Volatile Components in Agarwood from Laos and Thailand: A Comparative Study and Evaluation of Their Medicinal and Cosmetic Potential

Cho, Woojin; Jung, Kwang Ho; Woojin Cho; Kwang Ho Jung

doi:10.20402/ajbc.2025.0092

Asian J Beauty Cosmetol > Volume 23(4); 2025 > Article

라오스·태국 침향의 휘발성 성분: 7개국 침향 산지별 성분의 비교 및 뷰티·헬스케어

Research Article

Asian J Beauty Cosmetol 2025; 23(4): 523-567.

Published online: December 18, 2025

DOI: https://doi.org/10.20402/ajbc.2025.0092

라오스·태국 침향의 휘발성 성분: 7개국 침향 산지별 성분의 비교 및 뷰티·헬스케어

조우진, 정광호^*

IAA국제침향협회 연구소, 대구, 한국

Volatile Components in Agarwood from Laos and Thailand: A Comparative Study and Evaluation of Their Medicinal and Cosmetic Potential

Woojin Cho, Kwang Ho Jung^*

IAA (International Agarwood Association) Research Center, Daegu, Korea

老挝和泰国沉香挥发性成分：七个国家沉香成分的比较及其在美容和保健应用方面的潜力研究

曺旴槇, 鄭光浩^*

IAA国际沉香协会研究所，大邱，韩国

^*Corresponding author: Kwang Ho Jung, IAA (International Agarwood Association) Research Center, 325, Palgongsan-ro, Dong-gu, Daegu 41000, Korea. Tel.: +82 53 984 2838 Email: viit3138@daum.net

Received September 21, 2025 Revised October 29, 2025 Accepted November 28, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

요약

목적

본 연구는 라오스와 태국산 침향의 GC-MS 기반 휘발성 성분을 분석하고, 선행연구에서 보고된 베트남 등 5개 산지 결과와 통합하여 총 7개 산지의 성분을 바탕으로 헬스케어 및 뷰티 제품으로의 활용 가능성을 검토하고자 하였다.

방법

라오스 및 태국산 침향을 각각 시료 6, 7로 설정하고, 선행연구와 동일한 조건에서 GC-MS 분석을 수행하였다. 또한 시료 1-7에서 검출된 sesquiterpene 성분에 대해 국내외 주요 데이터베이스를 활용, 관련 in vitro 및 in vivo 문헌을 조사하여 생리활성 효과를 정리하였다.

결과

GC-MS 분석 결과, 라오스 및 태국산 침향은 선행 연구시료(시료 1-5)와 유사하게 휘발성 유기 화합물(volatile organic compounds, VOCs), monoterpene, sesquiterpene이 검출되었다. 7개 시료 모두에서 italicene ether, epi-γ-eudesmol, α-agarofuran의 3종의 공통 sesquiterpene이 확인되었으며, 이 외 3종의 VOC가 공통적으로 검출되었다. 총 38종의 성분에 대해 157편의 문헌을 검토한 결과, 항암, 항미생물, 항염증, 중추신경계 보호, 면역조절, 대사 증후군, 근골격 보호 등 15개 분야의 활성이 보고되었으며, 특히 염증성 사이토카인 조절을 통한 항염증 및 면역 균형 유지 기전이 가장 빈번하게 관찰되었다.

결론

침향은 독특한 향기를 나타내는 식물성 향료로 전통적으로 설사, 구토, 천식, 류마티즘 등 치료에 활용되어 왔으며, 최근에는 면역 증진과 체력 관리 소재로 주목받고 있다. 본 연구에서는 국내 최초로 베트남 등 7개국 산지의 침향 휘발성 성분을 비교하고, 문헌 검토를 통해 항암, 항염증, 아토피 개선, 면역 조절 등 다양한 생리활성을 확인하였다. 특히 항염증 및 면역 조절 활성을 중심으로 한 침향 sesquiterpene이 두드러졌으며, 이러한 특성은 향후 기능성 화장품, 건강기능식품, 아로마 제품 등으로의 응용 가능성을 보여준다. 따라서 본 연구는 침향의 기능성 원료화 및 헬스케어 및 뷰티 산업 활용을 위한 후속 연구를 위한 과학적 근거를 제공한다.

핵심용어: 침향, 아가우드, 항염증, 세스퀴테르펜, 뷰티·헬스케어

Abstract

Purpose

To provide a comprehensive volatile chemical profile of agarwood from Laos and Thailand using gas chromatography–mass spectrometry (GC–MS). The data were compared with results previously published from five other geographic sources, enabling a robust evaluation of agarwood’s suitability for pharmaceutical and cosmetic applications.

Methods

Volatile components of agarwood samples from Laos and Thailand (samples 6 and 7) were analyzed using the GC–MS protocols described in earlier studies. A subsequent evaluation of the sesquiterpenes identified in all seven samples was conducted using a systematic literature review of major databases, focusing on in vitro and in vivo reports of biological activity.

Results

GC–MS analysis revealed that agarwood from Laos and Thailand contained volatile organic compounds (VOCs), monoterpenes, and sesquiterpenes, consistent with previous reports. Across the seven samples, three common sequiterpenes–italicene ether, epi-γ-eudesmol, and α-agarofuranㅡthree shared VOCS were identified. The literature review of 38 compounds produced 157 references, categorized into 15 biological activity domains, including anticancer, antimicrobial, anti-inflammatory, neuroprotective, immunomodulatory, metabolic, and musculoskeletal effects. Anti-inflammatory pathways mediated by cytokine regulation were most frequently observed.

Conclusion

This is the first Korean comparative analysis of the volatile components of agarwood from seven geographic regions. The integrated GC–MS and literature-based findings highlight anti-inflammatory activity as a major biological mechanism. These results provide a solid foundation for future statistical analyses and in vitro/in vivo validation of individual compounds to advance agarwood research and its medicinal and cosmetic applications.

Keywords: Agarwood, Aloeswood, Anti-inflammatory, Sesquiterpene, Beauty and healthcare

中文摘要

目的

利用气相色谱-质谱联用技术(GC-MS)对老挝和泰国沉香的挥发性化学成分进行全面分析。并将所得数据与先前发表的来自其他五个地理区域的沉香结果进行比较，从而对沉香在医药和化妆品领域的应用潜力进行可靠的评估。

方法

采用先前研究中描述的GC-MS方法分析了来自老挝和泰国的沉香样品(样品6和7)的挥发性成分。随后，通过对主要数据库进行系统文献综述，重点关注体外和体内生物活性研究报告，对所有七个样品中鉴定的倍半萜类化合物进行了评估。

结果

GC-MS分析表明，老挝和泰国的沉香中含有挥发性有机化合物(VOCs)、单萜和倍半萜，与之前的报道一致。在所有7个样品中，鉴定出3种共同的倍半萜——italicene ether, epi-γ-eudesmol, α-agarofuran——以及共同的3种VOC。对38种化合物的文献检索共获得157篇参考文献，这些参考文献被归类为15个生物活性领域，包括抗癌、抗菌、抗炎、神经保护、免疫调节、代谢和肌肉骨骼效应。其中，细胞因子调节介导的抗炎通路最为常见。

结论

这是韩国首次对七个地理区域的沉香挥发性成分进行比较分析。结合气相色谱-质谱联用技术和文献资料，研究结果表明抗炎活性是沉香的主要生物学机制。这些结果为未来开展统计分析以及对单个化合物进行体外/体内验证奠定了坚实的基础，有助于推进沉香的研究及其在医药和化妆品领域的应用。

关键词: 沉香, 芦荟, 抗炎, 倍半萜烯, 美容·保健

Introduction

침향(沈香, agarwood, aloeswood)은 팥꽃나무과(Thymelaeaceae)에 속하는 Aquilaria crassna, A. malaccensis, A.agallocha, A. sinensis 등 상록성 교목이 외부 자극이나 미생물 감염에 반응하여 생성하는 방향성 수지(樹脂)이다. 자연 상태에서 수지가 형성되는 비율은 약 10%에 불과하며, 생성에는 수년이상이 소요된다(Shivanand et al., 2022).

침향은 독특한 향과 희소성으로 인해 아시아, 중동, 유럽 지역에서 향료 및 약재로 이용되어 왔으며, <본초강목>과 <동의보감>에도 약재로 기록되어 있다(Chen & Rao, 2022; López-Sampson, 2018). 현재는 오일, 분말, 향수, 화장품, 향 등으로 산업적 응용이 확대되고 있으며, 품질에 따라 kg 당 최고 100,000 USD에 거래되었다는 보고가 있다(Naef, 2011). 나무 조각, 가루, 오일, 선향, 향수 등의 형태로 유통되는 침향의 연간 시장 규모는 수십억 달러에 이를 것으로 추정된다(Shivanand et al., 2022).

침향에는 약 150종 이상의 휘발성 화합물이 보고되었으며, 주요 구성 성분은 세스퀴테르펜(sesquiterpene), 모노테르펜(monoterpene), 크로몬(chromones, 2-(2-phenylethyl)-4H-chromen-4-one derivatives) 계열이다(Naef, 2011; Wang et al., 2018a). 특히 세스퀴테르펜은 테르페노이드(terpenoid) 계열의 2차 대사산물로, 항균, 항염증, 항산화, 항암 등 활성이 보고되었다(Awouafack et al., 2013). 침향 추출물 및 주요 성분은 NO, TNF-α, IL-6, IL-1β, PGE 2 등 염증 매개체 억제를 통해 항염증 활성을 나타내며, 인슐린 민감성 개성 및 항당뇨 효과도 보고되었다(Alamil et al., 2022; Chen & Rao, 2022; Fadzil et al., 2024; Hashim et al., 2016; Wang et al., 2018b).

산지별 GC-MS 분석에서는 β-selinene, LC-MS에서는 α, β, γ-eudesmol 등 주요 세스퀴테르펜이 반복적으로 검출되었다(Park & Kim, 2019; Shin et al., 2011). 침향 메탄올 추출물의 in vitro 평가에서 nitric oxide (NO) 생성 억제 및 a-glucosidase 저해를 통해 항염증 및 항비만 활성이 확인되었고, 일부 연구에서는 항산화 및 피부 개선 효과도 보고되었다(Hwang et al., 2022; Lee et al., 2015; Park & Kim, 2019). 침향 향기 흡입에 의한 스트레스 감소와 정서 안정 효과와 유산균 발효 침향환의 항산화 효과활성 증대, 질병의 예방 또는 환자를 위한 맞춤형 식품인 ‘메디푸드’로 침향을 활용하는 방안 등 연구를 통해 향료를 넘어 다양한 헬스케어 및 뷰티 산업 소재로 침향의 가능성이 제시되었다(Jung, 2023; Liew, 2022; Park & Weon, 2022). 한편, 최근 침향 관련 제품과 건강기능식품에 대한 대중적 수요가 증가하고 있으므로 침향의 과학적 효능 규명과 산업적 활용 연구의 필요성이 대두되고 있다.

그러나 대부분의 선행 연구는 단일 국가의 침향에 국한되어 있거나 다국적 산지 간 휘발성 성분의 정량 비교나 생리활성 기전의 연계 분석은 부족하다. 특히 국내에서는 침향에서 유래한 세스퀴테르펜의 생리활성에 대한 연구 또한 초기단계에 머물러 있다.

이에 본 연구에서는 라오스와 태국산 침향의 휘발성 성분을 GC-MS로 분석하고, 선행연구에서 확보된 5개국(베트남, 캄보디아, 인도네시아, 말레이시아, 미얀마)의 데이터를 통합하여 총 7개 산지별 침향의 성분적 특성을 비교하였다(Jung & Lee, 2022). 또한, 각 성분의 문헌 기반 생리 활성을 체계적으로 검토하여 항균, 항암, 항염증, 피부 보호, 호흡기 보호 등 주요 기능을 분류하고, 뷰티 및 헬스케어 분야에서의 응용 가능성을 고찰하였다. 본 연구는 7개국 침향의 화학적 다양성과 생리활성 기전을 통합적으로 제시함으로써, 침향의 기능성 소재로서의 가치와 산업적 활용 가능성을 평가를 위한 기초자료를 제공하고자 한다.

