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Abstrak :
Latar belakang: Cisplatin diketahui sebagai agen kemoterapi yang paling sering digunakan dalam terapi keganasan hematologi dan tumor padat. Namun, efek samping cisplatin nefrotoksisitas menjadi masalah utama, sebab pemberian cisplatin sesuai dengan dosis terapeutik saja sudah menimbulkan kerusakan ginjal. Tujuan penelitian: Membuktikan efek kurkumin yang bersifat renoprotektif terhadap kerusakan ginjal yang diinduksi cisplatin melalui penurunan ekspresi endothelin-1 (ET-1). Endothelin-1 merupakan peptida yang berkaitan dengan fungsi ginjal, karena memiliki peran sebagai vasokonstriktor poten dan sebagai hemodinamik di organ ginjal. Metode: Sampel yang digunakan dalam penelitian ini berupa organ tersimpan dari penelitian Ni Made Dwi Sandhiutami, S.Si, M.Kes, Apt. Sampel dibagi dalam 4 kelompok perlakuan, yaitu kelompok tikus normal (N), kanker ovarium tanpa perlakuan (Ca), kanker ovarium perlakuan cisplatin (Cis), dan kanker ovarium perlakuan cisplatin+curcumin (Cur). Induksi kanker ovarium dengan cara injeksi 7,12-Dimethylbenz[a]anthracene (DMBA) melalui benang silk dan dirawat selama 20 minggu membentuk adanya tumor pada ovarium. Hasil: Hasil yang diperoleh memperlihatkan kelompok Ca mengalami peningkatan ET-1 sebesar 2,8555±0,69981, kelompok Cis terjadi peningkatan ET-1 sebesar 6,0965±2,1558, namun pada kelompok Cis+Cur terjadi penurunan ekspresi ET-1 sebesar 2,1616±0,71623. Meskipun, data pada pemeriksaan ekspresi ET-1 tidak berbeda bermakna secara statistik, namun pemberian kurkumin dapat dikatakan bermakna secara kondisi klinis karena menurunkan ekspresi ET-1 sebesar 64,5%. Pada pemeriksaan serum kreatinin, hanya kelompok tikus normal (N) dengan kelompok tikus kanker ovarium dengan perlakuan cisplatin (Cis) yang berbeda bermakna dan signifikan. Kesimpulan: Cisplatin bersifat nefrotoksisitas meskipun dalam dosis terapi, serta pemberian kurkumin bermanfaat sebab dapat bersifat renoprotektif bagi kerusakan ginjal yang diinduksi cisplatin. ......Introduction: Cisplatin is known as a chemotherapy agent that is most often used in the therapy of hematologic malignancies and solid tumors. However, the side effects of cisplatin nephrotoxicity are the main problem, because giving cisplatin in accordance with the therapeutic dose alone has caused kidney damage. Purpose of the study: To prove the effect of curcumin which is renoprotective against cisplatin-induced renal damage through decreased expression of endothelin-1 (ET-1). Endothelin-1 is a peptide related to kidney function, because it has a role as a potent vasoconstrictor and as a hemodynamic agent in the kidney. Methods: The samples used in this study were stored organs from research by Ni Made Dwi Sandhiutami, S.Si, M.Kes, Apt. Samples were divided into 4 treatment groups, namely normal mice (N), ovarian cancer without treatment (Ca), ovarian cancer treated with cisplatin (Cis), and ovarian cancer treated with cisplatin + curcumin (Cur). Ovarian cancer induction by injection of 7,12-Dimethylbenz [a] anthracene (DMBA) through silk thread and treated for 20 weeks to form a tumor in the ovary. Results: The results showed that the Ca group experienced an increase in ET-1 by 2.8555 ± 0.69981, the Cis group had an increase in ET-1 by 6.0965 ± 2.1558, but in the Cis + Cur group there was a decrease in ET-1 expression. equal to 2.1616 ± 0.71623. Although, the data on the examination of ET-1 expression were not statistically significant, but curcumin administration can be said to be clinically significant because it reduces the expression of ET-1 by 64.5%. In the serum creatinine examination, only the normal (N) group of mice with ovarian cancer mice treated with cisplatin (Cis) was significantly and significantly different. Conclusion: Cisplatin is nephrotoxicity even in therapeutic doses, and curcumin administration is beneficial because it can be renoprotective for cisplatin-induced renal damage

