Polycystic ovary syndrome: systematic review of recent research on theinvestigation of secondary metabolites for treatment

Ms. Victória Gomes Martins
OrcID
Dr. Gloria Narjara Santos da Silva
OrcID

    Ms. Victória Gomes Martins

    Federal University of Bahia (UFBA), Faculty of Pharmacy. Salvador, BA, Brazil.

    OrcID https://orcid.org/0000-0003-0505-7340

    Student of Pharmacy at the Federal University of Bahia; Scientific Initiation in the FitoEtnoBio research group at the UFBA Chemistry Institute in the areas of plant bioprospecting and natural product chemistry in the period (2019-2022); University Pharmacy Intern at the UFBA Faculty of Pharmacy (2023-current); Integrated Pharmacology Monitor (2023); Member of the Academic League of Pharmacology and Pharmacotherapy (2021-2023); Member of the Scientific Committee of the Academic League of Cosmetology in Pharmacy (2018-2019).

    Dr. Gloria Narjara Santos da Silva

    Federal University of Bahia (UFBA), Faculty of Pharmacy. Salvador, BA, Brazil.

    OrcID https://orcid.org/0000-0002-6584-201X

    He holds a degree in Pharmacy (2008) and a Master's degree in Pharmaceutical Sciences (2010) from the Federal University of Santa Maria (UFSM). He holds a PhD in Pharmaceutical Sciences (2014) from the Federal University of Rio Grande do Sul (UFRGS), with a sandwich internship at the Laboratory of Molecular and Cellular Biology of Plasmodium at the University of São Paulo (USP) (2011) and at the Department of Pharmacology and Physiology at Rutgers, The University of New Jersey, Newark, NJ, USA, (2013). Post-doctorate in the Graduate Program in Pharmaceutical Sciences - UFRGS (2014-2015) and Queen Mary University of London (QMUL), UK, (2016-2017). Advisor and professor in undergraduate and graduate courses at Universidade Regional Integrada (URI), Campus Frederico Westphalen, RS, (2014-2018) and at Universidade Federal de Goiás (UFG) as a substitute professor (2019-2021). Post-doctorate in the Postgraduate Program in Biological Sciences - PPGCB / UFG (2020-2021). Currently, she works as a Professor of Higher Education, Adjunct A, Class A, level I, in an Exclusive Dedication regime, in the Department of Medicine of the Faculty of Pharmacy of the Federal University of Bahia (UFBA). Main experience in research in the areas of medicinal chemistry and pharmacognosy, with emphasis on isolation, semi-synthesis, structural elucidation and evaluation of biological activity of plant chemical constituents and derivatives, especially of the terpene class.

Keywords

Women's Health
Polycystic Ovary Syndrome
Plant Secondary Metabolite
Preclinical and Clinical Research
In silico Prediction
Toxic Potentia

Abstract

The Polycystic Ovary Syndrome (PCOS) is a common disorder in women of reproductive age. PCOS carriers
are usually more susceptible to developing diabetes, cardiovascular diseases, and endometrial cancer,
resulting from inflammation, hyperandrogenism, and insulin resistance. Pharmacotherapy currently in use to
control PCOS has been accompanied by side effects, highlighting the relevance of research into new
treatments. Since secondary metabolites have shown potential in improving the symptomatic condition of
PCOS, this study aimed to conduct a systematic literature review addressing recent findings on this topic.
The databases used were BVS (Virtual Health Library), PubMed and Science Direct, with the inclusion
criteria being experimental articles in English, from the period 2020 to 2023, and isolated compounds from
plant species. As research resulted, 14 compounds were found, predominantly phenolic, with preclinical
and/or clinical studies. In the in silico analysis, 12 compounds did not violate Lipinski's and Veber's rules.
Regarding toxicity prediction, most compounds were classified in classes IV and V, considered to have
reduced toxicity if ingested. The data obtained point to the future of PCOS pharmacotherapy encompassing
compounds derived from natural sources. 