Methods

1. 라오스 및 태국산 침향의 휘발성 성분 분석

1) 시료

성분 분석 실험에 이용한 침향 sample 6, 7은 베트남 침향협회(Vietnam Agarwood Association)를 통하여 직접 구입하였다(Sample의 명칭은 선행 연구 sample 1-5 결과와 비교를 위해 연속 순번으로 명명하였다).

- Sample 6 (시료 6): 라오스산 침향

- Sample 7 (시료 7): 태국산 침향

2) 성분 분석 기기 및 조건

침향의 휘발성 성분 분석은 선행 연구와 동일한 분석기기와 분석조건을 적용하였다(Jung & Lee, 2022). GC-MS는 7890B Gas Chromatography & 5977B Mass Spectrometer Detector (Agilent Technologies, USA)를 사용하여 정성(定性)분석을 실시하였으며, 시료 중 휘발 성분의 분석은 Solid Phase Micro-extraction (SPME, 고체상 미세추출법)을 사용하였고 분석 조건은 다음 Table 1과 같다.

3) GC-MS 분석을 통해 검출된 휘발성 성분의 분류

GC-MS 분석 결과 검출된 시료 6, 7의 휘발성 성분 분석 결과는 선행 연구와 동일한 기준에 따라 휘발성 유기 화합물(volatile organic compounds, VOCs), 모노테르펜(monoterpenes) 및 세스퀴테르펜(sesquiterpenes)으로 분류하였다. 각 화합물의 검출시간(retention time, min)과 상대 검출 양(relative peak area, %)을 산출하였다.

2. 베트남 등 7개 국가별 침향의 휘발성 성분 비교 및 문헌 검토

1) 성분 비교 및 통계 분석

이번 연구에서 확인된 라오스 및 태국산 침향(시료 6, 7)의 GC-MS 분석 결과를 선행연구에서 확보된 베트남, 인도네시아, 말레이시아, 미얀마, 캄보디아 5개국 시료(시료 1-5)의 데이터와 통합하였다(Jung & Lee, 2022) (Table 3).

각 시료별 GC-MS 분석 결과 중 화합물의 상대 피크 면적(%)을 기준으로 비교·분석하였으며, 7개 산지 간 성분 조성의 유사도와 차이를 파악하기 위해 총 82개 성분에 대해 주성분 분석(principal component analysis, PCA)을 실시하였다. SPSS 통계 소프트웨어(ver. 19.0; IBM, USA)를 사용하여 산지별 침향의 구분되는 양상을 파악하였다.

2) 문헌 검색(Database)

침향 유래 성분의 생리활성 정보에 대한 문헌 검토를 위해, 주요 학술 데이터베이스PubMed, 한국전통지식포탈, 과학기술 지식인프라 사이언스온(ScienceON), Google Scholar를 활용하였다. 문헌 검색은 1990년 1월부터 2025년 8월까지 발표된 논문을 대상으로 수행하였으며, 검색 키워드는 “agarwood”, “aloeswood”, “Aquilaria crassna”, “A. malaccensis”, “A.sinensis”, “volatile compound”, “sesquiterpene”, “in vitro”, “in vivo”, “activity”, “efficacy”, “clinical” 등을 조합하여 사용하였다.

검색 결과는 제목, 초록 및 본문을 검토하여 침향 또는 그 유래 성분의 생리활성과 관련된 실험적 근거를 제시한 논문만을 최종적으로 포함하였다.

3) 성분별 생리활성 문헌 선정 기준

시료 1-7에서 검출된 모든 세스퀴테르펜 및 모노테르펜을 대상으로 1차 검색을 수행하였다. 각 성분별의 검출량(peak area, %)의 상대적 크기와 무관하게, 7개 산지 중 한 곳 이상에서 검출된 총 38종 성분을 검색 대상으로 포함하였다.

특정 화합물의 단일 분리 실험 결과가 보고되지 않은 경우에는, 동일 화합물이 다른 식물 추출물 내에서 보고된 생리활성 평가 결과도 참고하였다.

문헌 검색 결과, 총 167편 관련 논문을 확보하였으며, 중복 문헌 10편과 비영어 논문, 리뷰 논문 등을 제외한 157 편의 원문 논문을 최종 분석 대상으로 선정하였다(Figure 1). 각 문헌은 실험계(in vitro, in vivo, 임상연구)에 따라 구분하고, 주요 활성 분야(항균, 항염, 항산화, 피부 보호, 호흡기 보호 등)를 기준으로 분류하였다. 실험이 수행되지 않은 단순 문헌 고찰(review) 논문과 비영어권 문헌은 제외하였다. 문헌 선정 및 분석 절차의 개요는 Figure 1에 요약하였으며, 실험계에 따른 문헌 건수는 Figure 2에 요약하였다.

4) 데이터 해석 및 한계

각 논문에서 보고된 IC₅₀, EC₅₀ 등의 정량 지표가 있는 경우 해당 값을 함께 정리하였으며, 실험 간 모델과 조건의 차이를 고려하여 상대 비교 지표로만 활용하였다. 실험 설계 및 평가 지표의 다양성으로 인해 절대적 비교에는 한계가 있음을 명시하였다.

5) 항염증 기전 분석

확보된 157 편의 문헌 중“inflammation”, “anti-inflammation” 관련 키워드를 포함한 문헌을 선별하여 항염증 관련 기전을 중심으로 분석하였다. 각 문헌에서 보고된 in vitro 실험계의 염증 매개 인자(NF-κB, COX-2, IL-6, TNF-α 등)의 발현 변화 및 관련 신호전달 경로(NF-κB, MAPK, JAK/STAT, NLRP3) 억제 기전을 중심으로 정리하였다. 이후 각 성분별로 보고된 작용 기전을 비교하여 경로 간의 상호 연계성 및 주요 억제 타깃(TLR4/MyD88, NF-κB, COX-2, iNOS 등)을 통합적으로 분석하였다.

이를 바탕으로 침향 유래 세스퀴테르펜 및 모노테르펜의 항염증 작용 경로를 종합적으로 시각화하여 도식화(Figure 6)하였으며, 세포 내 염증 신호 흐름과 각 화합물의 억제 기전을 단순화하여 제시하였다.

Results and Discussion

1. 선행 문헌에서의 라오스 및 태국 침향 성분 분석 결과 비교

이미 보고된 데이터베이스를 활용하여 이번 라오스, 태국산 침향의 성분 분석결과와 비교하고자 아래와 같이 선행 연구문헌의 성분 보고내역을 검토하였다(Table 2).

1) 라오스 침향의 성분 분석 문헌

라오스 침향 등에 대하여 연소시켜 발생한 연기를 GC-MS로 분석한 결과 guaiol acetate, β-patchoulene, dehydrofukinone 등의 세스퀴테르펜 성분과 levoverbenone, (S)-cis-verbenol 등의 VOC 일부를 포함한 총 110종의 성분이 검출되었으며, 라오스 침향의 GC 패턴은 캄보디아 침향을 연소시켜 발생한 연기를 분석한 결과와 유사했다(Kao et al., 2018). 라오스 침향을 추출한 에센셜 오일은 GC-MS 분석 결과, n-hexadecanoic acid이 가장 높게 검출되었고, valerianol, jinkoeremol, agarospirol 등 세스퀴테르펜 성분이 검출되었다(Ngan et al., 2020).

2) 태국 침향의 성분 분석 문헌

태국 산지의 A.crassna, A.subintegra, A.malaccensis 등 품종별 침향나무에서 채취한 침향 수지의 에센셜 오일은 GC-MS 분석 결과 공통적으로 isoamyl dodecanoate 등 VOC와 epoxybulnesene, karanone, a-bisabolol acetate 등 세스퀴테르펜이 검출되었다(Pripdeevech et al., 2011). 한편 태국산 침향을 물, 초임계로 추출한 경우, γ-selinene, δ-guaiene, guaiol, selina-3,11-dien-9-one 등이, 에센셜 오일은 GC-MS 분석 결과 β-agarofuran, β-eudesmol, valerianol 등이 검출되었다(Ngan et al., 2020; Wetwitayaklung et al., 2009).

2. 라오스 및 태국산 침향(시료 6-7)의 휘발성 성분 분석(Table 3, Figure 3)

1) 라오스산 침향(시료 6) 성분 분석 결과

시료 6에서 세스퀴테르펜 중 agarospirol이 2.72%로 최다였으며, valerianol 1.916%, longifolene 1.857%, cedrol 1.699%, β-eudesmol 1.618%, italicene ether 1.165%, 7-epi-γ-eudesmol 1.136% 등이 뒤를 이었다. 선행 연구의 베트남산 침향(시료1)에서 검출된 α-santalol, dehydrofukinone, cyperene, valencene, γ-selinene, β-caryophyllene 등은 시료 6에서 검출되지 않았고, 베트남 및 라오스산 침향에서 공통으로 검출된 성분은 dehydrofukinone, β-dihydroagarofuran, β-elemene, italicene ether 등 총 18종으로 그 양에는 차이가 있었다.

모노테르펜 중 d-limonene이 0.14% 검출되었으며, VOC 중에서 diethyl phthalate (DEP)가 41.642%로 시료 6 전체 검출 성분 중 가장 많은 양이 검출된 성분이다. 그 외 VOC 중 benzaldehyde 2.098%, nonanal 0.977%, octanal 0.408%, hexanal 0.328%, heptanal 0.121%, furfural 0.121%, 2-nonanone 0.066% 등이 검출되었다.

2) 태국산 침향(시료 7) 성분 분석 결과

시료 7에서 검출량 기준 1,2위 성분은 세스퀴테르펜인 α-agarofuran, 10.784%, 7-epi-γ-eudesmol 10.528%이었다. 그 외 α-muurolene 6.597%, 2-isopropyl-5-methyl-9-methylenebicyclo[4.4.0]dec-1-ene 3.762%, cedrol 3.692%, acetophenone 1.401%, α-humulene 1.044% 등이 검출되었다. 선행 연구의 베트남산 침향(시료1)에서 검출된 α-santalol, elemol, α-, β-, γ-eudesmol, dehydrofukinone, cyperene, α-curcumene, valencene, γ-selinene, β-selinene 등은 시료 7에서는 검출되지 않았다.

반면에 베트남 및 태국 산지 공통으로 검출된 성분은 germacrene D, italicene ether, β-elemene 등 총 17종이었으며, 검출량의 차이가 있었다.

시료 7에서 검출된 모노테르펜은 없었으며, VOC인 benzaldehyde 4.136%, diethyl phthalate 3.7%, 1-octanal 0.337%, octanal 0.316%, nonanal 0.157%, heptanal 0.113%, 2-nonanone 0.072%, hexanal 0.058% 등이 검출되었다.

3. 7개 침향 산지별 통합 비교

1) 시료 1-7의 휘발성 성분의 검출량 비교

GC-MS 분석 결과, 7개 산지의 침향(시료 1-7)에서 α-agarofuran, 7-epi-γ-eudesmol 및 italicene ether는 공통적으로 검출되었다(Table 3, Figure 4).

이 외에 agarospirol, baimuxinal은 각각 6개 시료에서, cedrol, α-curcumene, β-dihydroagarofuran, δ-guaiene (α-bulnesene)은 각각 5개 시료에서 검출되었으며, dehydrofukinone, β-eudesmol, γ-eudesmol은 각각 4개의 시료에서 검출되었다.