Abstrak :
Latar belakang : Cisplatin adalah pilihan utama dalam penatalaksanaan kanker ovrium secara farmakologi. Namun, disisi lain cisplatin dapat menyebabkan kerusakan ginjal. Kerusakan ginjal akibat Cisplatin salah satunya terjadi karena perubahan aktivitas sistem endotelin ginjal sebagai pengatur hemodinamik ginjal. Secara teori kerusakan ini dapat dikurangi dengan pemberian ko-kemoterapi cisplatin yang memiliki sifat renoprotektif. Salah satu agen renoprotektif adalah Kurkumin. Salah satu manfaat kurkumin dapat mengurangi kerusakan ginjal karena bersifat renoprotektif. Penelitian ini bertujuan untuk mengetahui efek pemberian kurkumin sebagai ko-kemoterapi cisplatin terhadap ekspresi reseptor endothelin B (ETBR) dan gambaran hitopatologi pada ginjal tikus model kanker ovarium. Metode: Dua puluh empat tikus Wistar betina (150-200 gram) berusia 5 minggu dikelompokan menjadi empat kelompok: Normal (N), Kanker Ovarium tanpa pemberian obat (Ca), Cisplatin (Cis) adalah kelompok tikus kanker ovarium yang mendapat terapi cisplatin 4mg/KgBB selama tiga minggu, Cisplatin+Kurkumin (Cis+Cur) adalah kelompok tikus kanker ovarium yang diberi cisplatin 4mg/KgBB+ curcumin 100mg/KgBB selama tiga minggu. Setelah memasuki minggu ke-24, tikus dikorbankan dan diambil jaringan ginjal untuk dilakukan pengamatan secara histologi dan molekular. Hasil: gambaran histologi ginjal menunjukan perubahan struktur abrnomal. Akan tetapi perubahan struktur menuju kerusakan ginjal pada penelitian ini tidak signifikan. Selanjutnya, pengamatan ekspresi ETBR didapati ekspresi tertinggi pada kelompok tikus normal (N) dan terendah pada kelompok tikus dengan pemberian Cisplatin dan Kurkumin (Cis+Cur) dengan nilai p pada uji ANOVA Satu Arah sebesar 0.087 (signifikan jika p<0,05). Kesimpulan: pemberian kurkumin sebagai ko-kemoterapi cisplatin pada tikus model kanker ovarium tidak menyebabkan perubahan struktur histologi yang bermakna dan tidak menyebabkan peningkatan ekspresi ETBR yang signifikan. ......Background: Cisplatin is the main choice in pharmacological treatment of ovarian cancer. However, cisplatin can cause kidney damage. One of the causes of kidney damage due to cisplatin occurs due to changes in the activity of the renal endothelin system as a renal hemodynamic regulator. In theory, this damage can be reduced by giving cisplatin co-chemotherapy which has renoprotective properties. One of the renoprotective agents is curcumin. One of the benefits of curcumin is to reduce kidney damage because it is renoprotective. This study aims to determine the effect of curcumin administration as co-chemotherapy of cisplatin on endothelin B receptor expression (ETBR) and the histopathological description of ovarian cancer model rats. Methods: Twenty-four female Wistar rats (150-200 grams) aged 5 weeks were grouped into four groups: Normal (N), Ovarian Cancer without drug administration (Ca), Cisplatin (Cis) is a group of ovarian cancer mice receiving 4mg/KgBB cisplatin therapy for three weeks, Cisplatin + Curcumin (Cis + Cur) is a group of ovarian cancer mice that were given cisplatin 4mg / KgBB + curcumin 100mg / KgBB for three weeks. After entering the 24th week, the rats were sacrificed and kidney tissue was taken for histological and molecular observation. Result: The histology of the kidneys showed an abnormal structural change. However, the structural changes leading to kidney damage in this study were not significant. Furthermore, observations of ETBR expression found the highest expression in the normal (N) group of rats and the lowest in the group of rats given Cisplatin and Curcumin (Cis + Cur) with a p value in the One Way ANOVA test of 0.087 (significant if p <0.05). Conclusion: giving curcumin as co-chemotherapy of cisplatin in ovarian cancer model mice did not cause significant changes in histological structure and did not cause a significant increase in ETBR expression

