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"Latar belakang. Doksorubisin (DOK), suatu antibiotika antrasiklin, digunakan secara luas untuk terapi antikanker, namun penggunaan DOK dapat menimbulkan efek samping, salah satunya gangguan kognitif. Penggunaan kemoterapi berbasis DOK menunjukkan hingga 76% pasien mengalami penurunan kognitif. Kerusakan otak akibat penggunaan DOK disebabkan oleh peningkatan TNF-α di otak melalui uptake reseptor di sawar darah otak dan peningkatan produksi melalui aktivasi NF-κB. Peningkatan TNF-α lebih lanjut dapat menyebabkan inflamasi kronis yang dapat menimbulkan kematian sel saraf atau penyakit degenerasi saraf. Mangiferin (MAG) merupakan salah satu senyawa neuroprotektif, akan tetapi efek terhadap kerusakan otak akibat pemberian DOK belum diketahui. Penelitian ini bertujuan untuk mengetahui efek MAG terhadap kerusakan otak yang ditimbulkan oleh pemberian DOK. Metode. Penelitian dilakukan terhadap tikus Sprague-Dawley yang diinduksi menggunakan DOK dengan dosis total 15 mg/kgBB secara i.p mulai minggu kedua. Pemberian MAG dilakukan secara p.o dengan dosis 30 dan 60 mg/kgBB selama 7 minggu. Parameter yang diamati adalah fungsi kognitif, inflamasi (TNF-α, NF-κB dan iNOS), stres oksidatif (SOD dan MDA) dan histopatologi dengan pewarnaan HE. Hasil. Pemberian DOK menyebabkan gangguan kognitif yang ditandai dengan penurunan penggiliran labirin Y dan penurunan indeks diskriminasi pada pengenalan obyek baru, disertai peningkatan parameter inflamasi yaitu ekspresi TNF-α, NF-κB dan iNOS. Pemberian MAG bersama DOK menyebabkan peningkatan fungsi kognitif, penurunan inflamasi dan penurunan stres oksidatif serta histopatologi dewan pewarna HE. Kesimpulan. Berdasarkan hasil pemeriksaan parameter pada penelitian mengindikasikan bahwa mangiferin memiliki efek neuroproteksi terhadap pemberian DOK.

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Introduction. Doxorubicin (DOK), an anthracycline antibiotic, is widely used for anticancer therapy, but the use of DOK causing side effects, one of them is cognitive impairment. Up to 76% of patients experienced cognitive decline caused by DOK-based chemotherapy. Brain damage due to the use of DOK lead by an increase in TNF-α in the brain through the receptors uptake in the blood brain barrier and increasing production through activation of NF-κB. Increased TNF-α can further lead to chronic inflammation which can lead nerve cells death or nerve degeneration diseases. Mangiferin (MAG) is one of the neuroprotective compound, but the effect on brain damage induced by DOK is still unknown. This study aims to determine the effect of MAG on brain damage induced by DOK.

Methods. Research carried out on Sprague-Dawley rats induced by DOK i.p with total dose 15 mg/kg that divided into 6 dose and given within 2 weeks, started from 2nd week. The rats was administrated by MAG p.o with dose 30 and 60 mg/kg daily for 7 weeks. Parameters measured were cognitive function, inflammatory parameters (TNF-α, NF-κB and iNOS), oxidative stress parameters (SOD and MDA) and histopatology using HE staining.

Results. DOK cause cognitive disorders that characterized by decreased Y maze alteration and discrimination index in new object recognition, and accompanied by increasing inflammatory parameters that showed in increasing TNF-α, NF-κB and iNOS expressions. Coadministration MAG with DOK led an increasing on cognitive function, reducing the inflammation and oxidative stress.

Conclusion. Based on the results of the study, MAG indicated has a neuroprotective effect on brain damage induced by DOK"

"Prevalensi talasemia di Indonesia cukup tinggi. Pengobatan talasemia berupa transfusi darah menyebabkan penumpukan besi di organ-organ tubuh dan kerusakan sel. Pemberian deferoxamine sebagai kelator besi banyak menimbulkan efek samping dan mahal. Oleh karena itu, diperlukan pengobatan dengan bahan yang lebih aman dan terjangkau dengan memanfaatkan bahan alami yang memiliki efek kelasi besi. Ektrak air daun Mangifera foetida L. terbukti memiliki efek kelasi terhadap feritin serum penderita talasemia, namun belum diteliti apakah ekstrak etanol daun Mangifera foetida L. juga menunjukkan efek kelasi terhadap feritin. Penelitian ini merupakan studi eksperimental pada tujuh serum pasien talasemia yang dibagi ke dalam tujuh kelompok perlakuan secara ex vivo yaitu: serum, mangiferin, mangiferin ditambah serum, ekstrak etanol 0,5 mg dan 0,75 mg, ekstrak etanol 0,5 mg dan 0,75 mg ditambah serum, namun yang akan dianalisis hanya empat kelompok yaitu: serum, mangiferin ditambah serum, ekstrak etanol 0,5 dan 0,75 mg ditambah serum. Nilai absorbansi setiap kelompok diukur menggunakan spektrofotometer dengan panjang gelombang ()=280 nm.Hasil uji statistik One Way Anova menunjukkan bahwa terdapat perbedaan bermakna antara kelompok perlakuan (p<0,001). Uji Post Hoc didapatkan hasil bahwa ekstrak etanol daun Mangifera foetida L. dosis 0,5 mg memiliki efek kelasi yang sama dengan dosis 0,75 mg (p=0,133). Ekstrak etanol daun Mangifera foetida L. dosis 0,5 mg memiliki efek kelasi yang sama dengan mangiferin murni (p=0,52), sedangkan dosis 0,75 mg memiliki efek kelasi yang berbeda (p=0,001). Perbedaan efek kelasi ini kemungkinan disebabkan oleh perbedaan dosis ekstrak etanol.

