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Abstrak :
Latar Belakang: Cisplatin adalah obat antineoplastik berbasis platinum yang dipakai untuk berbagai jenis kanker. Walaupun memiliki efikasi yang tinggi, cisplatin memiliki efek samping yang berbahaya, yaitu gagal ginjal akut yang disebabkan oleh stres oksidatif dan inflamasi. Kurkumin diketahui memiliki efek antioksidatif dan antiinflamasi pada gagal ginjal akut yang disebabkan oleh cisplatin, walaupun memiliki bioavailabilitas yang rendah. Hal ini dapat diatasi dengan menggunakan nanokurkumin. Penelitian ini bertujuan untuk membandingkan efektivitas kurkumin dan nanokurkumin dalam melindungi ginjal akibat pemberian dosis tunggal cisplatin, terutama pada ekspresi Nrf2 dan Keap1: Tikus Sprague-dawley jantan (n=25) dikelompokkan menjadi 5 kelompok (Kontrol, cisplatin, cisplatin + curcumin, cisplatin + nanokurkumin 50 mg/kgBB/hari, cisplatin + nanokurkumin 100mg/kgBB/hari, dan dikorbankan 9 hari setelah perlakuan. Sampel ginjal diambil dan dilakukan RT-PCR untuk Nrf2 dan Keap1 Hasil: Pemeriksaan ekspresi gen Nrf2 ditemukan tidak terdapat hubungan yang signifikan antarkelompok (p>0.05). Namun, pada pemeriksaan ekspresi gen Keap1, terlihat ekspresinya lebih tinggi pada tikus yang mendapatkan cisplatin dibandingkan kelompok normal dan ekspresi gen Keap1 juga terlihat lebih tinggi pada kelompok dengan 100mg nanokurkuminKesimpulan Nanokurkumin dapat meningkatkan ekpresi Keap1, walaupun tidak signifikan secara statistik. Hal ini dapat disebabkan oleh karena peningkatan aktivasi Nrf2 yang menyebabkan umpan balik negatif sehingga menurunkan ekspresi Keap1
Background: Cisplatin is a platinum-based drug that is used for various type of cancer. Despite its high efficacy, cisplatin has a very destructive side effect, which is acute kidney failure due to oxidative stress and inflammation. Curcumin has been shown to possess anti-oxidative and anti-inflammatory effect in cisplatin-induced AKI, despite its poor bioavailability, which can be managed by administering nanocurcumin. This study aims to compare the effectivity of curcumin and nanocurcumin in protecting kidney doe to single-dose cisplatin administration, especially in the antioxidative gene Nrf2 and its inhibitor Keap1 Method: Male Sprague-Dawley rat (n=25) are divided into 5 groups (Control, Cisplatin, Cisplatin + Curcumin, Cisplatin + Nanocurcumin 50mg/kgBW, Cisplatin + Nanocurcumin 100mg/kgBW) and sacrificed 9 days after treatment. Kidney sample is taken and RT-PCR for Nrf2 and Keap1 is done.Results: Result of RT-PCR shows no statistical significance in Nrf2 expression across the group (p>0.05). However, Keap1 level was increased in rats treated with 100mg Nanocurcumin. Conculsion: that nanocurcumin can increase Keap1 level but not significantly. This might be caused by increased Nrf2 activation which induce negative feedback thus increasing Keap1 transcription level.

