Login Register Cart 0
Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Iron Chelation and Antioxidant Properties of Withania somnifera (Ashwagandha) Restore Fertility in Men and Women

Author(s): Ruchira Joshi, Pratik Yadav, Siddhi Bagwe-Parab, Hardeep Singh Tuli*, Harpal Singh Buttar and Ginpreet Kaur*

Volume 19, Issue 7, 2023

Published on: 28 April, 2023

Article ID: e100223213568 Pages: 12

DOI: 10.2174/1573407219666230210101925

Open Access Journals Promotions 2
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.

Keywords: Ashwagandha, iron-overload infertility, hypogonadism, iron chelation, antioxidant, phytomedicine.

[1]
Wang, J.; Pantopoulos, K. Regulation of cellular iron metabolism. Biochem. J., 2011, 434(3), 365-381.
[http://dx.doi.org/10.1042/BJ20101825] [PMID: 21348856]
[2]
Wise, T.; Lunstra, D.D.; Rohrer, G.A.; Ford, J.J. Relationships of testicular iron and ferritin concentrations with testicular weight and sperm production in boars12. J. Anim. Sci., 2003, 81(2), 503-511.
[http://dx.doi.org/10.2527/2003.812503x] [PMID: 12643495]
[3]
Merker, H.J.; Vormann, J.; Günther, T. Iron-induced injury of rat testis. Andrologia, 1996, 28(5), 267-273.
[http://dx.doi.org/10.1111/j.1439-0272.1996.tb02795.x] [PMID: 8893095]
[4]
De Lourdes Pereira, M.; Costa, F.G. Spermatogenesis recovery in the mouse after iron injury. Hum. Exp. Toxicol., 2003, 22(5), 275-279.
[http://dx.doi.org/10.1191/0960327103ht344oa] [PMID: 12774891]
[5]
Gunel-Ozcan, A.; Basar, M.M. Kısa, U.; Ankaralı, H.C. Hereditary haemochromatosis gene (HFE) H63D mutation shows an association with abnormal sperm motility. Mol. Biol. Rep., 2009, 36(7), 1709-1714.
[http://dx.doi.org/10.1007/s11033-008-9372-7] [PMID: 18846434]
[6]
Anderson, D.; Schmid, T.; Baumgartner, A. Male-mediated developmental toxicity. Asian J. Androl., 2014, 16(1), 81-88.
[http://dx.doi.org/10.4103/1008-682X.122342] [PMID: 24369136]
[7]
Uitz, P.M.; Hartleb, S.; Schaefer, S.; Al-Fakhri, N.; Kann, P.H. Pituitary function in patients with hereditary haemochromatosis. Horm. Metab. Res., 2013, 45(1), 54-61.
[PMID: 23033214]
[8]
Chen, M.J.; Peng, S.S.F.; Lu, M.Y.; Yang, Y.L.; Jou, S.T.; Chang, H.H.; Chen, S.U.; Lin, D.T.; Lin, K.H. Effect of iron overload on impaired fertility in male patients with transfusion-dependent beta-thalassemia. Pediatr. Res., 2018, 83(3), 655-661.
[http://dx.doi.org/10.1038/pr.2017.296] [PMID: 29166371]
[9]
Noetzli, L.J.; Panigrahy, A.; Mittelman, S.D.; Hyderi, A.; Dongelyan, A.; Coates, T.D.; Wood, J.C. Pituitary iron and volume predict hypogonadism in transfusional iron overload. Am. J. Hematol., 2012, 87(2), 167-171.
[http://dx.doi.org/10.1002/ajh.22247] [PMID: 22213195]
[10]
Chern, J.P.S. Lin, K.H.; Lu, M.Y.; Lin, D.T.; Jou, S.T.; Yang, Y.L.; Chang, H.H.; Su, S.; Lin, K.S. β-Thalassemia major births after national screening program in taiwan. Pediatr. Blood Cancer, 2008, 50(1), 58-61.
[http://dx.doi.org/10.1002/pbc.21185] [PMID: 17427230]
[11]
Bagwe-Parab, S.; Kaur, G. Molecular targets and therapeutic interventions for iron induced neurodegeneration. Brain Res. Bull., 2020, 156, 1-9.
[http://dx.doi.org/10.1016/j.brainresbull.2019.12.011] [PMID: 31866454]
[12]
Rund, D. Rachmilewitz, E. β-. Thalassemia. N. Engl. J. Med., 2005, 353(11), 1135-1146.
