Ethanol extract of Cyclea barbata Miers induces follicle development through 17ß-estradiol level and LHR expression
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HIGHLIGHTS
- Docking analysis revealed that there are four novel compounds in barbata, including Zearalenone, Bis(2-ethylhexyl) phthalate, Benzanthrone, and Octytldecyl phthalate have stronger affinity -9.7; -9.6; -9,2; and -7.7 kcal/mol, respectively.
- The extract of barbata leaves increased follicle development (75%) by elevating estrogen levels and LHR expression at all doses.
ABSTRACT
Objective: Infertility, often linked to anovulation from impaired follicular maturation, affects millions globally. Cyclea barbata Miers, a plant with estrogen-like properties, may enhance follicle development through hormonal modulation. This study evaluated the ethanol extract of C. barbata leaves for its ability to promote in vitro follicle development by increasing 17ß-estradiol levels and luteinizing hormone receptor (LHR) expression.
Materials and Methods: Molecular docking analysis identified four novel compounds in C. barbata—Zearalenone, Bis(2-ethylhexyl) phthalate, Benzanthrone, and Octyl decyl phthalate—with binding affinities of -9.7, -9.6, -9.2, and -7.7 kcal/mol to estrogen receptor alpha (ESRa). Secondary follicles (2-3 mm) from goat ovaries were cultured in vitro using TCM-199 medium supplemented with 10% FBS, PMSG, hCG, and C. barbata extract at 25, 50, or 100 ppm for six days. Follicle maturation was assessed via microscopy for size, cumulus-oocyte complex formation, and polar body extrusion. 17ß-estradiol levels and LHR expression were analyzed using one-way ANOVA and LSD tests.
Results: The 100 ppm dose achieved 75% follicle maturation, significantly higher than 25% at lower doses and controls. It increased 17ß-estradiol levels (36.83 ± 2.33 pg/mL, p < 0.000) and LHR expression (261.874 ± 54.606, p < 0.000), with dose-dependent effects confirmed by statistical analysis.
Conclusion: C. barbata extract at 100 ppm enhances follicular maturation by elevating 17ß-estradiol and LHR expression, likely due to its estrogenic compounds. Further in vivo and clinical studies are needed to confirm its therapeutic potential for ovulatory disorders.
Hsueh AJW, Kawamura K, Cheng Y, Fauser BCJM. Intraovarian control of early folliculogenesis. Endocr Rev. 2015 Feb;36(1):1–24.
Hanson B, Johnstone E, Dorais J, Silver B, Peterson CM, Hotaling J. Female infertility, infertility-associated diagnoses, and comorbidities: a review. J Assist Reprod Genet. 2017 Feb 5;34(2):167–77.
Omani Samani R, Almasi Hashiani A, Razavi M, Vesali S, Rezaeinejad M, Maroufizadeh S, et al. The prevalence of menstrual disorders in Iran: A systematic review and meta-analysis. Int J Reprod Biomed. 2018 Nov;16(11):665–78.
Bendarska-Czerwińska A, Zmarzły N, Morawiec E, Panfil A, Bryś K, Czarniecka J, et al. Endocrine disorders and fertility and pregnancy: An update. Front Endocrinol (Lausanne). 2023 Jan 17;13.
Duffy DM, Ko C, Jo M, Brannstrom M, Curry TE. Ovulation: Parallels With Inflammatory Processes. Endocr Rev. 2019 Apr 1;40(2):369–416.
Febrianto S, Praharsini FV, Annas ZF, Hanifa NI. Cyclea barbata L. Miers.: Penggunaan tradisional, fitokimia, dan aktivitas farmakologi. Sasambo Journal of Pharmacy. 2022 Sep 30;3(2):69–82.
Santi I, Putra B, Wahyuni S. Testing the effects of green cincau leaves (Cyclea barbata Miers) ethanol extract as an anti-inflammatory on white rats induced by caragen. As-syifaa. 2017;9(1):58–66.
Noviyanti N, Yueniwati Y, Ali M, Rahardjo B, Permatasari GW. Cyclea barbata Miers Ethanol Extract and Coclaurine Induce Estrogen Receptor α in the Development of Follicle Pre-ovulation. Open Access Maced J Med Sci. 2020 May 25;8(A):434–40.
Hafid A, Karja N, Setiadi M. Kompetensi Maturasi dan Fertilisasi Oosit Domba Prapubertas Secara In Vitro (Developmental Competence Of Maturation And Fertilization Prepubertal Sheep Oocytes In Vitro). Jurnal Veteriner. 2017 Apr 12;18(1):51–8.
Kiptiyah K, Widodo W, Ciptadi G, Aulanni’am A, Widodo MA, Sumitro SB. 10-Gingerol as an inducer of apoptosis through HTR1A in cumulus cells: In-vitro and in-silico studies. J Taibah Univ Med Sci. 2017 Oct;12(5):397–406.
Harris A, Rahayu S, Ciptadi G. The morphological measurement of immature oocyte obtained from follicle different size in Indonesian local goat. International Journal of Biosciences (IJB). 2014 Feb 27;4(4):211–6.
Satria YE, Yusuf TL, Amrozi. Penentuan Waktu Optimal Kawin Berdasarkan Ultrasonografi Ovarium dengan Gejala Klinis Estrus pada Kambing Peranakan Etawa (Determination Of Optimal Mating Time Based On Ovary Ultrasonography With Estrous Clinical Symptoms In
Etawa Crossbreed Goat). Jurnal Veteriner. 2016;17(1):64–70.
Widyastuti R, Syamsunarno MRAA, Saili T, Boediono A. Oocyte Quality and Subsequent In Vitro Maturation of Sheep Oocyte-Cumulus Complex from Ovary with Presence and Absence of Corpus Luteum. KnE Life Sciences. 2017 Dec 3;3(6):166.
Reichman D, Rosenwaks Z. The impact of genetic steroid disorders on human fertility. J Steroid Biochem Mol Biol. 2017 Jan;165:131–6.
Vrtačnik P, Ostanek B, Mencej-Bedrač S, Marc J. The many faces of estrogen signaling. Biochem Med (Zagreb). 2014;24(3):329–42.
Saxena VK, De K, Kumar D, Naqvi SMK, Krishnaswamy N, Tiwari AK. Induction of ovulation in anestrus ewes using a dopamine receptor antagonist. Theriogenology. 2015 Nov;84(8):1362–6.
Kishi H, Kitahara Y, Imai F, Nakao K, Suwa H. Expression of the gonadotropin receptors during follicular development. Reprod Med Biol. 2018 Jan 7;17(1):11–9.
Sarhan D, El Mazny A, Taha T, Aziz A, Azmy O, Fakhry D, et al. Estradiol and luteinizing hormone concentrations in the follicular aspirate during ovum pickup as predictors of in vitro fertilization (IVF) outcome. Middle East Fertil Soc J. 2017 Mar;22(1):27–32.
Samardzija D, Pogrmic-Majkic K, Fa S, Glisic B, Stanic B, Andric N. Atrazine blocks ovulation via suppression of Lhr and Cyp19a1 mRNA and estradiol secretion in immature gonadotropin-treated rats. Reproductive Toxicology. 2016 Jun;61:10–8.
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