Perbedaan Efek Flavonoid Ekstrak Buah Phaleria Macrocarpa Dengan Terapi Standar Terhadap Kadar Interferon Gamma Dan Mucin 1 Pada Model Endometriosis (Mus Musculus)

Mali, Maria Antonia Barbara Batu and Dr. dr. Sutrisno, Sp.OG (K) and Dr. dr. I Wayan Agung Indrawan, Sp.OG (K) FISQua (2023) Perbedaan Efek Flavonoid Ekstrak Buah Phaleria Macrocarpa Dengan Terapi Standar Terhadap Kadar Interferon Gamma Dan Mucin 1 Pada Model Endometriosis (Mus Musculus). Magister thesis, Universitas Brawijaya.

Abstract

Endometriosis merupakan penyakit kronis ini yang bergantung pada estrogen, ditandai oleh adanya kelenjar dan stroma endometrium yang tumbuh dan berkembang di luar uterus, membentuk kista ovarium, dan fibrosis serta mempengaruhi banyak organ panggul. Penyakit ini terjadi pada 10% wanita usia reproduksi, dengan hampir separuh penderita mengeluh nyeri, infertilitas, atau bahkan keduanya. Gejala endometriosis beragam dan sulit didiagnosis pada awalnya karena nyeri panggul kronis diduga bersumber dari penyakit penyerta lainnya. Satu-satunya standar emas penegakan diagnosis endometriosis adalah melalui laparoskopi dengan konfirmasi histologis. Akan tetapi, tindakan ini mahal dan sering terjadi komplikasi; serta risiko kekambuhan masih terus ada. Terapi standar berfokus pada perbaikan hormonal untuk mengatasi gejala. Dienogest efektif meredakan nyeri dan mengurangi lesi, tetapi perdarahan bercak, penurunan kepadatan mineral tulang, bahkan depresi dilaporkan sebagai efek samping. Sementara itu, Leuprolide Acetat merupakan agonis GnRH yang efektif menghilangkan nyeri dan menghambat perkembangan lesi endometriosis, namun penggunaannya dibatasi dalam jangka pendek karena efek sampingnya yang berat. Endometriosis ditandai dengan nyeri dan infertilitas. IFN-Ɣ merupakan biomarker non invasif yang perannya dalam endometriosis masih sulit dipahami. IFN-Ɣ merupakan sitokin proinflamasi sekaligus antiinflamasi yang mekanisme kerjanya berbeda bergantung pada konteks perkembangan penyakit. Sementara itu, MUC-1 adalah glikoprotein yang berperan dalam proteksi epitel dan implantasi embrio. Ekspresi MUC-1 diatur oleh progesteron dan sitokin proinflamasi diantaranya IFN-Ɣ. Alternatif terapi yang dikembangkan saat ini adalah ekstrak flavonoid dari buah Phaleria macrocarpa yang memiliki sifat antiinflamasi dan antioksidan. Penelitian ini bertujuan untuk melihat perbedaan efek ekstrak flavonoid buah Phaleria macrocarpa dan terapi standar (Dienogest dan Leuprolide Acetat) terhadap kadar serum IFN-Ɣ dan MUC-1. Desain yang digunakan adalah studi in vivo dengan rancangan kelompok kontrol yang pengukuran hasilnya 1 kali setelah perlakuan diberikan. Sampel berupa mencit (Mus musculus), strain