[http://dx.doi.org/10.1056/NEJMra050436] [PMID: 16162884]
[13]
Chern, J.P.S.; Lin, K.H.; Tsai, W.Y.; Wang, S.C.; Lu, M.Y.; Lin, D.T.; Lin, K.S.; Lo, S.H. Hypogonadotropic hypogonadism and hematologic phenotype in patients with transfusion-dependent beta-thalassemia. J. Pediatr. Hematol. Oncol., 2003, 25(11), 880-884.
[http://dx.doi.org/10.1097/00043426-200311000-00011] [PMID: 14608198]
[14]
Macchi, C.; Steffani, L.; Oleari, R.; Lettieri, A.; Valenti, L.; Dongiovanni, P.; Romero-Ruiz, A.; Tena-Sempere, M.; Cariboni, A.; Magni, P.; Ruscica, M. Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms. Mol. Cell. Endocrinol., 2017, 454, 135-145.
[http://dx.doi.org/10.1016/j.mce.2017.06.019] [PMID: 28648620]
[15]
Aggarwal, V.; Tuli, H.; Varol, A.; Thakral, F.; Yerer, M.; Sak, K.; Varol, M.; Jain, A.; Khan, M.; Sethi, G. Role of reactive oxygen species in cancer progression: Molecular mechanisms and recent advancements. Biomolecules, 2019, 9(11), 735.
[http://dx.doi.org/10.3390/biom9110735] [PMID: 31766246]
[16]
Dillard, D.M. Phytotherapeutic support for infertility: Evaluating the evidence. In: Fertility, Pregnancy, and Wellness; Elsevier Amsterdam, 2022, pp. 281-292.
[http://dx.doi.org/10.1016/B978-0-12-818309-0.00010-1]
[17]
Singh, N.; Bhalla, M.; De Jager, P.; Gilca, M. An overview on Ashwagandha: A Rasayana (rejuvenator) of Ayurveda. Afr. J. Tradit. Complement. Altern. Med., 2011, 8(5S)(Suppl.), 208-213.
[http://dx.doi.org/10.4314/ajtcam.v8i5S.9] [PMID: 22754076]
[18]
Umadevi, M. Traditional and medicinal uses of Withania somnifera. Pharma Innov., 2012, 1(9, Part A), 102.
[19]
Langade, D.; Thakare, V.; Kanchi, S.; Kelgane, S. Clinical evaluation of the pharmacological impact of Ashwagandha root extract on sleep in healthy volunteers and insomnia patients: A double-blind, randomized, parallel-group, placebo-controlled study. J. Ethnopharmacol., 2021, 264, 113276.
[http://dx.doi.org/10.1016/j.jep.2020.113276] [PMID: 32818573]
[20]
Abdel-Magied, E.M.; Abdel-Rahman, H.A.; Harraz, F.M. The effect of aqueous extracts of Cynomorium coccineum and Withania somnifera on testicular development in immature Wistar rats. J. Ethnopharmacol., 2001, 75(1), 1-4.
[http://dx.doi.org/10.1016/S0378-8741(00)00348-2] [PMID: 11282435]
[21]
Ahmad, M.K.; Mahdi, A.A.; Shukla, K.K.; Islam, N.; Rajender, S.; Madhukar, D.; Shankhwar, S.N.; Ahmad, S. Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males. Fertil. Steril., 2010, 94(3), 989-996.
[http://dx.doi.org/10.1016/j.fertnstert.2009.04.046] [PMID: 19501822]
[22]
Candelario, M.; Cuellar, E.; Reyes-Ruiz, J.M.; Darabedian, N.; Feimeng, Z.; Miledi, R.; Russo-Neustadt, A.; Limon, A. Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors. J. Ethnopharmacol., 2015, 171, 264-272.
[http://dx.doi.org/10.1016/j.jep.2015.05.058] [PMID: 26068424]
[23]
Kulkarni, S.K.; Dhir, A. Withania somnifera: An Indian ginseng. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2008, 32(5), 1093-1105.
[http://dx.doi.org/10.1016/j.pnpbp.2007.09.011] [PMID: 17959291]
[24]
Deshpande, A.; Irani, N.; Balkrishnan, R.; Benny, I.R. A randomized, double blind, placebo controlled study to evaluate the effects of Ashwagandha (Withania somnifera) extract on sleep quality in healthy adults. Sleep Med., 2020, 72, 28-36.
