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"Kelebihan besi dapat terjadi akibat transfusi berulang dan peningkatan absorpsi besi pada pasien talasemia. Talasemia dapat menyebabkan splenomegali dan hiperaktivitas limpa, sedangkan kelebihan besi menyebabkan kerusakan DNA dan stress oksidatif. Mangiferin dalam buah Phaleria macrocarpa memiliki potensi sebagai agen pengkelat besi dan antioksidan. Penelitian ini bertujuan untuk menguji ekstrak etanol buah Mahkota Dewa dalam menurunkan kadar besi organ limpa tikus yang mengalami iron overload. Tikus Sprague-Dawley 30 ekor dikelompokkan menjadi normal, kontrol negatif, deferiprone 462,5 mg/kgBB, mangiferin 50 mg/kgBB, Phaleria macrocarpa 100 mg/kgBB (PM1), dan Phaleria macrocarpa 200 mg/kgBB (PM2). Setiap kelompok, kecuali normal, diinjeksikan iron sucrose 15 mg sebanyak 2 kali seminggu secara intraperitoneal. Pada minggu ke-7, dilakukan pengambilan organ limpa untuk dibuatkan homogenat. Homogenat direaksikan dengan HNO3 dan asam perklorat, kemudian ditambahkan aquades dan disaring sebelum kadar besi diukur menggunakan Atomic Absorption Spectrometry (AAS). Kadar besi dimasukkan ke dalam rumus dan dianalisis dengan Kruskall-Wallis. Seluruh kelompok yang diinduksi besi memiliki kadar besi lebih tinggi dibandingkan kelompok normal. Kelompok deferiprone, mangferin, dan PM1 memiliki kadar besi cenderung lebih tinggi daripada kelompok negatif, sedangkan kadar besi PM2 cenderung lebih rendah. Kelompok PM2 menurunkan kadar besi lebih besar daripada PM1, mangiferin, dan deferiprone.

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Iron overload can happen due to repeated transfusion and increased iron absorption in thalassemia patients. Thalassemia can cause splenomegaly and hypersplenism, while iron overload causes DNA’s damage and oxidative stress. Mangiferin from Phaleria macrocarpa’s fruit has potential as iron chelator and antioxidant. This study intends to evaluate ethanol extract of Phaleria macrocarpa’s fruit in reducing iron value in spleen from iron overloaded rats. A total of 30 Sprague-Dawley rats were sorted into normal group, negative control, deferiprone 462,5 mg/kgBW, mangiferin 50 mg/kgBW, Phaleria macrocarpa 100 mg/kgBW (PM1), and Phaleria macrocarpa 200 mg/kgBW (PM2). Every group, except normal, was administered with iron sucrose 15 mg twice a week through intraperitoneal. At week 7th, spleen organs were taken to create homogenates. Homogenates were reacted with HNO3 and perchlorate acid, then added with aquades and filtered before iron levels were measured by Atomic Absorption Spectrometry (AAS). Iron levels were inputted in the formula and analyzed using Kruskall-Wallis. All induced groups have higher iron levels compared to the normal group. Deferiprone, mangiferin, and PM1 tended to have higher iron levels compared to negative control, while iron levels of PM2 tended to be lower. PM2 group reduced iron levels more than PM1, mangiferin, and deferiprone."