BALB/c, betina, sehat, umur 6-8 minggu, dan tidak mati saat penelitian berlangsung. Total sampel sebanyak 40 ekor dibagi dalam 8 kelompok yaitu K-, K+, P1 (flavonoid 3.75 mg/hari), P2 (flavonoid 7.5 mg/hari), P3 (flavonoid 11.25 mg/hari), P4 (flavonoid 15 mg/hari), DNG (Dienogest) dan LA (Leuprolide Acetat). Pembuatan model mencit endometriosis dan pemberian perlakuan dikerjakan selama 30 hari. Selanjutnya, sampel serum darah mencit diperiksa menggunakan Enzyme-Linked Immunosorbent Assay (ELISA) untuk mengukur kadar serum IFN-Ɣ dan MUC-1. Analisis data dilakukan dengan cara univariat, bivariat, maupun multivariat menggunakan software IBM Statistic Versi 25. Hasil uji One Way ANOVA menunjukkan bahwa kadar IFN-Ɣ menurun baik pada kelompok P1 maupun pada kelompok LA, namun efek penurunan keduanya tidak signifikan dibandingkan dengan K- dan K+. Pada kelompok P2, P3, P4, dan DNG, kadarnya justru meningkat, namun efek peningkatan ketiganya tidak signifikan dibandingkan dengan K- dan K+. Jika efek peningkatan pada P2 dan P4 dibandingkan dengan efek penurunan pada kelompok LA, maka perbedaan itu signifikan. Sementara itu, hasil uji Dunnett T3 menunjukkan bahwa kadar MUC-1 meningkat pada semua kelompok perlakuan (P1, P2, P3, P4, DNG, dan LA). Akan tetapi, efek peningkatan yang signifikan hanya terdapat pada kelompok P1 dibandingkan dengan kelompok K+ (p=0.036). Selanjutnya, hasil uji korelasi Pearson menunjukkan bahwa peningkatan dosis flavonoid memiliki kekuatan hubungan positif yang cukup wajar (r = 0.494) dengan kadar serum IFNvii Ɣ dan hubungan ini bermakna (p=0.027). Namun hasilnya berlawanan dengan kadar serum MUC-1, ditunjukkan dengan hubungan negatif yang sangat rendah (r=-0.136) terbukti tidak bermakna (p=0.568). Kesimpulan dari penelitian ini adalah bahwa pemberian flavonoid ekstrak buah Phaleria macrocarpa mampu menurunkan dan meningkatkan kadar serum IFN-Ɣ pada model mencit endometriosis (Mus musculus) bergantung pada dosis. Demikian pula, Leuprolide Acetat menurunkan kadar serum IFN-Ɣ. Sedangkan Dienogest meningkatkan serum IFN-Ɣ. Namun, tidak ada perbedaan efek penurunan maupun peningkatan yang signifikan jika dibandingkan dengan kelompok kontrol. Ada perbedaan efek yang signifikan antara pemberian flavonoid dosis 7.5 dan 15 mg/hari dengan Leuprolide Acetat. Sementara itu, pemberian flavonoid ekstrak buah Phaleria macrocarpa, Dienogest, maupun Leuprolide Acetat, ketiganya mampu meningkatkan kadar serum MUC-1 pada model mencit endometriosis (Mus musculus). Tidak ada perbedaan efek yang signifikan antara flavonoid berbagai dosis dengan terapi standar, meskipun kelompok flavonoid 3.75 mg/hari berbeda signifikan dibandingkan kelompok kontrol positif.