산지별 주요 세스퀴테르펜 성분은 다음과 같았다.

-베트남산(시료 1): dehydrofukinone (14.73%)

-인도네시아산(시료 2): 5-epi-aristolochene (8.271%)

-말레이시아산(시료 3): α-agarofuran (15.808%)

-미얀마산(시료 4): italicene ether (16.242%)

-캄보디아산(시료 5): agarospirol (12.128%)

-라오스(시료 6): agarospirol (2.72%)

-태국산(시료 7): α-agarofuran (10.784%)

이처럼 산지별 침향에서 검출된 세스퀴테르펜의 종류와 상대 면적(%)은 뚜렷한 차이를 보였다. 또한, 항염증, 항균 등 생리 활성이 보고된 해당 성분만을 대상으로 총 검출 성분수와 상대면적을 비교한 결과, 베트남산(시료 1)이 27종, 총 58.213%로 가장 많았으며, 그 외 산지는 각각 15-25종, 약 18-54% 수준이었다(시료 2: 15종, 24.448%; 시료 3: 22종, 45.882%; 시료 4: 19종, 47.638%; 시료 5: 25종, 53.715%; 시료 6, 22종, 18.24%; 시료 7, 18종, 43.172%).

7개 산지에서 공통 검출된 VOCs은 benzaldehyde, nonanal, octanal, 세스퀴테르펜은 α-agarofuran, italicene ether, epi-γ-eudesmol 이었다(Figure 4). 또한 diethyl phthalate는 베트남산(시료 1)를 제외한 시료 2-7에서 검출되었다.

한편, 각 산지에서만 검출된 고유 세스퀴테르펜도 확인되었다. 예를 들어, 베트남산(시료 1)에서는 9-hydroxy-isolongifolene, muurola-4,10(14)-dien-1.β.-ol, germacrene D, valencene, (3aR,3bR,6aR,7aR)-2,2,3b-trimethyl-4-methylene-decahydro-cyclopenta[a]pentalen-6a-ol, (3aR,4R,7R)-1,4,9,9-tetramethyl-3,4,5,6,7,8-hexahydro-2H-3a,7-methanoazulen-2-one, eremophilone 등 7종, 인도네시아산(시료 2)에서 5-epi-aristolochene, α-eudesmol, β-patchoulene등 3종, 말레이시아산(시료 3)은 dihydro-cis-.α.-copaene-8-ol, 1,4-dimethyl-7-(prop-1-en-2-yl)decahydroazulen-4-ol의 2종, 미얀마산(시료 4)은 aromadendrene, 캄보디아산(시료 5)은 neoisolongifolene, alloaromadendrene, nerolidol, cyperone 등 4종, 라오스산(시료 6)은 α-patchoulene, cyperenone의 2종, 태국산(시료 7)은 α-muurolene, guaiol의 2종의 고유 성분이 각각 검출되었다.

특히 Table 4에 제시한 heatmap은 산지별 주요 세스퀴테르펜 조성 프로파일의 상대적 패턴을 시각화한 것으로, 베트남산 시료에서 전반적으로 높은 함량 분포를 보여준다. 이러한 시각적 패턴은 향후 산지별 침향의 화학적 프로파일 특성 연구와의 비교 분석 시 유의미한 연계 근거로 활용될 것으로 기대된다.

이러한 결과를 바탕으로 침향 산지와 휘발성 성분 조성의 유사성을 통계적으로 비교하기 위해 PCA 분석을 수행하였다.

2) 침향 산지별 휘발성 성분의 PCA 분석 결과

GC-MS 분석을 통해 얻은 82개 휘발성 성분의 상대 면적(relative peak area, %) 데이터(Table 3)를 이용하여, 7개 산지별 침향의 성분 조성 유사도를 주성분분석(Principal component analysis, PCA)으로 평가하였다(Table 6). Peak area에 대해 Kaiser-Meyer-Olkin(KMO) 측도를 산출한 결과, KMO 값은 0.667로 나타나 요인분석적용에 적절한 표본 적합성을 나타냈다. 또한, Bartlett의 구형성 검정 결과, χ²=135.542 (p<0.001)로 통계적으로 유의하여 변수 간 상관관계가 존재함을 확인하였으며, 이에 따라 요인분석 수행의 타당성이 확보되었다. 그리고 주성분 추출법(principal component extraction method)을 적용하고 베리맥스 회전(Varimax rotation)을 통해 탐색적 요인분석 결과, 추출된 요인들의 총 누적 설명력은 70.059%로 나타났다. 이러한 결과는 주성분 분석(PCA)을 통해 산지별 침향의 화학적 성분 패턴에서 유의한 차이가 존재함을 확인한 결과와 동일한 의미를 갖는다.

PCA 결과, 7개 산지의 침향은 총 3개의 주요 요인(principal components)으로 도출되었다(Figure 5).

-요인 1 (PC1): 말레이시아, 캄보디아, 태국산 시료

-요인 2 (PC2): 인도네시아, 미얀마, 라오스산 시료

-요인 3 (PC3): 베트남산(A.crassna)

이러한 결과는 침향의 휘발성 성분 패턴이 지리적 기원에 따라 뚜렷하게 차별화됨을 보여주며, 향후 원산지 판별이나 품질 특성 평가에 활용될 수 있을 것으로 판단된다.

또한, 각 산지별 구분에 기여하는 주요 성분을 도출하기 위한 추가 분석을 수행하였으나 통계적으로 유의한 변수(variable loading)는 확인되지 않았다. 따라서 향후 지표성분(marker compound)의 규명 및 성분 프로파일(chemical profile)에 대한 보완 연구가 이루어진다면 산지별 침향의 품질관리 및 품질 일관성 확보에 기여할 것으로 기대된다.

4. 침향에서 검출된 성분의 생리활성 문헌 검토 결과

1) 침향 유래 성분의 활성 문헌 검토 결과 요약

베트남을 비롯한 7개 산지별 침향의 GC-MS를 통한 휘발성 성분 분석결과에 대하여 생리 활성이 보고된 세스퀴테르펜 및 모노테르펜 38종의 총 157 편의 연구 문헌을 확인하고 유사한 활성 분야별로 통합하였다(Table 7). 한가지 성분에서 여러 분야의 활성이 보고된 경우 분야별로 분류하였으며, 추출물에서 해당 성분이 포함되어 있으면서 성분 분석으로 평가한 활성 결과도 포함하였다.

38종 성분 중 모노테르펜인 d-limonene을 제외한 α-agarofuran 등은 세스퀴테르펜이었으며, 각 성분에 대한 in vitro 및 in vivo 생리 활성 문헌은 15 가지 분야 (항균, 항염증, 항암, 호흡기 보호, 대사 관련 활성 등)로 분류하고 종합적으로 고찰했다. β-Caryophyllene은 항암, 항미생물, 항염증, 신경, 대사질환예방 등 총 13가지 분야로 가장 많은 활성이 보고된 성분이었고, nootkatone은 항염증, 방충, 항비만, 심혈관 보호 활성 등 11가지 분야, cedrol은 신경 보호, 호흡기 보호, 항비만, 탈모 완화 등 11가지 분야의 활성이 보고되었다(Table 5).

-38종 성분: α-agarofuran, 7-epi-γ-eudesmol (epi-γ-eudesmol), agarospirol, baimuxinal, cedrol, α-curcumene, β-dihydroagarofuran, δ-guaiene (α-bulnesene), dehydrofukinone, β-eudesmol, γ-eudesmol, δ-cadinene, β-caryophyllene, β-elemene, β-selinene, trans-calamenene, α-copaene, cyperene, elemol, germacrene D, α-humulene, longifolene, nootkatone, α-santalol, α-selinene, γ-selinene, spathulenol, valerenol, alloaromadendrene, α-cedrene, hinesol, nerolidol, valerianol, d-limonene, α-eudesmol, α-cyperone, valencene, β-patchoulene

위 38종 성분 중 21종 성분에서 공통적으로 항암 활성이 가장 많이 보고되었다. 그 뒤를 이어 항미생물(19종), 당뇨·대사 등 심혈관계 보호(18종), 항염증(14종), 중추신경계(CNS)(13종), 아토피·탈모 등 피부 관련 활성(9종) 등이 보고되었다. 활성 문헌은 실험 형태 별로 분류하였을 때, in vitro 방법 75편, in vivo 69편의 문헌이었으며, 기타 in vitro/in vivo 5편, clinical study 6편, in silico 1편, in vivo/ex vivo 1편이었다(Figure 2).

2) 침향 유래 성분의 생리활성(상세)

a. 항암 활성(anticancer activity)

β-Elemene은 비소세포폐암, 전립선암, 간암 등에서 세포주기 정지와 apoptosis를 유발하여 항암 효과를 나타냈다(Dai et al., 2013; Li et al., 2010; Wang et al., 2005). β-Caryophyllene은 대장암, 췌장암, 림프종 등에서 세포 이동, 증식, 생존을 억제하고 apoptosis를 촉진하는 세포독성을 보였다(Amiel et al., 2012; Dahham et al., 2015; Fidyt et al., 2016). Hinesol은 백혈병 세포에서, β-dihydroagarofuran은 유방암, 폐암, 전립선암 세포에서 각각 미토콘드리아 기능 장애를 매개로 세포 성장을 억제하였다(González-Chavarría et al., 2020; Masuda et al., 2015). 또한 α-curcumene은 난소암, δ-cadinene은 간암, α-santalol은 피부암, 유방암, 전립선암 등 각각 다양한 암종에서 세포 성장 억제와 apoptosis를 유발하였다(Bommareddy et al., 2018; Bommareddy et al., 2012; Hui et al., 2015; Kaur et al., 2005; Santha et al., 2013; Shin & Lee, 2013).

Cedrol은 교모세포종 치료제 temozolomide와 병용 시 항암 효과가 상승하였고, 세포주기 연관 항암 활성이 증진되었다(Chang et al., 2020). β-Eudesmol은 간암 세포의 증식과 혈관 신생을 억제하여 간접적인 종양 억제효과를 보였다(Bomfim et al., 2013; Ma et al., 2008; Tsuneki et al., 2005). γ-Eudesmol은 대장암, α-humulene은 유방암, 대장암, trans-calamenene과 caryophyllene는 유방암 세포에서 항증식 또는 세포독성을 나타냈다(Hadri et al., 2010; Yagi et al., 2016). 또한 α-curcumene은 유방암 세포의 이동과 침습을 억제하여 전이 억제에 기여하였고, spathulenol은 백혈병 및 난소암 세포주에서 증식을 억제하였다(Al-Amin et al., 2023; Brito et al., 2018). Limonene은 위암에서 apoptosis 유도 및 혈관 신생 억제 활성을 나타냈고, β-eudesmol은 혈관 내피세포(HUVEC)에서 혈관 신생을 차단하였다(Lu et al., 2004; Ma et al., 2008).

Longifolene은 전립선암, 구강암 세포 독성을 나타내면서 정상 세포에 대한 독성은 최소화했다(Grover et al., 2022). α-Selinene는 폐경 후 유방암 여성에서 aromatase P450 효소를 억제하였고, α-copaene은 신경 모세포종에 대한 독성 효과를 나타냈다(Alakanse et al., 2019; Turkez et al., 2014). Nerolidol은 발암물질을 통한 대장암 유도를 억제하는 활성을 나타냈다(Wattenberg, 1991).

b. 항미생물 활성(antimicrobial activity: antifungal, antibacterial and antivirus activity)

β-Caryophyllene, spathulenol, germacrene-D를 주요 성분으로 함유한 오레가노(Origanum vulgare ssp. Vulgare) 에센셜 오일은 박테리아, 곰팡이, 효모 등에 대한 억제 활성을 보였으며, germacrene-D을 함유한 Cosmos bipinnatus 잎의 에센셜 오일도 그람음성균과 그람양성균 모두에 억제 활성을 나타냈다(Olajuyigbe & Ashafa, 2014). β-Eudesmol, γ-eudesmol, δ-selinene, α-eudesmol 등이 풍부한 Litsea kostermansii 잎 에센셜 오일, β-elemene, β-eudesmol, β-caryophyllene, β-selinene, elemol 등을 포함하는 Aphanamixis polystachya 오일, 그리고 valerianol 등을 함유하는 중국산 침향의 에센셜 오일 역시 다양한 그람양성균, 그람음성균과 진균, 다제내성균에 대해 항균 활성을 보였다(Ho et al., 2009; Mei, 2008; Rahman et al., 2017).