"Kelebihan besi dapat menyebabkan kerusakan organ akibat pembentukan radikal bebas dan ferroptosis, terutama pada hati sebagai organ utama penyimpanan besi. Efikasi deferiprone sebagai kelator standar yang paling banyak digunakan di Indonesia untuk menurunkan kadar besi hati masih tidak adekuat dan memiliki potensi hepatotoksik. Penelitian ini bertujuan untuk melihat efek kombinasi deferiprone dengan ekstrak etanol buah Phaleria macrocarpa (PM) yang sudah terbukti mampu mengkelat besi untuk mengatasi kelebihan besi pada tikus model hemosiderosis serta melihat interaksi senyawa aktif ekstrak PM dengan transporter uptake besi (DMT-1 dan ZIP-14) secara in-silico. Tikus dibagi menjadi enam kelompok, yaitu normal (N), kontrol negatif (KN), deferiprone (D), kombinasi deferiprone dosis lazim+ekstrak PM (DPM1) dan kombinasi deferiprone setengah dosis lazim+ekstrak PM (DPM2). Induksi kelebihan besi dilakukan dengan injeksi iron-dextran (intraperitoneal) selama 8 minggu. Terapi dimulai pada minggu ke-4 hingga ke-8. Parameter yang diukur meliputi kadar besi dan malondialdehid (MDA) hati, aktivitas ALT dan AST plasma, kadar GSH, TNF-α, ekspresi mRNA GPx4 pada hati, serta pemeriksaan histopatologi. Penelitian in-silico dilakukan dengan pendekatan homology modeling dan molecular docking. Hasil penelitian pada tikus menunjukkan bahwa seluruh kelompok terapi belum mampu menurunkan kadar besi hati secara bermakna dibandingkan kelompok KN, tetapi kelompok DPM-2 menunjukkan penurunan kadar besi yang paling baik. Secara histopatologis, terjadi penurunan akumulasi besi yang bermakna pada kelompok DPM-2. Penurunan kadar besi tersebut disertai dengan penurunan kadar MDA, ALT dan AST yang lebih baik dibandingkan monoterapi dengan deferiprone. Terapi kombinasi menyebabkan peningkatan GSH yang tidak bermakna dan belum mampu meningkatkan ekspresi mRNA GPx4. Hasil molecular docking menunjukkan bahwa beberapa senyawa di dalam ekstrak PM dapat berinteraksi dengan transporter DMT-1 dan ZIP-14 dengan binding energy yang cukup baik. Efek inhibisi terhadap transporter harus dibuktikan lebih lanjut secara in-vitro atau in-vivo.

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Iron overload can lead to organ damage through the formation of free radicals and ferroptosis, particularly affecting the liver as the primary iron storage organ. The efficacy of deferiprone, the most commonly used standard chelator in Indonesia for reducing liver iron levels, remains inadequate and poses potential hepatotoxic risks. This study aims to investigate the effects of combining deferiprone with ethanol extract of Phaleria macrocarpa fruit (PM), which has demonstrated iron-chelating properties, in addressing iron overload in a rat model of hemosiderosis. Additionally, the study examines the interaction of active compounds in PM extract with iron uptake transporters (DMT-1 and ZIP-14) through in-silico methods. Rats were divided into six groups: normal (N), negative control (KN), deferiprone (D), combination of standard dose deferiprone and PM extract (DPM1), and combination of half-dose deferiprone and PM extract (DPM2). Iron overload was induced via intraperitoneal injection of iron-dextran for 8 weeks. Therapy commenced from week 4 to week 8. Parameters measured included liver iron and malondialdehyde (MDA) levels, plasma ALT and AST activities, liver GSH levels, TNF-α levels, and mRNA GPx4 expression, and histopathological examination. In-silico studies employed homology modeling and molecular docking approaches. Results indicated that none of the therapy groups significantly reduced liver iron levels compared to the KN group, but the DPM2 group showed the most substantial reduction in iron levels. Histopathological analysis revealed a significant decrease in iron accumulation in the DPM2 group. This iron reduction was accompanied by better reductions in MDA, ALT, and AST levels compared to deferiprone monotherapy. The combination therapy resulted in a non-significant increase in GSH levels and did not enhance mRNA GPx4 expression. Molecular docking results indicated that several compounds in the PM extract could interact with DMT-1 and ZIP-14 transporters with favorable binding energies. To confirm whether these interactions can result in transporter inhibition, further validation through in-vitro or in-vivo studies is necessary."