Anti-Fertility Potential of Aceh Areca Nut Seed Extract: Phytochemical Analysis and Molecular Docking Study
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Areca nut seeds are rich in alkaloids, terpenoids, flavonoids, phenolics, and tannins, which exhibit antibacterial, anti-oxidant, anti-inflammatory, and anti-fertility properties. However, the specific active constituents of Aceh areca nut seeds and their impact on anti-fertility effects remain unknown. This study aims to identify the active compounds in the ethanolic extract of locally obtained Aceh areca nut (Areca catechu) seeds and assess their potential as inhibitors of Follicle Stimulating Hormone (FSH), testosterone, Bone Morphogenic Protein 4 (BMP4), Mothers Against Decapentaplegic Signaling 1 (SMAD1), and protamine 1 by molecular docking approach. The composition of the ethanolic extract of Acehnese areca nut seeds was determined through phytochemical analysis, 2,2-diphenyl-1picrylhydrazyl (DPPH) assay, Fourier Transform Infra-Red (FT-IR), Gas Chromatography-Mass Spectrometry (GC-MS) analysis while the biological activity of its compounds was evaluated through molecular docking. Phytochemical test results showed the presence of alkaloids, terpenoids, flavonoids, phenolics and tannins in the ethanolic extract of Aceh areca nut seeds. The antioxidant activity was very strong with an IC50 value of 28.215 ppm. GC-MS analysis identified the compound n-hexadecanoic acid (32.29%) as the main component in the ethanolic extract of Aceh areca nut seeds, along with cis-vaccenic acid (14.75%) which is a fatty acid. Molecular docking analysis showed that lupeol and stigmasta-3,5-diene demonstrated superior binding energies compared to a standard anti-fertility agent. These findings suggest that compounds from the ethanolic extract of Acehnese areca nut seeds have potential as inhibitors of FSH, testosterone, protamine 1, BMP4, SMAD1 based on their binding energies for further testing as new anti-fertility agents.
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[1] Sun, H., Yu, W., Li, H., Hu, X., & Wang, X. (2024). Bioactive components of areca nut: an overview of their positive impacts targeting different organs. Nutrients, 16(5), 695. doi:10.3390/nu16050695.
[2] Guo, Z., Wang, Z., Luo, Y., Ma, L., Hu, X., Chen, F., Li, D., & Jia, M. (2024). Extraction and identification of bioactive compounds from areca nut (Areca catechu L.) and potential for future applications. Food Frontiers, 5(5), 1909–1932. doi:10.1002/fft2.443.
[3] Ansari, A., Mahmood, T., Bagga, P., Ahsan, F., Shamim, A., Ahmad, S., Shariq, M., & Parveen, S. (2021). Areca catechu: A phytopharmacological legwork. Food Frontiers, 2(2), 163–183. doi:10.1002/fft2.70.
[4] Wu, J., Cui, C., Zhang, H., Liu, D., Schreiber, L., Qin, W., & Wan, Y. (2021). Identifying new compounds with potential pharmaceutical and physiological activity in Areca catechu and Areca triandra via a non-targeted metabolomic approach. Phytochemical Analysis, 32(6), 970–981. doi:10.1002/pca.3039.
[5] Hazra, S., Pal, D., Das, P., Mitra, D., Mondal, T., & Ghosh, D. (2024). Pre-clinical study on hypo-testicular activity of hydro-ethanol (60:40) extract of Areca catechu (L.) in albino rat: Dose-dependent response. International Journal of Ayurvedic Medicine, 15(2), 480–489. doi:10.47552/ijam.v15i2.4669.
[6] Zahara, E., Darmawi, Balqis, U., & Soraya, C. (2024). The Potential of Ethanol Extract of Aleurites Moluccanus Leaves as TNF-α Inhibitor in Oral Incision Wound Care Model. Journal of Human, Earth, and Future, 5(4), 674–687. doi:10.28991/HEF-2024-05-04-010.
[7] Rahman, A. O., Purwakanthi, A., & Dewi, H. (2020). Antifertility effect of betel nut (Areca catechu L) in male rat. Medisains, 18(2), 52. doi:10.30595/medisains.v18i2.7588.
[8] Kafle, S., Shanbhag, T., Shenoy, S., Amuthan, A., Prabhu, K., Mohan, S., Somayaji, S. N., & Shrestha, J. (2011). Antifertility effect of Areca catechu in male albino rats. International Journal of Pharmaceutical Sciences Review and Research, 10(1), 79–82.