Abstrak :
Pendahuluan: Hampir 85% kasus karsinoma ovarium terjadi overekspresi endothelin-1 (ET-1) yang memodulasi persinyalan tumorigenesis dan metastasis. Disisi lain, cisplatin sebagai kemoterapi kanker ovarium menimbulkan efek samping dan resistensi terapi. Berbagai penelitian menunjukkan kurkumin berpotensi sebagai antikanker yang meningkatkan efikasi cisplatin dan menekan overekspresi ET-1 pada lini sel nonkanker. Namun, belum banyak penelitian yang mengidentifikasi penekanan ekspresi ET-1 oleh kurkumin dalam regimen terapi bersama cisplatin di kanker ovarium. Oleh karena itu, penelitian ini bertujuan melihat efek ko-kemoterapi kurkumin bersama cisplatin pada kanker ovarium terkait ekspresi relatif mRNA ET-1. Metode: Jaringan ovarium tersimpan dari 24 tikus betina galur Wistar dibagi kedalam 4 kelompok: tikus yang hanya dibedah dan diberi aquadest (sham), tikus yang diimplantasi DMBA tanpa intervensi terapi, tikus yang diimplantasi DMBA dan diberi terapi tunggal cisplatin intraperitoneal 4 mg/kgBB/minggu, tikus yang diimplantasi DMBA dengan diberi terapi cisplatin 4 mg/kgBB/minggu dan kurkumin oral 100 mg/kgBB/hari. Implantasi DMBA dilakukan selama 28 minggu dan intervensi pada hewan coba selama 4 minggu. Setelah itu, jaringan ovarium tersimpan dianalisis ekspresi relatif mRNA ET-1 dengan mesin qRT-PCR menggunakan metode Livak-Schmittgen (2(-Ct)). Hasil: Didapatkan rerata ekspresi relatif mRNA ET-1 [p=0,021] pada kelompok sham (0,349±0,24), kelompok DMBA (3,117±1,532), kelompok DMBA+cisplatin (0,993±0,651), dan kelompok DMBA+kurkumin+cisplatin (0,117±0,081). Ketiga kelompok tidak memiliki perbedaan bermakna dibandingkan sham. Meski demikian, terdapat perbedaan bermakna pada kelompok kombinasi cisplatin serta ko-kemoterapi kurkumin dengan kelompok tanpa intervensi terapi [p=0,019]. Kesimpulan: Terjadi penurunan ekspresi relatif mRNA endothelin-1 di jaringan ovarium model tikus yang diinduksi DMBA setelah pemberian kombinasi cisplatin dan ko-kemoterapi kurkumin. ......Introduction: Endothelin-1 overexpression happens in 85% ovarian carcinoma cases that modulate metastatic and tumorigenesis. Meanwhile, cisplatin as ovarian cancer chemotherapy cause side effects and therapy resistances. Prior studies show potential effect of curcumin as an anticancer could enhance cisplatin efficacy and attenuate ET-1 overexpression in non-cancer cell lines. However, not many studies have identified suppression effect of ET-1 expression by curcumin with cisplatin in ovarian cancer. Therefore, this study is conducted to identify the effect of curcumin with cisplatin in ovarian cancer treatment especially its relation to relative expression of ET-1 mRNA. Methods: Frozen ovarian tissue samples from 24 female Wistar rats were divided into 4 groups: a group that only operated on and treated with distilled-water (sham), group with DMBA-implantation, group with DMBA-implantation and intraperitoneal cisplatin 4mg/kgBW/week, group with DMBA-implantation and cisplatin with same dose as before plus oral curcumin 100mg/kgBW/day. After 28 weeks of DMBA-implantation and 4 weeks of intervention, frozen ovarian tissue samples were taken to measure its relative expression of ET-1 mRNA level with qRT-PCR machine. Results: The mean of relative expression of ET-1 mRNA level [p=0,021] in frozen tissue sample of sham group (0,349±0,24), DMBA-implantation group (3,117±1,532), DMBA+cisplatin-treated group (0,993±0,651), and DMBA+curcumin+cisplatin-treated group (0,117±0,081). This study shows those 3 groups did not have significant difference compared with sham. But among group with cisplatin+curcumin-treated compared to DMBA-implantation shows a significant difference (p=0,019). Conclusion: The relative expression of ET-1 mRNA in ovarian tissue of DMBA-induced rats model decreases after given by a combination of cisplatin+curcumin co-chemotherapy.