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Latar Belakang: Penyakit ginjal kronik (PGK) merupakan penyakit progresif dan ireversibel yang mempunyai berbagai komplikasi serius serta belum ada terapi yang dapat memperbaiki kerusakan ginjal yang telah terjadi. Beberapa studi menunjukkan stres oksidatif berperan dalam patogenesis penyakit ini. Stres oksidatif terjadi akibat ketidakseimbangan produksi ROS dan pertahanan antioksidan. Nrf2 merupakan faktor transkripsi yang terlibat dalam mekanisme pertahanan sel dalam mengatasi stres oksidatif. Penelitian ini bertujuan untuk mengetahui aktivitas kuersetin sebagai aktivator Nrf2 dalam menghambat progresivitas penyakit ginjal yang diinduksi nefrektomi 5/6. Metode: Tikus Sprague-Dawley jantan dikelompokkan secara acak dalam kelompok kontrol normal (C), kontrol nefrektomi 5/6 (Nx), nefrektomi 5/6 yang diberi kuersetin dengan dosis 100 mg/kgbb/hari/p.o. (NxQ), nefrektomi 5/6 dan diberi kaptopril dengan dosis 10 mg/kgbb/hari/p.o. (NxK). Hewan coba diterminasi diakhir perlakuan untuk diambil darah, urin, dan organ ginjalnya. Pemeriksaan yang dilakukan adalah pemeriksaan proteinuria, kreatinin urin dan plasma, ureum plasma, kadar MDA plasma dan jaringan, aktivitas glutation peroksidase (GPx), kerusakan jaringan (histopatologi) dan ekspresi Nrf2 (imunohistokimia). Hasil: Hasil penelitian menunjukkan bahwa nefrektomi 5/6 dapat menimbulkan peningkatan proteinuria, ureum plasma, dan derajat fibrosis ginjal secara signifikan. Nefrektomi 5/6 cenderung meningkatkan kreatinin plasma, kadar MDA ginjal, aktivitas GPx, dan menurunkan MDA plasma serta ekspresi Nrf2. Kuersetin tidak mempengaruhi proteinuria, ureum dan kreatinin plasma, dan derajat fibrosis ginjal. Kuersetin cenderung menurunkan kadar MDA dan meningkatkan aktivitas enzim GPx serta ekspresi Nrf2. Kesimpulan: Kuersetin tidak mempengaruhi proteinuria, ureum dan kreatinin plasma serta kerusakan struktur jaringan atau fibrosis ginjal. Kuersetin cenderung menurunkan kadar MDA dan meningkatkan aktivitas enzim GPx serta cenderung meningkatkan ekspresi Nrf2.

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ABSTRACT
Background: Chronic Kidney Disease (CKD) is a progressive and irreversible condition that has several serious complications and currently there has no single therapy that can repair kidney damage was occurred. Some studies suggest a role of oxidative stress in the pathogenesis of this disease. Oxidative stress is caused by an imbalance of ROS production and antioxidant defenses. Nrf2 is a transcription factor involved in cell defense mechanisms againts oxidative stress. This study was aimed to determine the quercetin activity as Nrf2 activator in inhibit the progression of 5/6 nephrectomy induced CKD in male rats. Method: Sprague-Dawley rats were randomly divided into normal control group (C), untreated 5/6 nephrectomy (Nx), quercetin-treated 5/6 nephrectomy, NxQ (100 mg / kg / day orally), captopril-treated 5/6 nephrectomy, NxK (10 mg / kg / day orally). Animal models was sacrificed at the end of intervention to take blood to measure creatinine, urea, and MDA, urine to measure protein and creatinine, and kidney organ to measure levels of MDA, glutathione peroxidase (GPx) activity, and renal damage (histopathology) and Nrf2 expression (immunohistochemistry). Results: The results showed that 5/6 nephrectomy may cause an increased of proteinuria, plasma urea, and grade of renal fibrosis significantly. 