References

  1. Vilar L. Endocrinologia Clínica. 7th ed. 2021. 6ª ed. Rio de Janeiro: Guanabara Koogan, 2021. ISBN:
  2. -85-277-3032-7.
  3. Mitra S, Saharia, GK, Jena SK. Cardio-metabolic risk in Rotterdam clinical phenotypes of PCOS. Ann
  4. Endocrinol. 2024; 85(1): 44-7. ISSN: 0003-4266. [https://doi.org/10.1016/j.ando.2023.06.001].
  5. Escobar-Moreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev
  6. Endocrinol. 2018; 14(5): 270-84. ISSN: 1759-5037. [https://doi.org/10.1038/nrendo.2018.24].
  7. Azziz R. Polycystic ovary syndrome. Obst Gynec. 2018; 132(1): 321-36. ISSN: 0029-7844.
  8. [https://doi.org/10.1097/AOG.0000000000002698].
  9. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness
  10. and medicinal chemistry friendliness of small molecules. Sci Rep. 2017; 7(42717):. ISSN: 2045-2322.
  11. [https://doi.org/10.1038/srep42717].
  12. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to
  13. estimate solubility and permeability in drug discovery and development settings. Adv Drug Deli Rev. 1997;
  14. (1-3): 3-25. ISSN: 0169-409X. [https://doi.org/10.1016/S0169-409X(96)00423-1].
  15. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence
  16. the oral bioavailability of drug candidates. J Med Chem. 2002; 45(12): 2615-23. ISSN: 0022-2623.
  17. [https://doi.org/10.1021/jm020017n]
  18. Banerjee P, Kemmler E, Dunkel M, Preissner R. ProTox 3.0: a webserver for the prediction of toxicity of
  19. chemicals. Nucl Acid Res. 2024; 52 (W1): W513-20. ISSN: 1362-4962.
  20. [https://doi.org/10.1093/nar/gkae303].
  21. PCASRM: Practice Committee of the American Society for Reproductive Medicine. Role of metformin for
  22. ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): a guideline. Fertil Steril.
  23. ; 108(3): 426-41. ISSN: 0015-0282. [https://doi.org/10.1016/j.fertnstert.2017.06.026].
  24. Cena H, Chiovato L, Nappi RE. Obesity, polycystic ovary syndrome, and infertility: a new avenue for
  25. GLP-1 receptor agonists. J Clin Endocrin Metab. 2020; 105(8): e2695-e2709. ISSN: 1945-7197.
  26. [https://doi.org/10.1210/clinem/dgaa285].
  27. Jung W, Choi H, Kim J, Kim J, Kim W, Nurkolis F, et al. Effects of natural products on polycystic ovary
  28. syndrome: From traditional medicine to modern drug discovery. Heliyon. 2023; 9(10): e20889. ISSN: 2405-
  29. [https://doi.org/10.1016/j.heliyon.2023.e20889].
  30. Choi JH, Jang M, Kim EJ, Lee MJ, Park KS, Kim SH, et al. Korean Red Ginseng alleviates
  31. dehydroepiandrosterone-induced polycystic ovarian syndrome in rats via its anti-inflammatory and
  32. antioxidant activities. J Ginseng Res. 2020; 44(6): 790-8. ISSN: e2093-4947.
  33. [https://doi.org/10.1016/j.jgr.2019.08.007].
  34. Zhang Y, Guo X, Ma S, Ma H, Li H, Wang Y, et al. The treatment with complementary and alternative
  35. traditional Chinese medicine for menstrual disorders with polycystic ovary syndrome. Evid Based
  36. Complement Alternat Med. 2021; 2021(6678398): 1-19. ISSN: 1741-4288.
  37. [https://doi.org/10.1155/2021/6678398].
  38. Moreno NT, Santos L, Udulutsch RG. Etnobotânica aliada à saúde da mulher no SUS: um estudo com
  39. a Comunidade Tradicional Caiçara do Sertão do Ubatumirim/Ubatuba/SP. Rev Fitos. 2024; 18(1): e1533.
  40. e-ISSN: 2446-4775. [https://doi.org/10.32712/2446-4775.2024.1533].
  41. Iervolino M, Lepore E, Forte G, Laganà AS, Buzzaccarini G, Unfer V. Natural molecules in the