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Thalassemia has a high prevalence in Indonesia. Treatment of thalassemia with blood transfusion causing iron accumulation in the organs and damaging cells. Chelating agent, deferoxamine causes side effects and expensive. Therefore, it?s needed a safer and cheaper treatment by utilizing natural ingredients which have chelating effect. Water extract of Mangifera foetida L. leaf was proven to have the chelating effect on serum thalassemia patients, but there was no research the effects in the ethanol extract. The purpose of this study was to prove the effects of ethanol extract as a chelating agent.

This study used an experimental study using seven serums of patients with thalassemia by ex vivo and devided into seven treatments: serum, mangiferin, mangiferin plus serum, etanol extract 0,5 mg and 0,75 mg, etanol extract 0,5 mg and 0,75 plus serum, however only four treatments will be analized: serum, mangiferin plus serum, etanol extract 0,5 mg and 0,75 mg plus serum. They were measured in a spectrophotometer with (SOH)=280 nm.

The result by One Way Anova statistical test showed that there was significant difference between groups (p <0.001). Post Hoc test showed that the ethanol extract 0,5 mg has the same chelating effect with ethanol extract 0,75 mg (p = 0,133). Ethanol extract 0,5 mg has the same effect of iron chelation with the mangiferin (p=0,52), while ethanol extract 0,75 mg has different effect (p=0,001). The difference of chelating effect maybe caused by the difference of extract dose."

"ABSTRAKLatar Belakang: Mangiferin merupakan senyawa bioaktif yang diketahui dapat menghambat fibrosis, yaitu proses reversibel akibat jejas pada hati. Penelitian ini bertujuan untuk membuktikan efek mangiferin dalam menghambat fibrogenesis melalui hambatan terhadap ekspresi mRNA TGF-?, yaitu sitokin profibrogenik utama. Metode: Penelitian eksperimental ini menggunakan RNA yang diisolasi untuk mendapatkan cDNA, di mana kelompok perlakuan diberikan tioasetamid 200 mg/kg BB sebanyak 3 kali/minggu selama 5 minggu oleh Arozal W, dkk. Perlakuan dibagi menjadi kelompok kontrol, tioasetamid 200 mg/kg BB, tioasetamid 200 mg/kg BB mangiferin 50 mg/kg BB/hari, dan tioasetamid 200 mg/kg BB mangiferin 100 mg/kg BB/hari. Tingkat ekspresi mRNA TGF-? diukur dengan RT-PCR dan dihitung dengan metode Livak. Hasil: Terdapat peningkatan ekspresi mRNA TGF-? pada kelompok yang hanya diberikan tioasetamid terhadap kelompok kontrol. Pada kelompok yang diberikan mangiferin, terdapat penurunan ekspresi mRNA TGF-? terhadap kelompok yang hanya diberikan mangiferin, dengan penurunan ekspresi mRNA pada kelompok yang diberikan mangiferin 50 mg/kg BB/hari lebih besar. Kesimpulan: Mangiferin dapat menurunkan tingkat ekspresi mRNA TGF-? pada hati tikus yang diinduksi oleh tioasetamid, namun efeknya tidak linear antara dosis mangiferin dengan respon yang diberikan.

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ABSTRACT

Background Mangiferin is a bioactive compound that is known to inhibit fibrosis, a reversible process that occurs as a result of liver injury. This study aims to prove the antifibrotic effect of mangiferin through inhibition of mRNA expression of TGF , which is the main profibrogenic cytokine. Method This experimental design uses isolated RNA to get cDNA, which treatment groups are given thioacetamid with dose of 200 mg kg BW, three times a week for five weeks consecutively, in study from Arozal W, et al. The treatment groups are control group, thioacetamid 200 mg kg BW, thioacetamid 200 mg kg BW mangiferin 50 mg kg BW day, and thioacetamid 200 mg kg BW mangiferin 100 mg kg BW day. The expression of TGF mRNA is measured with RT PCR and quantified with Livak method. Result There is an increase mRNA expression of TGF in group that was given thioacetamide only compare to the control group. In the groups that were on treatment of mangiferin, the mRNA expressions of TGF are lower than the thioacetamid only group. The mRNA expression of TGF of the group that was given mangiferin of dose 50 mg kg BW day is also lower compare to the group that was given higher dose of mangiferin. Conclusion Mangiferin can lower the expression of TGF in rats liver induced by thioacetamide. However, mangiferin does not give linear effect between dose and response."

