Electronic Theses and Dissertation

Mastitis pada sapi merupakan penyakit inflamasi ambing yang menyebabkan kerugian ekonomi signifikan akibat penurunan produksi dan kualitas susu. Terapi antibiotik konvensional menghadapi tantangan resistensi bakteri dan efek pasca-bakterisida yang memicu mastitis berulang. Penelitian ini bertujuan mengidentifikasi protein target dan mekanisme aksi molekuler thymol sebagai terapi alternatif mastitis sapi menggunakan pendekatan jejaring farmakologi. Analisis in silico mengungkapkan tiga protein target thymol yang beririsan dengan gen mastitis sapi: CXCR2, CYP19A1, dan ALB. Analisis Gene Ontology menunjukkan keterlibatan gen-gen tersebut dalam respon terhadap stimulus eksternal, respon inflamasi, stres oksidatif, migrasi leukosit, dan sistem imun. Analisis KEGG mengidentifikasi tujuh jalur signaling kunci: PI3K/Akt/mTOR, NF-κB, JAK-STAT, TNF, Chemokine, Steroid hormone biosynthesis, dan Thyroid hormone synthesis. Thymol terlibat dalam tiga jalur utama melalui: (1) CXCR2 dalam Chemokine signaling pathway yang mengatur rekrutmen neutrofil, (2) CYP19A1 dalam Steroid hormone biosynthesis yang memodulasi keseimbangan estrogen, dan (3) ALB dalam Thyroid hormone synthesis yang mengatur transport hormon dan senyawa bioaktif. Analisis protein-protein interaction mengidentifikasi 10 hub utama (IL6, IL-1β, TNF, IFNG, CCL2, CD4, IL4, IL17A, TLR4, CXCL8) yang tidak secara langsung ditarget thymol, namun thymol bekerja melalui modulasi sistemik pada titik kunci regulasi imun dan hormonal. Hasil penelitian menyimpulkan bahwa thymol berpotensi sebagai terapi antimastitis melalui mekanisme multi-target yang mencakup efek antimikroba, antiinflamasi, antioksidan, dan imunomodulator.

Kata kunci: Mastitis sapi; network pharmacology; thymol

Mastitis in cows is an inflammatory disease of the udder that causes significant economic losses due to reduced milk production and quality. Conventional antibiotic therapy faces challenges of bacterial resistance and post-bactericidal effects that trigger recurrent mastitis. This study aims to identify target proteins and the molecular mechanism of action of thymol as an alternative therapy for mastitis in cows using a pharmacology network approach. In silico analysis revealed three thymol target proteins that intersect with bovine mastitis genes: CXCR2, CYP19A1, and ALB. Gene Ontology analysis showed the involvement of these genes in responses to external stimuli, inflammatory responses, oxidative stress, leukocyte migration, and the immune system. KEGG analysis identified seven key signaling pathways: PI3K/Akt/mTOR, NF-κB, JAK-STAT, TNF, Chemokine, Steroid hormone biosynthesis, and Thyroid hormone synthesis. Thymol is involved in three main pathways through: (1) CXCR2 in the Chemokine signaling pathway that regulates neutrophil recruitment, (2) CYP19A1 in Steroid hormone biosynthesis that modulates estrogen balance, and (3) ALB in Thyroid hormone synthesis that regulates the transport of hormones and bioactive compounds. Protein-protein interaction analysis identified 10 key hubs (IL6, IL-1β, TNF, IFNG, CCL2, CD4, IL4, IL17A, TLR4, CXCL8) that are not directly targeted by thymol, but thymol acts through systemic modulation at key points of immune and hormonal regulation. The results of the study concluded that thymol has potential as an antimastitis therapy through a multi-target mechanism that includes antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory effects. Keywords: Bovine mastitis; network pharmacology; thymol