Abstrak :
Latar belakang: Terdapat peningkatan 80% ekspresi reseptor endothelin A dan 40% ekspresi endothelin B pada kanker ovarium. Peningkatan ekspresi reseptor endothelin A terbukti berperan dalam menyebabkan progresifitas dan metastasi kanker ovarium. REB berperan sebagai klirens endothelin-1 dan meningkatkan proses apoptosis. Cisplatin sebagai lini pertama pengobatan kanker ovarium memiliki efek samping dan berisiko mengembangkan kanker ovarium resistensi cisplatin. Kurkumin sebagai salah satu bahan alami terbukti memiliki potensi sebagai antikanker dan dapat meingkatkan efikasi cisplatin. Tujuan: penelitian ini adalah untuk melihat efektifitas kombinasi kurkumin dan cisplatin sebagai tatalaksana alternatif kanker ovarium dilihat dari ekspresi relatif mRNA reseptor endothelin A dan reseptor endothelin B. Metode: Homogenasi jaringan ovarium tersimpan yang dilanjutkan dengan sentrifugasi. Cairan supernatan diambil untuk dilakukan purifikasi. RNA yang terfurifikasi diubah menjadi cDNA. Selanjutnya, analisis dilakukan menggunakan mesin qRT-PCR, dengan metode Livak-Schmittgen 2(-Ct). Hasil: Ekspresi mRNA reseptor endothelin B pada kelompok normal (7,376±1,407), DMBA +Cis (1,701±1,096), DMBA+Cis+Cur (7,391±2,261), DMBA (0,649±0,221), dengan p<0,05. Hasil bermakna pada kelompok DMBA dan DMBA+Cis+Kur dengan p=0,014. Ekspresi mRNA reseptor endothelin A pada kelompok normal (0,698±0,366), DMBA+Cis (5,311±2,737), DMBA+Cis+Kur (7,502±2,476), DMBA (10,970±3,883), dengan p<0,05. Namun antar kelompok DMBA dan kelompok DMBA+Cis+Kur atau DMBA+Cis tidak ditemukan hasil bermakna p>0,05. Simpulan: Kombinasi kurkumin dan cisplatin yang diberikan pada tikus model kanker ovarium yang diinduksi DMBA, dapat memengaruhi jalur reseptor endothelin melalui peningkatan ekspresi relatif mRNA reseptor endothelin B, dan kecendrungan penurunan ekspresi reseptor endothelin A. ......Background: There was an 80% increase in endothelin A receptor expression and 40% endothelin B expression in ovarian cancer. Increased expression of endothelin A receptors has been shown to play a role in causing progression and metastasis of ovarian cancer. REB acts as endothelin-1 clearance and increases the apoptotic process. Cisplatin as the first line of ovarian cancer treatment has side effects and the risk of developing cisplatin- resistant ovarian cancer. Curcumin as a natural ingredient is proven to have potential as an anticancer and can increase the efficacy of cisplatin. The purpose of this study was to determine the effectiveness of the combination of curcumin and cisplatin as an alternative treatment for ovarian cancer in terms of the relative expression of endothelin A and endothelin B receptor mRNAs. Methods: Homogenation of stored ovarian tissue followed by centrifugation. The supernatant fluid is taken for purification. The purified RNA is converted into cDNA. Furthermore, the analysis was performed using a qRT- PCR machine, with the Livak-Schmittgen methode 2(-Ct). Results: The expression of mRNA endothelin B receptor in normal (7.376 ± 1.407), DMBA + Cis (1.701 ± 1.096), DMBA + Cis + Cur (7.391 ± 2.261), DMBA (0.649 ± 0.221) groups, with p <0.05. The results were significant in the DMBA and DMBA + Cis + Kur groups with p = 0.014. The expression of endothelin A receptor mRNA in normal (0.698 ± 0.366), DMBA + Cis (5.311 ± 2.737), DMBA + Cis + Kur (7.502 ± 2.476), DMBA (10.970 ± 3.883) groups, with p <0.05. However, between the DMBA group and the DMBA + Cis + Kur or DMBA + Cis group there were no significant results found with p> 0.05. Conclusion: The combination of curcumin and cisplatin given to DMBA-induced ovarian cancer model mice can affect the endothelin receptor pathway through an increase in the relative expression of endothelin B receptor mRNA, and a tendency to decrease the expression of endothelin A receptors.

