(P09-038-24) A Network Pharmacology Analysis Reveals the Potential Anti-Inflammatory And Anticancer Effects of Fermented Pineapple Peel Solution via The JAK-STAT and PI3K/Akt Pathways

Objectives: This research aimed to examine the underlying mechanisms by which fermented pineapple peel (FPPS) demonstrates its anti-inflammatory and anticancer activities.

Methods: The pineapple peel underwent spontaneous fermentation with brown sugar. Compounds from methanolic and n-hexane extracts were identified using GC-MS. Anti-inflammatory compounds with bioactivity ≥ 0.7 were analyzed via PassOnline. Network pharmacology used diseases-associated genes for inflammation, neoplasms, and cancer. GSEA performed GO and KEGG pathway enrichment analysis. Molecular bindings of compounds with inflammatory proteins were investigated. Eight effective compounds were selected for further analysis based on their anti-inflammatory activity and plant sources.

Results: The study identified several pathways related to cancer, indicating that these compounds can target specific cellular pathways involved in cancer progression. The JAK-STAT pathway, known for controlling inflammatory and autoimmune conditions, was found to be important in regulating inflammation. The PI3K/Akt signaling pathway, which influences tumor formation and the inflammatory response in various cancer types, was also identified as a key player. The compounds identified in the study were found to inhibit these pathways, leading to reduced inflammation, inhibited growth of cancer cells, and promotion of cell death (apoptosis). Molecular docking found maltose binding strongly to acetylcholinesterase and 5HT2A receptors, lactose to nocipeptin, IL-6, and 5HT2A receptors, and desulphosinigrin to human acetylcholinesterase and 5HT2A receptors.

Conclusions: Our findings suggest that FPPS has the potential to be a hopeful avenue for the creation of novel medications or treatments aimed at the prevention or management of cancer and inflammatory condition.

Funding Sources: This work was funded by the Directorate of Research, Technology, and Community Service of the Ministry of Education, Culture, Research, and Technology, Republic of Indonesia under the National Competitive Basic Research Scheme during the fiscal year 2023 (Main contract number 053/E5/PG.02.00.PL/2023 and derivative contract number 189/UN12.13/LT/2023).