Icariin, A Novel Promising Complementary Therapeutic Strategy In The Management Of Female Infertility: A Literature Review
DOI:
https://doi.org/10.31661/gmj.v12i.2528Keywords:
Icariin, Female Infertility, Female Reproductive SystemAbstract
The prevalence of pre-menopausal female infertility is increasing considerably due to various causes such as environmental pollutants, increased administration of chemotherapeutics and radiation exposure, microbial infections, and genetic/epigenetic alterations. However, the current therapeutical strategies remain unfavorite as the disadvantages are strongly challenging. Icariin (ICI) is a phytoestrogen that exerts some promising properties in order to alleviate female infertility. Therefore, the current literature review aimed to evaluate the conducted studies regarding the beneficial impacts of ICI on the female reproductive system and female fecundity. The findings of the present study revealed that ICI is able to modulate the levels of reproductive hormones as it causes a significant decrement in the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) while increasing the levels of estrogen and progesterone. Furthermore, the administration of ICI results in a dramatic alteration in the expression of sex steroids’ receptors, particularly in female reproductive tissues. In addition, preserving ovarian follicular reserve, improving the ovarian and uterine histoarchitecture, elongating the estrous cycle duration, and eventually advancing the female fecundity are other major effects of ICI on the female reproductive system. Despite these desired beneficial properties, the current knowledge appears to be insufficient, hence further investigations, particularly on humans, are encouraged. To the best of our knowledge, this review provides a comprehensive information regarding the beneficial effects of Icariin on female infertility for the firs time
References
Feng J, Wang J, Zhang Y, Zhang Y, Jia L, Zhang D et al. The efficacy of complementary and alternative medicine in the treatment of female infertility. Evid Based Complement Alternat Med. 2021;2021.
https://doi.org/10.1155/2021/6634309
PMid:33986820 PMCid:PMC8093064
Liao Y-H, Lin J-G, Lin C-C, Tsai C-C, Lai H-L, Li T-C. Traditional Chinese medicine treatment associated with female infertility in Taiwan: a population-based case-control study. Evid Based Complement Alternat Med. 2020;2020.
https://doi.org/10.1155/2020/3951741
PMid:33381200 PMCid:PMC7749771
Pradhan MR, Patel SK, Patel S. Risk Factors and spatial clustering of primary infertility in India. J infertil reprod biol. 2021;9(1):27-34.
Jafari Khorchani M, Samare-Najaf M, Abbasi A, Vakili S, Zal F. Effects of quercetin, vitamin E, and estrogen on Metabolic-Related factors in uterus and serum of ovariectomized rat models. Gynecol Endocrinol. 2021;37(8):764-8.
https://doi.org/10.1080/09513590.2021.1879784
PMid:33525940
Rahbar A, Abbasi M. A brief clinical overview of etiological factors in infertility. J infertil reprod biol. 2020;8(1):6-8.
https://doi.org/10.47277/JIRB/8(1)/6
Jamali N, Zal F, Mostafavi-Pour Z, Samare-Najaf M, Poordast T, Dehghanian A. Ameliorative effects of quercetin and metformin and their combination against experimental endometriosis in rats. Reprod Sci. 2021;28(3):683-92.
https://doi.org/10.1007/s43032-020-00377-2
PMid:33141412
Bhardwaj JK, Mittal M, Saraf P, Kumari P. Pesticides induced oxidative stress and female infertility: a review. Toxin Reviews. 2018; 2;39(1):1-3.
https://doi.org/10.1080/15569543.2018.1474926
Soleimani A. Environmental Pollution: a Risk Factor for Female Fertility-A Letter to Editor. J infertil reprod biol. 2020;8(4):66-7.
Samare-Najaf M, Samareh A, Jamali N, Abbasi A, Clark CC, Khorchani MJ et al. Adverse Effects and Safety of Etirinotecan Pegol, a Novel Topoisomerase Inhibitor, in Cancer Treatment: A Systematic Review. Curr Cancer Ther Rev. 2021;17(3):234-43.
https://doi.org/10.2174/1573394717666210202103502
Samare-Najaf M, Zal F, Safari S. Primary and secondary markers of doxorubicin-induced female infertility and the alleviative properties of quercetin and vitamin E in a rat model. Reprod Toxicol. 2020;96:316-26.
https://doi.org/10.1016/j.reprotox.2020.07.015
PMid:32810592
Bala R, Singh V, Rajender S, Singh K. Environment, lifestyle, and female infertility. Reprod Sci. 2021;28(3):617-38.
https://doi.org/10.1007/s43032-020-00279-3
PMid:32748224
Kahyaoglu S, Gulsen P, Gurbuz O, Kose C, Kahyaoglu I, Gulerman HC et al. Emotional Stress Lowers Follicular Output Rate (FORT) of Unexplained Infertile or Poor Responder Women unlike Women with Male Infertility without any Prognostic Effect on Cycle Outcomes during Ovulation Induction for In Vitro Fertilization. J infertil reprod biol. 2021;9(3):109-16.