"Latar Belakang : Penumpukan besi di organ akibat kondisi iron overload dapat menyebabkan gagal fungsi organ limpa sehingga terjadi splenomegali dan harus dilakukan splenektomi. Kondisi ini dapat diatasi dengan pemberian kelasi besi, salah satu kandidat dari alam adalah mangiferin. Buah mahkota dewa (Phaleria macrocarpa) diketahui memiliki kandungan mangiferin. Penelitian ini bertujuan untuk menganalisis kadar mangiferin di organ limpa tikus model hemosiderosis setelah diberikan ekstrak etanol buah Phaleria macrocarpa. Metode : Penelitian menggunakan organ limpa dari 15 tikus Sprague-Dawley model besi berlebih dibagi menjadi 3 kelompok. Masingmasing kelompok diberikan perlakuan sesuai dengan kelompoknya, yaitu mangiferin tunggal 50 mg/KgBB, ekstrak etanol buah Phaleria macrocarpa dosis 100 mg/KgBB, dan 200 mg/KgBB. Kemudian kadar mangiferin dihitung menggunakan alat HPLC. Hasil : Rata-rata kadar mangiferin pada organ limpa tikus pada kelompok M adalah sebesar 4950.06±1272.10 (ng/g), kelompok PM1 3942.72±600.29 (ng/g), dan PM2 3572.00±768.73 (ng/g). Ketiga kelompok perlakuan tidak menghasilkan perbedaan yang signifikan. Kesimpulan : Pemberian ekstrak etanol buah Phaleria macrocarpa menghasilkan kadar mangiferin yang mendekati hasil dari pemberian mangiferin tunggal, pemberian kelompok PM1 paling mendekati hasil dari pemberian kelompok M. Peningkatan dosis ekstrak etanol tidak menghasilkan kadar mangiferin yang sebanding, hasil mangiferin pemberian kelompok PM2 cenderung lebih rendah dibanding kelompok PM1.

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Introduction : Excess iron in the spleen due to iron overload leading to organ failure, resulting in splenomegaly, necessitating splenectomy. One natural candidate to adress this issue is mangiferin, found in Mahkota dewa fruit (Phaleria macrocarpa). This research aims to analyze the level of mangiferin in spleen of hemosiderosis-modeled rats after administering Phalerica macrocarpa fruit ethanol extract. Method :This research used spleens from 15 Sprague-Dawley hemosiderosis-modeled rats divided into 3 groups. Each group was given three different treatments : mangiferin 50 mg/KgBB, ethanol extract of Phaleria macrocarpa fruit 100 mg/KgBB and 200 mg/KgBB. The mangiferin level were calculate using HPLC. Results :The average of mangiferin level of group M was 4950.06±1272.10 (ng/g), group PM1 was 3942.72±600.29 (ng/g), and group PM2 was 3572.00±768.73 (ng/g). There were no significant results. Conclusion : The administration of ethanol extract from Phaleria macrocarpa fruit results mangiferin levels that are close to the results obtained from the administration of pure mangiferin. Among the groups, PM1's administration yields results closest to those of group M (mangiferin). Increasing the dose of ethanol extract does not result in proportionally higher mangiferin levels; the mangiferin levels from the PM2 group tend to be lower than those of the PM1 group."

"Mangiferin berperan sebagai antioksidan dan bersifat kardioprotektif, di mana jantung merupakan organ yang esensial pada kehidupan manusia. Namun, absorpsi dan bioavailabilitasnya rendah, sehingga distribusi pada organ juga rendah. Absorpsi dan distribusi obat yang rendah dapat ditingkatkan dengan menggunakan nanopartikel kitosan-alginat sebagai sistem pengirimannya. Sehingga, penelitian ini dilakukan untuk membandingkan kadar mangiferin dan mangiferin nanopartikel kitosan-alginat pada organ jantung tikus. Organ jantung tersimpan dari 24 tikus jantan Sprague-Dawley dibagi ke dalam 4 kelompok, yaitu organ jantung dari tikus yang diberikan mangiferin konvensional dan diterminasi pada jam ke-3 (MK3), mangiferin nanopartikel kitosan-alginat dan diterminasi pada jam ke-3 (MNP3), mangiferin konvensional dan diterminasi pada jam ke-5,5 (MK5,5), dan mangiferin nanopartikel kitosan-alginat pada jam ke-5,5 (MNP5,5). Pemberian mangiferin dilakukan secara oral dengan dosis 50 mg/kgBB. Kadar mangiferin diukur menggunakan HPLC dan mengacu pada metode Estuningtyas. Kadar mangiferin konvensional dan mangiferin nanopartikel kitosan-alginat pada jantung tikus Sprague-Dawley di jam ke-3 berturut-turut adalah 344.80 ± 254.78 ng/g dan 412.48 ± 268.99 ng/g dengan Sig = 0.664. Kadar mangiferin konvensional dan mangiferin nanopartikel kitosan-alginat pada jantung tikus Sprague-Dawley di jam ke-5,5 berturut-turut adalah 1102.21 ± 241.25 ng/g, dan 1429.26 ± 311.45 ng/g dengan Sig = 0.069. Kadar mangiferin di jantung tikus Sprague-Dawley setelah pemberian mangiferin konvensional dan mangiferin nanopartikel kitosan-alginat tidak berbeda bermakna baik pada jam ke-3 maupun jam ke-5,5.

