Fucoxanthin-Rich Brown Algae Extract Improves Male Reproductive Function on Streptozotocin-Nicotinamide-Induced Diabetic Rat Model

Abstract

Hypogonadism and oxidative stress are occurring commonly in men with diabetes and associated male infertility. This study aimed to investigate the capability of anti-oxidative and anti-inflammatory properties of fucoxanthin as well as to evaluate its protective effects on male reproduction in diabetic rats. The RAW 264.7 macrophage cells were used to evaluate the anti-oxidative and anti-inflammatory activity. Thirty male Sprague-Dawley rats were induced by streptozotocin-nicotinamide for a diabetes model and fed either with three different doses of fucoxanthin (13, 26, and 65 mg/kg) or rosiglitazone (0.571 mg/kg) for four weeks. The fucoxanthin significantly inhibited nitric oxide production and reduced reactive oxygen species level in lipopolysaccharide-induced RAW 264.7 cells. In the animal study, fucoxanthin administration improved insulin resistance, restored sperm motility, decreased abnormal sperm number, and inhibited lipid peroxidation. Moreover, it restored GPR54 and SOCS-3 mRNA expression in the hypothalamus and recovered luteinizing hormone level, as well as the testosterone level. In conclusion, fucoxanthin not only possessed antioxidant and anti-inflammatory properties but also decreased the diabetes signs and symptoms as well as improved spermatogenesis and male reproductive function.

Keywords: diabetes; fucoxanthin; hypogonadism; male reproduction; spermatogenesis.

Figure 1

Effects of fucoxanthin (FXN) on (A) RAW 264.7 macrophage cells viability, (B) nitric oxide, (C) superoxide, and (D) hydrogen peroxide productions. The cells were stimulated by lipopolysaccharides (LPS, 1 µg/mL). Data are shown as the mean ± S.D. of three independent experiments. The values with different letters (a–f) represent significant differences (p < 0.05) as analyzed by Duncan’s multiple range test. Normal, unstimulated cells; control, untreated cells.

Figure 2

Effects of fucoxanthin on plasma glucose after treatment for four weeks. (A) Oral glucose tolerance test (OGTT) and (B) area under the curve (AUC) of plasma glucose. Data are shown as the mean ± S.D. (n = 5). The values with different letters (a–c) represent significant differences (p < 0.05) as analyzed by Duncan’s multiple range test. C, control; DM, diabetes; DMF, diabetes treated with fucoxanthin; DMR, diabetes treated with rosiglitazone.

Figure 3

Effects of fucoxanthin on (A) reactive oxygen species (ROS) and (B) superoxide productions in rat sperm after treatment for four weeks. Data are shown as the mean ± S.D. (n = 5). The values with different letters (a–c) represent significant differences (p < 0.05) as analyzed by Duncan’s multiple range test. C, control; DM, diabetes; DMF, diabetes treated with fucoxanthin; DMR, diabetes treated with rosiglitazone.

Figure 4

Effects of fucoxanthin on malondialdehyde (MDA) level in rat plasma, testis, and sperm after treatment for four weeks. Data are shown as the mean ± S.D. (n = 5). The values with different letters (a–c) represent significant differences (p < 0.05) as analyzed by Duncan’s multiple range test. C, control; DM, diabetes; DMF, diabetes treated with fucoxanthin; DMR, diabetes treated with rosiglitazone.

Figure 5

Effects of fucoxanthin on proinflammatory cytokines after treatment for four weeks. (A) Tumor necrosis factor (TNF)-α level in plasma and testis, and (B) Interleukin (IL)-6 level in plasma and testis. Data are shown as the mean ± S.D. (n = 5). The values with different letters (a–c) represent significant differences (p < 0.05) as analyzed by Duncan’s multiple range test. C, control; DM, diabetes; DMF, diabetes treated with fucoxanthin; DMR, diabetes treated with rosiglitazone.

Figure 6

Effects of fucoxanthin on SOCS-3 mRNA expression in rat hypothalamus after treatment for four weeks. Data are showed as the mean ± S.D. (n = 5). The values with different letters (a–c) represent significant differences (p < 0.05) as analyzed by Duncan’s multiple range test. C, control; DM, diabetes; DMF, diabetes treated with fucoxanthin; DMR, diabetes treated with rosiglitazone; SOCS-3, suppressors of cytokine signaling-3.

Figure 7

Effects of fucoxanthin on relative (A) Kiss1 and (B) GPR54 mRNA expression in rat hypothalamus after treatment for four weeks. Data are shown as the mean ± S.D. (n = 5). The values with different letters (a–c) represent significant differences (p < 0.05) as analyzed by Duncan’s multiple range test. C, control; DM, diabetes; DMF, diabetes treated with fucoxanthin; DMR, diabetes treated with rosiglitazone; GPR54, G-protein coupling receptor (Kiss1 receptor).

Figure 8

Effects of fucoxanthin on (A) testicular morphology and (B) thickness of seminiferous tubule diameter after treatment for four weeks. Data are shown as the mean ± S.D. (n = 5). The values with different letters (a–c) represent significant differences (p < 0.05) as analyzed by Duncan’s multiple range test. Black arrow, Leydig cell; white arrow, Sertoli cell; C, control; DM, diabetes; DMF, diabetes treated with fucoxanthin; DMR, diabetes treated with rosiglitazone.

Figure 9

The flowchart of fucoxanthin treatment against streptozotocin-nicotinamide (STZ-NA)-induced diabetes Sprague-Dawley (SD) rat model. DM, diabetes; DMF, diabetes treated with fucoxanthin; DMR, diabetes treated with rosiglitazone.