Skip to content
2000
Volume 31, Issue 28
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Introduction

Atrophic vaginitis (AV) is a common and frequently occurring disease, lacking effective curative measures. Exploring the mechanism of vaginal mucosal homeostasis from the perspective of metabolites has great research prospects.

Methods

We compared the metabolic profiles of vaginal secretions between AV patients and healthy individuals liquid chromatography-tandem mass spectrometry (LC-MS/MS). We further explored effective and sensitive metabolites and metabolic pathways for senile vaginitis through bioinformatics analysis and experimental verification. Through untargeted metabolomics analysis, we screened 561 differential metabolites in two groups of vaginal secretion samples. These differential metabolites were mainly concentrated in fatty acids/carboxylic acids, glycerophospholipids, organic oxides, steroids, and their derivatives. They were mainly enriched in purine metabolism, diabetic cardiomyopathy generation, and choline metabolism pathways.

Results

The receiver operating characteristic analysis showed the metabolites (., guggulsterone, umbelliprenin, and inosinic acid) to have good discrimination ability for the AV group. In addition, we also explored the potential mechanism of action of umbelliprenin at the cellular level.

Conclusion

This study is expected to provide a new perspective for understanding the relationship between metabolites and the pathogenesis of AV.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128362600250203051056056
2025-02-06
2025-10-26