Abstrak :
Latar belakang: Mortalitas yang tinggi pada kanker ovarium utamanya disebabkan oleh progresi, kemoresistensi, dan rekurensinya. Diketahui progresivitas dan kemoresistensi kanker ovarium dipengaruhi oleh aksis endothelin, yang melibatkan endothelin-1 dan reseptor endothelin melalui proses epithelial-to-mesenchymal transition (EMT), sehingga menargetkan aksis ini merupakan prospek yang menjanjikan dalam pengembangan agen sensitisasi yang efektif. Kurkumin, senyawa herbal yang banyak di Indonesia, berpotensi menjadi agen ko-kemoterapi kanker ovarium, namun mekanismenya masih belum banyak diketahui. Penelitian sebelumnya menemukan bahwa kurkumin mampu menekan jalur endothelin di beberapa galur sel. Tujuan: Penelitian eksperimental dilakukan untuk menganalisis aktivitas kurkumin sebagai agen ko-kemoterapi cisplatin dalam memodulasi aksis endothelin pada sel SKOV3. Metode: Sampel terbagi menjadi tiga kelompok, yaitu kelompok kontrol (hanya diberikan vehicle), kelompok cisplatin 3,75 μM, serta kelompok kurkumin 5 μM dan cisplatin 3,75 μM. Sel diinkubasi selama 48 jam setelah pemberian perlakuan. Setelah 48 jam, dilakukan pemeriksaan ekspresi mRNA endothelin-1, reseptor endothelin A, dan reseptor endothelin B menggunakan metode qRT-PCR. Hasil: Terdapat penurunan signifikan ekspresi mRNA endothelin-1 pada sel SKOV3 yang diberikan kurkumin bersama cisplatin (0,55±0,32; p=0,005) dibandingkan dengan kelompok kontrol (3,35±2,80). Tidak ditemukan perbedaan dalam ekspresi mRNA reseptor endothelin A dan B yang signifikan antar kelompok. Kesimpulan: Kurkumin sebagai agen ko-kemoterapi cisplatin mampu memodulasi aksis endothelin melalui penekanan ekspresi mRNA endothelin-1, namun tidak melalui penekanan ekspresi mRNA reseptor endothelin A maupun B. ......Background: The high mortality of ovarian cancer is mainly attributed to its progression, chemoresistance to cisplatin, and recurrence. This progression and chemoresistance is mediated by the endothelin axis, which involves endothelin-1 and endothelin receptors through epithelial-to-mesenchymal transition (EMT) process, so targeting this axis is a promising prospect in developing an effective chemosensitizer. According to previous studies, curcumin, a ubiquitous herbal compound in Indonesia, has the potential to be a co-chemotherapeutic agent in ovarian cancer, but its mechanism in cancer progression is still unknown. Previous studies show that curcumin has the ability to modulate endothelin axis in non cancer cells. Objective: To analyze the activity of curcumin as a co-chemotherapeutic agent with cisplatin in modulating endothelin axis in SKOV3 cells. Methods: Sample is divided into three groups: control group (only given vehicle), cisplatin 3,75 μM group, and curcumin 5 μM and cisplatin 3,75 μM group. Cells are then incubated for 48 hours. After 48 hours, expression of endothelin-1, endothelin receptor A, and endothelin receptor B mRNAs are measured by qRT-PCR. Results: There is a significant decrease in endothelin-1 mRNA expression in SKOV3 cells treated with curcumin and cisplatin (0,55±0,32; p=0,005) compared to control group (3,35±2,80). There is no significant difference of endothelin receptor A and B mRNA expression between each group. Conclusion: Curcumin as a co-chemotherapeutic agent with cisplatin potentially modulates endothelin axis through repression of endothelin-1 mRNA expression, but not endothelin receptor mRNA A or B expression.