  42. management of polycystic ovary syndrome (PCOS): an analytical review. Nutrients. 2021; 13(5): 1-12.
  43. ISSN: 2072-6643. [https://doi.org/10.3390/nu13051677].
  44. Wu J, Li J, Li W, Sun B, Xie J, Cheng W, et al. Achyranthis bidentatae radix enhanced articular
  45. distribution and anti-inflammatory effect of berberine in Sanmiao Wan using an acute gouty arthritis rat
  46. model. J Ethnopharmacol. 2018; 221: 100–8. ISSN: 0378-8741.
  47. [https://doi.org/10.1016/j.jep.2018.04.025].
  48. Jin F, Xie T, Huang X, Zhao X. Berberine inhibits angiogenesis in glioblastoma xenografts by targeting
  49. the VEGFR2/ERK pathway. Pharm Biol. 2018; 56(1): 665–71. ISSN: 1388-0209.
  50. [https://doi.org/10.1080/13880209.2018.1548627].
  51. Zhang N, Liu X, Zhuang L, Liu X, Zhao H, Shan Y, et al. Berberine decreases insulin resistance in a
  52. PCOS rats by improving GLUT4: dual regulation of the PI3K/AKT and MAPK pathways. Regul Tox and
  53. Pharm. 2020; 110(104544): 1-6. ISSN: 0273-2300. [https://doi.org/10.1016/j.yrtph.2019.104544].
  54. Fernandes FHA, Salgado HRN. Gallic Acid: Review of the Methods of Determination and Quantification.
  55. Crit Rev Anal Chem. 2016; 46(3): 257-65. ISSN: 1547-6510.
  56. [https://doi.org/10.1080/10408347.2015.1095064].
  57. Choubey S, Varughese LR, Kumar V, Beniwal V. Medicinal importance of gallic acid and its ester
  58. derivatives: a patent review. Pharm Pat Anal. 2015; 4(4): 305-15. ISSN: 2046-8954.
  59. [https://doi.org/10.4155/ppa.15.14].
  60. Shah MZH, Soni M, Shrivastava VK, Mir MA, Muzamil S. Gallic acid reverses ovarian disturbances in
  61. mice with letrozole-induced PCOS via modulating Adipo R1 expression. Tox Rep. 2022; 9(2022): 1938-49.
  62. ISSN: 2214-7500. [https://doi.org/10.1016/j.toxrep.2022.10.009].
  63. Patisaul HB, Jefferson W. The pros and cons of phytoestrogens. Front Neuroendocrinol. 2010; 31(4):
  64. –19. ISSN: 0091-3022. [https://doi.org/10.1016/j.yfrne.2010.03.003].
  65. Kim IS. Current perspectives on the beneficial effects of soybean isoflavones and their metabolites for
  66. humans. Antioxidants. 2021; 10(7): 1064. ISSN: 2076-3921. [https://doi.org/10.3390/antiox10071064].
  67. Kotipalli RSS, Patnaik SS, Kumar JM, Ramakrishna S, Muralidharan K. Biochanin-A attenuates DHEAinduced polycystic ovary syndrome via upregulation of GDF9 and BMP15 signaling in vivo. Life Sci. 2023;
  68. (121795): 1-12. ISSN: 0024-3205. [https://doi.org/10.1016/j.lfs.2023.121795].
  69. Choi SH, Shapiro H, Robinson GE, Irvine J, Neuman J, Rosen B, et al. Psychological side-effects of
  70. clomiphene citrate and human menopausal gonadotrophin. J Psychosom. Obstet Gynaecol. 2005; 26(2):
  71. -100. ISSN: 1743-8942. [https://doi.org/10.1080/01443610400022983].
  72. Arun N, Nalini N. Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats. Plant
  73. Foods Hum Nutr. 2002; 57(1): 41–52. ISSN: 0921-9668. [https://doi.org/10.1023/a:1013106527829].
  74. Pari L, Murugan P. Effect of tetrahydrocurcumin on blood glucose, plasma insulin and hepatic key
  75. enzymes in streptozotocin induced diabetic rats. J Basic Clin Physiol Pharmacol. 2005; 16(4): 257-74.
  76. ISSN: 2191-0286. [https://doi.org/10.1515/jbcpp.2005.16.4.257].
  77. Abuelezz NZ, Shabana ME, Abdel-Mageed HM, Rashed L, Morcos GN. Nanocurcumin alleviates insulin
  78. resistance and pancreatic deficits in polycystic ovary syndrome rats: Insights on PI3K/AkT/mTOR and TNF-α modulations. Life Sci. 2020; 256(118003): 1-11. ISSN: 0024-3205.
