Cytotoxic Potensial and Molecular Docking of Essential Oil Piper Aduncum Flowers Against Cervical Cancer Cells

Authors

  • Indah Rahmadani Andalas University, Indonesia
  • Mai Efdi Andalas University, Indonesia
  • Suryati Suryati Andalas University, Indonesia

DOI:

https://doi.org/10.33394/hjkk.v12i4.12479

Keywords:

cervical cancer, cytotoxic, essential oil, molecular docking, Piper aduncum

Abstract

Piper aduncum L., commonly known as spiked pepper, is a medicinal plant traditionally used to treat various diseases due to its diverse, active compounds. This article investigates the chemical composition, cytotoxic bioactivity in vitro and the silico of the essential oil (EO) from the flowers of Piper aduncum collected in Padang City, Indonesia. The EO was obtained by hydrodistillation using a Clevenger-type apparatus and characterized by gas chromatography-mass spectrometry (GC-MS). The in vitro cytotoxicity of the EO was assessed against cervical cancer (HeLa cancer cell line) using the MTT assay and further explored through molecular docking approaches. The main constituent of the essential oil from the flowers was dillapiol (31.68%). The LC50 and IC50 values were 31.3471 µg/mL and 65.83 µg/mL, respectively. Computational screening was performed to observe the interactions between active compounds and proteins AKT and ERK2 using molecular docking. AKT and ERK2 act as critical regulators in the PI3K/Akt and ERK/MEK signaling pathways and are potential drug targets for cancer therapy. The compounds used complied with ADMET analysis and toxicity profile. However, it is noteworthy that there have been no previous reports on the essential oil from Piper aduncum flowers from Padang City specifically targeting cervical cancer, which molecular docking studies have complemented. The results suggest that the essential oil from the flowers of Piper aduncum can be further studied as a potential lead in drug discovery for cervical cancer.

References

Abedinpour, N., Ghanbariasad, A., Taghinezhad, A., & Osanloo, M. (2021). Preparation of Nanoemulsions of Mentha piperita Essential Oil and Investigation of Their Cytotoxic Effect on Human Breast Cancer Lines. BioNanoScience, 11(2), 428–436. https://doi.org/10.1007/s12668-021-00827-4

Almas, I., Innocent, E., Machumi, F., & Kisinza, W. (2018). Effect of Geographical location on yield and chemical composition of essential oils from three Eucalyptus species growing in Tanzania. äºšæ´²ä¼ ç»ŸåŒ»è¯, 14(1), 1–12.

Amna, U., Wahyuningsih, P., Saidi, N., & Nasution, R. (2019). Evaluation of cytotoxic activity from Temurui (Murraya koenigii [Linn.] Spreng) leaf extracts against HeLa cell line using MTT assay. Journal of Advanced Pharmaceutical Technology & Research, 10(2), 51.

Bernuci, K. Z., Iwanaga, C. C., Fernandez-Andrade, C. M., Lorenzetti, F. B., Torres-Santos, E. C., Faiões, V. D., Gonçalves, J. E., Do Amaral, W., Deschamps, C., Scodro, R. B., Cardoso, R. F., Baldin, V. P., & Cortez, D. A. (2016). Evaluation of Chemical Composition and Antileishmanial and Antituberculosis Activities of Essential Oils of Piper Species. In Molecules (Vol. 21, Issue 12). https://doi.org/10.3390/molecules21121698

Bilqies, Z. L. F., Andriani, S., & Yanto, E. S. (2021). Formulasi Sediaan Gel Antiseptik Daun Sirih Hijau (Piper betle linn) dengan Basis Biji Rami (Linum usitatissimum) dan Penambahan Sari Jeruk Nipis (Citrus x aurantiifolia) SEBAGAI AROMA. Journal of Holistic and Health Sciences, 4(2), 114–119. https://doi.org/10.51873/jhhs.v4i2.79

Cardoso, J. C., de Oliveira, M. E. B. S., & Cardoso, F. de C. I. (2019). Advances and challenges on the in vitro production of secondary metabolites from medicinal plants. Horticultura Brasileira, 37(2), 124–132. https://doi.org/10.1590/s0102-053620190201

Cells, M.-, Cells, T., Soemardji, A. A., & Tan, M. I. (2022). Cytotoxic Effects of Kirinyuh Herb ( Austroeupatorium inulaefolium ( Kunth ) R . d . King & H . Robinson ) Extracts and Fractions on BSLT ,. 14(2), 374–378.