[http://dx.doi.org/10.1016/j.sleep.2020.03.012] [PMID: 32540634]
[25]
Murthy, S.V.; Fathima, S.N.; Mote, R. Hydroalcoholic extract of Ashwagandha improves sleep by modulating GABA/histamine receptors and EEG slow-wave pattern in in vitro-in vivo experimental models. Prev. Nutr. Food Sci., 2022, 27(1), 108-120.
[http://dx.doi.org/10.3746/pnf.2022.27.1.108] [PMID: 35465115]
[26]
Zahiruddin, S.; Basist, P.; Parveen, A.; Parveen, R.; Khan, W. Gaurav; Ahmad, S. Ashwagandha in brain disorders: A review of recent developments. J. Ethnopharmacol., 2020, 257, 112876.
[http://dx.doi.org/10.1016/j.jep.2020.112876] [PMID: 32305638]
[27]
RajaSankar. S.; Manivasagam, T.; Sankar, V.; Prakash, S.; Muthusamy, R.; Krishnamurti, A.; Surendran, S. Withania somnifera root extract improves catecholamines and physiological abnormalities seen in a Parkinson’s disease model mouse. J. Ethnopharmacol., 2009, 125(3), 369-373.
[http://dx.doi.org/10.1016/j.jep.2009.08.003] [PMID: 19666100]
[28]
Surendran, S.; Rajasankar, S. Parkinson’s disease: Oxidative stress and therapeutic approaches. Neurol. Sci., 2010, 31(5), 531-540.
[http://dx.doi.org/10.1007/s10072-010-0245-1] [PMID: 20221655]
[29]
Sankar, S.; Manivasagam, T.; Krishnamurti, A.; Ramanathan, M. The neuroprotective effect of Withania somnifera root extract in MPTP-intoxicated mice: An analysis of behavioral and biochemical varibles. Cell. Mol. Biol. Lett., 2007, 12(4), 473-481.
[http://dx.doi.org/10.2478/s11658-007-0015-0] [PMID: 17415533]
[30]
Bhattacharya, A.; Ghosal, S.; Bhattacharya, S.K. Anti-oxidant effect of Withania somnifera glycowithanolides in chronic footshock stress-induced perturbations of oxidative free radical scavenging enzymes and lipid peroxidation in rat frontal cortex and striatum. J. Ethnopharmacol., 2001, 74(1), 1-6.
[http://dx.doi.org/10.1016/S0378-8741(00)00309-3] [PMID: 11137343]
[31]
Tuli, H.S.; Sharma, A.; Thakur, A. Natural moieties as anti-inflammatory agents-recent patents. Recent Pat. Inflamm. Allergy Drug Discov., 2019, 13(2), 83-83.
[http://dx.doi.org/10.2174/1872213X1302191122124225] [PMID: 31814544]
[32]
Aggarwal, V. Molecular mechanisms of action of epigallocatechin gallate in cancer: Recent trends and advancement. Semin. Cancer Biol., 2020.
[http://dx.doi.org/10.1016/j.semcancer.2020.05.011] [PMID: 32461153]
[33]
Singh, D.; Sood, Y.; Rani, N.; Kaur, G. Review on Ashwagandha: A wonder plant 2022. Available from: https://easychair.org/publications/preprint/QWgf
[34]
Yin, H.; Cho, D.H.; Park, S.J.; Han, S.K. GABA-mimetic actions of Withania somnifera on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice. Am. J. Chin. Med., 2013, 41(5), 1043-1051.
[http://dx.doi.org/10.1142/S0192415X13500705] [PMID: 24117067]
[35]
Watanabe, M.; Fukuda, A.; Nabekura, J. The role of GABA in the regulation of GnRH neurons. Front. Neurosci., 2014, 8, 387.
[http://dx.doi.org/10.3389/fnins.2014.00387] [PMID: 25506316]
[36]
Kataria, H.; Gupta, M.; Lakhman, S.; Kaur, G. Withania somnifera aqueous extract facilitates the expression and release of GnRH: In vitro and in vivo study. Neurochem. Int., 2015, 89, 111-119.
[http://dx.doi.org/10.1016/j.neuint.2015.08.001] [PMID: 26257126]
[37]
Kadam, P.D. Efficacy of neem seed extract ± Ashwagandha for the treatment of endometritis in buffaloes. Indian J. Anim. Reprod., 2019, 40, 38-41.
