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2000
Volume 31, Issue 24
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

The challenges posed by excessive global population growth remain significant. Hormonal female contraceptive pills, which have been approved for over 60 years, serve as an important means of contraception; however, many women experience adverse effects after taking these pills, including abnormalities in blood clotting, dizziness, headaches, and vomiting. In this context, male contraceptives have emerged as a prominent area of research. Unfortunately, most male contraceptives are still in the experimental or clinical research stages. Therefore, screening for active ingredients that can specifically inhibit sperm function from natural drug active ingredient libraries holds substantial clinical and practical significance. In this manuscript, we review the inhibitory effects of various natural drug active monomers on sperm function and their underlying molecular mechanisms, aiming to provide theoretical insights for the future development of novel male contraceptives.

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2025-03-05
2025-09-03

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References

  1. Baldeon-VacaG. MaratheJ.G. PolitchJ.A. MausserE. PudneyJ. DoudJ. NadorE. ZeitlinL. PaulyM. MoenchT.R. BrennanM. WhaleyK.J. AndersonD.J. Production and characterization of a human antisperm monoclonal antibody against CD52g for topical contraception in women.EBioMedicine20216910347810.1016/j.ebiom.2021.10347834256345
     [Google Scholar]
  2. GialerakiA. ValsamiS. PittarasT. PanayiotakopoulosG. PolitouM. Oral contraceptives and HRT risk of Thrombosis.Clin. Appl. Thromb. Hemost.201824221722510.1177/107602961668380228049361
     [Google Scholar]
  3. RosenbergK. Hormonal contraceptives increase breast cancer risk.Am. J. Nurs.2018118369
     [Google Scholar]
  4. PiotrowskaK. WangC. SwerdloffR.S. LiuP.Y. Male hormonal contraception: Hope and promise.Lancet Diabetes Endocrinol.20175321422310.1016/S2213‑8587(16)00034‑626915313
     [Google Scholar]
  5. YanM. WangL. ChengC.Y. Testis toxicants: lesson from Traditional Chinese Medicine (TCM).Adv. Exp. Med. Biol.2021138130731910.1007/978‑3‑030‑77779‑1_1534453743
     [Google Scholar]
  6. De-JunH.U. Ze-YanP.E.N.G. Dong-ChuH.E. Progress in the study of pharmacological effects of Lei Gong Teng.Med. Herit.20183705586592
     [Google Scholar]
  7. Pan-YongH.U. Zhen-LinL.I. She-BanP.U. Progress in the study of Lei Gong Teng.Chinese Wild Plant Res 201332213
     [Google Scholar]
  8. QianS.Z. Tripterygium wilfordii, a chinese herb effective in male fertility regulation.Contraception198736333534510.1016/0010‑7824(87)90104‑13315438
     [Google Scholar]
  9. DaiY. SunL. HanS. XuS. WangL. DingY. Proteomic study on the reproductive toxicity of Tripterygium glycosides in rats.Front. Pharmacol.2022131388896810.3389/fphar.2022.88896835668950
     [Google Scholar]
  10. BraissantO. FoufelleF. ScottoC. DauçaM. WahliW. Differential expression of peroxisome proliferator-activated receptors (PPARs): Tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat.Endocrinology1996137135436610.1210/endo.137.1.85366368536636
     [Google Scholar]
