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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

Research Article

In Silico and In Vitro Study: COX-2 Inhibition by Ethanol Extract of Dayak Onion Bulb (Eleutherine Americana Merr) as Treatment Innovation of Benign Prostatic Hyperplasia (BPH)

Author(s): Hendra Sutapa, Mochammad Aris Widodo, Basuki Bambang Purnomo, Doddy M. Soebadi and Edvin Prawira Negara*

Volume 20, Issue 1, 2021

Published on: 04 March, 2020

Page: [68 - 74] Pages: 7

DOI: 10.2174/1871523019666200304121702

Price: $65

Abstract

Introduction: Benign Prostatic Hyperplasia (BPH) is a benign tumor in males, which is histopathologically known with an increase of epithelial cells and prostatic stroma. Androgens, estrogens, stroma-epithelial interactions, growth factors, and chronic inflammation play a key role in the occurrence of BPH. Chronic inflammation in BPH is characterized by excessive expression of COX-2, which will trigger the expression of Bcl-2 anti-apoptotic protein. Dayak onion (Eleutherine Americana Merr) is a typical Kalimantan plant that is known as the treatment for prostate disease. This plant contains flavonoids which can inhibit the COX-2 enzyme thus causing a reduction in the production of prostaglandin E2.

Methods: This research was experimental research computationally and in vitro laboratory experimental research to determine COX-2 inhibitory activity by ethanol extracts of Dayak onion.

Results and Discussion: In in silico flavonoid, it was strongly related to COX-2 receptor on the active side of TYR371. Thus, it had the potential to inhibit COX-2. COX-2 inhibitor would cause BCL-2 to be inactive so that apoptosis occurr in BPH. In the in vitro research using human whole blood assay, the Dayak Onion bulb ethanol extract had IC50 COX-2 of 40.57 ng/ml and IC50 COX-1 of 364.89 ng/ml. Therefore, the ratio of IC50 COX-2 to IC50 COX-1 was 0.11.

Conclusion: Ethanol extract of Dayak onion bulb has an inhibitory activity against COX-2. Thus, it has a potential of being an innovation for BPH treatment. Patient Summary: A healthy male, age 25-35 years old (history taking, physical and laboratory examination), and not using NSAIDs for the past 2 weeks.

Keywords: Benign prostatic hyperplasia, COX-2 inhibitor, dayak onion bulb, eleutherine americana merr, ethanol extract, Kalimantan plant.