Emokpae MA, Eromosele CO, Ajibade HO. Alterations in Lipid Profile and Indices of Atherogenicity among Infertile Women Seeking Conception by Assisted Reproductive Technology. J infertil reprod biol. 2020;8(3):61-5.
Bhardwaj JK, Panchal H, Saraf P. Ameliorating effects of natural antioxidant compounds on female infertility: a review. Reprod Sci. 2021;28(5):1227-56.
https://doi.org/10.1007/s43032-020-00312-5
PMid:32935256
Tiwari K, Batra S, Tanwar R, Prasad S. Comparison of Molecular Test with Hystero-Laparoscopy in Detection of Genital Tuberculosis amongst Women with Infertility. J infertil reprod biol. 2021;9(2):105-8.
Gao J, Fu Y, Song L, Long M, Zhang Y, Qin J et al. Proapoptotic Effect of Icariin on Human Ovarian Cancer Cells via the NF-κ B/PI3K-AKT Signaling Pathway: A Network Pharmacology-Directed Experimental Investigation. The American Journal of Chinese Medicine. 2022;50(02):589-619.
https://doi.org/10.1142/S0192415X22500239
PMid:35114909
Song T, Yang J, Liu P, Liu M, Li D, Xiao Y et al. Icariin self-crosslinked network functionalized strontium-doped bioceramic scaffolds synergistically enhanced the healing of osteoporotic bone defects. Composites Part B: Engineering. 2022;235:109759.
https://doi.org/10.1016/j.compositesb.2022.109759
Yuan J-y, Tong Z-y, Dong Y-c, Zhao J-y, Shang Y. Research progress on icariin, a traditional Chinese medicine extract, in the treatment of asthma. Allergol Immunopathol (Madr). 2022;50(1):9-16.
https://doi.org/10.15586/aei.v50i1.490
PMid:34873891
Zeng Y, Xiong Y, Yang T, Wang Y, Zeng J, Zhou S et al. Icariin and its metabolites as potential protective phytochemicals against cardiovascular disease: from effects to molecular mechanisms. Biomed Pharmacother. 2022;147:112642.
https://doi.org/10.1016/j.biopha.2022.112642
PMid:35078094
Mikhael S, Punjala-Patel A, Gavrilova-Jordan L. Hypothalamic-pituitary-ovarian axis disorders impacting female fertility. Biomedicines. 2019;7(1):5.
https://doi.org/10.3390/biomedicines7010005
PMid:30621143 PMCid:PMC6466056
Da Broi MG, Ferriani RA, Navarro PA. Ethiopathogenic mechanisms of endometriosis-related infertility. JBRA Assisted Reproduction. 2019;23(3):273.
https://doi.org/10.5935/1518-0557.20190029
PMid:31091056 PMCid:PMC6724396
Smith OE, Roussel V, Morin F, Ongaro L, Zhou X, Bertucci MC et al. Steroidogenic factor 1 regulation of the hypothalamic-pituitary-ovarian axis of adult female mice. Endocrinology. 2022;163(4):bqac028.
https://doi.org/10.1210/endocr/bqac028
PMid:35247045
Al Abdali FH, Gowri V. The Etiology of Infertility and Treatment Outcome in Couples Aged 40 Years or more in a Non-IVF Setting. J infertil reprod biol. 2021;9(2):87-92.
