Electronic Theses and Dissertation

PREDIKSI ENZIM BROMELIN DALAM KEEMPUKAN
DAGING SAPI MENGGUNAKAN METODE
NETWORK PHARMACOLOGY

ABSTRAK
Keempukan daging sapi merupakan indikator kualitas daging utama yang sangat dipengaruhi oleh proses proteolisis pascapemotongan, terutama oleh sistem calpain-calpastatin (CAPN/CAST). Namun, bukti terbaru menunjukkan bahwa respon inflamasi dan stres oksidatif juga berperan signifikan dengan memodulasi lingkungan biokimia otot. Bromelin, enzim proteolitik dari nanas, diduga dapat meningkatkan keempukan, namun mekanisme kerjanya secara sistem biologis belum sepenuhnya dipahami. Penelitian ini bertujuan untuk menganalisis mekanisme biologis bromelin dalam meningkatkan keempukan daging sapi melalui pendekatan Network Pharmacology. Sebanyak 266 gen terkait keempukan daging sapi berhasil diidentifikasi. Analisis jejaring mengungkapkan 10 gen inti, yaitu IL6, IL1B, IFNG, TNF, IL18, ACTB, IL17A, ALB, IL4, dan CD4, yang didominasi oleh gen-gen yang terlibat dalam respon inflamasi dan imun. Dari 6 gen target bromelin, terdapat 3 gen irisan dengan gen keempukan daging: HSPB1, SOD1 dan CTSB. Analisis GO mengonfirmasi keterlibatan proses biologis seperti respon inflamasi, aktivasi leukosit, regulasi apoptosis, dan proses oksidasi reduksi. Penelitian ini mengungkapkan bahwa mekanisme keempukan daging sapi melibatkan jejaring kompleks yang tidak hanya mencakup sistem proteolitik konvensional (CAPN/CAST), tetapi juga gen-gen inflamasi dan struktural. Bromelin diduga meningkatkan keempukan melalui interaksi tidak langsung dengan gen targetnya (HSPB1, SOD1 dan CTSB) untuk menciptakan lingkungan mikro yang optimal bagi proteolisis endogen, dengan cara menghidrolisis protein struktural, memodulasi stres oksidatif, dan memicu apoptosis. Pendekatan Network Pharmacology memberikan perspektif holistik untuk memahami mekanisme aksi bromelin dan dasar pengembangan aplikasinya.

Kata Kunci: Bromelin, gen inflamasi, keempukan daging, network pharmacology, proteolisis

THE PREDICTION OF BROMELAIN ENZYME IN BEEF TENDERIZATION USING NETWORK PHARMACOLOGY METHODOLOGY ABSTRACT Beef tenderness is a primary quality attribute heavily influenced by post-mortem proteolysis, primarily by the calpain-calpastatin (CAPN/CAST) system. However, recent evidence suggests that inflammatory responses and oxidative stress also play significant roles by modulating the muscle biochemical environment. Bromelain, a proteolytic enzyme from pineapple, is suspected to enhance tenderness, but its mechanism of action within biological systems is not fully understood. This study aims to analyze the potential of bromelain in improving beef tenderness through a Network Pharmacology approach. A total of 266 genes related to beef tenderness were successfully identified. Network analysis revealed 10 hub genes: IL6, IL1B, IFNG, TNF, IL18, ACTB, IL17A, ALB, IL4, and CD4, which are predominantly genes involved in inflammatory and immune responses. From 6 bromelain target genes, 3 overlapped with beef tenderness genes: HSPB1, SOD1 and CTSB. GO analysis confirmed the involvement of biological processes such as inflammatory response, leukocyte activation, regulation of apoptosis, and oxidation-reduction processes. This study reveals that the mechanism of beef tenderness involves a complex network that not only includes the conventional proteolytic system (CAPN/CAST) but also inflammatory and structural genes. Bromelain is hypothesized to improve tenderness through indirect interaction with its target genes (ATP2A1, COL1A1, HSPB1, SOD1, MYH1, CTSB) to create an optimal microenvironment for endogenous proteolysis, by hydrolyzing structural proteins, modulating oxidative stress, and triggering apoptosis. The Network Pharmacology approach provides a holistic perspective for understanding bromelain's mechanism of action and the basis for its application development. Keywords: Bromelain, inflammatory genes, meat tenderness, network pharmacology, proteolysis