  79. [https://doi.org/10.1016/j.lfs.2020.118003].
  80. Abhari SMF, Khanbabaei R, Roodbari, NH, Parivar K, Yaghmaei P. Curcumin-loaded superparamagnetic iron oxide nanoparticle affects on apoptotic factors expression and histological changes in a
  81. prepubertal mouse model of polycystic ovary syndrome-induced by dehydroepiandrosterone-A molecular
  82. and stereological study. Life Sci. 2020; 249(117515): 1-9. ISSN: 0024-3205.
  83. [https://doi.org/10.1016/j.lfs.2020.117515].
  84. Bari YN, Babapour V, Ahmadi A, Kheybari MZ, Akbari G. The effect of curcumin on embryonic in vitro
  85. development in experimental polycystic ovary syndrome: An experimental study. Int J Reprod Biomed.
  86. ; 19(11): 997–1004. ISSN: 1680-6433. [https://doi.org/10.18502/ijrm.v19i11.9915].
  87. Jamilian M, Foroozanfard F, Kavossian E, Aghadavod E, Shafabakhsh R, Hoseini A, et al. Effects of
  88. curcumin on body weight, glycemic control and serum lipids in women with polycystic ovary syndrome: A
  89. randomized, double-blind, placebo-controlled trial. Clin nutr ESPEN. 2020; 36(2020): 128-33. ISSN: 2405-
  90. [https://doi.org/10.1016/j.clnesp.2020.01.005].
  91. Heshmati J, Moini A, Sepidarkish M, Morvaridzadeh M, Salehi M, Palmowski A, et al. Effects of curcumin
  92. supplementation on blood glucose, insulin resistance and androgens in patients with polycystic ovary
  93. syndrome: A randomized double-blind placebo-controlled clinical trial. Phytomed. 2021; 80(153395): 1-7.
  94. ISSN: 0944-7113. [https://doi.org/10.1016/j.phymed.2020.153395].
  95. Ghanbarzadeh-Ghashti N, Ghanbari-Homaie S, Shaseb E, Abbasalizadeh S, Mirghafourvand M. The
  96. effect of Curcumin on metabolic parameters and androgen level in women with polycystic ovary syndrome:
  97. a randomized controlled trial. BMC Endoc Disor. 2023; 23(40): 1-10. ISSN: 1472-6823.
  98. [https://doi.org/10.1186/s12902-023-01295-5].
  99. Shi YS, Li CB, Li XY, Wu J, Li Y, Fu X, et al. Fisetin attenuates metabolic dysfunction in mice challenged
  100. with a high-fructose diet. J Agric Food Chem. 2018; 66(31): 8291-8. ISSN: 1520-5118.
  101. [https://doi.org/10.1021/acs.jafc.8b02140].
  102. Prasath GS, Pillai SI, Subramanian SP. Fisetin improves glucose homeostasis through the inhibition of
  103. gluconeogenic enzymes in hepatic tissues of streptozotocin induced diabetic rats. Eur J Pharmacol. 2014;
  104. : 248-54. ISSN: 0014-2999. [https://doi.org/10.1016/j.ejphar.2014.06.065].
  105. Kim SC, Kim YH, Son SW, Moon EY, Pyo S, Um SH, Fisetin induces Sirt1 expression while inhibiting
  106. early adipogenesis in 3T3-L1 cells. Biochem Biophys Res Commun. 2015; 467(4): 638-44. ISSN: 1090-
  107. [ https://doi.org/10.1016/j.bbrc.2015.10.094 ].
  108. Mihanfar A, Nouri M, Roshangar L, Khadem-Ansari MH. Ameliorative effects of fisetin in letrozoleinduced rat model of polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2021; 213(105954): 1-10.
  109. ISSN: 0960-0760. [https://doi.org/10.1016/j.jsbmb.2021.105954].
  110. Indran IR, Zhang SJ, Zhang ZW, Sun F, Gong Y, Wang X, et al. Selective estrogen receptor modulator
  111. effects of Epimedium extracts on breast cancer and uterine growth in nude mice. Planta Med. 2014; 80(1):
  112. -8. ISSN: 0032-0943. [https://doi.org/10.1055/s-0033-1360112].
  113. Tang Y, Li Y, Xin D, Chen L, Xiong Z, Yu X. Icariin alleviates osteoarthritis by regulating autophagy of