Abstrak :
Latar belakang: Kanker ovarium diduga dapat menyebabkan penurunan fungsi dan kerusakan ginjal. Cisplatin salah satu terapi kanker ovarium bersifat nefrotoksik. Kerusakan ginjal ini terjadi melalui berbagai mekanisme, salah satunya adalah peningkatan ekspresi ETAR. Kurkumin diduga mampu menurunkan ekspresi ETAR pada jaringan ginjal yang rusak. Penelitian ini bertujuan untuk mengetahui efek ko-kemoterapi kurkumin pada cisplatin terhadap ekspresi ETAR serta gambaran histopatologi jaringan ginjal pada tikus model kanker ovarium. Metode: 24 tikus wistar betina dibagi menjadi empat kelompok: Kelompok normal sham (N), kanker ovarium tanpa perlakuan (Ca), kanker ovarium yang mendapat 4 mg/KgBB cisplatin (Cis), dan kanker ovarium yang mendapat 4 mg/KgBB cisplatin +100 mg/KgBB kurkumin (Cis+Cur). Setelah 3 minggu tikus dikorbankan, ginjal tikus diambil untuk pengamatan histopatolgi serta ekspresi mRNA ETAR. Hasil: Pada pengamatan histopatologi Masson Trichrome ditemukan fokus fibrosis pada kelompok tikus Ca dan Cis. Melalui qRT-PCR diketahui bahwa ekspresi mRNA pada kelompok Ca dan Cis relatif sama, namun meningkat masing-masing sebesar 133% (2,33 kali lipat) dan 123% (2,23 kali lipat) dibandingkan dengan kelompok normal. Sedangkan pada kelompok Cis+Cur terdapat penurunan ekspresi mRNA sebesar 31,5% (0.315 lebih rendah) dan 34,4% (0.344 lebih rendah) berurutan dibanding kelompok Cis dan Cur. Tidak ditemukan perbedaan bermakna secara statistik antar kelompok uji. Kesimpulan: Kanker ovarium dapat memicu kerusakan ginjal pada tiku dibuktikan dengan peningkatan ekspresi mRNA ETAR dan fokus fibrosis. Pemberian cisplatin pada dosis terapeutik tidak meningkatkan ekspresi mRNA ETAR pada jaringan tikus model kanker ovarium, meski demikian pemberian kurkumin sebagai ko-kemoterapi menurunkan ekspresi mRNA ETAR dan fokus fibrosis meskipun tidak bermakna secara statistik. ......Background: Ovarian cancer is believed can lead to renal functional deterioration Furthermore, cisplatin as chemotherapeutic agent has nephrotoxic effects. Increased expression of the Endothelin A receptor (ETAR) is thought to be one of the mechanisms. Curcumin is believed to have protective effects in injured kidney. This study is to evaluate the co-chemotherapy effects of curcumin for cisplatin upon ETAR expression and histopathological appearances in rats’ kidney. Method: Total of 24 wistar rats, devided into four treatment groups: normal group (N), ovarian cancer without treatment group (Ca), ovarian cancer which received cisplatin 4 mg/kgBW group (Cis), and ovarian cancer which received cisplatin 4 mg/kgBW + 100 mg/kgBW curcumin group (Cis+Cur). Kidney tissue specimen was obtained for histopathological examination and ETAR messenger ribonucleic acid (mRNA) expression. Results: Fibrosis foci were found at kidney tissue of Ca and Cis group. The mRNA expression level among Ca and Cis group were relatively equivalent; however increased by 133% (2,33 fold) and by 123% (2,23 fold), respectively compared to N group. Meanwhile, the Cis + Cur group decreased by 31.5% (0.315 lower) and 34.4 % (0.344 lower) compared to Cis and Ca group respectively. There are no statistical significant among the experiment groups. Conclusion: Ovarian cancer is associated with kidney injury, demonstrated by increased of ETAR mRNA and fibrosis foci formation. Therapeutic dose cisplatin do not increased ETAR mRNA in the kidney of ovarian cancer rat. Curcumin administration as co-chemotherapeutic agent result in the decrease of ETAR mRNA level and the decrease of fibrosis foci formation.