α-Copaene은 쇠고기 수프 내 S. aureus, E. coli, B. Cereus 등의 성장을 억제하여 식품 방부 효과를 기대할 수 있으며, α-curcumene은 항생제 imipenem 등과 병용 시 포도상구균에 대한 시너지 효과를 보여 내성 문제 해결 가능성을 시사하였다(Chen et al., 2024; da Silva et al., 2015). Nootkatone과 spathulenol를 함유한 Xylopia sericea 열매 오일은 식중독 및 세균감염 관련 병원균, 특히 포도상구균 S. aureus 등에 높은 항균 활성을 보였고, β-selinene을 함유하는 Platycladus orientalis의 오일은 인체 장내세균을, α-cedrene을 포함한 삼나무 오일은 혐기성 박테리아 및 효모를 각각 억제하였고, α-cedrene을 포함하는 Citrus acida 껍질 오일은 항산화 및 항균 활성을 보였다(Choudhary et al., 2007; Farha et al., 2020; Johnston et al., 2001; Kim & Lee, 2015; Mahmud et al., 2009).

β-Caryophyllene은 치주질환을 유발하는 병원균뿐만 아니라, 항생제 kanamycin과 유사한 수준의 항균 효과를 확인하여 천연 항생제 후보로서 주목받았으며, δ-cadinene을 함유한 Schinus molle 추출물은 호흡기 감염 관련 S. pneumoniae에 대해 항균 활성을 나타냈으며, nerolidol은 황색포도상구균, 충치균 및 다중약물내성균에 대한 활성을 나타냈다(de Moura et al., 2021; Pérez-López et al., 2011; Yoo & Jwa, 2019). α-Curcumene은 항생제 imipenem 등과 병용 처리 시 항균 활성의 시너지 효과를 나타냈고, baimuxinal을 함유하는 A.sinensis 오일은 그람양성균에 대해 항생제 gentamicin보다 우수한 항균 활성을 나타냈다(Chen et al., 2011; da Silva et al., 2015; Dahham et al., 2015; Moo et al, 2020).

항진균 활성 측면에서 germacrene D, δ-cadinene, alloaromadendrene은 피부진균 및 병원성 효모(Cryptococcus spp.) 등에, elemol과 eudesmol은 피부사상균 Trichophyton rubrum에 대해 우수한 억제 효과를 보였다(Kim et al., 2016; Piras et al., 2022). γ-Selinene은 포도상구균과 Candida spp.를 포함한 다양한 미생물에 활성을 나타냈으며, spathulenol은 항진균 효과뿐 아니라 결핵균의 성장 억제 활성도 보고되었고, nerolidol은 반려동물에서 흔히 백선을 유발하는 Trichophyton mentagrophytes 등을 억제하는 효능이 보고된 바 있다(Gijsen et al., 1995; Park et al., 2009; Wetwitayaklung et al., 2009).

항바이러스 활성으로 dihydroagarofuran은 Epstein-Bar Virus (EBV) 억제 효과가 확인되었고, Eucalyptus globulus 및 Corymbia citrodora 에센셜 오일 등에 함유된 d-limonene은 최근 COVID-19에 대한 억제 활성이 보고되었다(Panikar et al., 2021; Takaishi et al., 1992).

c. 항염증 활성(anti-inflammatory activity)

Agarofuran은 염증 신호를 전달하는 NF-κB의 발현과 NO 생성을 효과적으로 억제하였고, β-patchoulene, β-caryophyllene 또한 다양한 급성 염증 동물 모델에서 NF-κB의 전사 활성화 차단 및 TNF-α, IL-1β, IL-6 등 염증성 사이토카인 생산을 억제하는데, 특히 β-caryophyllene은 특이적으로 cannabinoid 2 (CB2) 수용체와 결합하는 특징이 있어서 대사질환인 비만, 제2형 당뇨병, 비알코올성 지방간 등의 치료 타겟으로 연구되고 있다(Alizadeh et al., 2020; Scandiffio et al., 2020; Zhang et al., 2016b). Nootkatone은 COX-2 효소 활성을 억제하고, 히스타민 H1 수용체 길항작용을 통한 IL-1β, TNF-α 등 염증성 사이토카인 생성 억제를 통한 급성 및 만성 염증 반응의 완화를 나타내었다(Bezerra Rodrigues Dantas et al., 2020).

FDA 승인 식품 향료에 속하는 nerolidol은 TNF-α, IL-1β 생성을 저해하여 acetic acid와 carageenan 유도 염증 모델에서 항염증 활성을 보였다(Chan et al., 2016; Fonsêca et al., 2016). α-Santalol은 인체 유래 피부 세포에서 LPS로 유도된 염증에 대해 PGE2와 TXB2의 생성을 용량 의존적으로 억제함으로써 국소 염증 조절 효과를 입증했다.

γ-Eudesmol이 풍부한 Jatropha pelargoniifolia 오일과 germacrene D, δ-cadinene, alloaromadendrene 등이 주성분인 Teucrium scordium 추출물, 그리고 elemol은 모두 carrageenan 유도 설치류의 발 부종을 억제하였으며, 이 중 J. pelargoniifolia 오일은 세포 외 기질 합성 및 체온 변화를 억제하여 indomethacin 대비 우월한 해열 효과를 보였고, elemol은 hot plate test에서 진통 효과를 나타냈다(Aati et al., 2019; Ladeira et al., 2023; Piras et al., 2022). β-Selinene을 함유한 Callicarpa macrophylla 추출물은 ibuprofen 대비 부종 부피를 유의미하게 감소시켰고, formaldehyde 유도 염증 모델에서 중간 단계의 억제 효과를 보였다(Chandra et al., 2017). 또한 α-humulene과 caryophyllene의 경우, TNF-α 및 IL-1β 생성을 억제하면서 급성 염증 모델인 ovalbumin 및 carageenan 유도 마우스의 발 부종을 dexamethasone과 동등한 수준으로 감소시키는 효과를 나타냈다(Fernandes et al., 2007).

Limonene은 염증성 대장염 랫드 모델에서 TGF-β 및 ERK1/2 신호 전달 경로를 제어하여 조직 재형성 및 섬유화 억제 작용을 나타냈다(Yu et al., 2017). Psidium guineense의 에센셜 오일 및 이에 함유된 spathulenol은 흉막염 및 부종 유발 모델에서 항염증 및 항결핵 활성을 동시에 나타냈으며, 다양한 염증성 질환에서의 다기능성을 입증하였다(do Nascimento et al., 2018).

d. 신경계 활성(neurologic activity: sedative, anti-anxiety, antipsychotic, anticonvulsant, neuroprotective activity)

Agarofuran 등이 포함된 인도네시아산 침향 추출물은 마우스에서 자발적 운동성과 직장 온도가 유의하게 감소하고, hexobarbiturate에 의해 유도된 수면 시간이 유의미하게 연장되어 시상하부를 통한 중추신경계 작용 가능성이 제시되었다(Okugawa et al., 1993). Agarospirol과 jinkoh-eremol 역시 유사하게 마우스의 활동량과 체온을 저하시키는 효과를 보였으며, cedrol 등을 함유한 아로마오일은 치매 노인의 수면 장애를 유의미하게 개선하는 임상효과가 보고되었다(Okugawa et al., 1996; Takeda et al., 2017).

β-Dihydroagarofuran 구조의 알카로이드(alkaloid) 및 트리테르펜(triterpene)은 모노아민(monoamine) 신호 전달 강화 활성을 통해, valerenol은 GABAA 수용체에 결합하여, 그리고 limonene은 adenosin A2A 수용체를 매개로 편도체 내 도파민, GABA 기능 조절을 통해 항불안 활성을 나타냈다(Benke et al., 2009; Ishola et al., 2022; Song et al., 2021). Nootkatone은 반복 투여 시 NF-κB/NLRP3 경로 억제를 통한 신경 염증 완화로 우울 유사 행동을 경감시켰다(Zhao et al., 2023a).

Dehydrofukinone은 GABA A 수용체 조절로 세포의 칼슘 유입을 억제하고, 마우스에서 pentylenetetrazole (PTZ) 유도 발작을 지연시켰으며, β-caryophyllene 역시 PTZ 유도 경련을 억제를 통해 항경련제로 개발 가능성이 확인되었다(de Oliveira et al., 2016; Garlet et al., 2015; Garlet et al., 2017). α-Santalol은 마우스에서 스트레스 노출 후 진정 효과를 나타냈고, sandalwood 오일에 함유된 형태로는 성인의 피부 흡수 실험에서 이완과 진정 효과를 나타냈다(Hongratanaworakit et al., 2004; Satou et al., 2015).

또한 Nootkatone은 알츠하이머성 치매 마우스 모델에서 학습 및 기억 능력을 향상시켰으며 elemol과 limonene은 acetylcholininesterase (AchE) 저해 활성과 함께 scopolamine 유발 기억력 저하 모델에서 단기 기억력을 개선하였고, limonene, curcumene, spathulenol, caryophyllene oxide등을 함유한 Aloysia citrodoradml 추출 오일은 항산화 및 라디컬 소거 작용으로 신경 세포 손상으로부터 보호 효과를 보였다(Abuhamdah et al., 2015; Amat-Ur-Rasool & Ahmed, 2015; Eddin et al., 2021; Wang et al., 2018c). β-Dihydroagarofuran 류 화합물과 β-caryophyllene은 각각 β-amyloid 유도 독성 및 노화 유도 모델에서 세포 생존력 증가, 인지기능 개선, 신경 염증 및 산화 억제를 통한 신경 보호 활성을 나타냈다(Chávez-Hurtado et al., 2020; Ning et al., 2015). 또한 침향 향기 흡입은 후두 절제자의 뇌 혈류량을 증가시켜 중추 신경계 매개 자율 신경계 조절과 관련된 생리적 변화 가능성을 제시하였다(Hori et al., 2012).

침향 유래 세스퀴테르펜의 중추신경계 신호 전달, GABAnergic 및 monoaminergic 경로, 항산화 및 항염증 작용을 통한 신경 흥분 조절, 수면 및 진정 유도, 항불안 및 항우울, 항경련, 신경세포 보호 등의 기능을 확인하였다. 이러한 소재들은 다양한 신경계 질환의 보완 대체 소재로 잠재력을 확인했다고 할 수 있다.

e. 대사 증후군 관련 효과(prevention of metabolic syndrome: diabetes, hyperlipidemia, hypertension, obesity)

α-Santalol은 당뇨 유발 마우스에서 혈당과 당화혈색소(HbA1c)를 크게 개선하고, 중성지방, 총콜레스테롤을 낮추고 HDL을 증가시켜 인슐린 저항성과 고지혈증을 동시에 완화하였다(Misra & Dey, 2013). β-Caryophyllene은 고지혈증 모델에서 총콜레스테롤, LDL, 중성지방을 감소시키고, 고지방 식이 모델에서 체중 증가와 공복 혈당을 억제하고 지방세포 분화를 저해하는 항비만 활성을 보였다(Baldissera et al., 2017; Scandiffio et al., 2020).