[38]
Li, S.; Zhou, Y.; Huang, Q.; Fu, X.; Zhang, L.; Gao, F.; Jin, Z.; Wu, L.; Shu, C.; Zhang, X.; Xu, W.; Shu, J. Iron overload in endometriosis peritoneal fluid induces early embryo ferroptosis mediated by HMOX1. Cell Death Discov., 2021, 7(1), 355.
[http://dx.doi.org/10.1038/s41420-021-00751-2] [PMID: 34782602]
[39]
Sengupta, P.; Agarwal, A.; Pogrebetskaya, M.; Roychoudhury, S.; Durairajanayagam, D.; Henkel, R. Role of Withania somnifera (Ashwagandha) in the management of male infertility. Reprod. Biomed. Online, 2018, 36(3), 311-326.
[http://dx.doi.org/10.1016/j.rbmo.2017.11.007] [PMID: 29277366]
[40]
Ambiye, V.R.; Langade, D.; Dongre, S.; Aptikar, P.; Kulkarni, M.; Dongre, A. Clinical evaluation of the spermatogenic activity of the root extract of Ashwagandha (Withania somnifera) in oligospermic males: A pilot study. Evid. Based Complement. Alternat. Med., 2013, 2013, 1-6.
[http://dx.doi.org/10.1155/2013/571420] [PMID: 24371462]
[41]
Dhamal, P.S.; Patil, M.L. Case study on successful ayurvedic management of male infertility (Oligoasthenozoospermia). Int. J. Ayurveda, 2021, 6.
[42]
Dongre, S.; Langade, D.; Bhattacharyya, S. Efficacy and Safety of Ashwagandha (Withania somnifera) root extract in improving sexual function in women: A pilot study. BioMed Res. Int., 2015, 2015, 1-9.
[http://dx.doi.org/10.1155/2015/284154] [PMID: 26504795]
[43]
Bhattacharya, S.K.; Bhattacharya, A.; Sairam, K.; Ghosal, S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: An experimental study. Phytomedicine, 2000, 7(6), 463-469.
[http://dx.doi.org/10.1016/S0944-7113(00)80030-6] [PMID: 11194174]
[44]
Lopresti, A.L.; Smith, S.J.; Malvi, H.; Kodgule, R. An investigation into the stress-relieving and pharmacological actions of an Ashwagandha (Withania somnifera) extract. Medicine (Baltimore), 2019, 98(37), e17186.
[http://dx.doi.org/10.1097/MD.0000000000017186] [PMID: 31517876]
[45]
Shenoy, S.; Chaskar, U.; Sandhu, J.; Paadhi, M. Effects of eight-week supplementation of Ashwagandha on cardiorespiratory endurance in elite Indian cyclists. J. Ayurveda Integr. Med., 2012, 3(4), 209-214.
[http://dx.doi.org/10.4103/0975-9476.104444] [PMID: 23326093]
[46]
Lee, D.H.; Ahn, J.; Jang, Y.J.; Seo, H.D.; Ha, T.Y.; Kim, M.J.; Huh, Y.H.; Jung, C.H. Withania somnifera extract enhances energy expenditure via improving mitochondrial function in adipose tissue and skeletal muscle. Nutrients, 2020, 12(2), 431.
[http://dx.doi.org/10.3390/nu12020431] [PMID: 32046183]
[47]
Gopukumar, K.; Thanawala, S.; Somepalli, V.; Rao, T.S.S.; Thamatam, V.B.; Chauhan, S. Efficacy and safety of Ashwagandha root extract on cognitive functions in healthy, stressed adults: a randomized, double-blind, placebo-controlled study. Evid. Based Complement. Alternat. Med., 2021, 2021, 1-10.
[http://dx.doi.org/10.1155/2021/8254344] [PMID: 34858513]
[48]
Gupta, Y.K.; Srivastava, A.; Sharma, S.; Kumar, G.; Rao, T.D. Efficacy & safety evaluation of Ayurvedic treatment (Ashwagandha powder & Sidh Makardhwaj) in rheumatoid arthritis patients: A pilot prospective study. Indian J. Med. Res., 2015, 141(1), 100-106.
[http://dx.doi.org/10.4103/0971-5916.154510] [PMID: 25857501]
[49]
Gurunath, S.; Pandian, Z.; Anderson, R.A.; Bhattacharya, S. Defining infertility-A systematic review of prevalence studies. Hum. Reprod. Update, 2011, 17(5), 575-588.