  11. MinutoliL. AntonuccioP. PolitoF. BittoA. SquadritoF. IrreraN. NicotinaP.A. FazzariC. MontaltoA.S. Di StefanoV. RomeoC. AltavillaD. Peroxisome proliferator activated receptor beta/delta activation prevents extracellular regulated kinase 1/2 phosphorylation and protects the testis from ischemia and reperfusion injury.J. Urol.200918141913192110.1016/j.juro.2008.11.09519237170
     [Google Scholar]
  12. DengC.Y. LvM. LuoB.H. ZhaoS.Z. MoZ.C. XieY.J. The role of the PI3K/AKT/mTOR signalling pathway in male reproduction.Curr. Mol. Med.202121753954810.2174/18755666MTEyfMDM0x33272176
     [Google Scholar]
  13. HeZ. KokkinakiM. DymM. Signaling molecules and pathways regulating the fate of spermatogonial stem cells.Microsc. Res. Tech.200972858659510.1002/jemt.2069819263492
     [Google Scholar]
  14. HuangW QuanC DuanP. TangS ChenW YangK Nonylphenol induced apoptosis and autophagy involving the Akt/ mTOR pathway in prepubertal Sprague-Dawley male rats in vivo and in vitro.Toxicology2016373415310.1016/j.tox.2016.11.00627832966
     [Google Scholar]
  15. ZhangJ. ZhangX. LiuY. SuZ. DawarF.U. DanH. HeY. GuiJ.F. MeiJ. Leucine mediates autophagosome-lysosome fusion and improves sperm motility by activating the PI3K/Akt pathway.Oncotarget201786711180711181810.18632/oncotarget.2291029340093
     [Google Scholar]
  16. CuiD.X. NiuZ.C. TangX. CaiC.Z. XuD.Q. FuR.J. LiuW.J. WangY.W. TangY.P. Celastrol induced the autophagy of spermatogonia cells contributed to tripterygium glycosides-related testicular injury.Reprod. Toxicol.202412610860410.1016/j.reprotox.2024.10860438703919
     [Google Scholar]
  17. MizushimaN. YoshimoriT. How to interpret LC3 immunoblotting.Autophagy20073654254510.4161/auto.460017611390
     [Google Scholar]
  18. LueY. HikimA.P.S. WangC. LeungA. BaravarianS. ReutrakulV. SangsawanR. ChaichanaS. SwerdloffR.S. Triptolide: A potential male contraceptive.J. Androl.199819447948610.1002/j.1939‑4640.1998.tb02042.x9733151
     [Google Scholar]
  19. LiJ. ChenD. SuoJ. LiJ. ZhangY. WangY. DengZ. ZhangQ. MaB. Triptolide induced spermatogenesis dysfunction via ferroptosis activation by promoting K63-linked GPX4 polyubiquitination in spermatocytes.Chem. Biol. Interact.202439911113010.1016/j.cbi.2024.11113038960301
     [Google Scholar]
  20. ZhangW. LiuY. LiaoY. ZhuC. ZouZ. GPX4, ferroptosis, and diseases.Biomed. Pharmacother.202417411651210.1016/j.biopha.2024.11651238574617
     [Google Scholar]
  21. YangF. RenL. ZhuoL. AnandaS. LiuL. Involvement of oxidative stress in the mechanism of triptolide-induced acute nephrotoxicity in rats.Exp. Toxicol. Pathol.2012647-890591110.1016/j.etp.2011.03.01321530203
     [Google Scholar]
  22. FuQ. HuangX. ShuB. XueM. ZhangP. WangT. LiuL. JiangZ. ZhangL. Inhibition of mitochondrial respiratory chain is involved in triptolide-induced liver injury.Fitoterapia20118281241124810.1016/j.fitote.2011.08.01921907767
     [Google Scholar]
  23. WangL. YeW. HuiL. LiuX. GuoY. Male contraception of triptonide and its function mechanism.Zhongguo Yi Xue Ke Xue Yuan Xue Bao200022322322612903464
     [Google Scholar]
  24. ChangZ. QinW. ZhengH. ScheggK. HanL. LiuX. WangY. WangZ. McSwigginH. PengH. YuanS. WuJ. WangY. ZhuS. JiangY. NieH. TangY. ZhouY. HitchcockM.J.M. TangY. YanW. Triptonide is a reversible non-hormonal male contraceptive agent in mice and non-human primates.Nat. Commun.2021121125310.1038/s41467‑021‑21517‑533623031