Abstrak :
Penyakit neurodegeneratif cenderung meningkat seiring bertambahnya usia, dan salah satu penyebabnya adalah stres oksidatif. Stres oksidatif terjadi ketika peningkatan ROS yang berlebihan tidak dapat diimbangi oleh antioksidan tubuh. Peningkatan ROS dapat disebabkan oleh pemberian H2O2, namun dapat diatasi dengan pemberian antioksidan eksogen seperti Moringa oleifera (MO) yang kaya akan flavonoid. Tujuan dari penelitian ini adalah untuk menganalisis efek ekstrak air MO pada sel neuroblastoma SH-SY5Y yang terpapar H2O2, dengan fokus pada stres oksidatif, apoptosis, dan penanda neuroprotektif. Metode penelitian dilakukan secara in vitro menggunakan sel SH-SY5Y yang diuji dengan berbagai konsentrasi H2O2 atau MO. Hasil penelitian menunjukkan bahwa pemberian ekstrak air MO pada konsentrasi 25 ug/ml dapat mencegah stres oksidatif pada sel SH-SY5Y yang terpapar H2O2 dengan konsentrasi 1 mM. Mekanisme penurunan stres oksidatif ditandai dengan peningkatan ekspresi mRNA SOD1, GPx1, dan katalase, serta penurunan apoptosis yang ditandai dengan penurunan ekspresi mRNA Bax dan Caspase-3. Pemberian ekstrak air MO juga meningkatkan ekspresi mRNA BDNF. Oleh karena itu, MO memiliki potensi sebagai agen antioksidan yang efektif dalam melindungi sel saraf dari kerusakan oksidatif dan mencegah neurodegenerasi yang terkait dengan stres oksidatif. Penelitian ini memberikan pandangan awal yang menjanjikan untuk pengembangan ekstrak MO dengan fokus pada stres oksidatif, apoptosis, dan penanda neuroprotektif lebih lanjut di masa depan. ......Neurodegenerative diseases tend to increase with age, and one of the causes is oxidative stress. Oxidative stress occurs when excessive reactive oxygen species (ROS) cannot be balanced by the body's antioxidants. Increased ROS can be induced by hydrogen peroxide (H2O2) administration, but it can be mitigated by the administration of exogenous antioxidants such as Moringa oleifera (MO), which is rich in flavonoids. The objective of this research was to analyze the effects of MO water extract on SH-SY5Y neuroblastoma cells treated with H2O2, focusing on oxidative stress, apoptosis, and neuroprotective markers. The research was conducted in vitro using SH-SY5Y cells exposed to various concentrations of H2O2 or MO. The results showed that the administration of MO water extracts at a concentration of 25 μg/ml could prevent oxidative stress in SH-SY5Y cells treated with 1 mM H2O2. The mechanism of oxidative stress reduction was characterized by increased mRNA expression of SOD1, GPx1, and catalase, as well as decreased apoptosis indicated by decreased mRNA expression of Bax and Caspase-3. The administration of MO water extract also increased BDNF mRNA expression. Therefore, MO has the potential as an effective antioxidant agent to protect nerve cells from oxidative damage and prevent oxidative stress-related neurodegeneration. This research provides promising preliminary insights for further development of MO extract focusing on Oxidative Stress, Apoptosis, and Neuroprotective markers in the future.

Abstrak :
Moringa oleifera (MO) telah terbukti memiliki efek neuroprotektif, namun efek neuroprotektif melalui jalur senescence belum diketahui. Penelitian ini bertujuan untuk mengetahui efek neuroprotektif ekstrak air daun (MOE) dan minyak biji MO (MOO) terhadap disfungsi otak melalui jalur senescence pada mencit yang diberi diet tinggi lemak dan fruktosa. Mencit DDY jantan sebanyak 10 ekor dibagi secara acak menjadi 4 kelompok: Normal; Diet Tinggi Lemak + Fruktosa 25% (HFD+FR); HFD+FR + MOE 500 mg/kgBB (HFD+FR+MOE); dan HFD+FR + MOO 2 mL/kgBB (HFD+FR+MOO). Dilakukan penilaian kognitif dengan Uji Y-maze dan Novel Objective Recognition (NOR). Dianalisis ekspresi p16, p21, dan BDNF dengan metode RT-PCR serta pewarnaan SA-β-Gal pada jaringan otak. Dilakukan analisis interaksi senyawa ekstrak air daun dan minyak biji Moringa oleifera terhadap protein target dengan molecular docking. Hasil analisis menunjukkan bahwa pemberian bersama MOE maupun MOO dapat meningkatkan persentase alternasi dan pengenalan objek baru, menurunkan ekspresi p16 dan p21, meningkat ekspresi BDNF, menurunkan intensitas warna biru pada organ otak. Berdasarkan analisis dengan molecular docking menunjukkan adanya interaksi senyawa terhadap reseptor TrkB. Temuan-temuan ini menunjukkan ekstrak air daun dan minyak biji Moringa oleifera memiliki potensi neuroprotektif melalui jalur senescence. ......Moringa oleifera (MO) has been shown to have neuroprotective effects, but neuroprotective effects through the senescence pathway are not yet known. This study aimed to determine the neuroprotective effect of leaf water extract (MOE) and MO seed oil (MOO) against brain dysfunction through the senescence pathway in mice fed a diet high in fat and fructose. 10 male DDY mice were randomly divided into 4 groups: Normal; High Fat + Fructose Diet 25% (HFD+FR); HFD+FR + MOE 500 mg/kgBB (HFD+FR+MOE); and HFD+FR + MOO 2 mL/kgBB (HFD+FR+MOO). Cognitive assessment was carried out with the Y-maze Test and Novel Objective Recognition (NOR). Expression of p16, p21, and BDNF was analyzed by RT-PCR method and SA-β-Gal staining in brain tissue. Analysis of the interaction of leaf water extract compounds and Moringa oleifera seed oil on target proteins by molecular docking was carried out. The results of the analysis showed that co-administration of MOE and MOO can increase the percentage of alternation and recognition of new objects, decrease p16 and p21 expression, increase BDNF expression, decrease the intensity of blue color in brain organs. Based on analysis with molecular docking showed the interaction of compounds with TrkB receptor. These findings suggest the leaf water extract and seed oil of Moringa oleifera have neuroprotective potential through the senescence pathway.