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Mangiferin acts as an antioxidant and has cardioprotective properties, in which the heart is an organ that is essential to human life. However, mangiferin has a very low absorption and bioavailability, thus low organ distribution. The low absorption and distribution of the drug can be increased by using chitosan-alginate nanoparticle as the delivery system. Therefore, this study aimed to compare the levels of mangiferin and mangiferin chitosan-alginate nanoparticle in Sprague-Dawley rat heart organs. The stored heart organs of 24 male Sprague-Dawley rats were divided into 4 groups, which are heart organs from rats given conventional mangiferin and sacrificed after 3 hours (MK3), chitosan-alginate nanoparticle mangiferin and sacrificed after 3 hours (MNP3), conventional mangiferin and sacrificed after 5.5 hours (MK5.5), and chitosan-alginate nanoparticle mangiferin and sacrificed after 5.5 hours (MNP5.5). Mangiferin was administered orally at a dose of 50 mg/kgBW. Mangiferin levels were measured using HPLC and referred to the Estuningtyas method. The levels of conventional mangiferin and chitosan-alginate nanoparticle mangiferin in the heart of Sprague-Dawley rats after 3 hours respectively are 344.80 ± 254.78 ng/g and 412.48 ± 268.99 ng/g with Sig = 0.664. The levels of conventional mangiferin and chitosan-alginate nanoparticle mangiferin in the heart of Sprague-Dawley rats after 5,5 hours respectively are 1102.21 ± 241.25 ng/g and 1429.26 ± 311.45 ng/g with Sig = 0.069. The levels of mangiferin in the heart of Sprague-Dawley rats after 3 and 5.5 hours oral administration of conventional mangiferin and chitosan-alginate nanoparticle mangiferin are not significantly different."

"Iron overload disebabkan oleh transfusi darah jangka panjang pada penderita hemoglobinopati. Iron overload menyebabkan stress oksidatif yang meningkatkan produksi malondialdehid (MDA) yang dapat menyebabkan penyakit paru obstruktif kronis. Mangiferin yang terkandung dalam buah Phaleria macrocarpa memiliki potensi sebagai kelator besi dan antioksidan. Penelitian ini bertujuan untuk menguji efektivitas ekstrak etanol buah Phaleria macrocarpa dalam menurunkan kadar MDA paru tikus Sprague-Dawley. Sebanyak 30 tikus Sprague-Dawley menjadi kelompok normal, kontrol negatif, deferiprone 462,5 mg/kgBB, mangiferin 50 mg/kgBB, Phaleria macrocarpa 100 mg/kgBB (PM1) dan 200 mg/kgBB (PM2). Besi dekstran 15 mg diberikan dua kali seminggu secara intraperitoneal pada semua kelompok kecuali normal. Pada minggu ke-7, organ paru sampel diambil untuk dibuatkan homogenat. Homogenat direaksikan dengan TBA dan TCA untuk mengukur kadar MDA dan direaksikan dengan reagen Bradford untuk mengukur protein jaringan yang kemudian diukur dengan spektrofotometer. Hasil yang didapatkan adalah kadar MDA dibagi dengan protein jaringan dan kemudian dilakukan analisis dengan One-Way ANOVA. Kadar MDA paru pada seluruh kelompok yang diinduksi besi cenderung meningkat dibandingkan normal. Kadar MDA pada kelompok PM1 dan mangiferin lebih rendah (p < 0,05) dari deferiprone, sedangkan PM2 dan deferiprone cenderung lebih tinggi dari kontrol negatif. Kelompok PM1 menurunkan kadar MDA lebih baik dibandingkan PM2 dan deferiprone.

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Iron overload is caused by long-term blood transfusion in hemoglobinopathies patients. Iron overload causes oxidative stress that increases malondialdehyde (MDA) production, which cause chronic obstructive pulmonary disease. Mangiferin contained in Phaleria macrocarpa fruit have potential as iron chelator and antioxidant. This study aimed to evaluate the effectiveness of Phaleria macrocarpa fruit ethanol extract in reducing lung MDA levels in Sprague-Dawley rats. Thirty Sprague-Dawley rats were divided into normal group, negative control, deferiprone 462.5 mg/kgBW, mangiferin 50 mg/kgBW, Phaleria macrocarpa 100 mg/kgBW (PM1) and 200 mg/kgBW (PM2). Iron dextran 15 mg was administered intraperitoneally twice a week in all groups except normal. At week 7, lung organs samples were taken to make homogenates. Homogenates were reacted with TBA and TCA to measure MDA levels and reacted with Bradford's reagent to measure tissue protein which was measured by spectrophotometer. Results obtained were MDA levels divided by tissue protein and then analyzed using One-Way ANOVA. Lung MDA levels in all iron-induced groups tended to increase compared to normal. MDA levels in the PM1 and mangiferin were lower (p < 0.05) than deferiprone, while PM2 and deferiprone tended to be higher than negative controls. PM1 group reduced MDA levels better than PM2 and deferiprone."