5/6 nephrectomy has trend to increased plasma creatinine, renal MDA levels, GPx activity, and decreased plasma MDA and Nrf2 expression. Quercetin did not decrease proteinuria, plasma urea and creatinine, and renal fibrosis grading. Quercetin tend to reduced levels of MDA, increased GPx enzyme activity, and expression of Nrf2. Conclusion: Quercetin does not affect proteinuria, plasma urea,plasma creatinine, and tissue damage or kidney fibrosis. Quercetin tend to reduced levels of MDA and increased the activity of GPx and Nrf2 expression.;Background: Chronic Kidney Disease (CKD) is a progressive and irreversible condition that has several serious complications and currently there has no single therapy that can repair kidney damage was occurred. Some studies suggest a role of oxidative stress in the pathogenesis of this disease. Oxidative stress is caused by an imbalance of ROS production and antioxidant defenses. Nrf2 is a transcription factor involved in cell defense mechanisms againts oxidative stress. This study was aimed to determine the quercetin activity as Nrf2 activator in inhibit the progression of 5/6 nephrectomy induced CKD in male rats. Method: Sprague-Dawley rats were randomly divided into normal control group (C), untreated 5/6 nephrectomy (Nx), quercetin-treated 5/6 nephrectomy, NxQ (100 mg / kg / day orally), captopril-treated 5/6 nephrectomy, NxK (10 mg / kg / day orally). Animal models was sacrificed at the end of intervention to take blood to measure creatinine, urea, and MDA, urine to measure protein and creatinine, and kidney organ to measure levels of MDA, glutathione peroxidase (GPx) activity, and renal damage (histopathology) and Nrf2 expression (immunohistochemistry). Results: The results showed that 5/6 nephrectomy may cause an increased of proteinuria, plasma urea, and grade of renal fibrosis significantly. 5/6 nephrectomy has trend to increased plasma creatinine, renal MDA levels, GPx activity, and decreased plasma MDA and Nrf2 expression. Quercetin did not decrease proteinuria, plasma urea and creatinine, and renal fibrosis grading. Quercetin tend to reduced levels of MDA, increased GPx enzyme activity, and expression of Nrf2. Conclusion: Quercetin does not affect proteinuria, plasma urea,plasma creatinine, and tissue damage or kidney fibrosis. Quercetin tend to reduced levels of MDA and increased the activity of GPx and Nrf2 expression., Background: Chronic Kidney Disease (CKD) is a progressive and irreversible condition that has several serious complications and currently there has no single therapy that can repair kidney damage was occurred. Some studies suggest a role of oxidative stress in the pathogenesis of this disease. Oxidative stress is caused by an imbalance of ROS production and antioxidant defenses. Nrf2 is a transcription factor involved in cell defense mechanisms againts oxidative stress. This study was aimed to determine the quercetin activity as Nrf2 activator in inhibit the progression of 5/6 nephrectomy induced CKD in male rats. Method: Sprague-Dawley rats were randomly divided into normal control group (C), untreated 5/6 nephrectomy (Nx), quercetin-treated 5/6 nephrectomy, NxQ (100 mg / kg / day orally), captopril-treated 5/6 nephrectomy, NxK (10 mg / kg / day orally). Animal models was sacrificed at the end of intervention to take blood to measure creatinine, urea, and MDA, urine to measure protein and creatinine, and kidney organ to measure levels of MDA, glutathione peroxidase (GPx) activity, and renal damage (histopathology) and Nrf2 expression (immunohistochemistry). Results: The results showed that 5/6 nephrectomy may cause an increased of proteinuria, plasma urea, and grade of renal fibrosis significantly. 5/6 nephrectomy has trend to increased plasma creatinine, renal MDA levels, GPx activity, and decreased plasma MDA and Nrf2 expression. Quercetin did not decrease proteinuria, plasma urea and creatinine, and renal fibrosis grading. Quercetin tend to reduced levels of MDA, increased GPx enzyme activity, and expression of Nrf2. Conclusion: Quercetin does not affect proteinuria, plasma urea,plasma creatinine, and tissue damage or kidney fibrosis. Quercetin tend to reduced levels of MDA and increased the activity of GPx and Nrf2 expression.]