     [Google Scholar]
  25. ZhengH. StrattonC.J. MorozumiK. JinJ. YanagimachiR. YanW. Lack of Spem1 causes aberrant cytoplasm removal, sperm deformation, and male infertility.Proc. Natl. Acad. Sci. USA2007104166852685710.1073/pnas.070166910417426145
     [Google Scholar]
  26. DongX. FuJ. YinX. CaoS. LiX. LinL. NiJ. Huyiligeqi Emodin: A review of its pharmacology, toxicity and pharmacokinetics.Phytother. Res.20163081207121810.1002/ptr.563127188216
     [Google Scholar]
  27. OshidaK. HirakataM. MaedaA. MiyoshiT. MiyamotoY. Toxicological effect of emodin in mouse testicular gene expression profile.J. Appl. Toxicol.201131879080010.1002/jat.163721319176
     [Google Scholar]
  28. YimH. LeeY.H. Chul Hoon LeeY.H. LeeS.K. Emodin, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum, selectively inhibits the activity of casein kinase II as a competitive inhibitor.Planta Med.199965100901310.1055/s‑1999‑1395310083837
     [Google Scholar]
  29. LuoT. LiN. HeY. WengS. WangT. ZouQ. ZengX. Emodin inhibits human sperm functions by reducing sperm [Ca2+]i and tyrosine phosphorylation.Reprod. Toxicol.201551142110.1016/j.reprotox.2014.11.00725463531
     [Google Scholar]
  30. YuanY. DingX. ChengY. KangH. LuoT. ZhangX. KuangH. ChenY. ZengX. ZhangD. PFOA evokes extracellular Ca2+ influx and compromises progesterone-induced response in human sperm.Chemosphere202024112507410.1016/j.chemosphere.2019.12507431627108
     [Google Scholar]
  31. AlasmariW. CostelloS. CorreiaJ. OxenhamS.K. MorrisJ. FernandesL. Ramalho-SantosJ. Kirkman-BrownJ. MichelangeliF. PublicoverS. BarrattC.R. Ca2+ signals generated by CatSper and Ca2+ stores regulate different behaviors in human sperm.J. Biol. Chem.201328896248625810.1074/jbc.M112.43935623344959
     [Google Scholar]
  32. NashK. LefievreL. Peralta-AriasR. MorrisJ. Morales-GarciaA. ConnollyT. CostelloS. Kirkman-BrownJ.C. PublicoverS.J. Techniques for imaging Ca2+ signaling in human sperm.J. Vis. Exp.201040199620567212
     [Google Scholar]
  33. JayasuriyaH. KoonchanokN.M. GeahlenR.L. McLaughlinJ.L. ChangC.J. Emodin, a protein tyrosine kinase inhibitor from Polygonum cuspidatum.J. Nat. Prod.199255569669810.1021/np50083a0261517743
     [Google Scholar]
  34. NazR.K. RajeshP.B. Role of tyrosine phosphorylation in sperm capacitation/acrosome reaction.Reprod. Biol. Endocrinol.2004217510.1186/1477‑7827‑2‑7515535886
     [Google Scholar]
  35. ChungJ.J. ShimS.H. EverleyR.A. GygiS.P. ZhuangX. ClaphamD.E. Structurally distinct Ca2+ signaling domains of sperm flagella orchestrate tyrosine phosphorylation and motility.Cell2014157480882210.1016/j.cell.2014.02.05624813608
     [Google Scholar]
  36. TamburrinoL. MarchianiS. MinettiF. FortiG. MuratoriM. BaldiE. The CatSper calcium channel in human sperm: Relation with motility and involvement in progesterone-induced acrosome reaction.Hum. Reprod.201429341842810.1093/humrep/det45424430778
     [Google Scholar]
  37. WangQ.X. WuC.Q. LiaoY.M. Study on the toxicity and its mechanisms of rhubarb and its major constituents.J. Toxicol.200721310302
     [Google Scholar]