"[ABSTRAKDoksorubisin merupakan salah satu antikanker golongan antrasiklin yang efektif,untuk keganasan di darah. Akan tetapi, seperti antikanker konvensional padaumumnya, penggunaan doksorubisin dapat menyebabkan berbagai efek samping padaorgan lain, misalnya pada testis sehingga penggunaannya di klinis menjadi terbatas.Hal ini disebabkan karena mekanisme antikanker doksorubisin dapat jugamenimbulkan toksisitas pada testis. Peningkatan stress oksidatif adalah salah satumekanisme dapat menyebabkan kerusakan pada organ tersebut. Mangiferin sebagaizat antioksidan alami, terkandung dalam Mangifera Indica L. diperkirakan dapatdigunakan untuk mengurangi toksisitas testis. Namun sampai saat ini, belum adapenelitian yang mengeksplor efek proteksi mangiferin terhadap kerusakan oksidatiftestis yang diinduksi doksorubisin.Penelitian ini menggunakan tikus jantan Sprague Dawley, yang dibagi menjadi empatkelompok. Masing-masing kelompok terdiri dari enam ekor tikus. Tikus padakelompok kontrol negatif diberikan doksorubisin secara intraperitoneal (dosis total 15mg/kgBB) dan kelompok normal diberikan NaCl 0,9%. Mangiferin (dosis 30 dan 60mg/kg BB) diberikan oral selama tujuh minggu. Setelah, tujuh minggu tikusdimatikan dan testis dikumpulkan untuk analisis parameter stress oksidatif biokimiakadar MDA (malonedyaldehide), aktivitas SOD (Superoxide Dysmutase), perubahanhistologi dan apoptosis kaspase-9 dan kaspase-12. Hasil penelitian menunjukkanbahwa pemberian doksorubisin selama dua minggu dapat meningkatkan kadar MDA,menyebabkan kerusakan sel spermatogenik, sel Sertoli dan penciutan diametertubulus seminiferus testis, peningkatan ekspresi kaspase-9 di sisi luminal yangdiberikan doksorubisin. Pemberian mangiferin dosis 30 dan 60 mg/kg BB selamatujuh minggu dapat mengurangi kerusakan sel spermatogenik dan sel Sertoli tubulusseminiferus testis, penurunan kadar MDA dan penurunan ekspresi kaspase-9 padakelompok perlakuan diberikan doksorubisin dan mangiferin. Perbaikan parameterparameterini mengindikasikan bahwa mangiferin mempunyai efek proteksi terhadapkerusakan sel spematogenik dan sel sertoli tubulus seminiferus testis tikus yangdiberikan doksorubisin.