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ABSTRAK
Penelitian ini merupakan penelitian eksperimental yang bertujuan mengetahui respon limfosit limpa mencit terhadap kondisi hipoksia relatif dan stres oksidatif karena imunisasi. Imunisasi dilakukan dengan cara induksi suspensi SDMD 2 kepada mencit melalui jalan intraperitoneum. Sampel yang digunakan adalah limfosit limpa mencit Balb/c jantan sebanyak 24 ekor yang dibagi ke dalam 4 kelompok yaitu kelompok kontrol tidak diimunisasi , kelompok 24 jam, 48 jam dan 72 jam. Limpa diambil berturut-turut setelah 0,24,48, dan 72 jam imunisasi. SDMT diperoleh dari darah limpa menggunakan larutan Ficoll 1.084, kemudian limfosit diisolasi dengan metode adheren. Ekspresi protein HIF-1?, HIF-2?, dan Nrf2 menggunakan metode ELISA; ekspresi relatif mRNA HIF-1?, HIF-2? diukur dengan metode qRT-PCR; dan aktivitas enzim GPx diukur dengan metode spektrofotometri. Protein HIF-1? meningkat secara signifikan pada 24 jam pertama setelah imunisasi, kemudian menurun setelah 48 jam dan 72 jam, ekspresi relatif mRNA HIF-1? meningkat setelah 48jam dan 72 jam. Hal ini disebabkan oleh protein HIF-1 distabilkan pada jam ke-24, setelah 48 jam dan 72 jam mRNA tidak ditranslasikan atau protein segera didegradasi. Protein HIF-2? meningkat secara signifikan setelah 72 jam imunisasi, sementara ekspresi relatif mRNA HIF-2? meningkat secara signifikan setelah 24 jam dan 72 jam setelah imunisasi. Hal ini menjelaskan bahwa protein HIF-2 bekerja pada hipoksia kronik. Protein Nrf2 mengalami peningkatan yang tidak signifikan setelah 48 jam. Aktivitas enzim GPx meningkat signifikan pada 24 jam pertama kemudian menurun setelahnya. Kemungkinan setelah 48 jam enzim GPx tidak bekerja sendiri dalam menetralkan radikal bebas, namun dibantu oleh enzim CAT yang juga diatur ekspesinya oleh Nrf2.

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ABSTRACT
This research use experimental method, the aim is to explore the mice rsquo s spleen lymphocytes responses towards relative hypoxia and oxidative stress due to immunization. The immunization performed by injecting 2 sheep red blood cell intraperitoneally. The samples are spleen lymphocytes from 24 male Balb c mice, divided into 4 groups control, 24 hours, 48 hours, and 72 hours group. Spleen was isolated after 0 hour, 24 hours, 48 hours and 72 hours after immunization. PBMC obtained from spleen blood through Ficoll 1.084 separation, then lymphocytes were isolated by adherent method. HIF 1 , HIF 2 and Nrf2 protein expression were analyzed with ELISA method, mRNA expression were analyzed with qRT PCR method, and GPx enzyme activity were analyzed through spectrophotometry. HIF 1 protein elevated significantly 24 hours post immunization and decreased afterwards while HIF 1 mRNA increase significantly after 47 hours and 72 hours post immunization. This result is due to stabilized HIF 1 protein on 24 hours group that give rise to its concentration while its mRNA remain low, while after 48 hours and 72 hours the mRNA expression increase but not translated into protein or the protein sin quickly degraded. HIF 2 protein increased significantly 72 hours post immunizaation while mRNA expression elevated on 24 hours and 72 hours group. This result suit the theory that HIF 2 protein works on chronic hypoxia. Nrf2 protein increase insignificantly on 48 hours post immunization and GPx activity rise significantly after 24 hours immunization and decrease afterwards. This may due to enzyme CAT helps enzyme GPx in neutralize free radical, in which CAT is also regulated by Nrf2 protein.

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Latar Belakang: Penyakit Ginjal Kronik PGK merupakan masalah kesehatan di seluruh penjuru dunia. PGK menjadi penyebab menurunnya kualitas hidup penderitanya sekaligus meningkatkan risiko kematian. Penyakit Ginjal Kronik ditandai dengan terjadinya kerusakan ginjal dalam waktu lama dan progresif. Gangguan pada PGK berkaitan dengan kejadian stres oksidatif, yaitu keadaan di mana Reactive Oxygen Species ROS terbentuk melebihi pertahanan antioksidan. Kuersetin sebagai bagian keluarga flavonoid diketahui memiliki aktivitas antioksidan. Penelitian sebelumnya mendapatkan bahwa pemberian kuersetin mampu meningkatkan ekspresi protein Nuclear factor related erythroid factor 2 Nrf2 di dalam nukleus pada tikus yang mengalami PGK. Penelitian ini merupakan penelitian lanjutan untuk mengkonfirmasi apakah peningkatan ekspresi protein Nrf2 di dalam nukleus terjadi pada tahap transkripsi. Metode: Jaringan ginjal tikus Sprague-Dawley dari penelitian terdahulu yang tersimpan pada suhu -80oC, diukur ekspresi mRNA Nrf2, Keap1dan HO1menggunakan qRT PCR. Terdapat 4 kelompok penelitian yaitu kelompok kontrol normal, kelompok dengan nefrektomi 5/6 berturut-turut diberi CMC 0,5 , kaptopril 10 mg/kgBB, dan kuersetin 100 mg/kgBB. Ekspresi mRNA Nrf2, Keap1 dan HO1dianalisis statistik menggunakan uji ANOVA yang dilanjutkan dengan multiple comparison post hoc dengan LSD, Kruskal-Wallis untuk data yang tidak memenuhi syarat uji ANOVA dimana perbedaan dianggap bermakna secara statistik bila p.