[http://dx.doi.org/10.1093/humupd/dmr015] [PMID: 21493634]
[50]
Krausz, C. Male infertility: Pathogenesis and clinical diagnosis. Best Pract. Res. Clin. Endocrinol. Metab., 2011, 25(2), 271-285.
[http://dx.doi.org/10.1016/j.beem.2010.08.006] [PMID: 21397198]
[51]
Agarwal, A.; Baskaran, S.; Parekh, N.; Cho, C.L.; Henkel, R.; Vij, S.; Arafa, M.; Panner Selvam, M.K.; Shah, R. Male infertility. Lancet, 2021, 397(10271), 319-333.
[http://dx.doi.org/10.1016/S0140-6736(20)32667-2] [PMID: 33308486]
[52]
Barati, E.; Nikzad, H.; Karimian, M. Oxidative stress and male infertility: Current knowledge of pathophysiology and role of antioxidant therapy in disease management. Cell. Mol. Life Sci., 2020, 77(1), 93-113.
[http://dx.doi.org/10.1007/s00018-019-03253-8] [PMID: 31377843]
[53]
RajaSankar. S.; Manivasagam, T.; Surendran, S. Ashwagandha leaf extract: A potential agent in treating oxidative damage and physiological abnormalities seen in a mouse model of Parkinson’s disease. Neurosci. Lett., 2009, 454(1), 11-15.
[http://dx.doi.org/10.1016/j.neulet.2009.02.044] [PMID: 19429045]
[54]
Naumova, I.; Castelo-Branco, C.; Casals, G. Psychological issues and sexual function in women with different infertility causes: Focus on polycystic ovary syndrome. Reprod. Sci., 2021, 28(10), 2830-2838.
[http://dx.doi.org/10.1007/s43032-021-00546-x] [PMID: 33763818]
[55]
Rooney, K.L.; Domar, A.D. The relationship between stress and infertility. Dialogues Clin. Neurosci., 2018, 20(1), 41-47.
[http://dx.doi.org/10.31887/DCNS.2018.20.1/klrooney] [PMID: 29946210]
[56]
Akbaribazm, M.; Goodarzi, N.; Rahimi, M. Female infertility and herbal medicine: An overview of the new findings. Food Sci. Nutr., 2021, 9(10), 5869-5882.
[http://dx.doi.org/10.1002/fsn3.2523] [PMID: 34646552]
[57]
Jurakulova, Akhmatovna Zebiniso Current issues of infertility diagnosis and treatment in women with internal genital endometriosis. Synergy: J. Ethics. Governance, 2021, 1(6), 77-84.
[58]
Isidori, A.M.; Giannetta, E.; Gianfrilli, D.; Greco, E.A.; Bonifacio, V.; Aversa, A.; Isidori, A.; Fabbri, A.; Lenzi, A. Effects of testosterone on sexual function in men: Results of a meta-analysis. Clin. Endocrinol. (Oxf.), 2005, 63(4), 381-394.
[http://dx.doi.org/10.1111/j.1365-2265.2005.02350.x] [PMID: 16181230]
[59]
Wang, C.; Cunningham, G.; Dobs, A.; Iranmanesh, A.; Matsumoto, A.M.; Snyder, P.J.; Weber, T.; Berman, N.; Hull, L.; Swerdloff, R.S. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J. Clin. Endocrinol. Metab., 2004, 89(5), 2085-2098.
[http://dx.doi.org/10.1210/jc.2003-032006] [PMID: 15126525]
[60]
Snyder, P.J.; Peachey, H.; Berlin, J.A.; Hannoush, P.; Haddad, G.; Dlewati, A.; Santanna, J.; Loh, L.; Lenrow, D.A.; Holmes, J.H.; Kapoor, S.C.; Atkinson, L.E.; Strom, B.L. Effects of testosterone replacement in hypogonadal men. J. Clin. Endocrinol. Metab., 2000, 85(8), 2670-2677.
[http://dx.doi.org/10.1210/jc.85.8.2670] [PMID: 10946864]
[61]
Yassin, A.A.; Doros, G. Testosterone therapy in hypogonadal men results in sustained and clinically meaningful weight loss. Clin. Obes., 2013, 3(3-4), 73-83.
[http://dx.doi.org/10.1111/cob.12022] [PMID: 24163704]
[62]
Yassin, D.J.; Doros, G.; Hammerer, P.G.; Yassin, A.A. Long-term testosterone treatment in elderly men with hypogonadism and erectile dysfunction reduces obesity parameters and improves metabolic syndrome and health-related quality of life. J. Sex. Med., 2014, 11(6), 1567-1576.