α-Cedrene은 후각 수용체(MOR23; mouse orfactory receptor 23)를 통한 포도당 흡수 조절과 전신 포도당의 항상성 유지 외에 지방 조직 내 열 생성 유전자 발현 증가와 지질 합성 억제를 통해 대사 증진 효과를 나타냈다(Kang et al., 2020). Cedrol은 고지방 식이 마우스에서 체중과 내장지방 축적을 억제하고 간 지방증 및 인슐린 저항성을 완화하여 대사 안정화 효과를 나타냈다(Zhao et al., 2023b). Nootkatone은 AMPK 활성화를 통해 지방 축적, 고혈당, 고인슐린혈증을 억제하며, 에너지 소비 증가와 혈중 렙틴 농도 균형 회복을 통해 종합적 에너지 대사 조절 효과를 보였다(Murase et al., 2010). d-Limonene은 항산화 작용으로 당뇨 관련 지질 대사 합병증을 예방하였다(Bacanlı et al., 2017).

이들 성분은 혈당 조절, 인슐린 민감성 향상, 지질 개선, 체중 증가 억제 등 복합적인 기전을 통해 대사증후군의 예방 및 개선에 대한 보조제로 활용될 가능성이 제시된다.

f. 진통 작용(analgesic activity)

Jinkoh-eremol, agarospirol, α-santalol 및 β-santalol 등은 dopamine 및 serotonin 수용체와 결합하여 기존 항정신병 약물인 chlorpromazine과 동등 이상 수준의 중추신경 내에서 통증과 가려움을 완화하는 활성을 나타냈고, acetic acid 유도 writhing 마우스 모델에서 유의한 진통 활성을 나타냈다(Okugawa et al., 2000). Longifolene은 opid 수용체 활성화를 통한 신경병성 통증 모델에서 진통 작용을 나타냈으며, pregabalin과 병용 투여할 경우 진통 활성이 증대되는 시너지 현상을 보였다(Sukmawan et al., 2023).

β-Caryophyllene은 다양한 설치류 통증 모델에서 진통 효과를 나타냈고, 특히 항암제 paclitaxel로 유도된 말초신경병증 마우스 모델에서 유의적인 신경병증 증상 완화 효과를 나타냈다(Fidyt et al., 2016; Segat et al., 2017).

γ-Eudesmol은 중추 진통 효과 평가 모델에서 양성대조군과 유사한 수준으로 유의한 진통 효과를 나타냈다. Hot plate와 acetic acid 유도 가려움 모델에서도 통증 완화 효과를 나타냈으나 그 효과는 indomethacin보다는 다소 낮았다(Aati et al., 2019).

g. 항방충 활성(insecticidal activity)

β-Selinene은 acetylcholinesterase (AchE) 저해를 통해 곤충의 신경전달을 방해하며, Spodoptera litura 유충의 활동성을 억제하였다(Liu et al., 2021). Cedrol은 농도 의존적으로 검은다리 진드기 유충의 사망률을 증가시키는 살충 효능을 나타냈다(Eller et al., 2014). β-Dihydroagarofuran 및 그 유도체는 Mythimna separata 나방에 대해 살충 활성을 보였고, longifolene 및 그 산화물은 흰개미에 대한 살충 효과를 나타내어 각각 해충에 대한 방제 자원으로의 활용을 기대할 수 있다(Mukai et al., 2017; Zhao et al., 2016).

h. 면역 조절(Immunomodulation activity: anti-anaphylactic, anti-rheumatoid arthritis, immunomodulatory)

β-Elemene을 자가면역성 뇌척수염 마우스 모델에 투여했을 때 T 세포 증식을 억제하고, IL-17, IL-6, IL-23 및 RORγt 생성을 감소시키고 Foxp3 발현 유도를 통해 자가면역 반응을 억제하였다(Zhang et al., 2011). Cedrol은 JAK3 신호 경로를 억제하여 류마티스성 관절염(RA) 모델에서 염증성 사이토카인 분비를 감소시키고 관절 부종을 개선하였다(Zhang et al., 2021). 또한 비만세포의 탈과립을 억제하여 아나필락시스 반응을 억제하는 항알러지 활성을 보였다(Chakraborty et al., 2017).

i. 피부 보호(dermatoprotective activity)

Cedrol은 피부 섬유아세포의 성장을 촉진하고, type I collagen과 elastin 등의 생성을 증가시켜 피부결 유지에 도움을 주었으며, cedrol 함유 크림 제형의 인체적용시험에서는 피부 탄력과 미세구조 개선 등의 효과가 확인되었다(Jin et al., 2012; Ryu et al., 2015). Elemol은 약물 내성 피부 병원균, 여드름 유발 박테리아에 대한 강한 항균 활성을 보였고, LPS, 여드름균 유도 염증성 사이토카인(NO, PGE2, TNF-a, IL-6 등) 생성을 억제하여 항염증 효과를 나타냈다(Kim et al., 2011; Yoon et al., 2009).

β-Elemene은 피부 각질세포 및 섬유아세포 평가계에서 IL-1a, IL-1b, IL-6, IL-8 등을 억제하고, 건선 유발 마우스에서 각질 세포의 장벽 기능 유지, 대식세포의 침윤과 염증성 사이토카인 발현 억제를 통해 건선 증상을 완화시켰다(Wang et al., 2022). β-Caryophyllene은 아토피 모델에서 EGR1, TSLP 발현을 감소시켰고, MAPK/EGR1/TSLP 신호전달 경로 억제를 통해 아토피 증상을 개선하였다(Ahn et al., 2022). Elemol 역시 아토피 모델에서 혈청 IgE 수치 감소, 진피 비만세포 침윤 억제, 피부 병변 완화를 보였다(Yang et al., 2015). Nootkatone은 피부 유래 HaCaT 세포에서 PKCζ 및 p38 MAPK 경로 억제를 통해 NF-κB 활성화를 차단하고, TNF-α 및 IFN-γ 유도 아토피성 염증 매개 물질 생성을 억제했다(Choi et al., 2014b). 또한 β-caryophyllene은 CB2 수용체 활성화를 통해 염증 반응과 통증을 완화하며, 세포 증식과 이동을 촉진시켜 상처 치유를 촉진시킨다고 보고되었다(Koyama et al., 2019). 또한 피부 상처 마우스 모델에서 항산화 인자인 IL-10과 GPx 수치는 증가되고, TNF-α, IFN-γ, IL-1β, IL-6 등 염증성 cytokine은 억제하여 상처 회복을 촉진하는 활성을 나타냈다(Gushiken et al., 2022). 한편, nerolidol은 피부 자극성이 낮은 피부 침투 촉진제로 활용 가능성이 제시되었다(Cornwell & Barry, 1994).

j. 탈모예방(preventive effects against alopecia)

Cedrol은 암 치료로 유발된 마우스 탈모 모델에서 탈모 및 모낭 손상을 억제하는 효과가 보고되었다(Chen et al., 2016). 전통적으로 모발 성장 촉진 효능이 알려진 Platycladus orientalis에서 분리한 cedrol은 제모한 암컷 마우스에서 용량 의존적으로 모발 성장을 촉진하는 활성을 보였다(Zhang et al., 2016a).

k. 소화기계 보호(gastroprotective activity)

Humulene은 급성 위염 모델에서 위 점막 손상을 감소시켰고, 비만세포에서 히스타민 분비를 억제하고 NF-κB 매개 염증 반응을 저해하여 염증을 완화하였으며, 점액 안정화 인자 mRNA 발현을 증가시켜 위점막 보호제로 가능성을 확인하였다(Yeo et al., 2021). Limonene은 아세트산 유발 위궤양 모델에서 위점막 상피세포의 치유를 촉진시키고 위 점액 생성을 증가시키는 동시에 COX-2 발현 및 혈관내피성장인자(VEGF) 발현 활성화를 통한 혈관형성을 증가시켜 위점막 치유를 촉진하였다(Moraes et al., 2013). β-Patchoulene은 위궤양 모델에서 용량 의존적으로 궤양 형성 부위와 점막하 부종을 감소시키고 항산화, 항염증 효과를 나타냈다(Liu et al., 2017). β-Caryophyllene은 in vitro에서 Helicobacter pylori의 성장을 억제하고 감염을 예방하였으며, 몽골리안 저빌 모델에서 6주간 투여 후 H.pylori 감염이 사라지는 결과를 나타내어 감염 예방 및 치료제로서의 가능성이 제시되었다(Woo et al., 2020).

l. 근골격 활성(skeletalmuscular activity)

Cedrol은 에스트로겐 결핍성 골다공증 모델에서 파골세포 분화와 골 흡수를 억제하고, ROS 생성과 NFATc1, NF-κB, MAPK 신호전달을 저해해 골 손실과 파괴를 감소시킨다(Xu et al., 2023). β-Caryophyllene은 관절염 유발 모델에서 항염증 효과를 발휘하며, 기존 치료제 methotrexate 또는 leflunomide와 병용 시 시너지 효과와 약물 부작용 완화도 보였다(El-Sheikh et al., 2019). Nootkatone은 골관절염 모델에서 연골 보호와 NF-κB 신호 억제를 통한 염증 반응을 감소시켰다(Xu et al., 2021). α-Cedrene은 근육 비대와 항위축 효과, 근력 향상을 나타냈고, 마우스 후각 수용체(MOR23) 발현 및 cAMP/PKA/cAMP 신호경로를 조절하여 골격근 위축증 개선 효과를 확인했다(Tong et al., 2018). 한편, β-eudesmol 은 유기인산염 중독으로 유발된 근육 경련, 떨림을 완화하여 기존 해독 치료의 보조제로 활용 가능성이 제시되었다(Chiou et al., 1995).

m. 심혈관계 보호(cardiovascular protective activity)

Nootkatone은 심근 손상 모델에서 NF-κB 경로 조절을 통한 심장 보호 효과를 나타냈다(Al-Salam et al., 2022). β-Caryophyllene은 급성 허혈성 뇌졸중 랫드 모델에서 NRF2/HO-1 경로 활성화를 통해 뇌 허혈성 손상을 억제하는 심혈관 및 뇌혈류 개선 활성을 보였다(Hu et al., 2022). α-Bulnesene (δ-guaiene)은 혈소판 응집을 억제하는 항혈액응고 활성을 나타냈다(Hsu et al., 2006).

n. 간기능 보호(hepatoprotective activity)

Nootkatone은 간세포에서 항염증, 항섬유화 활성을 나타냈고, α-cedrene은 후각수용체 자극에 따른 cAMP-PKA 경로를 통해 triglyceride 축적을 감소시켜 간 지방증 개선에 기여하였다(Kurdi et al., 2018; Tong et al., 2017). β-Caryophyllene은 간 쿠퍼세포에서 TLR4, RAGE 단백질 발현과 염증성 cytokine 생성 억제를 통한 간 보호 효과를 보였다(Cho et al., 2015).

o. 호흡기 보호(respiratory protective activity)

Nootkatone은 디젤 배기 입자(DEP)로 유발된 폐 손상 마우스 모델에 경구 투여 시 기도 과민 반응을 효과적으로 예방하였다. 폐 조직을 분석한 결과 폐포 내 대식세포와 염중성구 등 염증 세포 침윤이 감소하였으며, 산화 스트레스 관련 지표인 GSH, NO를 억제하고 TNF-α, NF-κB 경로를 차단하면서 항산화 및 항염증 효과를 나타냈다(Nemmar et al., 2018). 또한 천식 모델에서 Th2 사이토카인 IL-4, IL-5, IL-13 및 IgE 수치를 억제하고 NLRP3 활성화 완화하여 기도 염증을 감소시켰다(Gai et al., 2023). 또한, Spathulenol은 다제 내성과 광범위 내성 결핵균의 성장 억제 및 살균 활성으로 폐 감염예방 및 치료 가능성을 나타냈다(Dzul-Beh et al., 2019).

p. 신장기능 보호(nephroprotective activity)

β-Elemene는 요관 폐쇄로 유도된 신장질환 모델에서 JAK2/STAT3와 Smad3 신호 경로 억제를 통한 신장 섬유증 완화 효과를 나타냈으며, 이 기전은 만성 신장 질환 치료제로서 잠재성을 시사한다(Sun et al., 2022). Nootkatone은 신장 독성 모델에서 NF-κB, IL-1β, IL-6, TNF-α, iNOS 및 NOX4 mRNA의 발현을 하향 조절하는 동시에 항산화 관련 전사인자인 Nrf2 및 보호효소 HO-1 mRNA의 발현을 상향 조절하여 신장세포의 손상을 완화하고 신장 보호 효과를 발휘하였다(Dai et al., 2023).

q. 항산화 효과(antioxidation activity)

7-epi-γ-eudesmol (epi-γ-eudesmol)는 브라질 민간요법에서 혈당 조절에 사용하는 약용식물인 Bauhinia ungulata의 에센셜 오일에 포함된 주요 성분 중 하나로, DPPH 제거 등 항산화 활성을 나타냈다(Nunes de Andrade Medeiros et al., 2024).