  114. chondrocytes by mediating PI3K/AKT/mTOR signaling. Bioengineered. 2021; 12(1): 2984-99. ISSN: 2165-
  115. [https://doi.org/10.1080/21655979.2021.1943602].
  116. He C, Wang, Z, Shi, J. Pharmacological effects of Icariin. Adv Pharmacol. 2020; 87(2020): 179–203.
  117. ISSN: 2633-4682. [https://doi.org/10.1016/bs.apha.2019.10.004].
  118. Zuo L, Hai Y, Zhang R, Zuo B, Tian J, Li P, et al. Therapeutic potential of icariin in rats with letrozole and
  119. high-fat diet-induced polycystic ovary syndrome. Europ J Pharm. 2023; 953(175825): 1-14. ISSN: 0014-
  120. [https://doi.org/10.1016/j.ejphar.2023.175825 ].
  121. Cui CA, Jin DQ, Hwang YK, Lee IS, Hwang JK, Ha I et al. Macelignan attenuates LPS-induced
  122. inflammation and reduces LPS-induced spatial learning impairments in rats. Neurosci Lett. 2008;
  123. (1): 110-4. ISSN: 0304-3940. [https://doi.org/10.1016/j.neulet.2008.10.035].
  124. Jin DQ, Lim CS, Hwang JK, Ha I, Han JS. Antioxidant and anti-inflammatory activities of macelignan in
  125. murine hippocampal cell line and primary culture of rat microglial cells. Biochem. Biophys. Res Commun.
  126. ; 331(4): 1264-9. ISSN: 0006-291X. [https://doi.org/10.1016/j.bbrc.2005.04.036].
  127. Shi XJ, Du Y, Chen L, Chen, YY, Luo M, Cheng Y. Treatment of polycystic ovary syndrome and its
  128. associated psychiatric symptoms with the Mongolian medicine Nuangong Qiwei Pill and macelignan. J
  129. Ethnopharmacol. 2023; 317(116812): 1-12. ISSN: 0378-8741. [https://doi.org/10.1016/j.jep.2023.116812].
  130. Wu YX, Yang XY, Han BS, Hu YY, An T, Lv BH, et al. Naringenin regulates gut microbiota and
  131. SIRT1/PGC-1ɑ signaling pathway in rats with letrozole-induced polycystic ovary syndrome. Biomed
  132. Pharmacother. 2022; 153(113286). ISSN: 0753-3322. [https://doi.org/10.1016/j.biopha.2022.113286].
  133. Dashputre NL, Laddha UD, Patil SB, Kadam JD, Kshirsagar SJ. An insight to development and in-vitro,
  134. ex-vivo, in-vivo study of naringenin nanoparticles against letrozole induced polycystic ovarian syndrome in
  135. female wistar rats. J Drug Del Sci Tech. 2023; 90(105129): 1-19. ISSN: 1773-2247.
  136. [https://doi.org/10.1016/j.jddst.2023.105129].
  137. Rashid R, Tripathi R, Singh A, Sarkar S, Kawale A, Bader GN, et al. Naringenin improves ovarian health
  138. by reducing the serum androgen and eliminating follicular cysts in letrozole‐induced polycystic ovary
  139. syndrome in the Sprague Dawley rats. Phytoth Res. 2023; 37(9): 4018-4041. ISSN: 1099-1573.
  140. [https://doi.org/10.1002/ptr.7860].
  141. David AVA, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: a bioactive
  142. flavonoid. Phcog Rev. 2016; 10(20): 84-9. ISSN: 0973-7847. [https://doi.org/10.4103/0973-7847.194044].
  143. Mihanfar A, Nouri M, Roshangar L, Khadem-Ansari MH. Therapeutic potential of quercetin in an animal
  144. model of PCOS: Possible involvement of AMPK/SIRT-1 axis. Europ J Pharm. 2021; 900(174062): 1-9.
  145. ISSN: 0014-2999. [https://doi.org/10.1016/j.ejphar.2021.174062].
  146. Mahmoud AA, Elfiky AM, Abo-Zeid FS. The anti-androgenic effect of quercetin on hyperandrogenism
  147. and ovarian dysfunction induced in a dehydroepiandrosterone rat model of polycystic ovary syndrome.
  148. Steroids. 2022; 177(108936): 1-12. ISSN: 0039-128X. [https://doi.org/10.1016/j.steroids.2021.108936].
  149. Zheng S, Chen Y, Ma M, Li M. Mechanism of quercetin on the improvement of ovulation disorder and
