基於轉錄體與生物資訊網絡分析探討中國橄欖多醣之抗大腸癌活性與潛在多疾病調控作用

Abstract

中國橄欖(Canarium album L.)為一種藥食兩用植物，富含多種具生理活性的天然成分，兼具營養與藥用價值。本研究目的為結合細胞實驗與生物資訊分析系統性探討中國橄欖葉片多醣 (Chinese olive leaf polysaccharides, COLP) 潛在生物活性及抑制大腸癌細胞的分子機制。實驗結果顯示，COLP 擁有更高的產率與總糖含量，且展現最顯著的抗癌活性。為進一步挖掘其生物功能潛力，本研究結合轉錄體分析，發現 COLP 調控的差異表現基因主要富集於氧化壓力反應、膽固醇代謝與細胞週期等關鍵生物過程。在疾病關聯分析中，這些基因不僅與癌症高度相關，也涉及心血管疾病與失智症等多種病理機制。Connectivity Map結果亦顯示，COLP 誘導的基因特徵與多種抗癌藥物和神經精神類藥物(如多巴胺與血清素受體拮抗劑)高度相似，顯示其具多面向的潛能。基於上述生物資訊結果，我們進一步聚焦於三大疾病模組：失智症、動脈粥樣硬化與大腸癌，進行交集分析與蛋白質交互作用網絡構建。分析結果指出，COLP 可能透過調控細胞週期、氧化還原平衡及細胞外基質重塑等路徑，參與多種疾病的分子機制調控。之後考量到 COLP 對癌症的強烈關聯性，本研究後續對大腸癌細胞的功能評估。實驗證實COLP 處理可顯著促使大腸癌細胞進入 sub-G1 期，並上調 cleaved-caspase-9 與 cleaved-PARP 的表現，顯示其具誘導內源性細胞凋亡之作用。此外，亦發現抗腫瘤相關基因 NDRG1 在 COLP 處理後顯著上調。資料庫分析進一步驗證 NDRG1 在臨床大腸癌組織中表現降低，佐證其作為 COLP 潛在凋亡標靶的可能性。整體而言，本研究證實 COLP 透過生物資料庫顯示具多重生物活性的應用潛能並且具備抑制大腸癌的潛力。

The Chinese olive (Canarium album L.) is a traditional edible and medicinal plant known for its rich content of bioactive compounds with nutritional and pharmacological value. This study investigates the inhibitory potential of Chinese olive leaf polysaccharides (COLP) against colorectal cancer cells and explores their underlying molecular mechanisms. Transcriptomic and bioinformatic analyses were further conducted to uncover additional biological functions of COLP. Preliminary evaluation showed that COLP exhibited the most potent anticancer activity. Further analysis found that COLP significantly increased the proportion of cells in the sub-G1 phase of the cell cycle and upregulate cleaved-caspase-9 and cleaved-PARP expression, indicating its ability to trigger intrinsic apoptosis in colorectal cancer cells. Through TNMplot database analysis, the clinically relevant gene NDRG1 was identified and found to be significantly upregulated upon COLP treatment, suggesting its role as a potential apoptosis-related target of COLP. In addition, Gene Ontology enrichment analysis revealed that COLP-regulated differentially expressed genes were mainly involved in oxidative stress response, cholesterol metabolism, and cell cycle regulation. Connectivity Map analysis showed that the gene expression profile induced by COLP closely resembled those of various anticancer and neuroactive drugs, including dopamine and serotonin receptor antagonists. Furthermore, Disease Ontology enrichment analysis indicated that COLP-regulated genes were not only associated with cancer but also implicated in metabolic syndrome, cardiovascular diseases, and dementia. To explore the disease relevance of COLP, its regulated genes were compared with gene sets associated with dementia, atherosclerosis, and colorectal cancer. Protein-protein interaction analysis revealed that overlapping genes formed tightly connected networks within functional modules such as cell cycle regulation, redox processes, and extracellular matrix remodeling, suggesting COLP’s potential role in multi-disease modulation. Collectively, this study confirms the anticancer potential of COLP and highlights the value of using public transcriptomic resources to investigate the multitarget bioactivities of natural products.