Abstract
Withania somnifera (Ashwagandha) is one of the most renowned and revered medicinal plants in the Indian Ayurvedic system of medicine. Ashwagandha Rasayanas (tonics), capsules, tablets, and powdered herbs (churna) have been used for curing a wide variety of ailments, including reproductive problems, and for improving fertility in men and women as well as erectile dysfunction (ED) in men. Iron accumulation in reproductive organs is caused by excessive dietary intake of iron, dysregulation of iron transporters, chronic blood transfusions, and hemochromatosis. Iron overload produces oxidative stress and causes atrophy of ovaries and testes and hypogonadism, which leads to infertility in men and women. Emerging evidence from preclinical and clinical studies suggests that excessive iron-induced infertility results from dysfunction of the hypothalamic-pituitary-gonadal axis and consequently perturbs the secretion of sex hormones (GnRH, FSH, LH, estrogen, progesterone, and testosterone). The focus of this review is to summarize the pathophysiology of iron-overload toxicity of reproductive organs and the reversal of male/female infertility and libido with Ashwagandha. The bioactive ingredients of Ashwagandha appear to restore iron–overload infertility by acting on iron chelation and capturing iron free radicals (Fe+++) produced by the Fenton reaction. Many synthetic drugs have been tried for treating iron overload infertility, but the outcome has been inconsistent. Considering the high cost of these drugs, Ashwagandha may be a safer and more costeffective phytomedicine to cure iron-overload infertility and enhance libido in humans. Collectively, the iron chelation and antioxidant effects of Ashwagandha seem to reverse iron-overload infertility in men and women by improving testicular and ovarian functions.
[http://dx.doi.org/10.1042/BJ20101825] [PMID: 21348856]
[http://dx.doi.org/10.2527/2003.812503x] [PMID: 12643495]
[http://dx.doi.org/10.1111/j.1439-0272.1996.tb02795.x] [PMID: 8893095]
[http://dx.doi.org/10.1191/0960327103ht344oa] [PMID: 12774891]
[http://dx.doi.org/10.1007/s11033-008-9372-7] [PMID: 18846434]
[http://dx.doi.org/10.4103/1008-682X.122342] [PMID: 24369136]
[PMID: 23033214]
[http://dx.doi.org/10.1038/pr.2017.296] [PMID: 29166371]
[http://dx.doi.org/10.1002/ajh.22247] [PMID: 22213195]
[http://dx.doi.org/10.1002/pbc.21185] [PMID: 17427230]
[http://dx.doi.org/10.1016/j.brainresbull.2019.12.011] [PMID: 31866454]
[http://dx.doi.org/10.1056/NEJMra050436] [PMID: 16162884]
[http://dx.doi.org/10.1097/00043426-200311000-00011] [PMID: 14608198]
[http://dx.doi.org/10.1016/j.mce.2017.06.019] [PMID: 28648620]
[http://dx.doi.org/10.3390/biom9110735] [PMID: 31766246]
[http://dx.doi.org/10.1016/B978-0-12-818309-0.00010-1]
[http://dx.doi.org/10.4314/ajtcam.v8i5S.9] [PMID: 22754076]
[http://dx.doi.org/10.1016/j.jep.2020.113276] [PMID: 32818573]
[http://dx.doi.org/10.1016/S0378-8741(00)00348-2] [PMID: 11282435]
[http://dx.doi.org/10.1016/j.fertnstert.2009.04.046] [PMID: 19501822]
[http://dx.doi.org/10.1016/j.jep.2015.05.058] [PMID: 26068424]
[http://dx.doi.org/10.1016/j.pnpbp.2007.09.011] [PMID: 17959291]
[http://dx.doi.org/10.1016/j.sleep.2020.03.012] [PMID: 32540634]
[http://dx.doi.org/10.3746/pnf.2022.27.1.108] [PMID: 35465115]
[http://dx.doi.org/10.1016/j.jep.2020.112876] [PMID: 32305638]
[http://dx.doi.org/10.1016/j.jep.2009.08.003] [PMID: 19666100]
[http://dx.doi.org/10.1007/s10072-010-0245-1] [PMID: 20221655]
[http://dx.doi.org/10.2478/s11658-007-0015-0] [PMID: 17415533]
[http://dx.doi.org/10.1016/S0378-8741(00)00309-3] [PMID: 11137343]
[http://dx.doi.org/10.2174/1872213X1302191122124225] [PMID: 31814544]
