Ekstrak Buah Andaliman (Zanthoxylum acanthopodium DC.) sebagai penghambat Reseptor Angiotensin II Tipe 1 pada Hewan Model Preeklampsia akibat Retensi Garam

Safa, Muhammad Shafala and Prof. Dra. Fatchiyah, M.Kes., Ph.D and dr. Azmi Noer, M.Ked (Clin.Path), Sp.PK (2024) Ekstrak Buah Andaliman (Zanthoxylum acanthopodium DC.) sebagai penghambat Reseptor Angiotensin II Tipe 1 pada Hewan Model Preeklampsia akibat Retensi Garam. Magister thesis, Universitas Brawijaya.

Abstract

Preeklampsia (PE) adalah komplikasi serius pada kehamilan yang dicirikan dengan timbulnya hipertensi setelah minggu ke-20 kehamilan disertai proteinuria. Sistem ReninAngiotensin (RAS) dipercaya sebagai salah satu kontributor utama dalam patogenesis preeklampsia melalui aktivasi reseptor angiotensin II tipe 1 (AT1R). Penelitian ini bertujuan mengidentifikasi senyawa dari buah andaliman (Zanthoxylum acanthopodium DC.) yang berpotensi sebagai penghambat AT1R dengan pendekatan in silico, serta menganalisa pengaruh pemberian ekstrak metanol buah andaliman pada tekanan darah, proteinuria, ekspresi angiotensin-converting enzyme (ACE), dan ekspresi tumor necrosis factor alpha (TNF-a) hewan model PE dengan pendekatan in vivo. Penelitian in silico diawali pemodelan struktur protein AT1R berdasarkan sekuen gen AT1R hewan uji, dilanjutkan dengan analisis bioavailabilitas, bioaktivitas, dan molecular docking dari senyawa kandungan buah andaliman untuk memperoleh senyawa potensial penghambat AT1R. Penelitian in vivo menggunakan 5 kelompok tikus yaitu non-PE, PE, PE + candesartan 5 mg/kg, PE + andaliman 100 mg, dan PE + andaliman 200 mg. Induksi preeklampsia dilakukan pada hari ke 5-13 kehamilan dengan NaCl, dilanjutkan pemberian ekstrak metanol buah andaliman pada hari ke 14-21. Tekanan darah dan proteinuria diukur pada hari ke-5, 13, dan 21 masa kehamilan. Kadar TNF-a diukur dengan dot blot, sedangkan kadar ACE diukur dengan ELISA. Hasil penelitian menunjukan bahwa hewan model memenuhi kriteria preeklampsia, yaitu peningkatan tekanan darah dan terjadinya proteinuria. Analisis in silico mengidentifikasi 5 senyawa potensial, yaitu kaempferol, quercetin, resveratrol, farnesyl acetate, dan (E,E)- farnesyl acetone. Penghambatan ini didukung oleh perbaikan di tingkat fisiologi yaitu menurunnya tekanan darah dan tingkat proteinuria di akhir kehamilan. Selain itu pada tingkat molekuler ekstrak metanol buah andaliman dapat menurunkan overekspresi ACE yang dapat terjadi karena feedback loop setelah aktivasi AT1R, dan menurunkan ekspresi TNF-a yang merupakan downstream signaling dari aktivasi AT1R.

English Abstract

Preeclampsia (PE) is a serious pregnancy complication characterized by the appearance of hypertension after 20 weeks of gestation, accompanied by proteinuria. The renin-angiotensin system (RAS) is thought to contribute significantly to the pathogenesis of preeclampsia through activation of the angiotensin II type 1 receptor (AT1R). The aim of this study was to identify compounds from andaliman fruit (Zanthoxylum acanthopodium DC.) with potential as AT1R inhibitors using an in silico approach and to investigate the effects of methanolic extract from andaliman fruit on blood pressure, proteinuria and the expression of the Analyze angiotensin converting enzyme (ACE) and tumor necrosis factor alpha (TNF-α) in a PE animal model Using an in vivo approach. The in silico study started by modeling the AT1R protein structure based on the AT1R gene sequence of the animal model, followed by bioavailability, bioactivity and molecular docking analysis of the compounds found in andaliman fruits to evaluate their potential as AT1R inhibitor. The in vivo study included five groups of rats: non-PE, PE, PE + candesartan (5 mg/kg), PE + andaliman (100 mg/kg), and PE + andaliman (200 mg/kg). Preeclampsia was induced with NaCl from days 5 to 13 of gestation, followed by administration of methanolic extract of andaliman fruits from 14 to 21 days of gestation. Blood pressure and proteinuria were measured on days 5, 13, and 21. The TNF-α levels were assessed using dot blot, while the ACE levels were measured using ELISA. The results showed that the animal model met the criteria for preeclampsia by the appearance of blood pressure elevation and proteinuria. The in silico analysis identified five potential compounds as AT1R inhibitors, namely kaempferol, quercetin, resveratrol, farnesyl acetate and (E,E)-farnesylacetone. This AT1R inhibition was supported by physiological improvements, including reductions in blood pressure and proteinuria at the end of pregnancy. At the molecular level, andaliman fruit methanolic extract reduced ACE overexpression, which may be caused by a feedback loop following AT1R activation, and reduced TNF-α expression, a downstream signaling component of AT1R activation.

Item Type:	Thesis (Magister)
Identification Number:	0424090080
Divisions:	S2/S3 > Magister Biologi, Fakultas MIPA
Depositing User:	Unnamed user with username nova
Date Deposited:	04 Feb 2025 04:51
Last Modified:	04 Feb 2025 04:51
URI:	http://repository.ub.ac.id/id/eprint/235559

Text (DALAM MASA EMBARGO) MUHAMMAD SHAFALA SAFA.pdf Restricted to Registered users only Download (8MB)

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