3) 침향 유래 성분의 항염증 기전 기반 통합 해석

항염증 활성은 암, 대사질환, 피부질환 등 다양한 질환의 공통 병태 생리에 관여하는 핵심기전으로, 침향 성분이 나타내는 다중 생리활성을 이해하는 중심 축이라 할 수 있다. 이에 본 연구에서는 침향에서 검출된 주요 세스퀴테르펜 및 모노테르펜의 항염증 기전에 초점을 맞추어 분석하였다. 특히 NF-κB, MAPK, JAK/STAT, NLRP3 inflammasome 등의 주요 염증성 신호경로 억제와 함께, TNF-α, IL-1β, IL-6 등 염증성 사이토카인 및 iNOS, COX-2 등의 염증 매개 효소 생성 저해를 중심으로 고찰하였다. 이러한 경로 조절을 통해 다양한 염증 반응의 완화가 보고되었으며, 일부 성분은 항산화 또는 면역 조절 작용을 병행하여 조직 손상 완화에도 기여하는 것으로 나타났다(Table 8).

Cedrol은 류마티스 관절염 모델에서 p-JAK3를 선택적으로 억제하고 JAK/STAT 신호전달을 차단하여 IL-6, TNF-α 등 염증성 사이토카인 분비를 감소시켰으며, 경구투여시 비만세포 탈과립 및 히스타민 방출 억제를 통해 아나필락시스 반응을 완화하였다. 또한 RANKL 유도 골흡수 경로에서 ROS, NFATc1, NF-κB, MAPK 신호를 억제하여 파골세포 분화 억제 및 염증성 골파괴를 완화 활성을 나타냈다(Chakraborty et al., 2017; Xu et al., 2023; Zhang et al., 2021).

특히 β-caryophyllene (BCP)는 cannabinoid receptor 2 (CB2) 수용체 활성화를 통해 NF-κB, p38 MAPK, JNK 신호를 억제하고, TNF-α, IL-1β, IL-6, IL-17A, PGE 2, iNOS, COX-2 등의 분비를 억제하였다(Meeran et al., 2019; Picciolo et al., 2020; Segat et al., 2017). 아토피 모델에서는 BCP 0.1 mg/kg 경구투여 시, MAPK 경로 억제를 통해 IL-4 유도 EGR1, TSLP 발현을 저해하였고, 간 손상 모델에서 200 mg/kg 경구투여 시 TLR4, RAGE, p38, JNK, NF-κB, EGR1 등 신호 억제를 통해 급성 간 손상 및 염증 완화 효과를 보였다(Ahn et al., 2022; Cho et al., 2015; Gushiken et al., 2022). 카라기난 및 OVA 유도 발부종 모델에 50 mg/kg 으로 경구 투여 시, dexamethaxone과 동등 수준의 부종 억제 효능을 나타내었고, TNF-α, IL-1β, IL-6, IL-17A, PGE, iNOS, COX-2 등의 분비를 억제하였다(Picciolo et al., 2020).

Limonene은 raw 264.7 세포에 100-400 µg/mL 처리 시 농도 의존적으로 iNOS, COX-2 발현 감소, TNF-α, IL-1β, IL-6 등 사이토카인 억제활성을 나타냈고, UC 랫드 모델에 7일간 50 및 100 mg/kg 경구투여시 MMP-2, MMP-9 억제를 통한 ECM 분해 및 조직손상 완화, ERK 경로 조절, PGE2 및 TGF-β 억제를 통해 염증과 섬유화를 억제하였다(Yoon et al., 2010; Yu et al., 2017).

Cyperone은 raw 264.7 세포에 LPS 유도 염증반응에서 50 µM 농도처리 시 NF-κB 경로를 차단하여 염증 매개물질인 iNOS/COX-2 발현을 저해하고, NO, PGE 2 생성을 감소시키며 TNF-α, IL-1β 등 염증성 사이토카인 억제를 유도하여 강력한 in vitro 항염증 효과를 나타내었다(Salman et al., 2011).

β-patchoulene은 급성 염증 모델에서 TNF-α, IL-1β, IL-6 등 염증성 사이토카인과 PGE 2, NO 생성 억제, iNOS와 COX-2 발현 저해를 통해 염증 반응을 완화하였다(Gushiken et al., 2022).

한편, 일부 성분은 염증 조절과 더불어 면역세포 균형 및 항산화 신호 조절을 통해 조직 손상을 억제하였다.

β-Caryophyllene은 만성 심독성 랫드 모델에 50 mg/kg/day, i.p. 5주간 투여 시 TNF-α, IL-1β, IL-6 발현을 유의하게 억제하였고 심장 내 iNOS, COX-2 발현도 약 50% 수준으로 감소시켰으며, nootkatone은 HaCaT 세포에 10-100 μM 처리 시 NF-α/IFN-γ로 유도된 TARC/CCL17, MDC/CCL22 성장과 신호전달(p38 MAPK, PKCζ, NF-κB) 활성화를 약 30-85%까지 억제시키고, 항산화 효소 GPx 및 Nrf2/HO-1 경로 활성화, IL-10 증가를 통해 산화·염증 복합 반응으로부터 조직 보호 효과를 보였다(Choi et al., 2014; Dai et al., 2023; Meeran et al., 2019).

β-Elemene은 자가면역성 뇌척수염 마우스 모델에서 7일간 20, 40 mg/kg/day i.p. 투여 시, Th17 중심 염증성 사이토카인인 IL-17, IL-6, IL-23, RORγt이 감소하고 Treg 관련 Foxp3 발현 증가를 통해 Th17/Treg 균형 조절로 중추신경계 염증을 완화하였고, 신장 섬유화(UUO) 마우스 모델에서 7일간 50 mg/kg/day i.p. 투여 시 섬유화 마커 단백질이 감소하고 JAK2/STAT3, Smad3 인산화 차단 및 MyD88 발현 억제를 통해 조직의 염증과 섬유화를 감소시켰다(Sun et al., 2022; Zhang et al., 2011).

Guaiol은 NSCLC 세포에서 mTORC1/2 억제를 통한 autophagic cell death 유도로 항암 활성을 보였는데, 이는 항염증 관련 mTOR 억제 기전과 연계되어 추가 연구 가능성을 시사한다(Yang et al., 2018b).

α-Humulene은 알러지성 기도 염증모델 및 급성 염증 모델에서 50 mg/kg, p.o.투여 후, NF-κB 및 AP-1 전사인자 억제를 통해 염증 유전자 발현 감소, P-selection 발현 감소 및 중성구(neutrophil) 침윤억제, IL-5, TNF-α, IL-1β 등 염증 매개물질 감소 효과를 나타냈다(Medeiros et al., 2007; Rogerio et al., 2009).

Nootkatone은 또한 NF-κB, AP-1, NLRP3 inflammasome 억제를 통해 IL-1β, IL-6, TNF-α, IL-18, IL-4, IL-5, IL-13 등 다양한 염증 매개 물질을 감소시켰으며, 피부세포에서 TARC/CCL17과 MDC/CCL22 발현 억제, 신장 독성 모델에서 Nrf2/HO-1 경로 활성화를 나타냈다(Choi et al., 2014).

α-Santalol은 45 μM 및 90 μM 농도로 LPS로 유도된 피부세포 염증에 처리했을 때 완전억제수준의 IL-6, IL-8, TNF-α 생성과 PGE2, TXB2 같이 arachidonic acid 유도 대사물 생성을 억제하였다(Sharma et al., 2014).

α-Cedrene은 HepG2 세포에 100 μM 농도 처리 시 TG 축적량을 36% 감소시켰고, 지방간 마우스 모델에 경구 투여 시 지질 및 염증 관련 인자의 발현을 농도 의존적으로 감소시키는 활성이 나타났다(Tong et al., 2017).

Nerolidol은 다양한 항염증 마우스 모델에 200-400 mg/kg 경구 투여 시, TNF-α, IL-1β 억제 및 GABA 수용체 경로 활성화를 통해 염증과 신경성 통증을 동시에 완화하였다(Fonsêca et al., 2016).

요약하면, 침향에 포함된 주요 성분들은 NF-κB, COX/NO 경로, 부종 및 조직 손상 억제 등 다중 경로를 통해 항염증 활성을 보였다(Figure 6). 또한 항산화, 면역조절, 신호전달 조절을 복합적으로 매개함으로써 염증성 질환의 예방 및 치료 또는 헬스케어, 뷰티 산업에서의 기능성 소재로서 활용 가능성을 제시하였다.

위에 서술한 성분은 문헌 검토를 통해 평가방법 및 지표를 자세한 성분별 세부 실험조건과 활성 평가의 정량적 결과를 Table 8로 정리하였고 이를 바탕으로 NF-κB, MAPK, JAK/STAT, NLRP3 등 주요 염증 경로 간의 상호 연계성을 도식화하여 Figure 6에 정리하였다.

항염증 기전에 대해서는 Table 8을 기반으로 침향에서 유래한 β-caryophyllene, nootkatone, β-patchoulene, α-humulene, cedrol 등 성분에 대한 분석방법 및 표준품을 확보가 필요하다. NF-κb-COX-2 축의 정량 검증(in vitro IC₅₀, in vivo ED₅₀/효능 지수) 경로 차단제(co-treatment) 평가가 필요하다.

CB2/PPAR-γ·Nrf2/HO-1·NLRP3 경로를 통해 멀티 타깃으로 하는 β-caryophyllene 및 nootkatone의 복합 등 기전적 적합성이 확인되며, 피부(아토피, 상처), 호흡기, 대사/간 등의 항염증 처방을 조성하여 활성 측정 및 제품 개발 가능성을 검토할 만 하다.

Conclusion

본 연구는 라오스 및 태국산 침향의 휘발성 성분을 GC-MS로 분석하고 동일한 조건에서 측정한 기존 5개국 침향의 분석 결과와 통합하여 총 7개 침향 산지별 성분을 비교·분석하였다.

기존 연구들이 단일 국가 또는 제한된 지역의 시료에 국한되었던 것과 달리, 본 연구는 현재 주요 침향 산지 7개국 시료의 비교 분석을 통해 보다 넓은 지리적 관점에서 다루었다는 점에서 비교 연구의 의의를 지닌다. 또한 이러한 산지별 침향의 성분 함량과 조성 차이를 비교·분석함으로써 지리적 요인에 따른 성분 분포의 기초 자료를 제시하였다.