Durofil, A., Radice, M., Blanco-Salas, J., & Ruiz-Téllez, T. (2021). Piper aduncum essential oil: a promising insecticide, acaricide and antiparasitic. A review. Parasite (Paris, France), 28, 42. https://doi.org/10.1051/parasite/2021040

Fadlan, A., Warsito, T., & Sarmoko, S. (2022). Evaluasi Parameter Fisikokimia, Farmakokinetika, dan Farmakodinamika Senyawa Fisetin Dalam Desain Obat. Akta Kimia Indonesia, 7(1), 1. https://doi.org/10.12962/j25493736.v7i1.10879

Ferreira, O. O., Cruz, J. N., de Moraes, Â. A. B., Franco, C. de J. P., Lima, R. R., Dos Anjos, T. O., Siqueira, G. M., Do Nascimento, L. D., Cascaes, M. M., de Oliveira, M. S., & Andrade, E. H. de A. (2022). Essential Oil of the Plants Growing in the Brazilian Amazon: Chemical Composition, Antioxidants, and Biological Applications. Molecules, 27(14), 1–29. https://doi.org/10.3390/molecules27144373

Khalil, H. E., Ibrahim, H. I. M., Darrag, H. M., & Matsunami, K. (2022). Insight into analysis of essential oil from anisosciadium lanatum boiss.—chemical composition, molecular docking, and mitigation of hepg2 cancer cells through apoptotic markers. Plants, 11(1). https://doi.org/10.3390/plants11010066

Maia, J. G. S., Zohhbi, M. D. G. B., Andrade, E. H. A., Santos, A. S., da Silva, M. H. L., Luz, A. I. R., & Bastos, C. N. (1998). Constituents of the essential oil of Piper aduncum L. growing wild in the Amazon region. Flavour and Fragrance Journal, 13(4), 269–272.

Monzote, L., Scull, R., Cos, P., & Setzer, W. N. (2017). Essential Oil from Piper aduncum: Chemical Analysis, Antimicrobial Assessment, and Literature Review. Medicines (Basel, Switzerland), 4(3). https://doi.org/10.3390/medicines4030049

Morais, V. P., Cabral, F. V., Fernandes, C. C., & Miranda, M. L. D. (2023). Brief Review on Piper aduncum L., its Bioactive Metabolites and its Potential to Develop Bioproducts. Brazilian Archives of Biology and Technology, 66. https://doi.org/10.1590/1678-4324-2023220314

Nguyen, N. H., Ta, Q. T. H., Pham, Q. T., Luong, T. N. H., Van Trung Phung, T., Duong, H.-H., & Vo, V. G. (2020). Anticancer Activity of Novel Plant Extracts and. Molecules, 25(2912), 1–16.

Niksic, H., Becic, F., Koric, E., Gusic, I., Omeragic, E., Muratovic, S., Miladinovic, B., & Duric, K. (2021). Cytotoxicity screening of Thymus vulgaris L. essential oil in brine shrimp nauplii and cancer cell lines. Scientific Reports, 11(1), 1–9. https://doi.org/10.1038/s41598-021-92679-x

Okunade, K. S. (2020). Human papillomavirus and cervical cancer. Journal of Obstetrics and Gynaecology, 40(5), 602–608.

Pant, P., Pandey, S., & Dall’Acqua, S. (2021). The Influence of Environmental Conditions on Secondary Metabolites in Medicinal Plants: A Literature Review. Chemistry and Biodiversity, 18(11). https://doi.org/10.1002/cbdv.202100345

Putri, R. B., Nugrahaningsih, W., & Dewi, N. K. (2021). Uji Toksisitas Ekstrak Daun Cassava Terhadap Larva Artemia salina Leach dengan Metode Brine Shrimp Lethality Test. Indonesian Journal of Mathematics and Natural Sciences, 44(2), 86–91. https://doi.org/10.15294/ijmns.v44i2.33145

Rohimatun, Aisyah, M. D. N., Puspasari, L. T., & Rusmin, D. (2023). Toxicity and chemical compounds of Piper aduncum fruit extract against storage pest Sitophilus oryzae and Callosobruchus maculatus. IOP Conference Series: Earth and Environmental Science, 1253(1). https://doi.org/10.1088/1755-1315/1253/1/012001

S Mann, R., & E Kaufman, P. (2012). Natural product pesticides: their development, delivery and use against insect vectors. Mini-Reviews in Organic Chemistry, 9(2), 185–202.

Salehi, B., Zakaria, Z. A., Gyawali, R., Ibrahim, S. A., Rajkovic, J., Shinwari, Z. K., Khan, T., Sharifi-Rad, J., Ozleyen, A., Turkdonmez, E., Valussi, M., Tumer, T. B., Fidalgo, L. M., Martorell, M., & Setzer, W. N. (2019). Piper species: A comprehensive review on their phytochemistry, biological activities and applications. In Molecules (Vol. 24, Issue 7). https://doi.org/10.3390/molecules24071364

Santoni, A., Arifin, B., Ferdinal, N., Salim, E., Amelia, A., Zein, L., Mairanti, S., & Lestari, I. P. (2022). Analysis of Chemical Content, Cytotoxic and Antibacterial Activity Essential Oil of Lantana Camara Linn Leaves from Various Regions. Molekul, 17(2), 156–164.