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ABSTRACTDoxorubicin, one of the anthracycline anticancer class, is effective especially in bloodmalignancy. However, as in the general use of the conventional anticancer-drugs.Doxorubicin can cause various side effects in other organs, such as the testes so thatits use in clinical become limited. This is because of the anticancer mechanism cancause cytotoxicity on testes. The increased oxidative stress is the main mechanismthat can be the causal. Mangiferin as a natural antioxidant substance, contained inMangifera Indica L., is expected to reduce the toxicity. The Antioxidants areexpected to reduce the toxicity of the testes. But until now, no studies have exploredthe effects of mangiferin protection against oxidative damage induced testiculardoxorubicin.This study used male Sprague Dawley rats, which were divided into four groups.Each group consisted of six mice. Rats in the negative control group was givenintraperitoneal doxorubicin (total dose 15 mg/kg) and the normal group was givennormal saline 0.9%. Mangiferin (doses of 30 and 60 mg/kg) was administered orallyfor seven weeks to the treatment gtoups (both DOX and MAG were given). Afterseven weeks-off, testes of mice were collected for analysis of biochemical parametersi.e. oxidative stress levels of MDA and SOD activity, histology and apoptosis of thecaspase-9 and of the caspase-12. The results showed that administration ofdoxorubicin for two-weeks can cause damage to Sertoli, spermatogenic cells andshrinking of diameter of testicular seminiferous tubules, increasing the levels ofMDA, increasing in the expression of caspase-9 on the luminal side in the treatmentgroup was given doxorubicin. This possibility of the doxorubicin dose given is tootoxic to the testes in this study. Mangiferin dose administration of 30 and 60 mg / kgfor seven-weeks can reduce the damage of Sertoli and spermatogenic cells of thetesticular seminiferous tubules, decrease levels of MDA, reduce Sertoli,spermatogenic cell and diameter of the testicular seminiferous tubulus damage,decrease caspase-9 expression only on luminal side of the seminiferus tubulus in thegroups given both of doxorubicin and mangiferin. these parameters indicate thatmangiferin, which has antioxidant?s activity, provides protective effects againstoxidative damage in spematogenic and Sertoli cell testicular seminiferous tubules ofmice given doxorubicin, Doxorubicin, one of the anthracycline anticancer class, is effective especially in bloodmalignancy. However, as in the general use of the conventional anticancer-drugs.Doxorubicin can cause various side effects in other organs, such as the testes so thatits use in clinical become limited. This is because of the anticancer mechanism cancause cytotoxicity on testes. The increased oxidative stress is the main mechanismthat can be the causal. Mangiferin as a natural antioxidant substance, contained inMangifera Indica L., is expected to reduce the toxicity. The Antioxidants areexpected to reduce the toxicity of the testes. But until now, no studies have exploredthe effects of mangiferin protection against oxidative damage induced testiculardoxorubicin.This study used male Sprague Dawley rats, which were divided into four groups.Each group consisted of six mice. Rats in the negative control group was givenintraperitoneal doxorubicin (total dose 15 mg/kg) and the normal group was givennormal saline 0.9%. Mangiferin (doses of 30 and 60 mg/kg) was administered orallyfor seven weeks to the treatment gtoups (both DOX and MAG were given). Afterseven weeks-off, testes of mice were collected for analysis of biochemical parametersi.e. oxidative stress levels of MDA and SOD activity, histology and apoptosis of thecaspase-9 and of the caspase-12. The results showed that administration ofdoxorubicin for two-weeks can cause damage to Sertoli, spermatogenic cells andshrinking of diameter of testicular seminiferous tubules, increasing the levels ofMDA, increasing in the expression of caspase-9 on the luminal side in the treatmentgroup was given doxorubicin. This possibility of the doxorubicin dose given is tootoxic to the testes in this study. Mangiferin dose administration of 30 and 60 mg / kgfor seven-weeks can reduce the damage of Sertoli and spermatogenic cells of thetesticular seminiferous tubules, decrease levels of MDA, reduce Sertoli,spermatogenic cell and diameter of the testicular seminiferous tubulus damage,decrease caspase-9 expression only on luminal side of the seminiferus tubulus in thegroups given both of doxorubicin and mangiferin. these parameters indicate thatmangiferin, which has antioxidant’s activity, provides protective effects againstoxidative damage in spematogenic and Sertoli cell testicular seminiferous tubules ofmice given doxorubicin]"

"ABSTRAKMangiferin merupakan salah satu senyawa derivat xanton yaitu C-glikosilxanton yang berpotensi dikembangkan menjadi agen pengkelat besi namun bioavailabilitas pada pemberian secara oral sangat rendah dan kelarutannya kurang baik. Preparasi mangiferin dalam nanopartikel kitosan-alginat diharapkan dapat meningkatkan bioavailabilitas mangiferin karena dengan memperkecil ukuran mangiferin akan memperbesar luas permukaan dan meningkatkan interaksi dengan pelarut sehingga kelarutan akan meningkat. Nanopartikel juga dapat menghantarkan senyawa obat dengan baik sampai ke unit-unit kecil dalam tubuh, meningkatkan distribusi, serta obat tepat target, sehingga meningkatkan efek terapetik. Tujuan penelitian ini adalah untuk mengetahui berbagai parameter farmakokinetik nanopartikel kitosan-alginat mangiferin yang diberikan secara oral pada tikus. Penelitian dilakukan pada tikus jantan Sprague-Dawley yang diberi nanopartikel kitosan-alginat mangiferin sebesar 50 mg/kgBB secara oral. Darah diambil dari vena ekor pada 0; ½; 1; 2; 3; 4; 4½; 5; 5½ dan 6 jam setelah pemberian oral. Hati dan jantung diambil pada jam ke 4 dan 6 setelah pemberian oral. Analisis kadar mangiferin pada plasma, hati dan jantung menggunakan HPLC. Parameter farmakokinetik telah dihitung. Konsentrasi maksimum nanopartikel kitosan-alginat mangiferin dalam plasma mencapai 634,65 ± 10,37 ng/mL dengan Tmax 4 jam setelah pemberian oral dan waktu paruh eliminasi (t1/2) adalah 6,45 ± 0,15 jam. Konsentrasi nanopartikel kitosan-alginat mangiferin di jantung dan di hati pada jam keempat dan keenam setelah pemberian oral berturut-turut adalah 753,16 ± 93,48 ng/mL, 1976,55 ± 40,06 ng/mL, 1998,81 ± 72,25 ng/mL, dan 3562,81 ± 189,28 ng/mL. Peningkatan kadar mangiferin pada kelompok nanopartikel kitosan-alginat mangiferin di plasma, jantung dan hati menunjukkan bentuk nanopartikel kitosan-alginat mangiferin memiliki absopsi yang lebih baik dibanding kelompok mangiferin. Preparasi nanopartikel kitosan-alginat mangiferin dapat mempengaruhi profil farmakokinetik mangiferin pada plasma dan distribusinya pada hati dan jantung tikus.