English Abstract

Endometriosis is a chronic disease that is estrogen-dependent, characterized by the presence of endometrial glands and stroma growing and developing outside the uterus, forming ovarian cysts and fibrosis, and affecting multiple pelvic organs. This condition occurs in 10% of reproductive-age women, with nearly half of the patients experiencing pain, infertility, or even both. The symptoms of endometriosis are diverse and difficult to diagnose initially as chronic pelvic pain is often suspected to arise from other coexisting conditions. The only gold standard for confirming the diagnosis of endometriosis is through laparoscopy with histological confirmation. However, this procedure is costly and complications are frequent, and the risk of recurrence persists. Standard therapy focuses on hormonal manipulation to alleviate symptoms. Dienogest effectively reduces pain and diminishes lesions, but side effects such as spotting, decreased bone mineral density, and even depression have been reported. Meanwhile, Leuprolide Acetate is a GnRH agonist that effectively eliminates pain and inhibits the progression of endometriosis lesions, but its use is limited to the short term due to severe side effects. Endometriosis is characterized by pain and infertility. IFN-Ɣ is a non-invasive biomarker whose role in endometriosis remains poorly understood. IFN-Ɣ is a cytokine that functions as both pro-inflammatory and anti-inflammatory, with its mechanism of action varying depending on the disease development context. On the other hand, MUC-1 is a glycoprotein that plays a role in epithelial protection and embryo implantation. The expression of MUC-1 is regulated by progesterone and pro-inflammatory cytokines, including IFN-Ɣ. An emerging alternative therapy currently being developed is the flavonoid extract from Phaleria macrocarpa fruit, which possesses anti-inflammatory and antioxidant properties. This study aims to investigate the differences in the effects of flavonoid extract from Phaleria macrocarpa fruit and standard therapies (Dienogest and Leuprolide Acetate) on serum levels of IFN-Ɣ and MUC-1. The design employed is an in vivo study with a controlled group design, with outcome measurements taken once after the treatments are administered. The samples consist of female healthy BALB/c mice, aged 6-8 weeks, and are alive throughout the study. A total of 40 mice are divided into 8 groups: K- (negative control), K+ (positive control), P1 (flavonoid 3.75 mg/day), P2 (flavonoid 7.5 mg/day), P3 (flavonoid 11.25 mg/day), P4 (flavonoid 15 mg/day), DNG (Dienogest), and LA (Leuprolide Acetate). The establishment of the mouse endometriosis model and administration of treatments are conducted over a 30-day period. Subsequently, mouse serum samples are examined using Enzyme-Linked Immunosorbent Assay (ELISA) to measure the levels of serum IFN-Ɣ and MUC-1. Data analysis is performed using univariate, bivariate, and multivariate methods using IBM Statistics Version 25 software. The One Way ANOVA test results indicated that the levels of IFN-Ɣ decreased in both the P1 and LA groups; however, the reduction effects were not significant compared to the K- and K+ groups. In the P2, P3, P4, and DNG groups, the levels of IFN-Ɣ actually increased, but the elevation effects were not significant compared to the K- and K+ groups. When comparing the increase effects in the P2 and P4 groups to the decrease effect in the LA group, the difference was significant. Meanwhile, the Dunnett T3 test results revealed that the levels of MUC-1 increased in all treatment groups (P1, P2, P3, P4, DNG, and LA). However, a significant increase effect was only observed in the P1 group compared to the K+ group (p=0.036). Furthermore, the Pearson correlation test results demonstrated that the increasing dose of flavonoids had a moderately positive relationship (r = 0.494) with the serum levels of IFN-Ɣ, and this relationship was significant (p=0.027). However, the ix results were contrary for serum MUC-1 levels, as indicated by a very weak negative correlation (r=-0.136) that was statistically insignificant (p=0.568). The conclusion drawn from this study is that the administration of flavonoid extract from Phaleria macrocarpa fruit is capable of both decreasing and increasing serum levels of IFN-Ɣ in an endometriosis mouse model (Mus musculus), and this effect is dosedependent. Similarly, Leuprolide Acetate decreases serum IFN-Ɣ levels, while Dienogest increases them. However, there were no significant differences in the decrease or increase effects compared to the control group. A significant difference was observed between the administration of flavonoids at doses of 7.5 and 15 mg/day and Leuprolide Acetate. Meanwhile, the administration of flavonoid extract from Phaleria macrocarpa fruit, Dienogest, and Leuprolide Acetate all led to an increase in serum MUC-1 levels in the endometriosis mouse model (Mus musculus). There were no significant differences in the effects between different doses of flavonoids and standard therapies, although the 3.75 mg/day flavonoid group showed a significant difference compared to the positive control group.

Item Type:	Thesis (Magister)
Identification Number:	0423060073
Subjects:	600 Technology (Applied sciences) > 618 Gynecology, obstetrics, pediatrics, geriatrics > 618.2 Obstetrics
Divisions:	S2/S3 > Magister Kebidanan, Fakultas Kedokteran
Depositing User:	Endang Susworini
Date Deposited:	05 Dec 2023 06:25
Last Modified:	05 Dec 2023 06:25
URI:	http://repository.ub.ac.id/id/eprint/204809

Text (DALAM MASA MEMBARGO) MARIA ANTONIA BARBARA BATU MALI.pdf Restricted to Registered users only until 31 December 2025. Download (7MB)

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