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"Sesoot (G. picrorrhiza Miq.) merupakan sumber daya hayati yang memiliki potensi sitotoksik terhadap sel kanker payudara. Potensi ini memberikan peluang untuk penatalaksanaan kanker payudara melalui permodelan doksorubisin dan kombinasinya dengan sampel herbal. Penelitian ini untuk membuktikan potensi antikanker payudara terhadap sel MCF-7 dan T47D dari daging buah dan kulit buah sesoot (G. picrorrhiza Miq.) yang selanjutnya disebut buah. Telah dilakukan karakterisasi sampel secara kimia dan biomolekuler sehingga menghasilkan sampel terkarakterisasi, GpKar. Sitotoksisitasnya ditentukan dengan metode MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) Assay, lalu dilakukan uji kombinasi dengan doksorubisin untuk mendapatkan Combination Index (CI). Pengamatan induksi apoptosis dilakukan dengan metode Double Staining dan ekspresi protein Caspase 3 dengan metode Enzyme-linked Immunosorbent Assay (ELISA). GpKar memiliki LC50 terhadap larva Artemia salina Leach sebesar 21,110 μg/mL (paling kecil di antara 15 sampel lainnya). Pada uji terhadap sel Vero dengan konsentrasi 250 μg/mL hanya mematikan 11,844 %, tetapi mematikan sel T47D 50,825 % dan MCF-7 31,743 %. Kombinasinya dengan doksorubisin menghasilkan efek sinergis dalam mematikan sel MCF-7 pada konsentrasi 0,200 μg/mL doksorubisin dan konsentrasi GpKar maksimal 125,238 μg/mL (1/4 IC50) juga terhadap sel T47D pada konsentrasi 0,200 μg/mL doksorubisin dan konsentrasi GpKar maksimal 61,799 μg/mL (1/4 IC50). GpKar mempengaruhi induksi apoptosis pada konsetrasi 500,951 μg/mL (1 IC50) dengan menghasilkan persentasi kematian sel MCF-7 paling tinggi yaitu 99 % dan terhadap Sel T47D sebesar 91 %, pada konsentrasi 61,799 μg/mL (1/4 IC50) sedangkan terhadap sel Vero dapat menghasilkan persentase kematian paling rendah yaitu 2,100 % pada konsentrasi 132,943 μg/mL (1/4 IC50). Kombinasinya dengan doksorubisin menghasilkan persentase kematian yang lebih rendah akibat induksi apoptosis. GpKar dan kombinasinya dengan doksorubisin mampu meningkatan konsentrasi protein Caspase 3.

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Sesoot (G. picrorrhiza Miq.) is a medicinal plant which has cytotoxic activity against breast cancer cells. This potency provides the opportunity for treatment of breast cancer through doxorubicin modelling and its combination with herb. This study was done to prove the anti-breast cancer potency of the fruit and the hull of sesoot (G. picrorrhiza Miq.) hereinafter referred to as the fruit against MCf-7 cell and T47D cell. Chemical and Biomolecular Characterizations were done to obtain the characterized sample of GpKar. The cytotoxicity effect was determined using the method of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) Assay, and the combination test with doxorubicin resulting the Combination Index (CI). The apoptotic induction was observed using Double Staining Method and the Caspase 3 protein expression was observed using the method of Enzyme-Linked Immunosorbent Assay (ELISA). The LC50 of GpKar against the larvae of the Artemia salina Leach was 21.110 μg/mL (the least among 15 samples). The Gpkar concentration of 250 μg/mL was the least toxic in term of mortality against Vero cell (11.844 %), but toxic in term of mortality against T47D cell (50.825 %) and MCF-7 cell (31.743 %). The combination with doxorubicin resulted in the synergystic effect against MCF-7 cell (0.200 μg/mL doksorubicin with the maximum GpKar concentration of 125.238 μg/mL (1/4 IC50)) and also against T47D cell (0.200 μg/mL doxorubicin with the maximum GpKar concentration of 61.799 μg/mL (1/4 IC50)). GpKar induced the apoptosis at the concentration of 500.951 μg/mL (1 IC50) resulting the mortality percentage of the MCF-7 cell up to 99 % and up to 91 % against T47D cell at the concentration of 61.799 μg/mL (1/4 IC50) of GpKar, whereas the concentration of 132.943 μg/mL (1/4 IC50) of GpKar resulted in the lowest mortality percentage against Vero cell which was 2.100 %. The combination of GpKar with doxorubicin resulted in the lower mortality percentage as the consequence of apoptotic induction. GpKar and its combination with doxorubicin increased the concentration of the Caspase 3 protein."