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Background Chronic Kidney Disease CKD has been a problem all around the world as it causes the decrease of life quality and also raises the risk of death. Chronic kidney disease characterized with long time and progressively kidney failure. The alteration of CKD correlated to oxidative stress, a condition when Reactive oxygen species ROS produced more than antioxidant defense. Quercetin as a part of flavonoid, has been known to have an antioxidant activity. It has been showed in the previous study that quercetin increased intra nuclear Nuclear factor related erythroid factor 2 Nrf2 . This study proposed to confirm whether the increase of nuclear NRF2 is happened in transcription event. Method Kidney tissue of Sprague Dawley rat from previous study which had been saved in 80oC had measured the expression of Nrf2, Keap1 and HO1 mRNA by qRT PCR. There were 4 groups as the previous study, normal control group, 5 6 nephrectomy plus consecutively 0,5 CMC, 10 mg kgBW captopril, and 100 mg kgBW quercetin. Expression of Nrf2, Keap1 and HO1 mRNA had been analyzed statistically with ANOVA test and LSD multiple comparison post hoc. For data that are not fit to analyzed with ANOVA would be analyzed with Kruskal Wallis and Mann Whitney. The data considered as significantly different by p.

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Stres oksidatif telah diketahui menimbulkan efek yang merusak. Dalam fibrosis hati, stres oksidatif seolah-olah membentuk lingkaran setan yang menyebabkan perburukan fibrosis hati. Dalam hal ini, Nuclear Erythroid 2-Related Factor 2 (Nrf2) sebagai regulator antioksidan akan mengaktifkan sistem pertahanan antioksidan tubuh yang dapat memutus mata rantai fibrosis. Penelitian ini bertujuan untuk menganalisa ekspresi Nrf2 pada jaringan hati, menganalisa kadar Malondialdehyde (MDA) sebagai oksidan bebas dan Glutathione (GSH) sebagai pemulung oksidan. Selain itu, juga menilai pengaruh pemberian Sel Punca Mesenkim asal Tali Pusat (SPM-TP) 1 juta dan 3 juta pada fibrosis hati. Penelitian ini merupakan penelitian eksperimental dengan menggunakan bahan biologis tersimpan berupa jaringan hati tikus Wistar 14 minggu. Terdapat empat kelompok perlakuan yaitu, kelompok sehat, kelompok 2AAF/CCl4, kelompok 2AAF/CCl4 yang diberikan SPM-TP 1 juta dan 3 juta dengan menggunakan tiga parameter yang diperiksa pada masing-masing kelompok yaitu, MDA, GSH, dan Nrf2. Pemeriksaan MDA dan GSH dilakukan dengan menggunakan spektrofotometer, sedangkan pemeriksaan Nrf2 dinilai dengan menggunakan pulasan imunohistokimia dan kuantifikasi dengan ImageJ (IHC Profiller). Data terdistribusi normal yang diperoleh diuji dengan one way ANOVA  dan diuji post hoc Tukey sedangkan data tidak terdistribusi normal diuji dengan Kruskal Wallis dan post hoc Mann Whitney. Dari data-data tersebut didapatkan penurunan kadar MDA, peningkatan kadar GSH serta ekspresi Nrf2 pada kelompok yang diberikan SPM-TP 1 juta sedangkan pada kelompok yang diberikan SPM-TP 3 juta tidak menunjukkan hasil yang lebih baik. ......Oxidative stress has been known to have deleterious effects. In liver fibrosis, oxidative stress seems to form a vicious circle that causes liver fibrosis to worsen. In this case, Nuclear Erythroid 2-Related Factor 2 (Nrf2) as an antioxidant regulator will activate the body's antioxidant defense system which can break the chain of fibrosis. This study aims to analyze the expression of Nrf2 in liver tissue, also the levels of Malondialdehyde (MDA) as a free oxidant and Glutathione (GSH) as an oxidant