Aktivitas antiinflamasi sistemik ekstrak kecoa (Periplaneta americana) pada tikus model: studi in silico dan gambaran klinis

Abstract

Pemanfaatan ekstrak kecoa Periplaneta americana (P. americana) (EKP) sebagai obat antiinflamasi belum pernah dilakukan di Indonesia. Penelitian ini bertujuan untuk menganalisis aktivitas antiinflamasi sistemik ekstrak kecoa P. americana (EKP) pada tikus model systemic inflammatory response syndrome (SIRS) melalui bedah cecal ligation and puncture (CLP) yang dikaji melalui studi in silico dan gambaran klinis. Studi in silico menggunakan reseptor TNF-α converting enzyme, ligan pembanding deksametason, dan ligan uji 2-isopropoxy-5-phenyl-1,3,4-oxadiazole (satu), 2-amino-3,6-dimethylimidazo [4,5-b] pyridine (dua), dan 4,4'- (iminomethylene) bis(N,N-dimethylaniline) (tiga). Hewan model penelitian adalah 20 ekor tikus putih galur Sprague Dawley yang dibagi dalam empat kelompok yaitu yang diterapi dengan NaCl 0,9%, deksametason, dan EKP dosis berbeda. Hasil studi in silico nilai ∆G ligan alami yang paling negatif. Hasil nilai Ki ligan uji tiga yang terkecil. Nilai %BSS deksametason dan ligan uji tiga sebesar 9%. Hasil analisis Ro5 pada ketiga ligan uji diketahui bahwa semua ligan uji memenuhi lima aturan Ro5. Hasil studi gambaran klinis variabel suhu tubuh teramati tidak terdapat perbedaan yang signifikan antara kelompok dengan terapi NaCl 0,9%, deksametason, dan EKP 100 mg (P > 0,05). Perbedaan yang signifikan teramati antara kelompok terapi NaCl 0,9%, deksametason, dan EKP 50 mg dengan kelompok terapi EKP 100 mg (P < 0,05). Variabel napas, frekuensi jantung, dan total leukosit teramati tidak terdapat perbedaan yang signifikan antara semua kelompok (P > 0,05). Kesimpulan penelitian studi in silico menunjukan aktivitas antiinflamasi sistemik EKP dengan mekanisme inhibisi reseptor TACE. Studi gambaran klinis menunjukan aktivitas antiinflamasi EKP yang teramati dari tidak adanya perbedaan nyata dengan NaCl 0,9% dan deksametason. Variabel jumlah kejadian SIRS tikus model menunjukan deksametason adalah yang terbaik, sedangkan variabel persentase bertahan hidup menunjukan EKP 50 mg yang terbaik.

The use of Periplaneta americana (P. americana) cockroach extract (EKP) as an anti-inflammatory drug has never been done in Indonesia. This study aims to analyze the systemic anti-inflammatory activity of P. americana cockroach extract (EKP) in mice modeling systemic inflammatory response syndrome (SIRS) through cecal ligation and puncture (CLP) surgery assessed through in silico studies and clinical studies. The in silico study used TNF-α converting enzyme receptor, dexamethasone as control ligand, and test ligands 2-isopropoxy-5-phenyl-1,3,4-oxadiazole (one), 2-amino-3,6-dimethylimidazo[4,5-b]pyridine (two), and 4,4'-(iminomethylene)bis(N,N-dimethylaniline) (three). The animal model was 20 Sprague Dawley white rats divided into four groups, namely those treated with 0.9% NaCl, dexamethasone, and different doses of EKP. The results of the in silico study of the ∆G value of the native ligand were the most negative. The Ki values of the three test ligands were the smallest. The %BSS value of dexamethasone and test ligand three amounted to 9%. The results of Ro5 analysis on the three test ligands showed that all test ligands met the five Ro5 rules. The results of the clinical studies of body temperature variables observed no significant difference between groups with 0.9% NaCl, dexamethasone, and 100 mg EKP therapy (P > 0.05). Significant differences were observed between the 0.9% NaCl, dexamethasone, and EKP 50 mg therapy groups and the EKP 100 mg therapy group (P < 0.05). Respiratory variables, cardiac frequency, and total leukocytes observed no significant difference between all groups (P > 0.05). In conclusion, the in silico study showed systemic anti-inflammatory activity of EKP by the mechanism of TACE receptor inhibition. The clinical studies showed the anti-inflammatory activity of EKP which was observed from the absence of significant differences with NaCl 0.9% and dexamethasone. The variable of the number of SIRS events in the rat model showed dexamethasone was the best, while the variable of survival percentage showed EKP 50 mg was the best.