#NOPUBLISH 8/5/2024# Network pharmacology senyawa metabolit ekstrak etanol 70% akar kuning (Arcangelisia flava (L.) Merr.) terhadap kanker payudara

ABSTRAK:

Kanker payudara merupakan jenis kanker yang kerap terjadi pada wanita di dunia, dimana tatalaksananya tidak selektif membunuh sel kanker. Pengobatan herbal merupakan salah satu alternatif yang dapat meningkatkan kualitas hidup dan meringankan efek samping dari kemoterapi. Tujuan penelitian ini untuk mengetahui potensi tanaman Arcangelisia flava (L.) Merr. sebagai obat antikanker payudara, mengetahui profil fisikokimia, toksisitas, gen target dan jalur persinyalan terhadap kanker payudara. Metode penelitian diawali dari senyawa metabolit yang diperoleh dari metode UPLC-MS/MS. Senyawa metabolit dilakukan uji PASS untuk memprediksi aktivitas biologis terhadap kanker payudara dengan nilai Pa>0,7, prediksi fisikokimia didasarkan dengan hukum lima lipinski, dan uji toksisitas ditunjukkan dengan nilai LD50. Senyawa metabolit yang memenuhi seluruh uji tersebut dilakukan pendekatan network pharmacology dengan melakukan pengumpulan gen target senyawa melalui GeneCards dan gen target kanker payudara melalui DisGeNet. Gen target yang saling berhubungan antara senyawa dengan kanker payudara didapatkan dari diagram venn yang kemudian dilakukan visualisasi melalui cytoscape. Gen target tersebut dilakukan analisis protein-protein dan gen ontology melalui STRING serta dilakukan analisis jalur persinyalan melalui KEGG Pathway. Senyawa metabolit yang memenuhi uji PASS, prediksi fisikokimia dan toksisitas adalah 6,7-Dimethoxy-3,4-dihydroisoquinoline, Sinomenin, Dihydroberberine, Oxoberberine, Bulbocapnine, Cavidine, 9-OxoODE, gama-mangostin, alpha-Mangostin dan Mangostanin. Gen target senyawa yang berhubungan dengan kanker payudara adalah ABCB1, BAX, BCL2, BID, CASP8, CCND1, CDK1, CDK4, CHEK2, CXCL8, DICER1, EP300, GADD45A, GATA3, HIF1A, HSF1, LIN28B, MAPK1, MAPK14, MAPK3, MAPK8, MYC, NFKB1, NR3C1, PARP1, PPARG, PTEN, PTGS2, RAD51, SIRT1, STK11, TNFRSF10B, TOP1, dan TP53. Jalur persinyalan yang dilalui gen target senyawa dan kanker payudara adalah apoptosis. Berdasarkan pendekatan network pharmacology tanaman Arcangelisia flava (L.) Merr memiliki potensi terhadap kanker payudara.

ABSTRACT:
Breast cancer is a type of cancer that often occurs in women in the world, wherethe treatment is not selective in killing cancer cells. Herbal medicine is an alternative thatcan improve the quality of life and alleviate the side effects of chemotherapy. The purposeof this study was to determine the potential of Arcangelisia flava (L.) Merr. plant as ananticancer drug for breast cancer, knowing the physicochemical profile, toxicity, targetgenes and signaling pathways against breast cancer. The research method begins withmetabolite compounds obtained from UPLC-MS/MS method. Metabolite compounds weresubjected to PASS test to predict biological activity against breast cancer with Pa>0.7value, physicochemical prediction was based on Lipinski's five laws, and toxicity test wasshown by LD50 value. Metabolite compounds that fulfill all these tests are carried out anetwork pharmacology approach by collecting compound target genes through GeneCardsand breast cancer target genes through DisGeNet. Target genes that are interconnectedbetween compounds and breast cancer are obtained from Venn diagrams which are thenvisualized through cytoscape. The target genes were analyzed by protein-protein and geneontology through STRING and signaling pathway analysis through KEGG Pathway.Metabolite compounds that fulfill the PASS test, physicochemical prediction and toxicityare 6,7-Dimethoxy-3,4-dihydroisoquinoline, Sinomenin, Dihydroberberine, Oxoberberine,Bulbocapnine, Cavidine, 9-OxoODE, gama-mangostin, alpha-Mangostin andMangostanin. The compound target genes associated with breast cancer are ABCB1, BAX,BCL2, BID, CASP8, CCND1, CDK1, CDK4, CHEK2, CXCL8, DICER1, EP300,GADD45A, GATA3, HIF1A, HSF1, LIN28B, MAPK1, MAPK14, MAPK3, MAPK8,MYC, NFKB1, NR3C1, PARP1, PPARG, PTEN, PTGS2, RAD51, SIRT1, STK11,TNFRSF10B, TOP1, and TP53. The signaling pathway through which the compound andbreast cancer target genes pass is apoptosis. Based on network pharmacology approach,Arcangelisia flava (L.) Merr plant has potential against breast cancer.

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