[9] Ardiyansyah, F., & Utomo, T. (2014). Correlation of Follicle Stimulating Hormone and Luteinising Hormone with Testicular Sperm Biopsy Result. Indonesian Journal of Urology, 21(2), 1–5. doi:10.32421/juri.v21i2.35.
[10] Babu, S. R., Sadhnani, M. D., Swarna, M., Padmavathi, P., & Reddy, P. P. (2004). Evaluation of FSH, LH and testosterone levels in different subgroups of infertile males. Indian Journal of Clinical Biochemistry, 19(1), 45–49. doi:10.1007/BF02872388.
[11] Liu, Y., Wang, G., Zhang, F., & Dai, L. (2022). Correlation between serum levels of reproductive hormones and testicular spermatogenic function in men with azoospermia. Andrologia, 54(10), e14546. doi:10.1111/and.14546.
[12] Harborne, A. J. (1998). Phytochemical methods a guide to modern techniques of plant analysis. Springer Science & Business Media, Dordrecht, Germany.
[13] Sitio, R., Akmal, M., Marlina, & Gholib. (2024). Phytochemical screening of ethanolic extract of local Aceh lime (Citrus aurantifolia (Christm.) Swingle) peels. IOP Conference Series: Earth and Environmental Science, 1356(1), 012080. doi:10.1088/1755-1315/1356/1/012080.
[14] Sitio, R., Akmal, M., Marlina, M., & Gholib, G. (2024). Investigating Ethanolic Extract from Acehnese Lime (Citrus aurantifolia) Peel as Potential Anti-Hypercholesterolemia Agent. Journal of Human, Earth, and Future, 5(3), 348–365. doi:10.28991/hef-2024-05-03-04.
[15] Molyneux, P. (2004). The Use of the Stable Free Radical Diphenylpicryl-hydrazyl (DPPH) for Estimating Antioxidant Activity. Songklanakarin Journal of Science and Technology, 26(December), 211–219.
[16] Berman, H. M., Battistuz, T., Bhat, T. N., Bluhm, W. F., Bourne, P. E., Burkhardt, K., Feng, Z., Gilliland, G. L., Iype, L., Jain, S., Fagan, P., Marvin, J., Padilla, D., Ravichandran, V., Schneider, B., Thanki, N., Weissig, H., Westbrook, J. D., & Zardecki, C. (2002). The protein data bank. Acta Crystallographica Section D: Biological Crystallography, 58(6-I), 899–907. doi:10.1107/S0907444902003451.
[17] Maulydia, N. B., Khairan, K., Tallei, T. E., Salaswati, S., Musdalifah, A., Nabila, F. F., & Idroes, R. (2024). Exploring the Medicinal Potential of Blumea balsamifera: Insights from Molecular Docking and Molecular Dynamics Simulations Analyses. Malacca Pharmaceutics, 2(1), 33–40. doi:10.60084/mp.v2i1.168.
[18] Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky, L., Zhang, J., & Bolton, E. E. (2023). PubChem 2023 update. Nucleic Acids Research, 51(D1), D1373–D1380. doi:10.1093/nar/gkac956.
[19] Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461. doi:10.1002/jcc.21334.
[20] Louise, G., Salutan, H., & Billacura, M. P. (2015). Phytochemical Screening and Evaluation of the Toxicity, Antimicrobial and Anthelmintic Properties of the Different Extracts from the Air-dried Seeds of Areca catechu Linn. Conference: 2015 Annual Philippine-American Academy of Science and Engineering Meeting and Symposium, De La Salle University, Manila, Philippines.
[21] Nandiyanto, A. B. D., Oktiani, R., & Ragadhita, R. (2019). How to read and interpret ftir spectroscope of organic material. Indonesian Journal of Science and Technology, 4(1), 97–118. doi:10.17509/ijost.v4i1.15806.
[22] Hussein, H. J., Hadi, M. Y., & Hameed, I. H. (2016). Study of chemical composition of Foeniculum vulgare using Fourier transform infrared spectrophotometer and gas chromatography - mass spectrometry. Journal of Pharmacognosy and Phytotherapy, 8(3), 60–89. doi:10.5897/JPP2015.0372.