Abstrak :
Latar Belakang/Tujuan: Premature cellular senescence yang sering dikaitkan pada kondisi Diabetes Mellitus tipe 2 (DMT2) dapat meningkatkan berbagai risiko penyakit terkait usia. Time restricted feeding sebagai contoh puasa Ramadhan ditengarai dapat menghambat proses penuaan. Sejauh ini, telah banyak studi yang menilai efek puasa Ramadhan terhadap berbagai parameter metabolik dan antropometrik, namun belum ada studi yang mengevaluasi efek puasa Ramadhan terhadap biomarker aging yang dinilai melalui panjang telomer leukosit relatif (TLR). Metode: Studi dengan desain potong lintang dan kohort retrospektif pada subjek DMT2 dan subjek non-DM berusia 40 – 60 tahun yang menjalani ibadah puasa Ramadhan setidaknya selama minimal 14 hari pada bulan Mei – Juli 2018 dan bulan Mei – Juli 2019. Perbedaan rerata panjang TLR antar subjek DMT2 dan non-DM dianalisis dengan uji Mann Whitney sedangkan perbedaan rerata TLR pada subjek DMT2 yang berpuasa dianalisis dengan uji Wilcoxon. Hasil: Pada 39 subjek DMT2 dan 36 subjek non-DM subjek DMT2 yang ikut dalam penelitian ini didapatkan pemendekan panjang TLR yang bermakna pada subjek DMT2 dibandingkan dengan subjek non-DM (0,436 (0,034 –1,472) vs 1,905 (0,615 –12,380), p =0,000) dan didapatkan pemanjangan panjang TLR yang tidak bermakna pada 48 subjek DMT2 yang menjalani puasa minimal 14 hari (0,391 (0,021 – 1,515) vs 1,117 (0,528 –1,741), p=0,112), namun bermakna secara klinis. Kesimpulan: Pada subjek DMT2 terjadi pemendekan panjang TLR yang secara statistik bermakna dibandingkan subjek non-DM sedangkan pada subjek DMT2 yang menjalani puasa Ramadan didapatkan pemanjangan panjang TLR yang tidak bermakna secara statistik namun bermakna secara klinis. ......Background/Aim: Premature cellular senescence which is often associated with type 2 diabetes mellitus (T2DM) can increase the risk of various age-related diseases. Time restricted feeding such as Ramadhan fasting hypotesized could delay the aging process. So far, there have been many studies assessing the effects of Ramadan fasting on various metabolic and anthropometric parameters, but no studies have evaluated the effect of Ramadhan fasting on aging biomarkers assessed by the relative telomere leucocyte length. Method: An observational comparative dan cohort retrospective study was conducted from May to July 2018 and May to July 2019 on 40 – 60 years old T2DM and non-DM subjects. The mean difference between TD2M and control was analysed using Mann Whitney test and the mean difference relative telomere length in subjects with T2DM who underwent at least 14 days of Ramadan fasting was analyzed using Wilcoxon test. Results: A total of 36 subjects with type 2 diabetes dan 39 subjects non-DM who enrolled in this study, there were a significant decrease relative leucocyte telomere in subjects with type 2, compared with controls (0,436 (0,034 – 1,472) vs 1,905 (0,615 – 12,380), p =0,000) but there were statitically insignificant but clinically significant increase relative leucocyte telomere in subject with type 2 diabetes who underwent Ramadhan fasting at least 14 days (0,391 (0,021–1,515) vs 1,117 (0,528–1,741), p=0,112. Conclusions: In T2DM subjects, there were a statistically significant decrease relative leucocyte telomere compared with controls while there were statitically insignificant but clinically significant increase relative leucocyte telomere in subject with type 2 diabetes who underwent Ramadhan fasting.