Zheng X, Liu W, Liu J, Zhang C, Zhang L, Gao F et al. Dietary supplementation with icariin affects estrogen synthesis, vitellogenesis, and oocyte development in the Chinese mitten crab, Eriocheir sinensis. Front Mar Sci. 2020;7:161.
https://doi.org/10.3389/fmars.2020.00161
Nie X, Sheng W, Hou D, Liu Q, Wang R, Tan Y. Effect of Hyperin and Icariin on steroid hormone secretion in rat ovarian granulosa cells. Clin Chim Acta. 2019;495:646-51.
https://doi.org/10.1016/j.cca.2018.05.004
PMid:29729232
Kang HK, Lee S-B, Kwon H, Sung CK, Park YI, Dong M-S. Peripubertal administration of icariin and icaritin advances pubertal development in female rats. Biomol Ther (Seoul). 2012;20(2):189.
https://doi.org/10.4062/biomolther.2012.20.2.189
PMid:24116294 PMCid:PMC3792217
Lin J, Wu D, Jia L, Liang M, Liu S, Qin Z et al. The treatment of complementary and alternative medicine on premature ovarian failure. Evid Based Complement Alternat Med. 2021;2021.
https://doi.org/10.1155/2021/6677767
PMid:33936242 PMCid:PMC8062183
Shareghi-Oskoue O, Aghebati-Maleki L, Yousefi M. Transplantation of human umbilical cord mesenchymal stem cells to treat premature ovarian failure. Stem Cell Res Ther. 2021;12(1):1-13.
https://doi.org/10.1186/s13287-021-02529-w
PMid:34380572 PMCid:PMC8359553
Li N, Wang J, Wang X, Sun J, Li Z. Icariin exerts a protective effect against d-galactose induced premature ovarian failure via promoting DNA damage repair. Biomed Pharmacother. 2019;118:109218.
https://doi.org/10.1016/j.biopha.2019.109218
PMid:31330441
Ata B, Seyhan A, Seli E. Diminished ovarian reserve versus ovarian aging: overlaps and differences. Curr Opin Obstet Gynecol. 2019;31(3):139-47.
https://doi.org/10.1097/GCO.0000000000000536
PMid:30870184
Chiang JL, Shukla P, Pagidas K, Ahmed NS, Karri S, Gunn DD et al. Mitochondria in ovarian aging and reproductive longevity. Ageing Res Rev. 2020;63:101168.
https://doi.org/10.1016/j.arr.2020.101168
PMid:32896666 PMCid:PMC9375691
Uysal F, Ozturk S. The loss of global DNA methylation due to decreased DNMT expression in the postnatal mouse ovaries may associate with infertility emerging during ovarian aging. Histochem Cell Biol. 2020;154(3):301-14.
https://doi.org/10.1007/s00418-020-01890-w
PMid:32514790
Wang J-L, Liu B, Zhang C, Wang X-M, Zhen D, Huang X-M et al. Effects of icariin on ovarian function in d-galactose-induced aging mice. Theriogenology. 2019;125:157-67.
https://doi.org/10.1016/j.theriogenology.2018.10.028
PMid:30447495
Cao L-H, Qiao J-Y, Huang H-Y, Fang X-Y, Zhang R, Miao M-S et al. PI3K-AKT signaling activation and icariin: the potential effects on the perimenopausal depression-like rat model. Molecules. 2019;24(20):3700.
https://doi.org/10.3390/molecules24203700
PMid:31618892 PMCid:PMC6832648
Zhou L, Poon CC-W, Wong K-Y, Cao S, Yu W, Dong X et al. Prenylflavonoid Icariin Induces Estrogen Response Element-Independent Estrogenic Responses in a Tissue-Selective Manner. J Endocr Soc. 2020;4(2):bvz025.
https://doi.org/10.1210/jendso/bvz025
PMid:32051921 PMCid:PMC7007805
Fuentes N, Silveyra P. Estrogen receptor signaling mechanisms. Adv Protein Chem Struct Biol. 2019;116:135-70.
https://doi.org/10.1016/bs.apcsb.2019.01.001
PMid:31036290 PMCid:PMC6533072
Kayo D, Zempo B, Tomihara S, Oka Y, Kanda S. Gene knockout analysis reveals essentiality of estrogen receptor β1 (Esr2a) for female reproduction in medaka. Sci Rep. 2019;9(1):1-11.
https://doi.org/10.1038/s41598-019-45373-y
PMid:31222039 PMCid:PMC6586646
Robert H, Ferguson L, Reins O, Greco T, Prins ML, Folkerts M. Rodent Estrous Cycle Monitoring utilizing Vaginal Lavage: No Such Thing As a Normal Cycle. JoVE (Journal of Visualized Experiments). 2021(174):e62884.