  150. regulation of ovarian CNP/NPR2 in PCOS model rats. J Form Med Assoc. 2022; 121(6): 1081-92. ISSN:
  151. -6646. [https://doi.org/10.1016/j.jfma.2021.08.015].
  152. Tang J, Diao P, Shu X, Li L, Xiong L. Quercetin and Quercitrin Attenuates the Inflammatory Response
  153. and Oxidative Stress in LPS-Induced RAW264.7 Cells: In Vitro Assessment and a Theoretical Model.
  154. Biomed Res Int. 2019; 28(7039802): 1-8. ISSN: 2314-6141. [https://doi.org/10.1155/2019/7039802].
  155. Li M, Gao S, Kang M, Zhang X, Lan P, Wu X et al. Quercitrin alleviates lipid metabolism disorder in
  156. polycystic ovary syndrome-insulin resistance by upregulating PM20D1 in the PI3K/Akt pathway. Phytomed.
  157. ; 117(154908): 1-14. ISSN: 0944-7113. [https://doi.org/10.7150/10.1016/j.phymed.2023.154908].
  158. Ortega I, Duleba AJ. Ovarian actions of resveratrol. Ann N Y Acad Sci. 2015; 1348(1): 86-96. ISSN:
  159. -6632. [https://doi.org/10.1111/nyas.12875].
  160. Rege SD, Kumar S, Wilson DN, Tamura L, Geetha T, Mathews ST, et al. Resveratrol protects the brain
  161. of obese mice from oxidative damage. Oxid Med Cell Longev. 2013; 2013(429092): 1-7. ISSN: 1942-0994.
  162. [https://doi.org/10.1155/2013/419092].
  163. Rauf A, Imran M, Suleria HAR, Ahmad B, Peters DG, Mubarak MS. A comprehensive review of the
  164. health perspectives of resveratrol. Food Funct. 2017; 13;8(12): 4284-305. ISSN: 2042-650X.
  165. [https://doi.org/10.1039/c7fo01300k].
  166. Mansour A, Samadi M, Sanginabadi M, Gerami H, Karimi S, Hosseini S, et al. Effect of resveratrol on
  167. menstrual cyclicity, hyperandrogenism and metabolic profile in women with PCOS. Clin Nutri. 2021; 40(6):
  168. -12. ISSN: 0261-5614. [https://doi.org/10.1016/j.clnu.2021.02.004].
  169. Chen M, He C, Zhu K, Chen Z, Meng Z, Jiang X, et al. Resveratrol ameliorates polycystic ovary syndrome
  170. via transzonal projections within oocyte-granulosa cell communication. Theran. 2022; 12(2): 782-95. ISSN:
  171. -7640. [https://doi.org/10.7150/thno.67167].
  172. Liang Y, Xu ML, Gao X, Wang Y, Zhang LN, Li YC, et al. Resveratrol improves ovarian state by inhibiting
  173. apoptosis of granulosa cells. Gynecol Endocr. 2023; 39(1): 1-6. ISSN: 1473-0766.
  174. [https://doi.org/10.1080/09513590.2023.2181652].
  175. Chan WK, Tan LTH, Chan KG, Lee LH, Goh BH. Nerolidol: a sesquiterpene alcohol with multi-faceted
  176. pharmacological and biological activities. Molecules. 2016; 21(5): 1-40. ISSN: 1420-3049.
  177. [https://doi.org/10.3390/molecules21050529].
  178. Fonsêca DV, Salgado PR, Carvalho FL, Salvadori MGS, Penha ARS, Leite FC, Almeida RN. Nerolidol
  179. exhibits antinociceptive and anti‐inflammatory activity: involvement of the GABAergic system and
  180. proinflammatory cytokines. Fundam Clin Pharmacol. 2015; 30(1): 14-22. ISSN: 0767-3981.
  181. [https://doi.org/10.1111/fcp.12166].
  182. Carvalho RB, Almeida AAC, Campelo NB, Lellis DROD, Nunes LCC. Nerolidol and its pharmacological
  183. application in treating neurodegenerative diseases: A review. Recent Pat Biotechnol. 2018; 12(3), 158-68.
  184. ISSN: 1872-2083. [https://doi.org/10.2174/1872208312666171206123805].
  185. Türkmen NB, Yüce H, Aydın M, Taşlıdere A, Doğan A, Özek DA, et al. Nerolidol attenuates
  186. dehydroepiandrosterone-induced polycystic ovary syndrome in rats by regulating oxidative stress and
  187. decreasing apoptosis. Life Sci. 2023; 315(121380): 1-15. ISSN: 0024-3205.
  188. [https://doi.org/10.1016/j.lfs.2023.121380].