"ABSTRAKPendahuluan: Fibrosis hati yang diakibatkan oleh stres oksidatif ROS dan transformasifaktor pertumbuhan beta 1 TGF?-1 menjadi salah satu target dalam pencegahan danpengobatan fibrosis hati. Rumput laut coklat Turbinaria decuren diketahui mengandungfukoidan yang bersifat ionik memiliki bioaktivitas berdasarkan spesies dan berat molekulnamun belum diteliti secara intensif. Penelitian ini dilakukan dengan tujuan membuktikanefek antifibrosis ekstrak T. decuren terkarakterisasi eTkar melalui penghambatan aktivitasTGF-?1, MMP 13 dan Smad3 serta pengaruhnya terhadap decorin.Metode: Penelitian dilakukan di Labkesda Provinsi DKI Jakarta, Laboratorium HistologiFKUI, Laboratorium Farmakologi FKUI dan Laboratorium Terpadu FKUI. EkstrakT.decuren terkarakterisasi eTkar hasil penelitian tahap I akan diuji efeknya sebagaiantifibrosis melalui mekanisme preventif dan kuratif pada tikus jantan galur SpragueDawley SD yang diinduksi dengan CCl4. 50 dosis 1 ml/100 gram BB dua kali seminggselama 8 minggu. Enam puluh duatikus jantan galur SD dibagi 2 kelompok uji yaitu A: ujipreventif dan B: uji kuratif, masing-masing dibagi menjadi 7 kelompok perlakuan secaraacak. eTkar diberikan pada dosis 27,5, 55, 110 mg/kg BB p.o. Pada uji preventif eTkardiberikan 1 minggu sebelum dan 7 minggu bersamaan pemberian CCl4.. Pada pengujian kuratif diberikan CCl4 selama 2 minggu dan 6 minggu secara bersamaan dengan sampel uji.Pemeriksaan yang dilakukan: ALT, AST, ALP, GGT, MDA, GSH, protein total, TGF?-1,Smad3, MMP 13, decorin dan pemeriksaan histopatologi jaringan hati. Sebagaipembanding positif digunakan fukoidan 50 mg/Kg BB.Hasil: Pada uji preventif dosis eTkar yang mampu menekan luas fibrosis hati tertinggiadalah 27,5 mg/kg BB sebesar 69,89 lebih tinggi dari fukoidan dan berbeda bermaknadengan kontrol - . Pada dosis ini juga mampu menekan secara bermakna aktivitas TGF?1,MMP 13, ekspresi Smad3, decorin dan meningkatkan kadar GSH secara bermaknadibanding kontrol - , tetapi tidak bermakna untuk MDA. Pada uji kuratif, eTkar dosis 55mg/Kg BB mampu menekan persentase luas fibrosis hati sebesar 62,05 yang berbedabermakna dibanding kontrol - p

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ABSTRACT

Introduction. Liver fibrosis due to oxidative stress ROS and transforming growth factor beta 1 TGF 1 became one of the targets in the prevention and treatment of liver fibrosis. The brown seaweed T.decurens fucoidan containing ionic compounds have a potent bioactive potentials, which depends on species and molecular weight. but still unknown mechanism of action in inhibiting liver fibrosis. This study was conducted in order to prove the effect of the extract antifibrosis characterized by constraints on the expression of protein TGF 1, Smad3 and its effect on protein MMP 13 and decorin.

