover in Rats

Nada Oršolić et al. Int J Mol Sci. .
Free PMC article

Abstract

Nutrition is an important factor that influences bone metabolism, the endocrine and/or paracrine system, and bone-active mineral elements homeostasis. We studied antiosteoporotic effects of grape seed proanthocyanidins extract, icariin or alendronate (ALN) in retinoic acid-induced (13cRA) bone loss in rats. Proanthocyanidins and icariin have beneficial effects on bone health; they have improved the bone weight reduction, the length and the diameter of the bone, calcium, and phosphorus content in bone ash, bone mineral density (BMD), the biochemical markers of bone turnover and uterus atrophy induced by 13cRA. All results suggest that proanthocyanidins and icariin reverse osteoporosis in 13cRA rats by stimulating bone formation or regulating bone resorption by their antioxidative and estrogenic-like activity without toxic side-effects observed in ALN treatment.

Keywords: bone markers; icariin; proanthocyanidins; rats; retinoic acid-induced bone loss.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Changes in body weight at different time points: (a) during treatment with retinoic acid, (b) effect of icariin, proanthocyanidins and alendronate on the body weight change in rats after retinoic acid-induced bone loss. Rats were administered ig with retinoic acid suspension (80 mg kg−1) once daily for 14 days. After inducing osteoporosis with 13cRA, rats were administered ig with icariin (100 mg kg−1), proanthocyanidins (100 mg kg−1) or alendronate (40 mg kg−1) once daily for next 14 days. The animals were weighed just before the start of the experiment (starting weight of animals 225–250) and during the experiment on days 6, 12, 18, 24 and 30. The percentage change in weight was calculated for individual animals as Percentage change in weight = Final weight-Initial weight × 100/Final weight. Number of rats per group: 7. Statistically significantly different compared to control ( p < 0.05) on day 30. Δ Statistically significantly different compared to alendronate (Δ p < 0.05; ΔΔ p < 0.01) on day 30.
Figure 2
Figure 2
Histological examination of rats’ bone stained section with HE. (a) Control group showed normal architecture of the bone tissue (shown in box); (b) Retinoic acid-treated group (osteoporotic model) showed formation of multiple large intracortical cavities (shown in box) and thinning of the cortex and eroded endosteal bone surface (shown in box with *) (c); Proanthocyanidins (d) or icariin (e) showed complete recovery with essential features of the normal bone and complete formation of trabeculae and thickness with one or two small intracortical cavities (shown in box with *); (f) alendronate showed signs of improvemaent of femoral structure and the increased thickness (shown in box with ▬), size of the intracortical cavities are significantly reduced, while the inner surface of the cortex still shows irregularities in certain places (shown in box with *).
Figure 3
Figure 3
Effect of icariin, proanthocyanidins and alendronate on bone mineral content (a) bone mineral density (b) in rats with retinoic acid-induced bone loss. Rats were administered ig with retinoic acid suspension (80 mg kg−1) once daily for 14 days. After inducing osteoporosis with 13cRA, rats were administered ig with icariin (100 mg kg−1), proanthocyanidins (100 mg kg−1) or alendronate (40 mg kg−1) once daily for next 14 days. Bone mineral content (BMC) and bone mineral density (BMD) of each rat’s left femur were measured by dual-energy X-ray absorptiometry (DXA). BMD was calculated by the BMC of the measured area and reported as g/cm3. Number of rats per group: 7. (a) Statistically significant difference exists between: Prox., 13cRA vs. alendronate (** p ˂ 0.01), 13cRA vs. proanthocyanidins (* p < 0.05); icariin vs. alendronate ( p < 0.05);.Distal, 13cRA vs. alendronate (** p ˂ 0.01), 13cRA vs. proanthocyanidins (* p < 0.05); icariin vs. alendronate (◊◊ p < 0.01); (b) Statistically significant difference exists between: Prox., 13cRA vs. Control (* p < 0.05); 13cRA vs. proanthocyanidins (** p < 0.01); 13cRA vs. alendronate ( p < 0.01); Distal. 13cRA vs. proanthocyanidins (** p < 0.01); 13cRA vs. alendronate (*** p < 0.001); icariin vs. alendronate ( p < 0.05).
Figure 4
Figure 4
Effect of icariin, proanthocyanidins and alendronate on bone biochemical markers in rats with retinoic acid-induced bone loss. Bone biochemical markers (a) osteocalcin, a marker of bone formation and (b) β-CrossLaps (β-CTx) marker of bone resorption. Rats were administered ig with retinoic acid suspension (80 mg kg−1) once daily for 14 days. After inducing osteoporosis with 13cRA, rats were administered ig with icariin (100 mg kg−1), proanthocyanidins (100 mg kg−1) or alendronate (40 mg kg−1) once daily for next 14 days. Serum osteocalcin and β-CrossLaps (β-CTx) markers were measured by the electrochemiluminescence immunoassay “ECLIA”. Number of rats per group: 7. (a) Statistically significant difference exists between: 13cRA vs. control (** p < 0.01). (b) Statistically significant difference exists between: 13cRA vs. icariin (** p < 0.01); 13cRA vs. proanthocyanidins (* p < 0.05).
Figure 4
Figure 4
Effect of icariin, proanthocyanidins and alendronate on bone biochemical markers in rats with retinoic acid-induced bone loss. Bone biochemical markers (a) osteocalcin, a marker of bone formation and (b) β-CrossLaps (β-CTx) marker of bone resorption. Rats were administered ig with retinoic acid suspension (80 mg kg−1) once daily for 14 days. After inducing osteoporosis with 13cRA, rats were administered ig with icariin (100 mg kg−1), proanthocyanidins (100 mg kg−1) or alendronate (40 mg kg−1) once daily for next 14 days. Serum osteocalcin and β-CrossLaps (β-CTx) markers were measured by the electrochemiluminescence immunoassay “ECLIA”. Number of rats per group: 7. (a) Statistically significant difference exists between: 13cRA vs. control (** p < 0.01). (b) Statistically significant difference exists between: 13cRA vs. icariin (** p < 0.01); 13cRA vs. proanthocyanidins (* p < 0.05).

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