  • From This Site

    /content/journals/cpd/10.2174/0113816128362600250203051056056
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. LeeA. KimT.H. LeeH.H. KimY.S. EnkhboldT. LeeB. ParkY.J. SongK. Therapeutic approaches to atrophic vaginitis in postmenopausal women: A systematic review with a network meta-analysis of randomized controlled trials.J. Menopausal Med.201824111010.6118/jmm.2018.24.1.129765921
     [Google Scholar]
  2. PaladineH.L. DesaiU.A. Vaginitis: Diagnosis and treatment.Am. Fam. Physician201897532132929671516
     [Google Scholar]
  3. WasnikV.B. AcharyaN. MohammadS. Genitourinary syndrome of menopause: A narrative review focusing on its effects on the sexual health and quality of life of women.Cureus20231511e4814310.7759/cureus.4814338046779
     [Google Scholar]
  4. StikaC.S. Atrophic vaginitis.Dermatol. Ther.201023551452210.1111/j.1529‑8019.2010.01354.x20868405
     [Google Scholar]
  5. Pérez-LópezF.R. Vieira-BaptistaP. PhillipsN. Cohen-SacherB. FialhoS.C.A.V. StockdaleC.K. Clinical manifestations and evaluation of postmenopausal vulvovaginal atrophy.Gynecol. Endocrinol.202137874074510.1080/09513590.2021.193110034036849
     [Google Scholar]
  6. Palmeira-de-OliveiraR. Palmeira-de-OliveiraA. Martinez-de-OliveiraJ. New strategies for local treatment of vaginal infections.Adv. Drug Deliv. Rev.20159210512210.1016/j.addr.2015.06.00826144995
     [Google Scholar]
  7. WeberM.A. LimpensJ. RooversJ.P.W.R. Assessment of vaginal atrophy: A review.Int. Urogynecol. J. Pelvic Floor Dysfunct.2015261152810.1007/s00192‑014‑2464‑025047897
     [Google Scholar]
  8. LynchC. Vaginal estrogen therapy for the treatment of atrophic vaginitis.J Womens Health (Larchmt)200918101595160610.1089/jwh.2008.128119788364
     [Google Scholar]
  9. Crean-TateK.K. FaubionS.S. PedersonH.J. VencillJ.A. BaturP. Management of genitourinary syndrome of menopause in female cancer patients: A focus on vaginal hormonal therapy.Am. J. Obstet. Gynecol.2020222210311310.1016/j.ajog.2019.08.04331473229
     [Google Scholar]
  10. AliA. IftikharA. TabassumM. ImranR. ShaidM.U. HashmiM.R. SaadM. HumayunM. ImtiazS. BaigE. Efficacy and safety of intravaginal estrogen in the treatment of atrophic vaginitis: A systematic review and meta-analysis.J. Menopausal Med.20243028810310.6118/jmm.2303739315501
     [Google Scholar]
  11. ShimS. ParkK.M. ChungY.J. KimM.R. Updates on therapeutic alternatives for genitourinary syndrome of menopause: Hormonal and non-hormonal managements.J. Menopausal Med.20212711710.6118/jmm.2003433942583
     [Google Scholar]
  12. AyindeO. RossJ.D.C. The frequency and duration of side-effects associated with the use of oral metronidazole; A prospective study of VITA trial participants.Int. J. STD AIDS2023341289790210.1177/0956462423117950537395087
     [Google Scholar]
  13. YoshikataR. YamaguchiM. MaseY. TatsuyukiA. MyintK.Z.Y. OhtaH. Evaluation of the efficacy of Lactobacillus-containing feminine hygiene products on vaginal microbiome and genitourinary symptoms in pre- and postmenopausal women: A pilot randomized controlled trial.PLoS One20221712e027024210.1371/journal.pone.027024236584204
     [Google Scholar]
  14. SchymanskiE.L. JeonJ. GuldeR. FennerK. RuffM. SingerH.P. HollenderJ. Identifying small molecules via high resolution mass spectrometry: Communicating confidence.Environ. Sci. Technol.20144842097209810.1021/es500210524476540
     [Google Scholar]
  15. JangC. ChenL. RabinowitzJ.D. Metabolomics and isotope tracing.Cell2018173482283710.1016/j.cell.2018.03.05529727671
     [Google Scholar]
  16. RinschenM.M. IvanisevicJ. GieraM. SiuzdakG. Identification of bioactive metabolites using activity metabolomics.Nat. Rev. Mol. Cell Biol.201920635336710.1038/s41580‑019‑0108‑430814649
     [Google Scholar]
  17. RattrayN.J.W. DezielN.C. WallachJ.D. KhanS.A. VasiliouV. IoannidisJ.P.A. JohnsonC.H. Beyond genomics: Understanding exposotypes through metabolomics.Hum. Genomics2018121410.1186/s40246‑018‑0134‑x29373992
     [Google Scholar]
