The effects of myricitrin and vitamin E against reproductive changes induced by D-galactose as an aging model in female mice: An experimental study


Background: Aging is accompanied by decreasing general function in the cells and tissues. D-galactose (D-gal) induces aging and plays a role in the pathogenesis of it. Myricitrin is a plant-derived antioxidant.

Objective: The present study was performed to evaluate the effects of myricitrin on antioxidant defense, sex hormone levels, uterus, and ovarian histology in D-galinduced aging female mouse model.

Materials and Methods: In this experimental study, 72 female adult NMRI mice, weighing 30-35 gr, 3-4 months old, were randomly divided into six groups (n = 12/each): (I) Control (vehicle; normal saline), (II) D-gal at 500 mg/kg/d for 45 days, (III-V) D-gal + myricitrin-treated groups (these groups received myricitrin at 5, 10, and 20 mg/kg/d, and (VI) D-gal + 100 mg/kg/d vitamin E orally for the last 28 days. The antioxidant indices were done on the basis of colorimetric method, and sex hormone levels were measured by using enzyme-linked immunosorbent assay kits. Histological assessment of the uterus and ovaries were also evaluated.

Results: D-gal impaired the estrous cycle, also degenerative changes occur in the ovarian follicles and damage to the uterus and ovarian tissue occurrs. In D-gal group, the level of sex hormones (p = 0.03) and the total antioxidant capacity (p = 0.002) decreased, while the level of malondialdehyde and gonadotropins increased (p = 0.03). Myricitrin at lower doses and vitamin E ameliorated the D-gal effects.

Conclusion: These findings suggest that myricitrin can effectively prevent D-galinduced oxidation and aging in mice. The effect of myricitrin was equivalent and sometimes better than vitamin E.

Key words: Aging, D-galactose, Mice, Myricitrin, Vitamin E.

[1] Wang S, He G, Chen M, Zuo T, Xu W, Liu X. The role of antioxidant enzymes in the ovaries. Oxid Med Cell Longev. 2017; 2017: 4371714.

[2] Li YJ, Han Z, Ge L, Zhou CJ, Zhao YF, Wang DH, et al. C-phycocyanin protects against low fertility by inhibiting reactive oxygen species in aging mice. Oncotarget 2016; 7: 17393–17409.

[3] Zhao FF, Zhou YZ, Gao L, Qin XM, Du GH. Advances in the study of the rat model of aging induced by D-galactose. Yao Xue Xue Bao 2017; 52: 347–354.

[4] Ahangarpour A, Najimi SA, Farbood Y. Effects of Vitex agnus-castus fruit on sex hormones and antioxidant indices in a d-galactose-induced aging female mouse model. J Chin Med Assoc 2016; 79: 589–596.

[5] Chen H, Long Y, Guo L. Antiaging Effect of inula britannica on aging mouse model induced by d-galactose. Evid Based Complement Alternat Med 2016; 2016: 1–8.

[6] Chen W, Feng L, Shen Y, Su H, Li Y, Zhuang J, et al. Myricitrin inhibits acrylamide-mediated cytotoxicity in human Caco-2 cells by preventing oxidative stress. Biomed Res Int 2013; 2013: 1–7.

[7] Ahangarpour A, Lamoochi Z, Fathi Moghaddam H, Mansouri SM. Effects of portulaca oleracea ethanolic extract on reproductive system of aging female mice. Int J Reprod BioMed 2016; 14: 205–212.

[8] Huang Q, Gao B, Wang L, Hu YQ, Lu WG, Yang L, et al. Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines. Toxicol Appl Pharmacol 2014; 280: 550–560.

[9] Li J, Zhang M, Ma J. Myricitrin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation and migration through suppressing PDGFRβ/Akt/Erk signaling. Int J Clin Exp Med 2015; 8: 21715–21723.

[10] Ahangarpour A, Oroojan AA, Khorsandi L, Kouchak M, Badavi M. Solid lipid nanoparticles of myricitrin have antioxidant and antidiabetic effects on streptozotocinnicotinamide- induced diabetic model and myotube cell of male mouse. Oxid Med Cell Longev 2018; 2018: 7496936.

[11] Kassem ME, Ibrahim LF, Hussein SR, El-Sharawy R, El- Ansari MA, Hassanane MM, et al. Myricitrin and bioactive extract of Albizia amara leaves: DNA protection and modulation of fertility and antioxidant-related genes expression. Pharm Biol 2016; 54: 2404–2409.

[12] Soleimani Mehranjani M, Noorafshan A, Hamta A, Momeni HR, Abnosi MH, Mahmoodi M, et al. Effects of vitamin E on ovarian tissue of rats following treatment with pnonylphenol: A stereological study. Iran J Reprod Med 2010; 8: 1–9.

[13] Ekambaram G, Sampath Kumar SK, Joseph LD. Comparative study on the estimation of estrous cycle in mice by visual and vaginal lavage method. J Clin Diagn Res 2017; 11: AC05–AC07.

[14] Park JH, Choi TS. Polycystic ovary syndrome (PCOS)- like phenotypes in the d-galactose-induced aging mouse model. Biochem Biophys Res Commun 2012; 427: 701–704.

[15] Budni J, Pacheco R, da Silva S, Garcez ML, Mina F, Bellettini-Santos T, et al. Oral administration of d-galactose induces cognitive impairments and oxidative damage in rats. Behav Brain Res 2016; 302: 35–43.

[16] Ahangarpour A, Oroojan AA, Heidari H. Effects of exendin- 4 on male reproductive parameters of D-galactose induced aging mouse model. World J Mens Health 2014; 32: 176–183.

[17] Sekhon LH, Gupta S, Kim Y, Agarwal A. Female infertility and antioxidants. Current Women’s Health Reviews 2010; 6: 84–95.

[18] Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol 2012; 10: 49–80.

[19] Behrman HR, Kodaman PH, Preston SL and Gao S. Oxidative stress and the ovary. J Soc Gynecol Investig 2001; 8 (Suppl.): S40–42.

[20] Kannappan R, Gupta SC, Kim JH, Aggarwal BB. Tocotrienols fight cancer by targeting multiple cell signaling pathways. Genes Nutr 2012; 7: 43–52.

[21] Mohd Mutalip SS, Ab-Rahim S, Rajikin MH. Vitamin E as an antioxidant in female reproductive health. Antioxidants 2018; 7: 1–22.

[22] Bahadori MH, Sharami SH, Fakor F, Milani F, Pourmarzi D, Dalil-Heirati SF. Level of vitamin e in follicular fluid and serum and oocyte morphology and embryo quality in patients undergoing IVF treatment. J Family Reprod Health 2017; 11: 74–81.

[23] Cicek N, Eryilmaz OG, Sarikaya E, Gulerman C, Genc Y. Vitamin E effect on controlled ovarian stimulation of unexplained infertile women. J Assist Reprod Genet 2012; 29: 325–328.

[24] Ahangarpour A, Oroojan AA, Khorsandi L, Kouchak M, Badavi M. Antioxidant effect of myricitrin on hyperglycemia-induced oxidative stress in C2C12 cell. Cell Stress Chaperones 2018; 23: 773–781.

[25] Yan Z, Dai Y, Fu H, Zheng Y, Bao D, Yin Y, et al. Curcumin exerts a protective effect against premature ovarian failure in mice. J Mol Endocrinol 2018; 60: 261–271.

[26] Leeners B, Geary N, Tobler PN, Asarian L. Ovarian hormones and obesity. Hum Reprod Update 2017; 23: 300–321.