Effect Of Topical DLBS 1425 On Tissue Plasminogen Activator (tPA) Expression In Trabecular Meshwork Of Wistar Rats

  • Utami Widijanto JEC-CANDI@SEMARANG Eye Hospital,Semarang
  • Trilaksana Nugroho Department of Ophthalmology, Diponegoro University/dr. Kariadi Hospital
  • Maharani Cahyono Department of Ophthalmology, Diponegoro University/dr. Kariadi Hospital
Keywords: tissue plasminogen activator, trabecular meshwork, DLBS 1425, Phaleria macrocarpa


Introduction: Tissue plasminogen activator (tPA) in the trabecular meshwork (TM) is a serine protease that important to maintain the aquos outflow resistance by activating the matrix metalloproteinase (MMP). It can cause a degradation of the extracellular matrix, which can maintain the normal flow of aquos humor. However, the use of anti-inflammatory drugs has been shown to reduce the expression of tPA, leading to an increase in the outflow resistance. Therefore, we propose the use of DLBS 1425, an extract of Phaleria macrocarpa which has been proven to have anti-inflammatory effects.

Aim : This study aims to determine the expression of tPA in Wistar rats’ TM.

Methods : An experimental laboratory study with  post-test only randomized controlled group design was performed. Twenty-two Wistar rats were divided into two groups, the control and the experimental. The experimental group was given topical DLBS 1425 at a dose of 6 times / day, for 4 weeks. The control group was given drops of Hyalub Minidose® 6 times / day, for 4 weeks. tPA expression on TM was examined by immunohistochemical staining. Data were collected and processed using the SPSS 15.0 for Windows.

Results : The mean tPA expression in TM with Allred scores in the experimental group (0.18 ± 0.60) was significantly lower (p <0.001) than the control group (6.27 ± 0.91).

Conclusion : Topical DLBS 1425 suppresses the expression of tPA on the trabecular meshwork of Wistar rats.

Key words: tissue plasminogen activator, trabecular meshwork, DLBS 1425, Phaleria macrocarpa.


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1. Shuman MA, Polansky JR, Merkel C, Alvarado J. Tissue Plasminogen Activator in Cultured Human Trabecular Meshwork Cells. Invest Ophthalmol Vis Sci. 1998;29:401-5.
2. Smalley DM, Fitzgerald JE, Taylor DM, Cone RE, O’Rourke J. Tissue Plasminogen Activator Activity in Human Aqueous Humor. Invest Ophthalmol Vis Sci. 1994;35:48-53.
3. Wang Y, Taylor DM, Smalley DM, Cone RE, O’Rourke J. Increased Basal Levels of Free Plasminogen Activato Activity Found in Human Aqueous Humor. Invest Ophthalmol Vis Sci. 1994;35:3561-66.
4. Kumar S, Shah S, Tang HM, Smith M, Borras T, Danias J. Tissue Plasminogen Activator in Trabecular Meshwork Attenuates Steroid Induced Outflow Resistance in Mice. PLoS ONE. 2013;8(8):e72447.
5. Gerometta. Reduction of Steroid-Induced Intraocular PressureElevation in Sheep by Tissue Plasminogen Activator. Invest Ophthalmol Vis Sci. 2013;54:7903-9.
6. Dan JD, Belyea D, Gertner G, Leshen I, Lusky M, Miskin R. Plasminogen Activator Inhibitor-1 in The Aqueous Humor of Patients With and Without Glaucoma. Arch Ophthalmol. 2005;123:220-4.
7. Cesari M, Pahor M, Incaizi RA. Plasminogen Activator Inhibitor-1 (PAI-1): A Key Factor Linking Fibrinolysis and Age Related Subclinical and Clinical Conditions. Cardiovasc ther. 2010;28(5):e72-e91.
8. Kresno SB, editor. Ilmu Dasar Onkologi. 3rd ed. Jakarta: Badan Penerbit Fakultas Kedokteran Universitas Indonesia; 2012.
9. Hutama, S. Efek DLBS 1425 Topikal Berbagai Konsentrasi Terhaap Ekspresi COX -2 Kornea Tikus Wistar Pasca Trauma Basa [Dissertastion]. Semarang: Diponegoro University; 2016.
10. Ermawati S. Efektifitas DLBS 1425 Topikal Terhadap Ekspresi COX -2 Pada Kornea tikus Wistar Pasca Trauma Basa [Dissertastion]. Semarang: Diponegoro University; 2017.
11. Choudhury KR, Yagle KJ, Swanson PE, Krohn KA, Rajendran JG. A Robust Automated Measure of Average Antibody Staining In Immunohistochemistry Images. Journal of Histochemistry & Cytochemistry. 2010;58(2):95-107.
12. Easmin S, Sarker ZI, Ferdos S, Shamsudin SH, Yunus KB, Uddin MS,et al. Biocative Compounds and Advanced Processing Technology: Phaleria macrocarpa (sheff.) Boerl, a Review. J Chem Technol Biotechnology. 2015;90(6):981-91.
13. Othman S, Sarker S, Nahar L, Basar N. The Ethnomedicinal, Phytochemical and Pharmacological Properties of Phaleria macrocarpa (Scheff). Boerl. Tang Humanitas Medicine. 2014;4(4):e22.1-2.
14. Lin L, Wu C, Hu K. Tissue Plasminogen Activator Activates NF-kB Through a Pathway Involving Annexin A2/CD11b and Integrin-Linked Kinase. University of Pittsburgh School of Medicine; Pennsylvania. J Am Soc Nephrol. 2012;23(8):1329-38.
15. Tjandrawinata, RR, Arifin PZ, Tandrasasmita OM, Rahmi D,Aripin A. DLBS 1425, a Phaleria macrocarpa (Scheff.) Boerl. Extract confers anti proliferative and proapoptosis effects via eicosanoid pathway. Journal of Experimental Therapeutics and Oncology. 2010;8:187-201.
16. Giannarelli C, Negri F, Virdis A, Ghiadoni L, Cipriano A, Magagna A, et al. Nitric Oxide Modulates Tissue Plasminogen Activator Release in Normotensive Subjects and Hypertensive Patients. University of Pisa; Italy. American Heart Association. 2007;49:878-84.
17. Baker EA, Bergin FG, Leaper. Plasminogen Activator System, Vascular Endothelial Growth Factor, and Colorectal Cancer Progression. North Tees General Hospital; UK. J Clin Pathology. 2000;53:307-12.
18. Nakamoto R, Uetake H, Iida S, Kolev Y, Soumaoro T, Takagi Y, et al. Correlation Between Cyclooxygenase-2 Expression and Angiogeic Factors in Primary Tumors and Liver Metastases in Colorectal Cancer. Tokto Medical and Dental University; Japan. Jpn J Clinical Oncology. 2007;37(9):679-685.
19. Mandarana M. Efek DLBS 1425 Topikal Berbagai Konsentrasi Terhadap Ekspresi VEGF Kornea Tikus Wistar Pasca Trauma Basa [Dissertastion].Semarang: Diponegoro University;2016
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