7개 산지별 휘발성 성분의 통계 분석 결과, 말레이시아·캄보디아·태국(1그룹), 인도네시아·미얀마·라오스(2그룹), 베트남(3그룹)으로 유사도를 구분할 수 있었으며, 이는 지역적·생태적 요인에 따라 성분 조성이 상이함을 시사한다.

문헌 기반의 생리활성 분석 결과, 총 38종(이 중 37종은 세스퀴테르펜계)의 성분에서 항암, 항균, 항염증, 대사 관련 보호, 중추신경계 보호, 면역 조절, 진통, 항방충 등 15개 분야의 활성으로 구분할 수 있었다. 이 중에서도 특히 항염증 활성과 관련된 사이토카인 조절 기전이 가장 공통적으로 관찰되었으며, NF-κB, MAPK, JAK/STAT, NLRP3 inflammasome 등 주요 염증 신호전달 경로를 억제하여 TNF-α, IL-1β, IL-6 등 염증성 사이토카인 생성을 감소시키는 것으로 나타났다.

특히 cedrol, β-caryophyllene, α-humulene, nootkatone 등 주요 성분들은 각기 다른 모델에서 iNOS 및 COX-2 발현 억제, 산화 스트레스 완화, Nrf2/HO-1 경로 활성화를 통한 항산화 효소 증가, Th17/Treg 균형 조절 등을 통해 다중 표적형 항염증 활성을 보였다. 염증은 노화, 자가 면역질환, 피부 등 다양한 질병의 병태 기전에 관여하며, 이를 조절할 수 있는 천연 항염 소재에 대한 수요가 증가하고 있다. 따라서 이러한 복합 기전은 다중 표적(multi-target) 활성을 기반으로 염증 완화 및 면역 균형 유지에 기여할 수 있는 기능성 소재로서의 침향의 잠재력을 뒷받침한다.

또한 향후 연구에서는 각 산지별 시료를 동일한 조건을 추출하여 표준화된 in vitro 및 in vivo 평가계에서 항염증 효능을 정량적으로 검증하고, 성분 함량과 생리활성 간의 상관성을 규명하는 연구가 필요하다. 이를 통해 침향 성분의 생리활성 기전과 효능 간 연계성을 명확히 하고, 기능성 원료로서의 과학적 근거를 강화할 수 있을 것이다.

이와 같은 다성분·다기전적 특성은 침향이 의약품, 건강기능식품, 화장품 등 다양한 헬스케어 산업 분야에 응용될 수 있음을 시사한다. 특히 항염증 및 면역 조절 기전을 기반으로 한 관절·소화기·신체 면역 강화 관련 건강기능식품(정제, 캡슐, 차 형태 등), 피부 염증 완화와 장벽 개선을 위한 민감성 피부 및 아토피 케어용 기능성 화장품(에센스, 크림, 토너, 세럼 등), 항스트레스 및 심신 이완 효과를 활용한 향기 기반 생활 제품(선향, 오일, 롤온 에센스, 고체밤, 디퓨저 등), 항균·항산화 효능을 이용한 스킨케어·두피케어용 토닉 및 클렌징 제품군 등으로의 적용이 가능할 것으로 판단된다. 항염증 효능을 기능성 식품에 적용할 경우, 노화 관련 만성 염증에 기반한 대사성 질환(비만, 당뇨, 고지혈증 등)의 예방을 목표로 하는 건강기능식품 개발에도 활용할 수 있을 것으로 기대된다. 이러한 응용은 기존 합성 항염증제 대비 장기 섭취에 적합하면서도 부작용이 적어 침향의 기능성 소재로서의 산업적 가치와 실용화를 동시에 제고할 수 있을 것으로 판단된다.

향후에는 침향의 지표 성분 표준화, 용량-효능 관계 평가, 안정성 및 인체 적용 시험 등 후속 연구가 수행되어야 하며, 원료의 지속 가능한 확보 체계 구축 또한 병행되어야 한다. 이러한 연구의 축적을 통해 침향 유래 성분의 과학적 근거가 강화된다면, 향후 헬스케어, 뷰티 산업 전반에서 침향의 실질적 제품화 및 기능성 원료화로 이어질 수 있을 것으로 기대된다.

NOTES

Author's contribution

W.C. devised the project, the main conceptual ideas and proof outline.

W.C. designed all experimental investigations, collected GC-MS data, and analysed the data.

K.H.J. oversaw the project and assisted with experimental design.

W.C. wrote the manuscript with support from K.H.J.

All authors discussed the results and contributed to the final version of the manuscript.

Author details

Woojin Cho (Researcher)/Kwang Ho Jung (Director of Research Center), IAA (International Agarwood Association) Research Center, 325, Palgongsan-ro, Dong-gu, Daegu 41000, Korea.

Figure 1.

Flowchart of the literature selection process for studies on the biological activities of agarwood-derived compounds.

Figure 2.

Classification of published studies on the physiological activities of agarwood-derived compounds based on experimental methodology.

Figure 3.

GC-MS chromatogram of agarwood samples.

(A) Laitian agarwood (sample 6); (B) Thai agarwood (sample 7); (C) Vietnamese agarwood (A. crassna) (sample 1). 1, α-Santalol; 2, Cedrol; 3, Elemol; 4, α-Eudesmol; 5, γ-Eudesmol; 6, α-Agarofuran; 7, Dehydrofukinone; 8, Cyperene; 9, α-Curcumene; 10, Valencene; 11, γ-Selinene; 12, β-Selinene; 13, β-Caryophyllene; 14, α-Selinene; 15, Dihydroagarofuran; 16, Italicene ether; 17, Agarospirol; 18, Longifolene; 19, Valerianol; 20, 7-epi-γ-Eudesmol; ♦, Diethyl phthalate(DEP). See Table 3 for details.

Figure 4.

Volatile components identified by GC–MS across seven agarwood samples (relative peak area %).

※ Sample 1, Vietnamese agarwood (A. crassna); Sample 2, Indonesian agarwood; Sample 3, Malaysian agarwood; Sample 4, Myanmar agarwood; Sample 5, Cambodian agarwood; Sample 6, Laitian agarwood; and Sample 7, Thai agarwood.

Figure 5.

Principal component plot (PC1 vs. PC2) showing the grouping of seven agarwood origins based on their volatile compound profiles.

Figure 6.

Agarwood-derived compounds vs. inflammation pathways.

Connections illustrate the inhibitory or regulatory interactions between agarwood-derived sesquiterpenes, monoterpenes, and key inflammation-related signaling pathways.

Table 1.

Gas chromatography–mass spectrometry analysis conditions for the composition of agarwood and its volatile components

GC-MS	Agilent 7890B Gas Chromatography & 5977B Mass Spectrometer Detector
Method	SPME, fiber CAR/DVB/PDMS gray
Column	DB-WAX 60 m x 250μm x 0.25 μm
Oven temperature	40℃/2 min → 2℃/min → 220℃→ 20℃/min → 240℃/5 min
Run time	98 min
Injector temperature	250℃
Split	20 : 1
Carrier gas	He, flow 1 mL/min
Sampler	SPME-STD-v3.0
Incubation time	20 min
Incubation temp.	70℃
Sample extraction time	30 min

Table 2.

Previously reported chemical components in agarwood from Laos and Thailand

Source or origin	Sesquiterpenes	Volatile organic compounds (VOCs)	Ref.
Laitian agarwood	Rosifoliol, spatulenol, dehydrofukinone, β-patchoulene, bisabolene, levoverbenone, etc.	Heptadecanal, verbenol, 2,6,10-trimethyl-tetradecane, etc.	A (Kao et al., 2018)
Essential oil from Laos (A.crassna)	Valerianol, jinkoeremol, agarospirol, dihydrokaranone, etc.	n-Hexadecanoic acid, oleic acid, etc.	B (Ngan et al., 2020)
Essential oil from Thailand (A.crassna)	β-Agarofuran, valerianol, β-eudesmol, valenca-1(10),8-dien-11-ol, dihydroagarofuran15-al, dihydrokaranone, etc.	n-Hexadecanoic acid, etc.	B (Ngan et al., 2020)
Thai agarwood A.malaccensis, A.subintegra and A.crassna	Common to 3 species: agarospirol, β-agarofuran, karanone, etc.	-	C (Pripdeevech et al., 2011)
	A.subintegra: a-(Z)-atlantone
	A.crassna: valerianol, acorenone B, etc.
Thai agarwood (Unknown)	γ-Selinene, δ-guaiene, guaiol, selina-3,11-dien-9-one, agarospirol, selina-4,11-dien-14-al, etc.	Tetradecanal, hexadecanoic acid, etc.	D (Wetwitayaklung et al., 2009)

※ Samples 1–5* represent reorganized data from a previous study (Jung et al., 2022), whereas samples 6–7 (†) are the results analyzed in the present study.

Table 3.

Sesquiterpenes, monoterpenes, and simple volatile aromatic compounds from agarwood samples identified by GC–MS