  38. LiC.L. MaJ. ZhengL. LiH.J. LiP. Determination of emodin in L-02 cells and cell culture media with liquid chromatography–mass spectrometry: Application to a cellular toxicokinetic study.J. Pharm. Biomed. Anal.201271717810.1016/j.jpba.2012.07.03122944356
     [Google Scholar]
  39. WangC. Emodin induces apoptosis through caspase 3-dependent pathway in HK-2 cells.Toxicology20072312-3120128
     [Google Scholar]
  40. WangC. DaiX. LiuH. YiH. ZhouD. LiuC. MaM. JiangZ. ZhangL. Involvement of PPARγ in emodin-induced HK-2 cell apoptosis.Toxicol. In Vitro201529122823310.1016/j.tiv.2014.10.02125448808
     [Google Scholar]
  41. WangQ.X. WuC.Q. YangH.L. Cytotoxicity of free anthraquinone from Radix et Rhizoma Rhei to HK-2 Cells.Zhongguo Xin Yao Zazhi200716189199
     [Google Scholar]
  42. QiaoliY.A.N.G. ZhengyiG.U. HuaH.U.A.N.G. Research progress of the Chinese medicine bitter bean seeds.NW J Pharm.20112603232236
     [Google Scholar]
  43. LuoT. ZouQ. HeY. WangH. WangT. LiuM. ChenY. WangB. Matrine compromises mouse sperm functions by a [Ca2+]i-related mechanism.Reprod. Toxicol.201660697510.1016/j.reprotox.2016.02.00326867864
     [Google Scholar]
  44. RahbanR. NefS. CatSper: The complex main gate of calcium entry in mammalian spermatozoa.Mol. Cell. Endocrinol.202051811095110.1016/j.mce.2020.11095132712386
     [Google Scholar]
  45. GongX. GaoY. GuoG. VondranF.W.R. SchwartlanderR. EfimovaE. PlessG. SaueraI.M. NeuhausP. Effect of matrine on primary human hepatocytes in vitro.Cytotechnology201567225526510.1007/s10616‑013‑9680‑124445680
     [Google Scholar]
  46. LuZ.G. LiM.H. WangJ.S. WeiD.D. LiuQ.W. KongL.Y. Developmental toxicity and neurotoxicity of two matrine-type alkaloids, matrine and sophocarpine, in zebrafish (Danio rerio) embryos/larvae.Reprod. Toxicol.201447334110.1016/j.reprotox.2014.05.01524911943
     [Google Scholar]
  47. LiangP. YuanT.J. GuL.L. Study of hepatotoxicity and neural behavioral changes of sophora flavescens and matrine in mice.Chin. J. Modern Appl. Pharmacy20143214441448
     [Google Scholar]
  48. ZengB. WeiA. ZhouQ. YuanM. LeiK. LiuY. SongJ. GuoL. YeQ. Andrographolide: A review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches.Phytother. Res.202236133636410.1002/ptr.732434818697
     [Google Scholar]
  49. AkbarshaM.A. MurugaianP. Aspects of the male reproductive toxicity/male antifertility property of andrographolide in albino rats: Effect on the testis and the cauda epididymidal spermatozoa.Phytother. Res.200014643243510.1002/1099‑1573(200009)14:6<432::AID‑PTR622>3.0.CO;2‑I10960897
     [Google Scholar]
  50. OgundolaA.F. AkhigbeR.E. SakaW.A. AdeniyiA.O. AdeshinaO.S. BabalolaD.O. AkhigbeT.M. Contraceptive potential of Andrographis paniculata is via androgen suppression and not induction of oxidative stress in male Wistar rats.Tissue Cell20217310163210.1016/j.tice.2021.10163234479074
     [Google Scholar]
  51. WdowiakA. RaczkiewiczD. StasiakM. BojarI. Levels of FSH, LH and testosterone, and sperm DNA fragmentation.Neuroendocrinol. Lett.2014351737924625916
     [Google Scholar]
  52. CiampiE. Uribe-San-MartinR. CárcamoC. CruzJ.P. ReyesA. ReyesD. PintoC. VásquezM. BurgosR.A. HanckeJ. Efficacy of andrographolide in not active progressive multiple sclerosis: A prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial.BMC Neurol.202020117310.1186/s12883‑020‑01745‑w32380977
     [Google Scholar]