Method: The study was conducted in Labkesda DKI Jakarta province, Histology Laboratory, Pharmacology Laboratory and Integrated Laboratory School of Medicine FKUI. Characterized extracts brown seaweed T.decuren eTkar of the results of the phase I study was studied to investigate their effect as antifibrosis in animal model of fibrosis through preventive and curative mechanism on male rats Sprague Dawley SD induced by CCl by 50 CCl ndash 1 mL kg BW twice a week for 8 weeks p.o. Sixty two male rats SD divided into 2 groups, namely A test test preventive and B test curative. Each divided into 7 treatment groups at random. eTkar was given a three level doses, i.e 27,5, 55, 110 mg kg BW p.o. At preventive mechanism, eTkar was delivered for 1 week before and 7 weeks of concurrent CCl 4 administration. On curative mechanism, eTkar was delivered the last 6 weeks for 8 weeks CCl 4 adminstration simulaneously. The test parameters were biomarkers of liver injury ALT, AST, MDA and GSH liver , liver function ALP, GGT and albumin , 4 the degree of fibrosis fibrosis area, TGF 1 and MMP 13 activities, Smad and decorin expression, fatty area hispatologically . Fucoidan was used as positive control at the dose of 50 mg Kg BW.

Results: In the preventive method, the optimum dose of eTkar capable to suppress liver fibrosis was 27,5 mg kg BW by 69,89 of CCl group which was better than comercial fucoidan and significanly different. At this dose eTkar was able to significanly suppress the 4 activity TGF 1, MMP 13, expression Smad3 decorin and increase GSH level significanly different to group p."

"Senyawa andrografolida, metabolit sekunder pada tumbuhan Sambiloto (Andrographis paniculata), diketahui memiliki aktivitas antiplasmodia 50% in vitro (IC50) < 10 μM, sehingga layak dijadikan sebagai senyawa pemandu di dalam pencarian dan pengembangan obat antimalaria secara rasional. Enzim farnesil difosfat sintase P. falciparum (PfFPPS) merupakan target yang valid untuk obat antimalaria. Tujuan umum penelitian ini adalah membuktikan membuktikan hipotesis bahwa senyawa turunan andrografolida, yang rancangan strukturnya diperoleh melalui optimasi interaksi maya andrografolida dengan enzim PfFPPS berdasarkan pose penambatan maya substrat dan inhibitornya, memiliki aktivitas antiplasmodia in vitro yang lebih tinggi daripada aktivitas antiplasmodia in vitro andrografolida dan tidak toksik terhadap sel manusia. Melalui optimasi interaksi maya andrografolida dengan enzim PfFPPS berdasarkan pose penambatan maya substrat dan inhibitornya, telah diperoleh rancangan struktur turunan andrografolida yang baru yang berpotensi menghambat enzim PfFPPS. Melalui reaksi esterifikasi terhadap senyawa andrografolida, diperoleh senyawa 3,14-andrografolidabis(4'-kloro)benzoat (18). IC50 senyawa 18 terhadap P. falciparum galur 3D7 adalah: 131,60 μM. Persentase pertumbuhan sel DLD-1 di bawah pengaruh senyawa 18 hingga konsentrasi 63,74 μM adalah lebih dari 100%. Dengan demikian, senyawa turunan andrografolida tersebut memiliki aktivitas antiplasmodia in vitro yang lebih rendah daripada aktivitas antiplasmodia in vitro andrografolida, namun tidak toksik terhadap sel manusia.

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Andrographolide, a secondary metabolite of Sambiloto (Andrographis paniculata), has a 50% in vitro antiplasmodial activity (IC50) < 10 μM, that it is suitable as a lead compund in an antimalarial drug discovery and development. P. falciparum farnesyl diphosphate synthase (PfFPPS) is a valid target for antimalarial drug. The main objective of this research is to prove the hypothesis that andrographolide derivative, whose design was obtained throughout optimization of virtual interaction between andrographolide and PfFPPS based on the docking pose of its substrates and inhibitor, has a higher in vitro antiplasmodial activity than that of andrographolide and is not toxic towards human cells. Throughout optimization of virtual interaction between andrographolide and PfFPPS based on the docking pose of its substrates and inhibitor, design of novel andrographolide derivatives which are potential to inhibit PfFPPS was obtained. Throughout esterification on andrographolide, an andrographolide derivative was obtained: 3,14-andrographolidebis(4'-chloro)benzoate (18). IC50 of 18 against P. falciparum 3D7 was: 131.60 μM. Percentage of human DLD-1 cell growth under the influence of 18 up to 63.74 μM was more than 100%. Therefore, this andrographolide derivative has lower in vitro antiplasmodial activity than that of andrographolide, but is not toxic towards human cells."