Graphical Abstract
[1]
Roehrborn, C.G. Benign prostatic hyperplasia etiology, pathophysiology, epidemiology, and natural history of prostatic hyperplasia. Campbell-Walsh Urology, 10th Ed; Saunders: Philadelphia, 2012, pp. 2570-2610.
[http://dx.doi.org/10.1016/B978-1-4160-6911-9.00091-8]
[2]
Cooperberg, M.R.; Presti, J.C., Jr; Shinohara, K.; Carroll, P.R. McGraw. Neoplasm of the prostate gland. Smith & Tanagho’s. General Urology, 18th ed; Hill Lange: New York, 2013.
[3]
Kramer, G.; Mitteregger, D.; Marberger, M. Is benign prostatic hyperplasia (BPH) an immune inflammatory disease? Eur. Urol., 2007, 51(5), 1202-1216.
[http://dx.doi.org/10.1016/j.eururo.2006.12.011] [PMID: 17182170]
[4]
Sciarra, A.; Di Silverio, F.; Salciccia, S.; Autran Gomez, A.M.; Gentilucci, A.; Gentile, V. Inflammation and chronic prostatic diseases: evidence for a link? Eur. Urol., 2007, 52(4), 964-972.
[http://dx.doi.org/10.1016/j.eururo.2007.06.038] [PMID: 17618043]
[5]
Nickel, J.C. Inflammation and benign prostatic hyperplasia. Urol. Clin. North Am., 2008, 35(1), 109-115.
[http://dx.doi.org/10.1016/j.ucl.2007.09.012]
[6]
De Nunzio, C.; Kramer, G.; Marberger, M.; Montironi, R.; Nelson, W.; Schröder, F.; Sciarra, A.; Tubaro, A. The controversial relationship between benign prostatic hyperplasia and prostate cancer: the role of inflammation. Eur. Urol., 2011, 60(1), 106-117.
[http://dx.doi.org/10.1016/j.eururo.2011.03.055] [PMID: 21497433]
[7]
Kirschenbaum, A.; Klausner, A.P.; Lee, R.; Unger, P.; Yao, S.; Liu, X.H.; Levine, A.C. Expression of cyclooxygenase-1 and cyclooxygenase-2 in the human prostate. Urology, 2000, 56(4), 671-676.
[http://dx.doi.org/10.1016/S0090-4295(00)00674-9] [PMID: 11018637]
[8]
Wu, Q.; Zhou, Y.; Chen, L.; Shi, J.; Wang, C.Y.; Miao, L.; Klocker, H.; Park, I.; Lee, C.; Zhang, J. Benign prostatic hyperplasia (BPH) epithelial cell line BPH-1 induces aromatase expression in prostatic stromal cells via prostaglandin E2. J. Endocrinol., 2007, 195(1), 89-94.
[http://dx.doi.org/10.1677/JOE-06-0181] [PMID: 17911400]
[9]
Shao, J.; Jung, C.; Liu, C.; Sheng, H. Prostaglandin E2 Stimulates the β-catenin/T cell factor-dependent transcription in colon cancer. J. Biol. Chem., 2005, 280(28), 26565-26572.
[http://dx.doi.org/10.1074/jbc.M413056200] [PMID: 15899904]
[10]
Kim, B.H.; Kim, C.I.; Chang, H.S.; Choe, M.S.; Jung, H.R.; Kim, D.Y.; Park, C.H. Cyclooxygenase-2 overexpression in chronic inflammation associated with benign prostatic hyperplasia: Is it related to apoptosis and angiogenesis of prostate cancer? Korean J. Urol., 2011, 52(4), 253-259.
[http://dx.doi.org/10.4111/kju.2011.52.4.253] [PMID: 21556211]
[11]
Insanu, M.; Kusmardiyani, S.; Hartati, R. Recent studies on phytochemicals and pharmacological effects of Eleutherine americana Merr. Procedia Chem., 2014, 13, 221-228.
[http://dx.doi.org/10.1016/j.proche.2014.12.032]
[12]
Febrinda, AE.; Astawan, M.; Wresdiyati, T.; Yuliana, ND. Kapasitas antioksidan dan inhibitor alfa glukosidase ekstrak umbi bawang Dayak. J. Teknol. dan Industri Pangan, 2013, 24(2), 161-166.
[13]
Kim, H.P.; Son, K.H.; Chang, H.W.; Kang, S.S. Anti-inflammatory plant flavonoids and cellular action mechanisms. J. Pharmacol. Sci., 2004, 96(3), 229-245.
[http://dx.doi.org/10.1254/jphs.CRJ04003X] [PMID: 15539763]
[14]
Trott, O.; Olson, A.J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[PMID: 19499576]
[15]
Wolber, G.; Langer, T. LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J. Chem. Inf. Model., 2005, 45(1), 160-169.
[http://dx.doi.org/10.1021/ci049885e] [PMID: 15667141]
[16]
Feldman, M.; McMahon, A.T. Do cyclooxygenase-2 inhibitors provide benefits similar to those of traditional nonsteroidal anti-inflammatory drugs, with less gastrointestinal toxicity? Ann. Intern. Med., 2000, 132(2), 134-143.
[http://dx.doi.org/10.7326/0003-4819-132-2-200001180-00008] [PMID: 10644275]
[17]
Patrignani, P.; Panara, M.R.; Greco, A.; Fusco, O.; Natoli, C.; Iacobelli, S.; Cipollone, F.; Ganci, A.; Créminon, C.; Maclouf, J.; Patrono, C. Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. J. Pharmacol. Exp. Ther., 1994, 271(3), 1705-1712.
[PMID: 7996488]
[18]
Blain, H.; Boileau, C.; Lapicque, F.; Nédélec, E.; Loeuille, D.; Guillaume, C.; Gaucher, A.; Jeandel, C.; Netter, P.; Jouzeau, J.Y. Limitation of the in vitro whole blood assay for predicting the COX selectivity of NSAIDs in clinical use. Br. J. Clin. Pharmacol., 2002, 53(3), 255-265.
[http://dx.doi.org/10.1046/j.0306-5251.2001.01533.x] [PMID: 11874389]
[19]
Arthamin, M.Z.; Handono, K.; Widodo, M.A. Selektivitas hambatan flavonoid fraksi n-butanol ekstrak daun ungu (Graptophyllum pictum (L.) Griif.) terhadap isoenzim siklooksigenase. Madjalah Kedokt. Indones., 2004, 12(10), 409-416.
[20]
Brooks, P.; Emery, P.; Evans, J.F.; Fenner, H.; Hawkey, C.J.; Patrono, C.; Smolen, J.; Breedveld, F.; Day, R.; Dougados, M.; Ehrich, E.W.; Gijon-Baños, J.; Kvien, T.K.; Van Rijswijk, M.H.; Warner, T.; Zeidler, H. Interpreting the clinical significance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2. Rheumatology (Oxford), 1999, 38(8), 779-788.
[http://dx.doi.org/10.1093/rheumatology/38.8.779] [PMID: 10501435]
[21]
Paramita, S.; Nuryanto, M. Anti-inflammatory activity of bawang dayak (Eleutherine bulbosa (mill. Urb.)) Ethanol bulb extracts. J. Vocat. Health Stud., 2019, 2(2), 51.
[http://dx.doi.org/10.20473/jvhs.V2.I2.2018.51-55]

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