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ABSTRACTMangiferin is one of the xanthone derivative compounds, namely C-glicosylxanthones which has the potential to be developed into an iron chelating agent but the bioavailability of oral administration is very low, and its have poor solubility. The preparation of mangiferin in chitosan-alginate nanoparticles are expected to increase the bioavailability of mangiferin because by reducing particle size it will increase the surface area and increase interaction with the solvent so that solubility will increase. Nanoparticles can also deliver medicinal compounds well to small units in the body, increase distribution, and target drugs, thereby increasing therapeutic effects. The purpose of this study was to determine the various pharmacokinetic parameters of chitosan-alginate mangiferin nanoparticles given orally in rats. The study was conducted on Sprague-Dawley male rats were given 50 mg/ kgBW of chitosan-alginate mangiferin orally. Blood samples were taken from the tail vein at 0; ½; 1; 2; 3; 4; 4½; 5; 5½ and 6 hours after oral administration. Heart and liver organs are taken at the fourth and sixth hour after oral administration. Analysis of mangiferin levels in plasma, liver, and heart using HPLC. The pharmacokinetics parameters were calculated. The maximum concentration of chitosan-alginate mangiferin nanoparticles in plasma reached 634.65 ± 10.37 ng/mL with Tmax 4 hours after oral administration, and the apparent elimination half-life (t1/2) was 6,45 ± 0,15 hours. Concentrations in the heart and liver in the fourth and sixth hours after oral administration were 753,16 ± 93,48 ng/mL, 1976,55 ± 40,06 ng/mL, 1998,81 ± 72,25 ng/mL, and 3562,81 ± 189,28 ng/mL. Increased concentrations of chitosan-alginate mangiferin nanoparticles in plasma, heart, and liver showed that chitosan-alginate mangiferin nanoparticles had good absorption. Preparation of chitosan-alginate mangiferin nanoparticles can affect the pharmacokinetic profile of mangiferin in plasma and its distribution to the liver and heart of rats."

"ABSTRAKLatar Belakang: Mangiferin diketahui memiliki aktivitas sebagai agen pengikat besi, namun pemberian mangiferin melalui oral memiliki bioavailabilitas yang rendah. Sistem hantaran dengan nanopartikel diharapkan dapat meningkatkan bioavailabilitas dan efektivitas mangiferin. Penelitian bertujuan menguji efektivitas mangiferin nanopartikel kitosan-alginat dalam menurunkan kadar besi di plasma dan organ, kadar ferritin, transferrin, SGOT dan SGPT. Metode: Penelitian menggunakan desain eksperimental in vivo dengan hewan coba tikus Sprague-Dawley dibagi dalam 5 kelompok, yaitu kelompok normal, kelebihan besi, terapi mangiferin 50 mg/KgBB, terapi mangiferin dalam nanopartikel kitosanalginat 25 mg/KgBB, dan terapi mangiferin dalam nanopartikel kitosan-alginat 50 mg/KgBB. Pengukuran kadar Fe plasma, hati dan jantung, kadar Ferritin, kadar Transferrin, dan nilai aktivitas SGPT dan SGOT. Hasil: Kadar besi plasma, besi hati dan jantung, ferritin, dan transferrin pada kelompok kelebihan besi adalah 45,52 mg/L; 3661,98 μg/gram; 1734,4 μg/gram; 3578,16 ng/mL; 388,96 μg/dL, sedangkan pemberian terapi mangiferin 50 mg/KgBB (p < 0,05) menghasilkan 5,17 mg/L; 1572,96 μg/gram; 776,68 μg/gram; 1136,51 ng/mL; 272,18 μg/dL, pemberian terapi mangiferin dalam nanopartikel kitosan-alginat 25 mg/KgBB (p < 0,05) menghasilkan 5,74 mg/L; 1090,01 μg/gram; 753,90 μg/gram; 520,89 ng/mL; 231,97 μg/dL, pemberian terapi mangiferin dalam nanopartikel kitosan-alginat 50 mg/KgBB (p < 0,05) menghasilkan 3,34 mg/L; 1703,92 μg/gram; 759,2 μg/gram; 559,48 ng/mL; 235,70 μg/dL. Tidak terdapat perbedaan bermakna antar kelompok terhadap nilai aktivitas SGOT dan SGPT Kesimpulan: Mangiferin dalam nanopartikel kitosan-alginat efektif menurunkan kadar besi, ferritin, transferrin plasma, dan kadar besi di organ hati dan jantung, namun tidak menurunkan nilai aktivitas SGOT dan SGPT. Efektivitas mangiferin dalam nanopartikel kitosan-alginat tidak berbanding lurus dengan dosis.