[http://dx.doi.org/10.1111/jsm.12523] [PMID: 24712761]
[63]
Imanaka, S.; Yamada, Y.; Kawahara, N.; Kobayashi, H. A delicate redox balance between iron and heme oxygenase-1 as an essential biological feature of endometriosis. Arch. Med. Res., 2021, 52(6), 641-647.
[http://dx.doi.org/10.1016/j.arcmed.2021.03.006] [PMID: 33863580]
[64]
Hayashi, S.; Nakamura, T.; Motooka, Y.; Ito, F.; Jiang, L.; Akatsuka, S.; Iwase, A.; Kajiyama, H.; Kikkawa, F.; Toyokuni, S. Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice. Redox Biol., 2020, 37, 101726.
[http://dx.doi.org/10.1016/j.redox.2020.101726] [PMID: 32961443]
[65]
Zhou, Y.; Zhao, X.; Zhang, L.; Xia, Q.; Peng, Y.; Zhang, H.; Yan, D.; Yang, Z.; Li, J. Iron overload inhibits cell proliferation and promotes autophagy via PARP1/SIRT1 signaling in endometriosis and adenomyosis. Toxicology, 2022, 465, 153050.
[http://dx.doi.org/10.1016/j.tox.2021.153050] [PMID: 34826546]
[66]
Chen, X.; Zhou, Y.; Wu, D.; Shu, C.; Wu, R.; Li, S.; Huang, Q.; Shu, J. Iron overload compromises preimplantation mouse embryo development. Reprod. Toxicol., 2021, 105, 156-165.
[http://dx.doi.org/10.1016/j.reprotox.2021.08.010] [PMID: 34481919]
[67]
Tweed, M.J.; Roland, J.M. Lesson of the week: Haemochromatosis as an endocrine cause of subfertility. BMJ, 1998, 316(7135), 915-916.
[http://dx.doi.org/10.1136/bmj.316.7135.915] [PMID: 9552844]
[68]
Surampudi, P.N.; Wang, C.; Swerdloff, R.S. Hypogonadism and male sexual function.In: Pituitary Disorders; Wiley:Blackwell, 2013, pp. 179-192.
[http://dx.doi.org/10.1002/9781118559406.ch19]
[69]
Gabrielsen, J.S.; Lamb, D.J.; Lipshultz, L.I. Iron and a man’s reproductive health: The good, the bad, and the ugly. Curr. Urol. Rep., 2018, 19(8), 60.
[http://dx.doi.org/10.1007/s11934-018-0808-x] [PMID: 29858708]
[70]
Singer, S.T.; Vichinsky, E.P.; Gildengorin, G.; van Disseldorp, J.; Rosen, M.; Cedars, M.I. Reproductive capacity in iron overloaded women with thalassemia major. Blood, 2011, 118(10), 2878-2881.
[http://dx.doi.org/10.1182/blood-2011-06-360271] [PMID: 21757620]
[71]
Ni, Z.; Li, Y.; Song, D.; Ding, J.; Mei, S.; Sun, S.; Cheng, W.; Yu, J.; Zhou, L.; Kuang, Y.; Li, M.; Cai, Z.; Yu, C. Iron-overloaded follicular fluid increases the risk of endometriosis-related infertility by triggering granulosa cell ferroptosis and oocyte dysmaturity. Cell Death Dis., 2022, 13(7), 579.
[http://dx.doi.org/10.1038/s41419-022-05037-8] [PMID: 35787614]
[72]
Boroujeni, S.N.; Bossaghzadeh, F.; Malamiri, F.A.; Esmaeili, A.; Moudi, E. The most important medicinal plants affecting sperm and testosterone production: A systematic review. JBRA Assist. Reprod., 2021.
[http://dx.doi.org/10.5935/1518-0557.20210108] [PMID: 35234023]
[73]
Wellejus, A.; Poulsen, H.E.; Loft, S. Iron-induced oxidative DNA damage in rat sperm cells in vivo and in vitro. Free Radic. Res., 2000, 32(1), 75-83.
[http://dx.doi.org/10.1080/10715760000300081] [PMID: 10625219]
[74]
Safarinejad, M.R. Evaluation of semen quality, endocrine profile and hypothalamus-pituitary-testis axis in male patients with homozygous β-thalassemia major. J. Urol., 2008, 179(6), 2327-2332.
