네트워크 분석에 기반한 연교의 여드름에 대한 잠재적 치료 기전 연구

다국어 초록 (Multilingual Abstract)

Background and Objectives
In East Asia, as an alternative treatment for acne, medicines containing Forsythiae Fructus (FF) are widely used, and clinical studies have shown that they are effective, however, the mechanism is not clear. We analyzed the specific pathway of FF related to the treatment of acne and suggested its potential as an alternative treatment by comparing it with the existing standard treatment.

Materials and Methods
Active compounds of FF, which are expected to work effectively in vivo, are selected through TCMSP and target proteins acting on genes related to acne were collected using the STITCH database and the Human Gene database. A network was constructed using Cytoscape for the investigated target proteins, and pathways and potential mechanisms of acne treatment were analyzed using Clusterprofiler. The identified potential therapeutic mechanisms of FF were compared with those of standard medicines. Molecular docking was performed using Autodock Vina to predict the affinity between compounds and key proteins.

Results
From FF, 9 compounds that satisfied Oral Bioavailability(OB) and Drug Likeness(DL) criteria and 65 target proteins with high confidence in 'homo sapiens' were selected. After finding 17 proteins that intersect with acne-related genes, a PPI(Protein-Protein interaction) network was constructed to identify the main target proteins. The AGE-RAGE signaling pathway was the strongest pathway, and other major pathways were identified through KEGG pathway and GO analysis. Comparison between FF and standard drugs showed that they share several proteins related to inflammation, and the main proteins that FF exclusively possesses are JUN and SREBF. As a result of molecular docking between the active compound of FF and the main protein, the affinity was less than -6.3.

Conclusion
FF regulates inflammation through multiple interacting pathways and it is expected to treat by regulating pathways related to sebum secretion and hyperkeratinization and glucse metabolism that affect all stages. Compared to the standard medicines, it was confirmed that the mechanism that only FF has is an important anti-inflammatory pathway and sebum control pathway. Therefore, FF has potential as an alternative treatment for acne patients who resist or relapse to standard medicines.

목차 (Table of Contents)

• I. 서론 1
• II. 연구 방법 4
• 1. 연교의 활성 화합물 수집 및 유효한 화합물 선별. 6
• 2. 연교의 유효 활성 화합물의 표적 단백질 수집 6
• 3. 여드름 질환의 표적 단백질 수집. 6
• 4. 여드름과 연교의 공통 표적 수집. 6
• 5. 단백질-단백질 상호 작용(PPI) 네트워크 구축 및 분석. 7
• 6. 공통 표적에 대한 Functional Annotation Analysis. 7
• 7. 여드름에 쓰이는 표준 약제들의 여드름 관련 표적 수집. 8
• 8. 표준약과 연교의 여드름에 대한 표적 분석 8
• 9. 주요 단백질 표적과 활성 화합물 간의 분자 도킹 검증. 8
• III. 결과. 9
• 1. 연교의 활성 화합물 수집 및 유효 화합물 선별 9
• 2. 연교의 활성 화합물의 표적 단백질 추출. 10
• 3. 여드름과 연교의 공통 표적 단백질 수집. 10
• 4. 공통 표적 단백질의 상호 작용 네트워크(PPI Network) 분석 12
• 5. KEGG pathway 및 GO enrichment 분석. 13
• 6. 연교와 표준약과의 표적 비교 분석 18
• 7. 유효 활성 화합물과 주요 타깃 단백질 간의 Molecular docking. 19
• IV. 고찰. 22
• V. 결론. 33
• Abstract. 34
• 참고 문헌. 36