[23] Maulydia, N. B., Khairan, K., Tallei, T. E., Fauzi, F. M., & Idroes, R. (2024). Analysis of geothermal impact on metabolite compounds of heat-tolerant plant species using clustering and similarity cliff. Global Journal of Environmental Science and Management, 10(4), 1827–1842. doi:10.22034/gjesm.2024.04.20.
[24] Yang, W., Chen, X., Li, Y., Guo, S., Wang, Z., & Yu, X. (2020). Advances in Pharmacological Activities of Terpenoids. Natural Product Communications, 15(3), 1934578X20903555. doi:10.1177/1934578X20903555.
[25] Prakash, V. (2017). Terpenoids as source of anti-inflammatory compounds. Asian Journal of Pharmaceutical and Clinical Research, 10(3), 68–76. doi:10.22159/ajpcr.2017.v10i3.16435.
[26] Suleman, M. (2018). Antioxidants, its role in preventing free radicals and infectious diseases in human body. Pure and Applied Biology, 7(4), 380-388. doi:10.19045/bspab.2018.700197.
[27] Lourenço, S. C., Moldão-Martins, M., & Alves, V. D. (2019). Antioxidants of natural plant origins: From sources to food industry applications. Molecules, 24(22), 14–16. doi:10.3390/molecules24224132.
[28] Boligon, A. A. (2014). Technical Evaluation of Antioxidant Activity. Medicinal Chemistry, 4(7), 517–522. doi:10.4172/2161-0444.1000188.
[29] Walke, G., Gaurkar, S. S., Prasad, R., Lohakare, T., & Wanjari, M. (2023). The Impact of Oxidative Stress on Male Reproductive Function: Exploring the Role of Antioxidant Supplementation. Cureus, 15(7), 1–13. doi:10.7759/cureus.42583.
[30] Trüeb, R. M. (2015). The impact of oxidative stress on hair. International Journal of Cosmetic Science, 37, 25–30. doi:10.1111/ics.12286.
[31] Sharma, S., Ahire, D., Basit, A., Lajoie, M., Wang, C., Lee, M. S., Blithe, D. L., Amory, J. K., Singh, D. K., Heyward, S., & Prasad, B. (2022). Dimethandrolone, a Potential Male Contraceptive Pill, is Primarily Metabolized by the Highly Polymorphic UDP-Glucuronosyltransferase 2B17 Enzyme in Human Intestine and Liver. Drug Metabolism and Disposition, 50(12), 1493–1500. doi:10.1124/dmd.122.001041.
[32] Walker, W. H., & Cheng, J. (2005). FSH and testosterone signaling in Sertoli cells. Reproduction, 130(1), 15–28. doi:10.1530/rep.1.00358.
[33] Gunasekaran, M. (2022). Molecular docking analysis of lupeol with different cancer targets. Bioinformation, 18(3), 134–140. doi:10.6026/97320630018134.
[34] Saleem, M. (2009). Lupeol, a novel anti-inflammatory and anti-cancer dietary triterpene. Cancer Letters, 285(2), 109–115. doi:10.1016/j.canlet.2009.04.033.
[35] Patočka, J. (2012). Biologically active pentacyclic triterpenes and their current medicine signification. Journal of Applied Biomedicine, 10(3), 7–12. doi:10.32725/jab.2003.002.
[36] Wang, G., Tang, W., & Bidigare, R. R. (2005). Terpenoids as therapeutic drugs and pharmaceutical agents. In Natural products: drug discovery and therapeutic medicine. Humana Press, Totowa, United States.
[37] Upton, P. D., Long, L., Trembath, R. C., & Morrell, N. W. (2008). Functional characterization of bone morphogenetic protein binding sites and Smad1/5 activation in human vascular cells. Molecular Pharmacology, 73(2), 539–552. doi:10.1124/mol.107.041673.
[38] Pantsar, T., & Poso, A. (2018). Binding affinity via docking: Fact and fiction. Molecules, 23(8), 1899. doi:10.3390/molecules23081899.
[39] Shrestha, J., Shanbhag, T., Shenoy, S., Amuthan, A., Prabhu, K., Sharma, S., Banerjee, S., & Kafle, S. (2010). Antiovulatory and abortifacient effects of Areca catechu (betel nut) in female rats. Indian Journal of Pharmacology, 42(5), 306–311. doi:10.4103/0253-7613.70350.
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