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"Pendahuluan: Akumulasi zat besi berlebih, terutama pada pasien thalassemia yang menerima transfusi darah rutin, dapat memicu penyakit pernapasan seperti PPOK melalui pembentukan radikal bebas. Meskipun kelator besi seperti deferiprone efektif, deferiprone memiliki efek samping seperti neutropenia dan agranulositosis. Phaleria macrocarpa diketahui juga mengandung mangiferin yang bersifat antioksidan dan antiinflamasi. Tujuan penelitian ini untuk mengetahui efektivitas terapi kombinasi deferiprone dan ekstrak etanol P. macrocarpa sebagai alternatif untuk mengobati kondisi kelebihan zat besi dengan efek samping yang lebih rendah. Metode: Penelitian menggunakan tikus Sprague-Dawley (200-250 g) yang dibagi menjadi enam kelompok: Normal (N), Kontrol Negatif (KN), Deferiprone (D), Phaleria macrocarpa (PM), Kombinasi Dosis Penuh (DPM-1), dan Kombinasi Setengah Dosis (DPM-2). Tikus diinjeksi iron dextran 15 mg/x selama 8 minggu. Kelompok perlakuan menerima ekstrak etanol Phaleria macrocarpa (100 mg/kgBB) selama 4 minggu, sedangkan deferiprone diberikan dalam dosis penuh (462,5 mg/kgBB) atau setengah dosis (231,2 mg/kgBB) selama 4 minggu. Kadar zat besi dalam jaringan paru diukur menggunakan Atomic Absorption Spectrometry (AAS). Hasil: Kelompok PM menunjukkan penurunan kadar besi paling rendah di paru dibandingkan KN. Uji normalitas Shapiro-Wilk menunjukkan data terdistribusi normal (p>0,05). Uji One Way Anova tidak menemukan perbedaan signifikan antar kelompok (p>0,05), sehingga uji post hoc tidak dilakukan. Kesimpulan: Pemberian terapi deferiprone dan ekstrak Phaleria macrocarpa secara kombinasi tidak menunjukkan perbedaan yang signifikan dalam penurunan kadar besi di paru secara statistik. Namun, data menunjukkan kadar besi mengalami penurunan walaupun tidak signifkan pada kelompok PM dan DPM2.

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Introduction: Excessive iron accumulation, particularly in thalassemia patients who undergo regular blood transfusions, can lead to respiratory diseases like COPD, through free radical formation. Although iron chelators such as deferiprone are effective, they may cause side effects including neutropenia and agranulocytosis. Phaleria macrocarpa, containing mangiferin, has known antioxidant and anti-inflammatory properties. The study aims to evaluate the effectiveness of combining deferiprone with Phaleria macrocarpa extract for treating iron overload with fewer side effects. Methods: Sprague-Dawley rats (200–250 g) were divided into six groups: Normal (N), Negative Control (KN), Deferiprone (D), Phaleria macrocarpa (PM), Full-Dose Combination (DPM-1), and Half-Dose Combination (DPM-2). The rats were injected with 15 mg/x iron dextran for 8 weeks to induce iron overload. The treatment groups received ethanol extract of Phaleria macrocarpa (100 mg/kg body weight) for 4 weeks, while deferiprone was given at full dose (462.5 mg/kg body weight) or half dose (231.2 mg/kg body weight) for 4 weeks. Iron levels in lung tissues were measured using Atomic Absorption Spectrometry (AAS). Results: The PM group showed the lowest reduction in lung iron levels compared to KN. The Shapiro-Wilk test confirmed that the data were normally distributed (p>0.05). One-way Anova revealed no significant differences between groups (p>0.05), so post hoc tests weren’t conducted. Conclusion: Although the combination of deferiprone and Phaleria macrocarpa extract did not significantly reduce lung iron levels, The data showed that iron levels decreased, although not significantly, in the PM and DPM2 groups."