  18. ArmitageE.G. BarbasC. Metabolomics in cancer biomarker discovery: Current trends and future perspectives.J. Pharm. Biomed. Anal.20148711110.1016/j.jpba.2013.08.04124091079
     [Google Scholar]
  19. ZhaoY.Y. ChengX.L. VaziriN.D. LiuS. LinR.C. UPLC-based metabonomic applications for discovering biomarkers of diseases in clinical chemistry.Clin. Biochem.20144715162610.1016/j.clinbiochem.2014.07.01925087975
     [Google Scholar]
  20. ZhouB. XiaoJ.F. TuliL. RessomH.W. LC-MS-based metabolomics.Mol. Biosyst.20128247048110.1039/C1MB05350G22041788
     [Google Scholar]
  21. TanM. LuoH. LeeS. JinF. YangJ.S. MontellierE. BuchouT. ChengZ. RousseauxS. RajagopalN. LuZ. YeZ. ZhuQ. WysockaJ. YeY. KhochbinS. RenB. ZhaoY. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification.Cell201114661016102810.1016/j.cell.2011.08.00821925322
     [Google Scholar]
  22. PiazzaI. KochanowskiK. CappellettiV. FuhrerT. NoorE. SauerU. PicottiP. A map of protein-metabolite interactions reveals principles of chemical communication.Cell20181721-2358372.e2310.1016/j.cell.2017.12.00629307493
     [Google Scholar]
  23. ZhangY. WangH. ChenT. WangH. LiangX. ZhangY. DuanJ. QianS. QiaoK. ZhangL. LiuY. WangJ. C24‐Ceramide Drives Gallbladder Cancer Progression Through Directly Targeting Phosphatidylinositol 5‐Phosphate 4‐Kinase Type‐2 Gamma to Facilitate Mammalian Target of Rapamycin Signaling Activation.Hepatology202173269271210.1002/hep.3130432374916
     [Google Scholar]
  24. KimE.K. ParkJ.M. LimS. ChoiJ.W. KimH.S. SeokH. SeoJ.K. OhK. LeeD.S. KimK.T. RyuS.H. SuhP.G. Activation of AMP-activated protein kinase is essential for lysophosphatidic acid-induced cell migration in ovarian cancer cells.J. Biol. Chem.201128627240362404510.1074/jbc.M110.20990821602274
     [Google Scholar]
  25. ChenS. MaX. LiuY. ZhongZ. WeiC. LiM. ZhuX. Creatine promotes endometriosis by inducing ferroptosis resistance via suppression of PrP.Adv. Sci. (Weinh.)20241138240351710.1002/advs.20240351739119937
     [Google Scholar]
  26. MumfordS.L. DasharathyS.S. PollackA.Z. PerkinsN.J. MattisonD.R. ColeS.R. Wactawski-WendeJ. SchistermanE.F. Serum uric acid in relation to endogenous reproductive hormones during the menstrual cycle: Findings from the BioCycle study.Hum. Reprod.20132871853186210.1093/humrep/det08523562957
     [Google Scholar]
  27. Buszewska-ForajtaM. RachońD. StefaniakA. WawrzyniakR. KoniecznaA. KowalewskaA. MarkuszewskiM.J. Identification of the metabolic fingerprints in women with polycystic ovary syndrome using the multiplatform metabolomics technique.J. Steroid Biochem. Mol. Biol.201918617618410.1016/j.jsbmb.2018.10.01230670174
     [Google Scholar]
  28. AnN. ZhangM. ZhuQ.F. ChenY.Y. DengY.L. LiuX.Y. ZengQ. FengY.Q. Metabolomic analysis reveals association between decreased ovarian reserve and in vitro fertilization outcomes.Metabolites202414314310.3390/metabo1403014338535303
     [Google Scholar]
  29. AmabebeE. ReynoldsS. AnumbaD.O.C. Spectral binning of cervicovaginal fluid metabolites improves prediction of spontaneous preterm birth and Lactobacillus species dominance.Reproduction and Fertility202124L4L610.1530/RAF‑21‑006535118412
     [Google Scholar]
  30. LiuL. XuH.J. ChenJ.L. ChenZ. ZhanH.Y. XuD.X. ChenY. XuZ.F. ChenD.Z. Detection of vaginal metabolite changes in premature rupture of membrane patients in third trimester pregnancy: A prospective cohort study.Reprod. Sci.202128258559410.1007/s43032‑020‑00338‑933025530
     [Google Scholar]
  31. NelsonK.G. TakahashiT. BossertN.L. WalmerD.K. McLachlanJ.A. Epidermal growth factor replaces estrogen in the stimulation of female genital-tract growth and differentiation.Proc. Natl. Acad. Sci. USA1991881212510.1073/pnas.88.1.211986369
     [Google Scholar]
  32. Ignar-TrowbridgeD.M. NelsonK.G. BidwellM.C. CurtisS.W. WashburnT.F. McLachlanJ.A. KorachK.S. Coupling of dual signaling pathways: Epidermal growth factor action involves the estrogen receptor.Proc. Natl. Acad. Sci. USA199289104658466210.1073/pnas.89.10.46581584801