scavenger. In addition, it also assessed the effect of giving  Umbilical Cord Mesenchymal Stem Cells (UCMSCs) 1 million and 3 million on liver fibrosis. This study was an experimental study using stored biological material in the form of 14-week-old Wistar rat liver tissue. There were four treatment groups, namely the healthy group, the 2AAF/CCl4 group, the 2AAF/CCl4 group who were given UCMSCs 1 million and 3 million using three parameters examined in each group, namely MDA, GSH, and Nrf2. MDA and GSH examinations were carried out using a spectrophotometer, while the Nrf2 examination was assessed using immunohistochemical staining and quantification with ImageJ (IHC Profiler). Normally distributed data obtained was tested with one way ANOVA and Tukey's post hoc test while data that is not normally distributed was tested with Kruskal Wallis and post hoc Mann Whitney.  From these data it was found a decrease in MDA levels, an increase in GSH levels as well as Nrf2 expression in the group given UCMSCs 1 million while the group given UCMSCs 3 million showed no better results.

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Karsinoma hepatoseluler (HCC) merupakan masalah kesehatan global dengan tatalaksana yang belum optimal. Gambir adalah tanaman spesifik Indonesia, yang mengandung flavonoid, dan digunakan sebagai antikanker. Pada patogenesis HCC terjadi disregulasi CYGB, Nrf2, dan PDGFA. Jusman dkk mendapatkan bahwa senyawa dalam gambir dapat berikatan dengan PDGFA. Penelitian ini digunakan ekstrak etanol gambir (EG), dan bertujuan untuk menilai pengaruh EG terhadap viabilitas galur sel HepG2, dan ekspresi dari protein CYGB, Nrf2, dan PDGFA. Optimasi konsentrasi DMSO sebagai pelarut EG, dan konsentrasi EG pada HepG2 (IC50) dianalisis dengan uji MTT. Sel HepG2 diisolasi proteinnya dan ekspresi CYGB, Nrf2, dan PDGFA menggunakan ELISA. Analisis proliferasi sel HepG2 dengan uji BrdU. Hasil dari analisis viabilitas, proliferasi, dan ELISA dari kelompok kontrol dan perlakuan dibandingkan secara statistik. Hasil menunjukan pemberian EG konsentrasi 500; 1000; dan 2000 μg/mL menyebabkan penurunan viabilitas sel, proliferasi sel, serta penurunan ekspresi protein CYGB, Nrf2, dan PDGFA. Disimpulkan pemberian EG menurunkan viabilitas, dan proliferasi sel HepG2 serta terbukti menurunkan ekspresi CYGB, Nrf2, dan PDGFA. ......epatocellular carcinoma (HCC) is a global health problem with treatment has not provided optimal results. Gambir is an Indonesian specific plant, which contains flavonoids, and is used as an anticancer. In the pathogenesis of HCC dysregulation of Nrf2, CYGB, and PDGFA occurs. Jusman et al found that compounds in gambir can bind to PDGFA. This study used gambir ethanol extract (EG), and aimed to assess the effect of EG on HepG2 cell proliferation, as well as the expression of CYGB, Nrf2, and PDGFA. Optimization of DMSO concentration as EG solvent, and EG concentration in HepG2 (IC50) were analyzed by MTT test. Protein of HepG2 were isolated and expression of CYGB, Nrf2 and PDGFA used ELISA. Analysis of HepG2 cell proliferation with BrdU assay. Results from viability, proliferation, and ELISA analyses of the control and treatment groups were compared statistically. The results showed the administration of EG concentration 500; 1000; and 2000 μg/mL led to decreased cell viability, cell proliferation, and decreased expression of CYGB, Nrf2, and PDGFA proteins. It was concluded that EG administration decreased the viability, and proliferation of HepG2 cells and was shown to decrease the expression of CYGB, Nrf2, and PDGFA.