PMCid:PMC9888307
Medina-Laver Y, RodrÃguez-Varela C, Salsano S, Labarta E, DomÃnguez F. What do we know about classical and non-classical progesterone receptors in the human female reproductive tract? A review. Int J Mol Sci. 2021;22(20):11278.
https://doi.org/10.3390/ijms222011278
PMid:34681937 PMCid:PMC8538361
Xue L, Wang Y, Jiang Y, Han T, Nie Y, Zhao L et al. Comparative effects of er-xian decoction, epimedium herbs, and icariin with estrogen on bone and reproductive tissue in ovariectomized rats. Evid Based Complement Alternat Med. 2012;2012.
https://doi.org/10.1155/2012/241416
PMid:23227099 PMCid:PMC3511842
Dawood TN, Al-Araj AS, Abood DA. Stereological and Histopathological Effects of Trigonella foenum-graecum Seeds on Rabbits Ovary. Iraqi J Vet Med. 2020;44(E0)):28-32.
https://doi.org/10.30539/ijvm.v44i(E0).1016
Sakifard N, Fazelipour S, Davoudi P, Tootian Z, Sheibani MT. Stereological and functional study on ovarian follicles in surri mice following soybean consumption. Comp Clin Path. 2022:1-10.
https://doi.org/10.1007/s00580-022-03362-0
Samare-Najaf M, Zal F, Safari S, Koohpeyma F, Jamali N. Stereological and histopathological evaluation of doxorubicin-induced toxicity in female rats' ovary and uterus and palliative effects of quercetin and vitamin E. Hum Exp Toxicol. 2020;39(12):1710-24.
https://doi.org/10.1177/0960327120937329
PMid:32666839
Ghahremani-Nasab M, Ghanbari E, Jahanbani Y, Mehdizadeh A, Yousefi M. Premature ovarian failure and tissue engineering. J Cell. Physiol. 2020;235(5):4217-26.
https://doi.org/10.1002/jcp.29376
PMid:31663142
Ishizuka B. Current understanding of the etiology, symptomatology, and treatment options in premature ovarian insufficiency (POI). Front Endocrinol (Lausanne). 2021;12:626924.
https://doi.org/10.3389/fendo.2021.626924
PMid:33716979 PMCid:PMC7949002
Li X, Luan T, Zhao C, Zhang M, Dong L, Su Y et al. Effect of sildenafil citrate on treatment of infertility in women with a thin endometrium: a systematic review and meta-analysis. J Int Med Res. 2020;48(11):0300060520969584.
https://doi.org/10.1177/0300060520969584
PMid:33176524 PMCid:PMC7673063
Ranisavljevic N, Raad J, Anahory T, Grynberg M, Sonigo C. Embryo transfer strategy and therapeutic options in infertile patients with thin endometrium: a systematic review. J Assist Reprod Genet. 2019;36(11):2217-31.
https://doi.org/10.1007/s10815-019-01576-w
PMid:31502111 PMCid:PMC6885488
Le A, Wang Z, Dai X, Xiao T, Zhuo R, Zhang B et al. An experimental study on the use of icariin for improving thickness of thin endometrium. Genet Mol Res. 2017;16(1).
https://doi.org/10.4238/gmr16019126
PMid:28128406
Nian H, Ma M-H, Nian S-S, Xu L-L. Antiosteoporotic activity of icariin in ovariectomized rats. Phytomedicine. 2009;16(4):320-6.
https://doi.org/10.1016/j.phymed.2008.12.006
PMid:19269147
OrÅ¡olić N, Nemrava J, JeleÄ Å½, Kukolj M, Odeh D, Terzić S et al. The beneficial effect of proanthocyanidins and icariin on biochemical markers of bone turnover in rats. Int J Mol Sci. 2018;19(9):2746.
https://doi.org/10.3390/ijms19092746
PMid:30217029 PMCid:PMC6163320
Corbett CM, Dunn E, Loweth JA. Effects of sex and estrous cycle on the time course of incubation of cue-induced craving following extended-access cocaine self-administration. ENeuro. 2021;8(4).
https://doi.org/10.1523/ENEURO.0054-21.2021
PMid:34290059 PMCid:PMC8362687
Inoue S. Neural basis for estrous cycle-dependent control of female behaviors. Neurosci Res. 2022;176:1-8.
https://doi.org/10.1016/j.neures.2021.07.001
PMid:34331974
Chen H, Song L, Xu X, Han Z, Peng F, Zhang Q et al. The effect of icariin on autoimmune premature ovarian insufficiency via modulation of Nrf2/HO-1/Sirt1 pathway in mice. Reprod Biol. 2022;22(2):100638.
https://doi.org/10.1016/j.repbio.2022.100638
PMid:35344846
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