  189. Tang C, Zhao CC, Yi H, Geng ZJ, Wu XY, Zhang Y, et al. Traditional Tibetan medicine in cancer therapy
  190. by targeting apoptosis pathways. Front Pharmacol. 2020; 11(976): 1-19. ISSN: 1663-9812.
  191. [https://doi.org/10.3389/fphar.2020.00976].
  192. Nabavi SF, Braidy N, Orhan IE, Badiee A, Daglia M, Nabavi SM. Rhodiola rosea L. and alzheimer’s
  193. disease: from farm to pharmacy. Phytother Res. 2016; 30(4): 532-9. ISSN: 1099-1573. [
  194. https://doi.org/10.1002/ptr.5569 ].
  195. Zheng T, Bian F, Chen L, Wang Q, Jin S. Beneficial effects of Rhodiola and salidroside in diabetes:
  196. potential role of AMP-activated protein kinase. Mol Diagn Ther. 2019; 23(4): 489-98. ISSN: 1177-1062. [
  197. https://doi.org/10.1007/s40291-019-00402-4 ].
  198. Ji R, Jia FY, Chen X, Wang ZH, Jin WY, Yang J. Salidroside alleviates oxidative stress and apoptosis
  199. via AMPK/Nrf2 pathway in DHT-induced human granulosa cell line KGN. Arch Biochem Bioph. 2022;
  200. (109094): 1-13. ISSN: 0003-9861. [ https://doi.org/10.1016/j.abb.2021.109094 ].
  201. Kubo E, Chhunchha B, Singh P, Sasaki H, Singh DP. Sulforaphane reactivates cellular antioxidant
  202. defense by inducing Nrf2/ARE/Prdx6 activity during aging and oxidative stress. Sci Rep. 2017; 7(14130): 1-
  203. ISSN: 2045-2322. [ http://dx.doi.org/10.1038/s41598-017-14520-8 ].
  204. Taheri M, Roudbari NH, Amidi F, Parivar K. The protective effect of sulforaphane against oxidative stress
  205. in granulosa cells of patients with polycystic ovary syndrome (PCOS) through activation of AMPK/AKT/NRF2
  206. signaling pathway. Reprod Biol. 2021; 21(4): 1-8. ISSN: 1642-431X. [
  207. https://doi.org/10.1016/j.repbio.2021.100563 ].
  208. Lipinski CA. Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry
  209. structure and drug discovery project decisions. Adv Drug Deli Rev. 2016; 101: 34-41. ISSN: 0169-409X.
  210. [http://dx.doi.org/10.1016/j.addr.2016.04.029].
  211. Moreira ES, Ames-Sibin AP, Bonetti CI, Leal LE, Peralta RM, Sá-Nakanishi AB, et al. The short-term
  212. effects of berberine in the liver: narrow margins between benefits and toxicity. Tox Letters. 2022; 368: 56-
  213. ISSN: 0378-4274. [https://doi.org/10.1016/j.toxlet.2022.08.005].
  214. Pihl C, Granborg JR., Pinto FE, Bjerring P, Andersen F, Janfelt C, et al. Oral administration of quercetin
  215. and fisetin potentiates photocarcinogenesis in UVR-exposed hairless mice. Phytomed Plus. 2024; 4(2): 1-
  216. ISSN: 2667-0313. [https://doi.org/10.1016/j.phyplu.2024.100547].
  217. Huang R, Xia M, Nguyen DT, Zhao T, Sakamuru S, Zhao J, et al. Tox21Challenge to build predictive
  218. models of nuclear receptor and stress response pathways as mediated by exposure to environmental
  219. chemicals and drugs. Front Environ Sci. 2016; 3(85): 1-9. ISSN: 2296-665X.
  220. [https://doi.org/10.3389/fenvs.2015.00085].
PDF (Portuguese)
HTML (Portuguese)
XML (Portuguese)
Save bookmark

Author(s)

Metrics

  • Article viewed 417 time(s)

How to Cite

1.
Polycystic ovary syndrome: systematic review of recent research on theinvestigation of secondary metabolites for treatment. Rev Fitos [Internet]. 2025 Apr. 15 [cited 2025 Dec. 19];19:e1729. Available from: https://revistafitos.far.fiocruz.br/index.php/revista-fitos/article/view/1729
Crossref
Scopus
Google Scholar
Europe PMC
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright (c) 2025 Revista Fitos

Report an error