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Latar Belakang: Penyakit Parkinson (PD) merupakan penyakit neurodegeneratif dengan jumlah penderita yang banyak, namun tatalaksana penyakit ini tidak banyak berkembang. Aktivasi sistem nuclear factor erythroid-derived-2-like 2 (Nrf2) telah dibuktikan mampu menghambat patogenesis PD. Penelitian ini bertujuan untuk melihat potensi neuroprotektif andrografolida sebagai salah satu aktivator Nrf2 paling poten pada model PD in vivo yang diinduksi 1-metil-4-fenil-1,2,3,6-tetrahidropiridin (MPTP) Metode: Mencit C3H jantan diinduksi dengan MPTP melalui injeksi subkutan 12 mg/kgBB/kali sebanyak 4 kali dengan jarak 2 jam antar injeksi. Terapi selegilin 10 mg/kgBB/hari dan andrografolida dengan dosis 50 mg/kgBB/hari dan 5 mg/kgBB/hari diberikan per oral mulai satu hari setelah induksi selama 14 hari. Pada hari ke-15, pemeriksaan perilaku dilakukan kemudian hewan coba diterminasi dan organ otak diambil. Pemeriksaan lanjutan yang dilakukan adalah imunohistokimia terhadap tirosin hidroksilase (TH) dan Nrf2. Hasil: Selegilin dan andrografolida memperbaiki dengan signifikan defisit motorik akibat induksi MPTP. Perbaikan ini diikuti peningkatan jumlah rerata sel TH-positif di substansia nigra yang signifikan terhadap kontrol. Pemeriksaan ekspresi Nrf2 menunjukkan bahwa kelompok andrografolida memiliki rerata sel Nrf2-positif yang secara signifikan lebih tinggi dibandingkan kelompok lainnya. Hasil ini menunjukkan bahwa andrografolida memiliki aktivitas neuroprotektif yang mampu memperbaiki gangguan motorik pada mencit model PD yang dibuktikan dengan perbaikan gambaran histopatologi berupa peningkatan ekspresi TH. Aktivitas neuroprotektif ini dimediasi kerja andrografolida sebagai aktivator Nrf2. Kesimpulan: Hasil penelitian ini menunjukkan bahwa andrografolida memiliki aktivitas neuroprotektif pada mencit model PD yang diinduksi MPTP melalui sistem yang melibatkan Nrf2. ......Background: Parkinson’s disease (PD) is a neurodegenerative disease with abundant number of sufferers but without any progress in therapeutics development. Activation of nuclear factor erythroid-derived-2-like 2 (Nrf2) system has been proven to halt PD pathogenesis. This study aims to discover the neuroprotective potential of andrographolide as one of the most potent Nrf2 activator in in vivo PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Methods: Male C3H mice were induced using MPTP 12 mg/kgBW/injection via 4 subcutaneous injections 2 hours apart. Selegiline 10 mg/kgBW/day, andrographolide 50 mg/kgBW/day and andrographolide 5 mg/kgBW/day were given orally starting from the day after induction for 14 days. On the 15th day, behavior analysis was done then study animlas were sacrificed and brains collected. Further analyses done were immunohistochemistry using antibodies against tyrosine hydroxylase (TH) and Nrf2 Results: Both selegiline and andrographolide ameliorates the MPTP-induced motoric deficits. This amelioration was followed by significant increase of number of TH-positive cells in the substantia nigra. Nrf2 expression examination revealed that both of the andrographolide groups had significantly higher number of Nrf2-positive cells compared to other groups. These results showed that andrographolide has neuroprotective activities which are capable of ameliorating motoric deficits in PD mice model, proven by improvement of histopathologic results of TH-expression. This neuroprotective activity was mediated by andrographolide mechanism of action as an Nrf2 activator. Conclusion: This study showed that andrographolide has neuroprotective activities in MPTP-induced PD mice model via Nrf2-involving system.