[http://dx.doi.org/10.1016/j.juro.2008.01.103] [PMID: 18423706]
[75]
Sartorius, G.A.; Handelsman, D.J. Testicular dysfunction in systemic diseases. In: Andrology; Springer Berlin Heidelberg, 2010, pp. 339-364.
[http://dx.doi.org/10.1007/978-3-540-78355-8_18]
[76]
Perera, D.; Pizzey, A.; Campbell, A.; Katz, M.; Porter, J.; Petrou, M.; Irvine, D.S.; Chatterjee, R. Sperm DNA damage in potentially fertile homozygous -thalassaemia patients with iron overload. Hum. Reprod., 2002, 17(7), 1820-1825.
[http://dx.doi.org/10.1093/humrep/17.7.1820] [PMID: 12093845]
[77]
Sengupta, P.; Durairajanayagam, D.; Agarwal, A. Herbal medicine used to treat andrological problems: Asia and Indian subcontinent: Withania somnifera, Panax ginseng, Centella asiatica.In: Herbal Med. Androl; Elsevier, 2021, pp. 93-106.
[http://dx.doi.org/10.1016/B978-0-12-815565-3.00015-1]
[78]
Okobi, O.E. A systemic review on the association between infertility and sexual dysfunction among women utilizing female sexual function index as a measuring tool. Cureus, 2021, 13(6), e16006.
[http://dx.doi.org/10.7759/cureus.16006] [PMID: 34336497]
[79]
Chen, X. Potential involvement of iron overload in the pathogenesis of endometriosis-associated infertility. Biomed. J. Sci. Tech. Res., 2020, 24(5)
[http://dx.doi.org/10.26717/BJSTR.2020.24.004129]
[80]
Mascarenhas, M.; Rawnsley, V.; Balen, A. Iron overload directly affecting the ovaries in a patient with Diamond–Blackfan anaemia: A case report. Hum. Fertil. (Camb.), 2018, 21(4), 294-298.
[http://dx.doi.org/10.1080/14647273.2017.1342875] [PMID: 28643569]
[81]
Tsironi, M.; Petrakos, G.; Andriopoulos, P. Pregnancy in women with thalassemia: Challenges and solutions. Int. J. Womens Health, 2016, 8, 441-451.
[http://dx.doi.org/10.2147/IJWH.S89308] [PMID: 27660493]
[82]
Kaspate, D. To study an aphrodisiac activity of hydroalcoholic extract of Withania somnifera dried roots in female Wistar rats. Int. J. Pharm. Sci. Res., 2015, 2820-2836.
[83]
Dhas, S.A.; Selvaraj, T.; Citarasu, T.; Punitha, S.M.J.; Babu, M.M. Effect of supplemented diet with maturation plant extract on reproductive performance of Etroplus suratansis. Aquacult. Rep., 2015, 2, 58-62.
[http://dx.doi.org/10.1016/j.aqrep.2015.08.005]
[84]
Al-Qarawi, A.A.; Abdel-Rahman, H.A.; El-Badry, A.A.; Harraz, F.; Razig, N.A.; Abdel-Magied, E.M. The effect of extracts of Cynomorium coccineum and Withania somnifera on gonadotrophins and ovarian follicles of immature Wistar rats. Phytother. Res., 2000, 14(4), 288-290.
[http://dx.doi.org/10.1002/1099-1573(200006)14:4<288:AID-PTR603>3.0.CO;2-9] [PMID: 10861976]
[85]
Chaudhuri, D.; Ghate, N.B.; Sarkar, R.; Mandal, N. Phytochemical analysis and evaluation of antioxidant and free radical scavenging activity of Withania somnifera root. Asian J. Pharm. Clin. Res., 2012, 5(4), 193-1999.
[86]
Yadav Kumar, A.; Rai Chandra, D. In vitro screening of Ashwagandha root extracts for the maximum functional components. Pharma Innov., 2018, 7, 12-16.
[87]
Baghel, K.; Srivastava, R. Photoperiod dependent expression of estrogen receptor alpha in testes of Japanese quail: Involvement of Withania somnifera in apoptosis amelioration. Biochem. Biophys. Res. Commun., 2021, 534, 957-965.