"Latar belakang: Besi berlebih dalam tubuh manusia dapat memicu stress oksidatif dan menyebabkan kerusakan ginjal. Malondialdehid (MDA) merupakan produk samping peroksidasi lipid akibat stres oksidatif. Penelitian menunjukkan bahwa senyawa mangiferin yang terkandung dalam buah Phaleria macrocarpa bermanfaat sebagai pengkelat besi. Penelitian ini bertujuan untuk menganalisis efektivitas ekstrak etanol buah Phaleria macrocarpa dalam menurunkan kadar MDA pada ginjal tikus yang diberi besi berlebih. Metode: 30 tikus Sprague-Dawley dibagi dalam 6 kelompok, yaitu normal, kontrol negatif, Deferiprone 462,5 mg/kgBB, Mangiferin 50 mg/kgBB, ekstrak etanol Phaleria macrocarpa 100 mg/kgBB, dan 200 mg/kgBB. Kelompok perlakuan diinjeksikan besi sukrosa intraperitoneal (15 mg/kali) dua kali seminggu selama tiga minggu, dilanjutkan perlakuan sesuai kelompok. Pada minggu ke-7, organ ginjal diambil untuk dibuat homogenat yang selanjutnya diukur kadar proteinnya menggunakan metode Bradford. Kadar MDA diukur dengan Thiobarbituric Acid menggunakan spektrofotometer 530 nm, kemudian hasilnya dibagi kadar protein (nmol/mg protein). Uji statistik yang digunakan berupa perbandingan rerata >2 kelompok menggunakan One-Way ANOVA. Hasil: Semua kelompok induksi besi mengalami peningkatan MDA secara signifikan dibandingkan kelompok tanpa perlakuan. Pemberian mangiferin dan ekstrak etanol Phaleria macrocarpa 100 mg/kgBB berhasil menurunkan kadar MDA secara signifikan dibandingkan kelompok kontrol negatif. Selain itu, dosis 100 mg/kgBB juga memiliki hasil yang paling mendekati nilai normal (3,876 ± 0,248 vs 2,890 ± 0,497). Namun, pemberian dosis 200 mg/kgBB menunjukkan hasil kadar MDA yang paling tinggi (4,868 ± 0,774 nmol/mg protein). Kesimpulan: Pemberian ekstrak etanol buah Phaleria macrocarpa 100 mg/kgBB dapat menurunkan kadar MDA ginjal tikus Sprague-Dawley yang paling baik dibandingkan dosis 200 mg/kgBB maupun kontrol positif.

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Introduction: Iron overload in human body may induce oxidative stress and kidney failure. Malondialdehyde (MDA) is byproduct of oxidative stress induced lipid peroxidation. Studies shown that Mangiferin in Phaleria macrocarpa fruit also useful as chelator agent. This study aims to analyze the effectivity of Phaleria macrocarpa fruits ethanol extract on reducing kidney Malondialdehyde (MDA) levels in rats induced by iron overload. Method: Thirty Sprague-Dawley rats were divided into six groups: normal, negative control, Deferiprone 462.5 mg/kgBW, Mangiferin 50 mg/kgBW, Ethanol extract of Phaleria macrocarpa 100 mg/kgBW, and 200 mg/kgBW. Intervention groups received iron sucrose intraperitoneally (15 mg/times) biweekly for three weeks, followed by corresponding group intervention. At week 7, kidneys were taken to make homogenate. Each sample homogenate was measured its protein using Bradford and MDA level using Thiobarbituric Acid method by spectrophotometer 530 nm (nmol/mg protein). Statistical test used was mean difference among >2 groups using One-Way ANOVA. Result: Iron overload induction groups were associated with significantly higher MDA levels than normal. The administration of mangiferin and ethanol extract 100 mg/kgBW successfully reduced MDA level significantly compared to negative control. Besides, 100 mg/kgBW dose group had the closest MDA to normal (3.876 ± 0.248 vs. 2.890 ± 0.497). However, dose of 200 mg/kgBW showed the highest MDA (4,868 ± 0,774 nmol/mg protein). Conclusion: The administration of 100 mg/kgBW Phaleria macrocarpa fruits ethanol extract was associated with the best reduction of kidney MDA level in Sprague-Dawley rats induced by iron overload compared to either 200 mg/kgBW dose or positive control."

"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."