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ABSTRAK
Latar Belakang: Penyakit - penyakit kronik menduduki prevalensi tertinggi penyebab mortalitas penduduk di dunia. Peningkatan penyakit ginjal kronik sebagai penyebab kematian dunia sangat pesat dan menduduki tingkat kedua dibawah HIV/AIDS. Selain itu, progresi penyakit ginjal ke seringkali tidak disadari oleh penderita. Produksi radikal bebas dan factor risiko tradisional dari gagal ginjal seperti hipertensi, dyslipidemia dapat menyebabkan komplikasi ke bagian tubuh lainnya, terutama sistem kardiovaskular. Keap1 adalah sistem pendeteksi keseimbangan redoks utama dalam tubuh dan jalur Nrf2/ARE yang bergantung pada regulasi Keap1 menghasilkan antioksidan dalam tubuh. Mastin merupakan ekstrak kulit manggis yang diduga mengandung ?-mangostin yang telah terbukti mempunyai efek kardioprotektif. Dibutuhkan penelitian untuk mengetahui apakah mastin bertindak pada jalur Keap1/Nrf2 yang merupakan jalur yang menghasilkan antioksidan penangkal radikal bebas dalam tubuh.Metode: Tikus percobaan dibagi dalam 3 kelompok, yaitu kelompok normal N , kelompok 5/6 nefrektomi Nx dan kelompok 5/6 nefrektomi yang diberi mastin NxM dengan dosis ?-mangostin 200 mg/kgBB/hari selama 8 minggu. Setelah 8 minggu, tikus di dekapitasi dan diambil jaringan jantungnya. Digunakan metode One-Step real-time RT-PCR pada hasil sintesis cDNA jantung tikus agar mendapatkan expresi relatif dari gen Keap1.Hasil: Ekspresi gen Keap1 meningkat secara signifikan pada kelompok tikus Nx p < 0.05 , sedangkan ekspresi gen Keap1 menurun secara tidak signifikan pada kelompok tikus yang telah diberi mastin p > 0.05 Kesimpulan: Peningkatan ekspresi relative gen Keap1 pada kelompok Nx disebabkan karena disfungsi Keap1 yang disebabkan karena inflamasi kronik dan produksi radikal bebas yang sangat tinggi. Ditemukan juga bahwa pemberian mastin tidak berpengaruh pada jalur Keap1

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ABSTRACT
Background As the disease profile of the world changes, the leading cause of mortality in the world is chronic disease. The steep rise of chronic kidney disease as cause of mortality is just second to HIV AIDS. Chronic kidney disease CKD has a high burden profile because o fits expensive treatment cost and its rsquo silent rsquo epidemic in which the patients are often not aware of its progression. Generation of Reactive Oxygen Species ROS and the presence of traditional risk factors of CKD such as hypertension and dyslipidemia can cause systemic complication, expecially cardiovascular complication. Keap1 is the main redox signalling in the human body and Keap1 dependent pathway of Nrf2 ARE activation generates antioxidant in the body. Mastin is a mangosteen peel extract that contains mangosteen which has proven to be cardioprotective. A research is needed to find out whether mastin acts on Keap1 Nrf2 pathway which is the main pathway that generates antioxidant against ROS in the human body.Method Rats are divided into three groups which are normal group N , nephrectomy group Nx and nephrectomy group that is administered with mastin NxM with mangostin dosing of 200 mg kgBW day. After 8 weeks, rats will be decapitated and their heart tissue extracted and homogenized. The cDNA synthesized from the heart tissue will then be measured for the relative expression of keap1 gene using qRT PCR.Results The relative expression of keap1 gene increases significantly p 0,05 in the Nx group while the relative expression decreases not signicantly in the NxM group. p 0,05 Conclusions The increase of Keap1 gene expression in the nephrectomy group is due to the dysfunction of keap1 because of chronic inflammation and high ROS production because of subsequent tissue injury. Mastin administration does not affect the Keap1 pathway.