[ABSTRAK
Latar belakang. Doksorubisin (DOK), suatu antibiotika antrasiklin, digunakansecara luas untuk terapi antikanker, namun penggunaan DOK dapat menimbulkanefek samping, salah satunya gangguan kognitif. Penggunaan kemoterapi berbasisDOK menunjukkan hingga 76% pasien mengalami penurunan kognitif.Kerusakan otak akibat penggunaan DOK disebabkan oleh peningkatan TNF-α diotak melalui uptake reseptor di sawar darah otak dan peningkatan produksimelalui aktivasi NF-κB. Peningkatan TNF-α lebih lanjut dapat menyebabkaninflamasi kronis yang dapat menimbulkan kematian sel saraf atau penyakitdegenerasi saraf. Mangiferin (MAG) merupakan salah satu senyawaneuroprotektif, akan tetapi efek terhadap kerusakan otak akibat pemberian DOKbelum diketahui. Penelitian ini bertujuan untuk mengetahui efek MAG terhadapkerusakan otak yang ditimbulkan oleh pemberian DOK.Metode. Penelitian dilakukan terhadap tikus Sprague-Dawley yang diinduksimenggunakan DOK dengan dosis total 15 mg/kgBB secara i.p mulai minggukedua. Pemberian MAG dilakukan secara p.o dengan dosis 30 dan 60 mg/kgBBselama 7 minggu. Parameter yang diamati adalah fungsi kognitif, inflamasi (TNF-α, NF-κB dan iNOS), stres oksidatif (SOD dan MDA) dan histopatologi denganpewarnaan HE.Hasil. Pemberian DOK menyebabkan gangguan kognitif yang ditandai denganpenurunan penggiliran labirin Y dan penurunan indeks diskriminasi padapengenalan obyek baru, disertai peningkatan parameter inflamasi yaitu ekspresiTNF-α, NF-κB dan iNOS. Pemberian MAG bersama DOK menyebabkanpeningkatan fungsi kognitif, penurunan inflamasi dan penurunan stres oksidatifserta histopatologi dewan pewarna HE.Kesimpulan. Berdasarkan hasil pemeriksaan parameter pada penelitianmengindikasikan bahwa mangiferin memiliki efek neuroproteksi terhadappemberian DOK.

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ABSTRACT
Introduction. Doxorubicin (DOK), an anthracycline antibiotic, is widely used foranticancer therapy, but the use of DOK causing side effects, one of them iscognitive impairment. Up to 76% of patients experienced cognitive decline causedby DOK-based chemotherapy. Brain damage due to the use of DOK lead by anincrease in TNF-α in the brain through the receptors uptake in the blood brainbarrier and increasing production through activation of NF-κB. Increased TNF-αcan further lead to chronic inflammation which can lead nerve cells death or nervedegeneration diseases. Mangiferin (MAG) is one of the neuroprotectivecompound, but the effect on brain damage induced by DOK is still unknown. Thisstudy 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 withtotal dose 15 mg/kg that divided into 6 dose and given within 2 weeks, startedfrom 2nd week. The rats was administrated by MAG p.o with dose 30 and 60mg/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 mazealteration and discrimination index in new object recognition, and accompaniedby increasing inflammatory parameters that showed in increasing TNF-α, NF-κBand iNOS expressions. Coadministration MAG with DOK led an increasing oncognitive function, reducing the inflammation and oxidative stress.Conclusion. Based on the results of the study, MAG indicated has aneuroprotective effect on brain damage induced by DOK;Introduction. Doxorubicin (DOK), an anthracycline antibiotic, is widely used foranticancer therapy, but the use of DOK causing side effects, one of them iscognitive impairment. Up to 76% of patients experienced cognitive decline causedby DOK-based chemotherapy. Brain damage due to the use of DOK lead by anincrease in TNF-α in the brain through the receptors uptake in the blood brainbarrier and increasing production through activation of NF-κB. Increased TNF-αcan further lead to chronic inflammation which can lead nerve cells death or nervedegeneration diseases. Mangiferin (MAG) is one of the neuroprotectivecompound, but the effect on brain damage induced by DOK is still unknown. Thisstudy 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 withtotal dose 15 mg/kg that divided into 6 dose and given within 2 weeks, startedfrom 2nd week. The rats was administrated by MAG p.o with dose 30 and 60mg/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 mazealteration and discrimination index in new object recognition, and accompaniedby increasing inflammatory parameters that showed in increasing TNF-α, NF-κBand iNOS expressions. Coadministration MAG with DOK led an increasing oncognitive function, reducing the inflammation and oxidative stress.Conclusion. Based on the results of the study, MAG indicated has aneuroprotective effect on brain damage induced by DOK, Introduction. Doxorubicin (DOK), an anthracycline antibiotic, is widely used foranticancer therapy, but the use of DOK causing side effects, one of them iscognitive impairment. Up to 76% of patients experienced cognitive decline causedby DOK-based chemotherapy. Brain damage due to the use of DOK lead by anincrease in TNF-α in the brain through the receptors uptake in the blood brainbarrier and increasing production through activation of NF-κB. Increased TNF-αcan further lead to chronic inflammation which can lead nerve cells death or nervedegeneration diseases. Mangiferin (MAG) is one of the neuroprotectivecompound, but the effect on brain damage induced by DOK is still unknown. Thisstudy 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 withtotal dose 15 mg/kg that divided into 6 dose and given within 2 weeks, startedfrom 2nd week. The rats was administrated by MAG p.o with dose 30 and 60mg/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 mazealteration and discrimination index in new object recognition, and accompaniedby increasing inflammatory parameters that showed in increasing TNF-α, NF-κBand iNOS expressions. Coadministration MAG with DOK led an increasing oncognitive function, reducing the inflammation and oxidative stress.Conclusion. Based on the results of the study, MAG indicated has aneuroprotective effect on brain damage induced by DOK]