Silva, M. A. Da, Passarini, G. M., Martinez, L. D. N., Alves, V., & ... (2020). … plants of the genus piper l.(piperaceae): a review constituintes químicos e bioatividades de óleos essenciais do gênero piper L …. Researchgate.Net, May. https://www.researchgate.net/profile/Leandro_Martinez10/publication/341434822_CHEMICAL_CONSTITUENTS_AND_BIOACTIVITIES_OF_ESSENTIAL_OILS_FROM_PLANTS_OF_THE_GENUS_Piper_L_PIPERACEAE_A_REVIEW_CONSTITUINTES_QUIMICOS_E_BIOATIVIDADES_DE_OLEOS_ESSENCIAIS_DO_GENE

Suryati, Emil Salim, & Gustia Elizar. (2022). Potensi Antimikroba dan Toksisitas Minyak Atsiri yang Diisolasi dari Biji Jintan (Carum carvi L.). Jurnal Riset Kimia, 13(2), 198–207. https://doi.org/10.25077/jrk.v13i2.551

Suryati, Hefni, D., Wahyuni, F. S., & Dachriyanus. (2021). The cytotoxicity study of lantana camara Linn essential oil on HeLa cancer cells line. Pharmacognosy Journal, 13(6), 1498–1501. https://doi.org/10.5530/PJ.2021.13.190

Suryati, S., Aziz, E. D., Efdi, M., Wahyuni, F. S., & Hefni, D. (2021). Analysis of the essential oil from Lantana camara leaves and its cytotoxic potential against T-47D breast cancer cells. Jurnal Riset Kimia, 12(1), 1–9. https://doi.org/10.25077/jrk.v12i1.364

Taher, M., Amri, M. S., Susanti, D., Abdul Kudos, M. B., Md Nor, N. F. A., & Syukri, Y. (2020). Medicinal uses, phytochemistry, and pharmacological properties of piper aduncum L. Sains Malaysiana, 49(8), 1829–1851. https://doi.org/10.17576/jsm-2020-4908-07

Trisilawati, O., & Pitono, J. (2012). Pengaruh cekaman defisit air terhadap pembentukan bahan aktif pada purwoceng. Buletin Littro, 23(1), 34–47.

Ulia, R. V., Suryati, & Santoni, A. (2023). Cytotoxic Potential of Essential Oil Isolated from Semambu (Clibadium surinamese L) Leaves Against T47D Breast and HeLa Cervical Cancer Cells. Molekul, 18(2), 289–299. https://doi.org/10.20884/1.jm.2023.18.2.7816

Wibawa, I. P. A. H., Saraswaty, V., Kuswantoro, F., Andila, P. S., Wardhani, P. K., Tirta, I. G., & Sujarwo, W. (2019). A study of essential oil from an invasive Piper aduncum L. Jurnal Biologi Udayana, 23(2), 50. https://doi.org/10.24843/jbiounud.2019.v23.i02.p02

Yu, Z., Chen, Z., Su, Q., Ye, S., Yuan, H., Kuai, M., Lv, M., Tu, Z., Yang, X., Liu, R. R., Hu, G., & Li, Q. (2019). Dual inhibitors of RAF-MEK-ERK and PI3K-PDK1-AKT pathways: Design, synthesis and preliminary anticancer activity studies of 3-substituted-5-(phenylamino) indolone derivatives. Bioorganic and Medicinal Chemistry, 27(6), 944–954. https://doi.org/10.1016/j.bmc.2019.01.028

Zhou, J., Li, H., Wu, B., Zhu, L., Huang, Q., Guo, Z., He, Q., Wang, L., Peng, X., & Guo, T. (2024). Network pharmacology combined with experimental verification to explore the potential mechanism of naringenin in the treatment of cervical cancer. Scientific Reports, 14(1), 1860. https://doi.org/10.1038/s41598-024-52413-9

Downloads

Published

2024-08-30

How to Cite

Rahmadani, I., Efdi, M., & Suryati, S. (2024). Cytotoxic Potensial and Molecular Docking of Essential Oil Piper Aduncum Flowers Against Cervical Cancer Cells. Hydrogen: Jurnal Kependidikan Kimia, 12(4), 721–736. https://doi.org/10.33394/hjkk.v12i4.12479

Issue

Vol. 12 No. 4 (2024): August 2024

Section

Articles

Citation Check

License

License and Publishing Agreement
In submitting the manuscript to the journal, the authors certify that:

  1. They are authorized by their co-authors to enter into these arrangements.
  2. The work described has not been formally published before, except in the form of an abstract or as part of a published lecture, review, thesis, or overlay journal.
  3. That it is not under consideration for publication elsewhere,
  4. That its publication has been approved by all the author(s) and by the responsible authorities – tacitly or explicitly – of the institutes where the work has been carried out.
  5. They secure the right to reproduce any material that has already been published or copyrighted elsewhere.
  6. They agree to the following license and publishing agreement.

Copyright
Authors who publish with Hydrogen: Jurnal Kependidikan Kimia agree to the following terms:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License (CC BY-SA 4.0) that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal. 
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.

Licensing for Data Publication

Hydrogen: Jurnal Kependidikan Kimia uses a variety of waivers and licenses, that are specifically designed for and appropriate for the treatment of data: Open Data Commons Attribution License, http://www.opendatacommons.org/licenses/by/1.0/ (default) Other data publishing licenses may be allowed as exceptions (subject to approval by the editor on a case-by-case basis) and should be justified with a written statement from the author, which will be published with the article.