  53. CalabreseC. BermanS.H. BabishJ.G. MaX. ShintoL. DorrM. WellsK. WennerC.A. StandishL.J. A phase I trial of andrographolide in HIV positive patients and normal volunteers.Phytother. Res.200014533333810.1002/1099‑1573(200008)14:5<333::AID‑PTR584>3.0.CO;2‑D10925397
     [Google Scholar]
  54. HuY. ZhouX. ShiH. ShiW. YeS. ZhangH. The effect of tripterygium glucoside tablet on pharmacokinetics of losartan and its metabolite EXP3174 in rats.Biomed. Chromatogr.20173110e397310.1002/bmc.397328299812
     [Google Scholar]
  55. BoucettaH. WuW. HongT. ChengR. JiangJ. LiuC. SongM. HangT. Pharmacovigilance of herb- drug interactions: A pharmacokinetic study on the combined administration of tripterygium glycosides tablets and leflunomide tablets in rats by LC-MS/MS.Pharmaceuticals202215899110.3390/ph1508099136015140
     [Google Scholar]
  56. DiX. WangX. DiX. LiuY. Effect of piperine on the bioavailability and pharmacokinetics of emodin in rats.J. Pharm. Biomed. Anal.201511514414910.1016/j.jpba.2015.06.02726201645
     [Google Scholar]
  57. ZhangX. ZhangX. WangX. ZhaoM. Influence of andrographolide on the pharmacokinetics of warfarin in rats.Pharm. Biol.201856135135610.1080/13880209.2018.147843129983086
     [Google Scholar]
  58. SundhaniE. NugrohoA.E. NurrochmadA. PuspitasariI. Amalia PrihatiD. LukitaningsihE. Pharmacokinetic herb-drug interactions of glipizide with Andrographis paniculata (Burm. f.) and Andrographolide in normal and diabetic rats by validated HPLC method.Molecules20222720690110.3390/molecules2720690136296494
     [Google Scholar]
  59. LiuJ. ZhouY. LyuQ. YaoX. WangW. Targeted protein delivery based on stimuli-triggered nanomedicine.Exploration2024432023002510.1002/EXP.2023002538939867
     [Google Scholar]
  60. DuY. HuoY. YangQ. HanZ. HouL. CuiB. FanK. QiuY. ChenZ. HuangW. LuJ. ChengL. CaiW. KangL. Ultrasmall iron-gallic acid coordination polymer nanodots with antioxidative neuroprotection for PET/MR imaging-guided ischemia stroke therapy.Exploration2023312022004110.1002/EXP.2022004137323619
     [Google Scholar]
  61. WeiY.S. ChenY.L. LiW.Y. YangY.Y. LinS.J. WuC.H. YangJ.I. WangT.E. YuJ. TsaiP.S. Antioxidant nanoparticles restore cisplatin-induced male fertility defects by promoting MDC1-53bp1-associated non-homologous DNA repair mechanism and sperm intracellular calcium influx.Int. J. Nanomedicine2023184313432710.2147/IJN.S40862337576465
     [Google Scholar]
  62. SaidF. OmarA.R. MohamedA.S. DakroryA.I. AbdelazizM.H. Protective effects of chitosan-loaded pomegranate peel extract nanoparticles on infertility in diabetic male rats.Curr. Top. Med. Chem.20242410.2174/011568026630888224080617583139171473
     [Google Scholar]
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The Molecular Mechanisms of Natural Medicinal Active Ingredients Interfering with Male Fertility
Curr. Pharm. Des. 31, 1903 (2025); https://doi.org/10.2174/0113816128356183250207105548
/content/journals/cpd/10.2174/0113816128356183250207105548
/content/journals/cpd/10.2174/0113816128356183250207105548
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  • Article Type:     Review Article
Keyword(s): emodin; male contraceptive drug; Male fertility; natural medicine; Tripterygium wilfordii; triptolide

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