     [Google Scholar]
  33. NelsonK.G. SakaiY. EitzmanB. SteedT. McLachlanJ. Exposure to diethylstilbestrol during a critical developmental period of the mouse reproductive tract leads to persistent induction of two estrogen-regulated genes.Cell Growth Differ.1994565956068086337
     [Google Scholar]
  34. GoldsteinI. DicksB. KimN.N. HartzellR. Multidisciplinary overview of vaginal atrophy and associated genitourinary symptoms in postmenopausal women.Sex. Med.201312445310.1002/sm2.1725356287
     [Google Scholar]
  35. ShahM. MakwanaN. ChaudharyM. Vaginal pH as a diagnostic tool for menopause: A preliminary analysis.J Midlife Health202011313313610.4103/jmh.JMH_1_2033384535
     [Google Scholar]
  36. MiyagawaS. IguchiT. Epithelial estrogen receptor 1 intrinsically mediates squamous differentiation in the mouse vagina.Proc. Natl. Acad. Sci. USA201511242129861299110.1073/pnas.151355011226438838
     [Google Scholar]
  37. LeiS.T. LaiZ.Z. HouS.H. LiuY.K. LiM.Q. ZhaoD. Abnormal HCK /glutamine/autophagy axis promotes endometriosis development by impairing macrophage phagocytosis.Cell Prolif.20245711e1370210.1111/cpr.1370238956970
     [Google Scholar]
  38. DaiY. LinX. LiuN. ShiL. ZhuoF. HuangQ. GuW. ZhaoF. ZhangY. ZhangY. PanY. ZhangS. Integrative analysis of transcriptomic and metabolomic profiles reveals abnormal phosphatidylinositol metabolism in follicles from endometriosis‐associated infertility patients.J. Pathol.2023260324826010.1002/path.607936992523
     [Google Scholar]
  39. CaoX. Van PuttenJ.P.M. WöstenM.M.S.M. Biological functions of bacterial lysophospholipids.Advances in Microbial PhysiologyElsevier2023129154
     [Google Scholar]
  40. ZhengL. LinY. LuS. ZhangJ. BogdanovM. Biogenesis, transport and remodeling of lysophospholipids in Gram-negative bacteria.Biochim. Biophys. Acta Mol. Cell Biol. Lipids20171862111404141310.1016/j.bbalip.2016.11.01527956138
     [Google Scholar]
  41. LouL. ZhangP. PiaoR. WangY. Salmonella Pathogenicity Island 1 (SPI-1) and Its Complex Regulatory Network.Front. Cell. Infect. Microbiol.2019927010.3389/fcimb.2019.0027031428589
     [Google Scholar]
  42. SubramanianN. QadriA. Lysophospholipid sensing triggers secretion of flagellin from pathogenic salmonella.Nat. Immunol.20067658358910.1038/ni133616648855
     [Google Scholar]
  43. TangX. WangW. HongG. DuanC. ZhuS. TianY. HanC. QianW. LinR. HouX. Gut microbiota-mediated lysophosphatidylcholine generation promotes colitis in intestinal epithelium-specific Fut2 deficiency.J. Biomed. Sci.20212812010.1186/s12929‑021‑00711‑z33722220
     [Google Scholar]
  44. HessJ.R. GreenbergN.A. The role of nucleotides in the immune and gastrointestinal systems: Potential clinical applications.Nutr. Clin. Pract.201227228129410.1177/088453361143493322392907
     [Google Scholar]
  45. De VittoH. ArachchigeD.B. RichardsonB.C. FrenchJ.B. The intersection of purine and mitochondrial metabolism in cancer.Cells20211010260310.3390/cells1010260334685583
     [Google Scholar]
  46. TasakiE. SakuraiH. NitaoM. MatsuuraK. IuchiY. Uric acid, an important antioxidant contributing to survival in termites.PLoS One2017126e017942610.1371/journal.pone.017942628609463
     [Google Scholar]
  47. TsaoH.-M. LaiT.-S. ChangY.-C. HsiungC.-N. ChouY.-H. WuV.-C. LinS.-L. ChenY.-M. Serum urate and risk of chronic kidney disease: A mendelian randomization study using taiwan biobank.Mayo Clin Proc.202398451352110.1016/j.mayocp.2023.01.00436870858
     [Google Scholar]
  48. YangY. XianW. WuD. HuoZ. HongS. LiY. XiaoH. The role of obesity, type 2 diabetes, and metabolic factors in gout: A Mendelian randomization study.Front. Endocrinol. (Lausanne)20221391705610.3389/fendo.2022.91705635992130
     [Google Scholar]
  49. AlamA. LocherK.P. Structure and mechanism of human ABC transporters.Annu. Rev. Biophys.202352127530010.1146/annurev‑biophys‑111622‑09123236737602
     [Google Scholar]
  50. StefanS.M. Multi-target ABC transporter modulators: What next and where to go?Future Med. Chem.201911182353235810.4155/fmc‑2019‑018531516029