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ABSTRACTBackground: Mangiferin was known to have activity as an iron-chelating agent, but oral administration of mangiferin has poor bioavailability. Nanoparticles delivery system is expected to increase bioavailability and effectiveness of mangiferin. This study aims to examine the effectiveness of mangiferin in chitosanalginate nanoparticles in reducing iron levels in plasma and organs, ferritin, transferrin, SGOT and SGPT activities. Methods: This is an in vivo experimental study using Sprague-Dawley rats, divided into 5 groups, normal, iron overload, mangiferin 50mg/KgBW, mangiferin in chitosan-alginate nanoparticles 25mg/KgBW, and mangiferin in chitosanalginate nanoparticles 50mg/KgBW. Fe levels were measured in plasma, liver and heart. In addition ferritin levels, transferrin levels, and SGPT and SGOT activities also measure at day 29th. Results: Plasma iron levels, liver and heart iron levels, ferritin, and transferrin in the iron overload group were 45.52 mg/L; 3661.98 μg/gram; 1734.4 μg/gram; 3578.16 ng/mL; 388.96 μg/dL, treatment with mangiferin 50 mg/KgBW (p < 0.05) reduced those parameters to 5.17 mg/L; 1572.96 μg/gram; 776.68 μg/gram; 1136.51 ng/mL; 272.18 μg/dL, treatment with mangiferin in chitosan-alginate nanoparticles 25 mg/KgBW (p < 0.05) reduced those parameters 5.74 mg/L; 1090.01 μg/gram; 753.90 μg/gram; 520.89 ng/mL; 231.97 μg/dL, treatment with mangiferin in chitosan-alginate nanoparticles 50 mg/KgBW (p < 0.05) reduced those parameters 3.34 mg/L; 1703.92 μg/gram; 759.2 μg/gram; 559.48 ng/mL; 235.70 μg/dL. There is no significant difference in SGOT and SGPT activities. Conclusions: Mangiferin in chitosan-alginate nanoparticles was effective in preventing the increase of iron, ferritin, transferrin plasma levels, and iron levels in the liver and heart, but not prevent the increasing of SGOT and SGPT. The effectiveness of mangiferin in chitosan-alginate nanoparticles is not directly proportional to the dose."

"Mitokondria merupakan organel yang memetabolisme besi secara ekstensif, sehingga menjadi target kerusakan yang diinduksi besi pada kondisi hemosiderosis. Produksi reactive oxygen species (ROS) yang tinggi di mitokondria dapat lebih meningkat saat ada besi bebas yang kemudian memicu reaksi Fenton. Produksi ROS yang tinggi dapat menyebabkan stres oksidatif, sehingga regulasi konsentrasi besi harus diatur dengan ketat. Phaleria macrocarpa diketahui mengandung senyawa aktif mangiferin yang telah terbukti memiliki aktivitas kelasi besi, namun belum diketahui apakah dapat bekerja di mitokondria. Penelitian ini bertujuan untuk mengetahui efektivitas ekstrak etanol buah Phaleria macrocarpa dalam melindungi mitokondria hati dari kerusakan akibat besi dan kaitannya dengan transporter influks dan efluks besi di hati tikus model hemosiderosis. Penelitian ini menggunakan organ hati tersimpan dari tikus Sprague-Dawleyjantan sebanyak 30 ekor yang dibagi secara acak ke dalam 6 kelompok, yaitu normal (N) dan kelompok hemosiderosis tanpa terapi (Fe), diterapi deferiprone 462,5 mg/kgBB (Fe+DFP), mangiferin 50 mg/kgBB (Fe+M), serta ekstrak etanol buah Phaleria macrocarpa dosis 100 mg/kgBB (Fe+PM100) dan 200 mg/kgBB (Fe+PM200). Dilakukan analisis kadar MnSOD, copy number mtDNA, dan analisis ekspresi mRNA DMT1, ZIP14, MFRN1, MFRN2, ABCB7, dan ABCB8 yang dilaporkan berperan dalam transpor besi ke dalam sel dan mitokondria. Hasil penelitian menunjukkan bahwa ekstrak Phaleria macrocarpa memengaruhi ekspresi gen transporter besi namun tidak dapat memperbaiki penanda kerusakan mitokondria pada organ hati hemosiderosis.

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Mitochondria are organelles that metabolize iron extensively, making them targets for iron-induced damage. The high production of reactive oxygen species (ROS) in mitochondria can be further increased when there is free iron which then triggers the Fenton reaction. High ROS production can cause oxidative stress, so iron concentration regulation must be strictly regulated. Phaleria macrocarpa is known to contain the active compound mangiferin which has been shown to have iron chelation activity, but it is not yet known whether it can work in mitochondria. This study aims to determine the effectiveness of the ethanol extract of Phaleria macrocarpa fruit in protecting liver mitochondria from iron-induced damage and its relation to iron influx and efflux transporters in the liver of hemosiderosis rat models. This study used stored liver organs from 30 male Sprague-Dawley rats which were randomly divided into 6 groups, namely normal (N) and hemosiderosis groups without therapy (Fe), treated with deferiprone 462.5 mg/kgBW (Fe+DFP), mangiferin 50 mg/kgBW (Fe+M), and Phaleria macrocarpa fruit ethanolic extract at a dose of 100 mg/kgBW (Fe+PM100) and 200 mg/kgBW (Fe+PM200). Analysis of MnSOD levels, mtDNA copy number, and analysis of relative mRNA expression of DMT1, ZIP14, MFRN1, MFRN2, ABCB7, and ABCB8 were performed which were reported to play a role in iron transport into cells and mitochondria. The results showed that Phaleria macrocarpa extract has the potential to modulate the expression of iron transporter genes but was not able to ameliorate the mitochondrial damage marker in hemosiderosis liver."