[http://dx.doi.org/10.1016/j.bbrc.2020.10.064] [PMID: 33129445]
[88]
Pal, A.; Kumar, M.; Saharan, V.; Nehru, B. Anti-oxidant and free radical scavenging activity of Ashwagandha (Withania somnifera L.) leaves. J. Global Bio., 2015, 4, 1127-1137.
[89]
Mirjalili, M.; Moyano, E.; Bonfill, M.; Cusido, R.; Palazón, J. Steroidal lactones from Withania somnifera, an ancient plant for novel medicine. Molecules, 2009, 14(7), 2373-2393.
[http://dx.doi.org/10.3390/molecules14072373] [PMID: 19633611]
[90]
Saleem, S.; Muhammad, G.; Hussain, M.A.; Altaf, M.; Bukhari, S.N.A. Withania somnifera L.: Insights into the phytochemical profile, therapeutic potential, clinical trials, and future prospective. Iran. J. Basic Med. Sci., 2020, 23(12), 1501-1526.
[PMID: 33489024]
[91]
Sikandan, A.; Shinomiya, T.; Nagahara, Y. Ashwagandha root extract exerts anti inflammatory effects in HaCaT cells by inhibiting the MAPK/NF κB pathways and by regulating cytokines. Int. J. Mol. Med., 2018, 42(1), 425-434.
[http://dx.doi.org/10.3892/ijmm.2018.3608] [PMID: 29620265]
[92]
Zhang, F.; Wang, H.; Wang, X.; Jiang, G.; Liu, H.; Zhang, G.; Wang, H.; Fang, R.; Bu, X.; Cai, S.; Du, J. TGF-β induces M2-like macrophage polarization via SNAIL-mediated suppression of a pro-inflammatory phenotype. Oncotarget, 2016, 7(32), 52294-52306.
[http://dx.doi.org/10.18632/oncotarget.10561] [PMID: 27418133]
[93]
Wadhwa, R.; Singh, R.; Gao, R.; Shah, N.; Widodo, N.; Nakamoto, T.; Ishida, Y.; Terao, K.; Kaul, S.C. Water extract of Ashwagandha leaves has anticancer activity: identification of an active component and its mechanism of action. PLoS One, 2013, 8(10), e77189.
[http://dx.doi.org/10.1371/journal.pone.0077189] [PMID: 24130852]
[94]
Efferth, T.; Zacchino, S.; Georgiev, M.I.; Liu, L.; Wagner, H.; Panossian, A. Nobel Prize for artemisinin brings phytotherapy into the spotlight. Phytomedicine, 2015, 22(13), A1-A3.
[http://dx.doi.org/10.1016/j.phymed.2015.10.003] [PMID: 26563851]
[95]
Tuli, H.S.; Sak, K.; Gupta, D.S.; Kaur, G.; Aggarwal, D.; Chaturvedi Parashar, N.; Choudhary, R.; Yerer, M.B.; Kaur, J.; Kumar, M.; Garg, V.K.; Sethi, G. Anti-inflammatory and anticancer properties of birch bark-derived betulin: Recent developments. Plants, 2021, 10(12), 2663.
[http://dx.doi.org/10.3390/plants10122663] [PMID: 34961132]
[96]
Bagwe, S.; Tharappel, L.J.P.; Kaur, G.; Buttar, H.S. Bovine colostrum: An emerging nutraceutical. J. Complement. Integr. Med., 2015, 12(3), 175-185.
[http://dx.doi.org/10.1515/jcim-2014-0039] [PMID: 25781716]
[97]
Kaur, G.C.M. Amelioration of obesity, glucose intolerance, and oxidative stress in high-fat diet and low-dose streptozotocin-induced diabetic rats by combination consisting of “curcumin with piperine and quercetin. ISRN Pharmacol., 2012, 2012, 1-7.
[http://dx.doi.org/10.5402/2012/957283]
[98]
Kaur, G.; Patel, D.V.; Sawant, M.G. Evaluation of anti-osteoarthritic activity of Vigna mungo in papain induced osteoarthritis model. Indian J. Pharmacol., 2015, 47(1), 59-64.
[http://dx.doi.org/10.4103/0253-7613.150340] [PMID: 25821313]
[99]
Kumar, R.; Gautam, G.K.; Pundir, S.; Zaidi, S.; Gupta, C. Treatment of human infertility. Asian J. Res. Pharm. Sci., 2021, 11(2), 160-164.
[http://dx.doi.org/10.52711/2231-5659.2021-11-2-12]

Rights & Permissions Print Cite
Article Metrics
15
2
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy