Objective: To evaluate the anti-diabetic potential of leaf extract from Urena lobata (U. lobata) through dipeptidyl peptidase IV (DPP-IV) inhibitory activity. Methods: U. lobata leaf was extracted in hot water and ethanol. The activity of DPP-IV inhibitor was tested by in vitro study using gly-pro-p-nitroanilide as substrat of DPP-IV and vildagliptin, as standard reference. A product of the reactions between gly-pro-pnitroanilide and DPP-IV, was observed by microplate readers with l = 405 nm. All data were expressed as mean ± SD and the IC 50 value was determined by non linear regression curve fit. Active substances in leaf extract of U. lobata was analyzed by liquid chromatography-mass spectrometry. DPP-IV inhibitory activity of active compounds was evaluated in silico using docking server. Results: The ethanolic extract of U. lobata showed stronger DPP-IV inhibitor activity than water extract with the IC 50 values of 1 654.64 and 6 489.88 mg/mL, respectively.Vildagliptin, based on standard reference for DPP-IV inhibitor activity, has IC 50 value of 57.44 mg/mL. Based on in silico analysis, mangiferin, stigmasterol and b-sitosterol in U. lobata extract have a strong inhibitory activity on DPP-IV. Conclusions: The results showed that DPP-IV inhibitory activity of U. lobata is related to its active compounds such as mangiferin, stigmasterol and b-sitosterol.
Objective: To observe the effects of Centella asiatica (C. asiatica) methanolic extract on a-synuclein aggregation and its expression in rotenone-exposed zebrafish. Methods: Zebrafish (Danio rerio) were exposed to 5 mg/L rotenone for 28 days and coincubated with 2.5, 5.0 and 10.0 mg/mL of C. asiatica methanolic extract. The medium was changed every 48 h for maintain the concentration of rotenone and extract. After 28 days zebrafish were sacrificed on the ice block and protein was isolated from zebrafish brain for ELISA of dopamine and Western blotting of a-synuclein. Immunohistochemistry was conducted to observe the a-synuclein expressions from histopathological preparation of zebrafish brain. The head were soaked in 10% formaline for less than 24 h and embedded onto paraffin block, then sliced for immunohistochemistry using anti asynuclein antibody. We also measured zebrafish motility for 5 min in each week. Results: C. asiatica has important bioactive compounds such as asiaticoside that has antiinflammatory and antioxidant properties. It may inhibit cascade reaction due to oxidative stress induced by rotenone. Decreasing reactive oxygen species proposed probability of radical attack to a-synuclein protein that caused aggregation and increase of its expression.The motility of zebrafish was also maintained in C. asiatica groups due to the increasing dopamine level in rotenone-induced zebrafish. High level of reactive oxygen species inactivated enzyme for dopamine synthesis such as tyrosine hydroxylase, and oxidized dopamine itself. Oxidized dopamine increased a-synuclein aggregation. Thus, the dopamine level decreased in rotenone-induced zebrafish, but C. asiatica increased dopamine level. Conclusions: C. asiatica has a potential to be developed as an anti-Parkinson's disease treatment due to its capability for minimized the sign of Parkinson's such as a-synuclein aggregation and expression, increasing motility and dopamine as well.
AbstrakPenyembuhan luka merupakan proses dinamis yang kompleks yang ditandai dengan serangkaian peristiwa yang terjadi pada hampir semua jenis kerusakan jaringan. Pada fase awal reaksi inflamasi, neutrophil dan makrofag masuk ke dalam jaringan yang mengalami cedera dan sel -sel ini memproduksi Reactive Oxygen Species yang dapat memberikan efek menguntungkan maupun merugikan. Stres oksidatif yang terjadi merupakan kondisi yang menggambarkan ketidak seimbangan antara prooksidan atau radikal bebas dan antioksidan yang berfungsi mempertahankan kondisi terhadap kerusakan jaringan yang terjadi. Jadi stres oksidatif muncul apabila produksi Reactive Oxygen Species yang terjadi melebihi antioksidan yang ada sebagai pertahanan intrinsik. Reactive Oxygen Species dan Reactive Nitrogen Species merupakan komponen yang penting dalam proses penyembuhan luka dan perlu dalam kondisi homeostasis agar tidak menimbulkan stres oksidatif.Yang merupakan komponen utama ROS antara lain superoxide (O2 • ), hydroxyl radical (OH • ) dan hydrogen peroxide (H2O2), yang termasuk RNS meliputi nitric oxide (NO • ), nitrous oxide (NO2 • ), nitroxyl anion (HNO) dan peroxynitrite (ONOO -) yang bisa timbul akibat reaksi antara superoxide dan Nitric Oxide. Adanya kondisi yang berlebihan dari O2-pada luka dan kehadiran NO yang berlebihan dapat meningkatkan timbulnya stres oksidatif sehingga mengganggu proses penyembuhan luka. Stres oksidatif berperan pada fase inflamasi, proliferasi dan remodeling dengan cara meningkatkan angiogenesis dan mempengaruhi sel-sel yang lain termasuk sel endotel dalam mengeluarkan NO. Sehingga strategi dalam mengontrol stres oksidatif dengan cara meningkatkan antioksidan yang bersifat scavenger radikal bebas tehadap pembentukan superoxide yang berlebihan sehingga mencegah terjadinya gangguan pada proses penyembuhan luka.
AbstractWound healing is a complex dynamic process characterized by a series of events that occur in almost all type of tissue damage. In the early phase of the inflammatory response, neutrophils and macrophages enters into the injured tissue and the cells produce reactive oxygen species that can give a beneficial or detrimental effects. Oxidative stress is a condition occurs that shows imbalance between prooxidant or free radical and antioxidant that have a function to maintain the condition of the tissue damage that occurs. So Oxidative stress occurs when the production of Reactive Oxygen Species occurring is higher than the antioxidants existing as an intrinsic defense. Reactive Oxygen Species and Reactive Nitrogen Species are important components in the healing process of wounds and is necessary to be in the state of homeostasis to prevent oksidatif stress. The major components of ROS are superoxide (O2 • ), hydroxyl radical (OH • ) and hydrogen peroxide (H2O2), which includes RNS are nitric oxide (NO • ), nitrous oxide (NO2 • ), nitroxyl anion (HNO) and peroxynitrite (ONOO -) which could be form by the reaction between superoxide and nitric oxide. The existence of excessive O2 amount in the wound and th...
ABSTRAKHipertensi esensial disebabkan oleh multifaktorial dan merupakan penyakit yang kompleks karena melibatkan faktor genetik dan lingkungan atau interaksi antara keduanya. Polimorfisme kandidat gen secara genetik menentukan terjadinya hipertensi esensial. Salah satu polimorfisme yang berhubungan dengan hipertensi adalah gen CYP11B2 varian T(-344)C sebagai gen penyandi aldosterone synthase. Penelitian ini bertujuan untuk menganalisis interaksi antara faktor risiko non genetik dengan polimorfisme promoter region gen CYP11B2 varian T(-344)C pada pasien hipertensi esensial di wilayah pantai dan pegunungan, dengan desain case control study. Jumlah sampel masing-masing kelompok kasus dan kontrol sebanyak 50 orang, sehingga keseluruhan sampel penelitian sejumlah 100 orang. Penentuan polimorfisme gen CYP11B2 varian T(-344)C menggunakan isolasi DNA, polymerase chain reaction (PCR) dan analisis hasil restrictriction fragment lenght polymorphism (RFLP). Penelitian ini telah mengidentifikasi adanya polimorfisme promoter region gen CYP11B2 sebesar 8,3% pada pasien hipertensi esensial di wilayah pantai. Polimorfisme berupa adanya mutasi basa thymine (T) menjadi cytosine (C) pada kodon -344 pada 2 (dua) pasien hipertensi esensial di wilayah pantai. Kerentanan genetik ditemukan pada individu dengan genotip homozigot TT 3 (tiga) kali lebih banyak daripada genotip heterozigot TC yang mengalami hipertensi esensial baik di wilayah pantai maupun pegunungan dan genotip homozigot TT ditemukan 8 (delapan) kali lebih banyak dari pada genotip homozigot CC di wilayah pantai. Penelitian ini memperkuat bahwa genotip TT dan alel -344T berkaitan dengan kecenderungan genetik terjadinya hipertensi esensial.
Kata Kunci: Aldosterone synthase, gen CYP11B2 varian T(-344)C, hipertensi esensial, polimorfisme
ABSTRACT
Essential hypertension is a multifactorial and complex disease because it involves to interactions of genetic and environment factors. One of the polymorphisms that relation with hypertension is a T(-344)C variant CYP11B2 gene as a gene coding for aldosterone synthase. This study purposed to analyze the interaction between non genetic risk factors and the polymorphism of aldosterone synthase T(-344)C Variant CYP11B2 Gene Promoter Region in patiens with
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