     [Google Scholar]
  51. NakamuraT. NaguroI. IchijoH. Iron homeostasis and iron-regulated ROS in cell death, senescence and human diseases.Biochim. Biophys. Acta, Gen. Subj.2019186391398140910.1016/j.bbagen.2019.06.01031229492
     [Google Scholar]
  52. LiJ.Y. FengY.H. LiY.X. HeP.Y. ZhouQ.Y. TianY.P. YaoR.Q. YaoY.M. Ferritinophagy: A novel insight into the double‐edged sword in ferritinophagy–ferroptosis axis and human diseases.Cell Prolif.2024577e1362110.1111/cpr.1362138389491
     [Google Scholar]
  53. OliveiraN.S. LimaA.B.F. BritoJ.C.R. SarmentoA.C.A. GonçalvesA.K.S. EleutérioJ.Jr Postmenopausal vaginal microbiome and microbiota.Frontiers in Reproductive Health2022378093110.3389/frph.2021.78093136304005
     [Google Scholar]
  54. BarthomeufC. LimS. IranshahiM. CholletP. Umbelliprenin from Ferula szowitsiana inhibits the growth of human M4Beu metastatic pigmented malignant melanoma cells through cell-cycle arrest in G1 and induction of caspase-dependent apoptosis.Phytomedicine2008151-210311110.1016/j.phymed.2007.04.00117689942
     [Google Scholar]
  55. Naderi AlizadehM. RashidiM. MuhammadnejadA. Moeini ZanjaniT. ZiaiS.A. Antitumor effects of umbelliprenin in a mouse model of colorectal cancer.Iran. J. Pharm. Res.201817397698530127820
     [Google Scholar]
  56. ZhangL. SunX. SiJ. LiG. CaoL. Umbelliprenin isolated from Ferula sinkiangensis inhibits tumor growth and migration through the disturbance of Wnt signaling pathway in gastric cancer.PLoS One2019147e020716910.1371/journal.pone.020716931260453
     [Google Scholar]
  57. MugheesM. WajidS. SamimM. Cytotoxic potential of Artemisia absinthium extract loaded polymeric nanoparticles against breast cancer cells: Insight into the protein targets.Int. J. Pharm.202058611958310.1016/j.ijpharm.2020.11958332603837
     [Google Scholar]
  58. SultanM.H. ZuwaielA.A. MoniS.S. AlshahraniS. AlqahtaniS.S. MadkhaliO. ElmobarkM.E. Bioactive principles and potentiality of hot methanolic extract of the leaves from Artemisia absinthium L “in vitro cytotoxicity against human MCF-7 breast cancer cells, antibacterial study and wound healing activity”.Curr. Pharm. Biotechnol.202021151711172110.2174/138920102166620092815051932988347
     [Google Scholar]
  59. ShiraniK. IranshahiM. AskariV.R. GholizadehZ. ZadehA.A. ZeinaliM. HassaniF.V. TaherzadehZ. Comparative evaluation of the protective effects of oral administration of auraptene and umbelliprenin against CFA-induced chronic inflammation with polyarthritis in rats.Biomed. Pharmacother.202113911163510.1016/j.biopha.2021.11163534243601
     [Google Scholar]
  60. WangJ. WangJ. LiL. FengL. WangY.R. WangZ. TanN.H. RA-XII, a bicyclic hexapeptidic glucoside isolated from Rubia yunnanensis Diels, exerts antitumor activity by inhibiting protective autophagy and activating Akt-mTOR pathway in colorectal cancer cells.J. Ethnopharmacol.202126611343810.1016/j.jep.2020.11343833017635
     [Google Scholar]
  61. MohametL. HawkinsK. WardC.M. Loss of function of e-cadherin in embryonic stem cells and the relevance to models of tumorigenesis.J. Oncol.2011201111910.1155/2011/35261621197469
     [Google Scholar]
  62. SilvestreJ. KenisP.J.A. LeckbandD.E. Cadherin and integrin regulation of epithelial cell migration.Langmuir20092517100921009910.1021/la901109e19583181
     [Google Scholar]
/content/journals/cpd/10.2174/0113816128362600250203051056056
Loading
Untargeted Metabolomics Analysis of Vaginal Secretion Reveals Potential Pathogenesis of Atrophic Vaginitis
Curr. Pharm. Des. 31, 2290 (2025); https://doi.org/10.2174/0113816128362600250203051056056
/content/journals/cpd/10.2174/0113816128362600250203051056056
/content/journals/cpd/10.2174/0113816128362600250203051056056
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): Atrophic vaginitis; estrogen therapy; inflammation; pathogenesis; untargeted metabolomics; vaginal secretion

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test