[http://dx.doi.org/10.1016/j.semcancer.2020.05.011] [PMID: 32461153]
[http://dx.doi.org/10.1142/S0192415X13500705] [PMID: 24117067]
[http://dx.doi.org/10.3389/fnins.2014.00387] [PMID: 25506316]
[http://dx.doi.org/10.1016/j.neuint.2015.08.001] [PMID: 26257126]
[http://dx.doi.org/10.1038/s41420-021-00751-2] [PMID: 34782602]
[http://dx.doi.org/10.1016/j.rbmo.2017.11.007] [PMID: 29277366]
[http://dx.doi.org/10.1155/2013/571420] [PMID: 24371462]
[http://dx.doi.org/10.1155/2015/284154] [PMID: 26504795]
[http://dx.doi.org/10.1016/S0944-7113(00)80030-6] [PMID: 11194174]
[http://dx.doi.org/10.1097/MD.0000000000017186] [PMID: 31517876]
[http://dx.doi.org/10.4103/0975-9476.104444] [PMID: 23326093]
[http://dx.doi.org/10.3390/nu12020431] [PMID: 32046183]
[http://dx.doi.org/10.1155/2021/8254344] [PMID: 34858513]
[http://dx.doi.org/10.4103/0971-5916.154510] [PMID: 25857501]
[http://dx.doi.org/10.1093/humupd/dmr015] [PMID: 21493634]
[http://dx.doi.org/10.1016/j.beem.2010.08.006] [PMID: 21397198]
[http://dx.doi.org/10.1016/S0140-6736(20)32667-2] [PMID: 33308486]
[http://dx.doi.org/10.1007/s00018-019-03253-8] [PMID: 31377843]
[http://dx.doi.org/10.1016/j.neulet.2009.02.044] [PMID: 19429045]
[http://dx.doi.org/10.1007/s43032-021-00546-x] [PMID: 33763818]
[http://dx.doi.org/10.31887/DCNS.2018.20.1/klrooney] [PMID: 29946210]
[http://dx.doi.org/10.1002/fsn3.2523] [PMID: 34646552]
[http://dx.doi.org/10.1111/j.1365-2265.2005.02350.x] [PMID: 16181230]
[http://dx.doi.org/10.1210/jc.2003-032006] [PMID: 15126525]
[http://dx.doi.org/10.1210/jc.85.8.2670] [PMID: 10946864]
[http://dx.doi.org/10.1111/cob.12022] [PMID: 24163704]
[http://dx.doi.org/10.1111/jsm.12523] [PMID: 24712761]
[http://dx.doi.org/10.1016/j.arcmed.2021.03.006] [PMID: 33863580]
[http://dx.doi.org/10.1016/j.redox.2020.101726] [PMID: 32961443]
[http://dx.doi.org/10.1016/j.tox.2021.153050] [PMID: 34826546]
[http://dx.doi.org/10.1016/j.reprotox.2021.08.010] [PMID: 34481919]
[http://dx.doi.org/10.1136/bmj.316.7135.915] [PMID: 9552844]
[http://dx.doi.org/10.1002/9781118559406.ch19]
[http://dx.doi.org/10.1007/s11934-018-0808-x] [PMID: 29858708]
[http://dx.doi.org/10.1182/blood-2011-06-360271] [PMID: 21757620]
[http://dx.doi.org/10.1038/s41419-022-05037-8] [PMID: 35787614]
[http://dx.doi.org/10.5935/1518-0557.20210108] [PMID: 35234023]
[http://dx.doi.org/10.1080/10715760000300081] [PMID: 10625219]
[http://dx.doi.org/10.1016/j.juro.2008.01.103] [PMID: 18423706]
[http://dx.doi.org/10.1007/978-3-540-78355-8_18]
[http://dx.doi.org/10.1093/humrep/17.7.1820] [PMID: 12093845]
[http://dx.doi.org/10.1016/B978-0-12-815565-3.00015-1]
[http://dx.doi.org/10.7759/cureus.16006] [PMID: 34336497]
[http://dx.doi.org/10.26717/BJSTR.2020.24.004129]
[http://dx.doi.org/10.1080/14647273.2017.1342875] [PMID: 28643569]
[http://dx.doi.org/10.2147/IJWH.S89308] [PMID: 27660493]
[http://dx.doi.org/10.1016/j.aqrep.2015.08.005]
[http://dx.doi.org/10.1002/1099-1573(200006)14:4<288:AID-PTR603>3.0.CO;2-9] [PMID: 10861976]
[http://dx.doi.org/10.1016/j.bbrc.2020.10.064] [PMID: 33129445]
[http://dx.doi.org/10.3390/molecules14072373] [PMID: 19633611]
[PMID: 33489024]
[http://dx.doi.org/10.3892/ijmm.2018.3608] [PMID: 29620265]
[http://dx.doi.org/10.18632/oncotarget.10561] [PMID: 27418133]
[http://dx.doi.org/10.1371/journal.pone.0077189] [PMID: 24130852]
[http://dx.doi.org/10.1016/j.phymed.2015.10.003] [PMID: 26563851]
[http://dx.doi.org/10.3390/plants10122663] [PMID: 34961132]
[http://dx.doi.org/10.1515/jcim-2014-0039] [PMID: 25781716]
[http://dx.doi.org/10.5402/2012/957283]
[http://dx.doi.org/10.4103/0253-7613.150340] [PMID: 25821313]
[http://dx.doi.org/10.52711/2231-5659.2021-11-2-12]