Components	Retention time (min)	Ref¹⁾	Peak area (%)/sample no.
Components	Retention time (min)	Ref¹⁾	1^*	2^*	3^*	4^*	5^*	6 ^†	7 ^†
Monoterpenes
d-Limonene	-/21.672/-/-/-/21.728/-	C			0.092			0.14
trans-α-Bergamotene	45.087					0.272
(E)-1,3,6-octatriene, 3,7-dimethyl-,	45.272		0.035
Bicyclo[2.2.1]heptane, 7,7-dimethyl-2-methylene-	44.085		0.036
1,3,7-Octatriene, 3,7-dimethyl-	87.977						0.359
α-Phellandrene	60.098					0.264
Volatile organic compounds (VOCs)
Heptanal	20.953/20.89/20.898/-/-/20.96/20.867/20.96/20.867		0.031	0.074	0.031			0.268	0.113
o-Xylene	20.816		0.119
Furfural	-/-/-/-/38.453/38.567/-	C					0.055	0.121
Hexanal	14.98/14.962/-/14.976/-/15.035/14.919	C	0.021	0.046		0.021		0.328	0.058
o-Xylene	20.816	-	0.119
Ethyl benzene	17.417/17.357/17.362/17.369/ 17.288/-/-	-	0.118	0.134	0.072	0.048	0.049
Octanal	27.586/27.492/27.495/27.493/27.482/27.557/27.477	-	0.109	0.282	0.099	0.048	0.026	0.408	0.316
2-Nonanone	34.082/-/33.981/-/-/34.044/33.97	C	0.023		0.025			0.072	0.066
Nonanal	34.349/34.234/34.233/34.233/34.222/34.291/34.219	-	0.091	3.041	0.288	0.413	0.104	0.977	0.157
2-Ethyl-1-hexanol	40.637/40.555/40.559/40.554/40.548/-/-	-	0.13	1.209	0.178	3.36	0.062
Acetophenone	-/49.706/-/49.707/49.703/49.821/49.703	C		3.678		2.52	0.618	0.534	1.401
Benzaldehyde	42.272/42.112/41.745/42.112/42.109/42.225/42.107	C	0.299	8.507	0.273	2.736	2.012	2.098	4.136
1-Octanol	44.788/44.702/44.705/44.701/44.698/-/44.697	-	0.085	0.365	0.097	0.107	0.043		0.337
4-Phenyl-2-butanone	61.332/61.145/61.149, 68.185/61.145/61.152/-/-	-	0.429	5.239	3.925, 0.368	2.971	3.929
4-(4-methoxyphenyl)-2-butanone	82.001/81.789/81.787/81.784/81.791/-/-	-	0.152	0.505	0.17	0.247	0.307
Diethyl phthalate	-/85.288/85.297/85.289/85.291/85.401/85.282	-		6.202	11.18	7.167	6.183	41.642	3.7
Sesquiterpenes
α-Copaene	-/40.427/40.02/-/40.406/-/39.855	-		0.017	0.38		0.199		0.153
Cyperene	42.729, 48.004/-/-/-/42.52/-/-		0.213				0.071
Cyperene	42.729, 48.004/-/-/-/42.52/-/-		0.134				0.071
α-Cedrene	45.151/-/44.991/-/44.98/45.022/-	-	0.068		0.15		0.034	0.207
β-Caryophyllene	46.925/-/86.436/76.518/-/-/46.731		0.086		0.142	0.685			0.118
α-Guaiene	-/-/46.396/-/46.39/46.407/-				0.268		0.081	0.106
β-Elemene	46.508, 71.24, 71.748/-/-/-/-/46.367/46.308		0.371, 0.515, 0.033					0.083	0.165
γ-Selinene	48.71, 49.278, 52.368/-/78.653/52.155/-/-/-		0.025, 0.095, 0.261		0.414	0.109
β-Selinene	-/-/76.046/ 49.972/49.563, 53.281/-/-				0.167	0.059	0.027
β-Selinene	-/-/76.046/ 49.972/49.563, 53.281/-/-				0.167	0.059	0.043
α-Humulene	-/-/-/50.939/-/-/50.914	C,D				0.107			1.044
(4R,4aS,6S)-4,4a-Dimethyl-6-(prop-1-en-2-yl)-1,2,3,4,4a,5,6,7-octahydronaphthalene	51.793/-/-/51.595/51.569/-/-		3.124			7.312	0.325
5-epi-Aristolochene	52.694			8.271
δ-Guaiene (α-bulnesene)	72.609/72.419/53.13, 53.556/53.563/53.561/-/-		0.242	0.289	0.047, 1.168	1.18	0.519
Germacrene D	53.368, 78.857		0.036, 1.447
Aromadendrene	53.745					1.168
Dihydroagarofuran	54.182, 57.104/-/53.949, 79.407/ 53.966/53.988, 56.916/54.015, 56.964/-	-	0.903, 0.08		1.782, 1.658	2.014	2.862, 0.135	1.732, 0.13
Valencene	54.33		0.174
Italicene ether	54.452/54.253/54.261/54.281/54.279/54.305/54.251	-	1.473	2.1	4.923	16.242	6.771	1.165	3.46
δ-Cadinene	-/-/55.846/-/-/-/55.858				0.179				0.088
α-Curcumene	56.923/56.698/56.714/-/56.701/56.752/-	-	1.007	0.259	0.275		0.18	0.206
4a,5-Dimethyl-3-(prop-1-en-2-yl)-1,2,3,4,4a,5,6,7-octahydronaphthalen-1-ol	61.581/-/-/61.346/61.344/-/-		1.917			0.586	0.072
α-Agarofuran	63.297/63.107/63.15/63.111/63.12/63.172/63.126		0.154	0.129	15.808	0.841	3.358	0.936	10.784
Elemol	-/-/72.418/-/-/72.481/-				0.454			0.375
Epi-γ-eudesmol	73.814/73.608/73.624/73.617/73.63/73.681/73.624		0.566	0.537	5.21	0.95	5.688	1.136	10.528
Sesquithuriferol	-/-/-/-/-/74.018/73.957							0.247	0.379
Cedrol	-/74.221/74.222/74.225/-/74.288/74.221			1.132	0.081	0.302		1.699	3.692
(3aR,3bR,6aR,7aR)-2,2,3b-Trimethyl-4-methylene-decahydro-cyclopenta[a]pentalen-6a-ol	74.312		6.668
Guaiol	-/-/-/-/-/-/74.399								0.355
α-Santalol	74.859/-/-/74.669/-/-/-		2.255			1.075
Cyperenone	-/-/-/-/-/75.585/-							0.102
(3aR,4R,7R)-1,4,9,9-Tetramethyl-3,4,5,6,7,8-hexahydro-2H-3a,7-methanoazulen-2-one	75.726		1.624
Dihydro-cis-.α.-copaene-8-ol	75.733				2.116
γ-Eudesmol	-/76.582/-/-/76.601/76.657/76.395	C,D		1.214			0.51	0.222	0.068
Agarospirol	-/76.912/76.915/76.918/76.949, 77.497/76.981/76.591	B,C,D		1.748	1.265	2.842	11.714, 0.414	2.72	0.558
α-Patchoulene	77.468							0.167
α-Selinene	-/-/-/78.051/-/53.798/-	D				4.846		0.978
Longifolene	-/-/78.062/-/-/ 78.124/-				7.648			1.857
α-Muurolene	78.062								6.597
Neoisolongifolene	78.071						6.964
(-)-Aristolene	78.252/-/-/-/-/-/77.402		3.797						0.27
1,4-Dimethyl-7-(prop-1-en-2-yl)decahydroazulen-4-ol	78.397				1.108
Valerianol	-/-/-/78.655/-/78.728/-	B				2.737		1.916
Bicyclo[4.4.0]dec-1-ene, 2-isopropyl-5-methyl-9-methylene-	-/-/-/-/78.681/-/78.661						8.458		3.762
α-Eudesmol	78.939			1.543
β-Eudesmol (β-Selinenol)	-/79.336/-/79.341/79.346/79.407/-	B		6.667		1.446	1.555	1.618
9-Hydroxy-isolongifolene	80.703		8.513
Methyl isocostate	82.916/-/-/-/82.685/-/-		1.611				0.567
Eremophilone	84.275		1.502
Dehydrofukinone (Dihydrokaranone)	87.758, 88.173, 88.961/-/88.781/88.77/-/88.856/-	A	1.987, 7.931, 4.812		0.1	3.137		0.132
Muurola-4,10(14)-dien-1.β.-ol	88.394		3.73
Baimuxinal	96.517/-/96.366/-/96.373/96.445/96.364		0.565		0.346		2.166	0.374	0.667
trans-Calamenene	-/59.808/-/-/-/59.609/59.803			0.036				0.132	0.024
Spathulenol	82.621/-/-/-/ 87.373/		0.143				0.17
Valerenol	92.071/-/ 92.596/-/ 75.927/		0.156		0.193		0.072
Alloaromadendrene	78.395						0.139
Hinesol	-/77.488/-/-/-/-/77.485			0.42					0.46
Nerolidol	70.501						0.39
Cyperone	75.516						0.231
β-Patchoulene	33.926			0.086
Nootkatone	91.592/-/-/-/91.418/-/-		0.253				0.131
Number of sesquiterpene components			27	15	22	19	25	22	18
Total amount of sesquiterpene components detected (%)			58.213	24.448	45.882	47.638	53.715	18.24	43.172

Sample 1, Vietnamese agarwood (A. crassna); Sample 2, Indonesian agarwood; Sample 3, Malaysian agarwood; Sample 4, Myanmar agarwood; Sample 5, Cambodian agarwood; Sample 6, Laitian agarwood; and Sample 7, Thai agarwood.

※ Values are relative peak areas (%) (blank) : not detected.

※ Samples 1–5* are reorganized results reported in a prior study (Jung et al., 2022), while samples 6–7 (†) are results analyzed in this study.

Table 4.

Heatmap of sesquiterpenes profiles in agarwood samples

Components	Peak area (%)/sample no.
Components	1	2	3	4	5	6	7
α-Copaene	0.017	0.380	0.000	0.199	0.000	0.153	0.000
Cyperene	0.347	0.000	0.000	0.000	0.071	0.000	0.000
α-Cedrene	0.068	0.000	0.150	0.000	0.034	0.207	0.000
β-Caryophyllene	0.086	0.000	0.142	0.685	0.000	0.000	0.118
β-Elemene	0.919	0.000	0.000	0.000	0.000	0.083	0.165
γ-Selinene	0.376	0.000	0.414	0.109	0.000	0.000	0.000
α-Humulene	0.000	0.000	0.000	0.107	0.000	0.000	1.044
δ-Guaiene (α-bulnesene)	0.242	0.289	1.215	1.180	0.519	0.000	0.000
Germacrene D	1.483	0.000	0.000	0.000	0.000	0.000	0.000
Dihydroagarofuran	0.983	0.000	3.440	2.014	2.997	1.862	0.000
Valencene	0.174	0.000	0.000	0.000	0.000	0.000	0.000
Italicene ether	1.473	2.100	4.923	16.242	6.771	1.165	3.460
δ-cadinene	0.000	0.000	0.179	0.000	0.000	0.000	0.088
α-Curcumene	1.007	0.259	0.275	0.000	0.180	0.206	0.000
α-Agarofuran	0.154	0.129	15.808	0.841	3.358	0.936	10.784
Elemol	0.000	0.000	0.454	0.000	0.000	0.375	0.000
Epi-γ-eudesmol	0.566	0.537	5.210	0.950	5.688	1.136	10.528
Cedrol	0.000	1.132	0.081	0.302	0.000	1.699	3.692
α-Santalol	2.255	0.000	0.000	1.075	0.000	0.000	0.000
γ-Eudesmol	0.000	1.214	0.000	0.000	0.510	0.222	0.068
Agarospirol	0.000	1.748	1.265	2.842	12.128	2.720	0.558
Longifolene	0.000	0.000	7.648	0.000	0.000	1.857	0.000
Valerianol	0.000	0.000	0.000	2.737	0.000	1.916	0.000
α-Eudesmol	0.000	1.543	0.000	0.000	0.000	0.000	0.000
β-Eudesmol (β-Selinenol)	0.000	6.667	0.000	1.446	1.555	1.618	0.000
Dehydrofukinone (Dihydrokaranone)	14.730	0.000	0.100	3.137	0.000	0.132	0.000
Baimuxinal	0.565	0.000	0.346	0.000	2.166	0.374	0.667
trans-Calamenene	0.000	0.036	0.000	0.000	0.000	0.132	0.024
Spathulenol	0.143	0.000	0.000	0.000	0.170	0.000	0.000
Valerenol	0.156	0.000	0.193	0.000	0.072	0.000	0.000
Alloaromadendrene	0.000	0.000	0.000	0.000	0.139	0.000	0.000
Hinesol	0.000	0.420	0.000	0.000	0.000	0.000	0.460
Cyperone	0.000	0.000	0.000	0.000	0.231	0.000	0.000
Nootkatone	0.253	0.000	0.000	0.000	0.131	0.000	0.000

※ Sample 1, Vietnamese agarwood (A. crassna); Sample 2, Indonesian agarwood; Sample 3, Malaysian agarwood; Sample 4, Myanmar agarwood; Sample 5, Cambodian agarwood; Sample 6, Laotian agarwood; and Sample 7, Thai agarwood.

Rows and columns are clustered to highlight origin-specific trends; the color scale reflects within-class normalized abundance.

Table 5.

Physiological activities and functional classification of compounds derived from agarwood

No		1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38
No	Activities	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38
1	Anticancer	o		o	o	o		o	o	o	o		o	o	o	o	o	o	o	o		o	o	o										o		o
2	Antimicrobial	o	o		o	o	o			o	o	o	o			o					o	o	o	o				o	o	o	o								o
3	Anti-inflammatory	o	o		o	o		o	o		o	o			o		o				o						o						o
4	< Metabolism-related activity >
	Cardiovascular protective	o	o															o																	o		o
	Antidiabetic	o			o		o
	Anti-obesity		o	o			o
	Hepatoprotective	o	o				o
	Dyslipidemia	o
	Dyslipidemia in diabetics							o
	hepatoprotective in diabetics							o
5	<CNS activity>
	Neurologic	o	o	o	o			o					o												o													o
	Anti-alzheimer		o			o
	Antipsychotic																															o
6	<Dermatological activity>
	Dermatoprotective	o		o		o					o							o
	Atopic dermatitis	o	o			o
	Preventive effect against alopecia			o
7	<Musculoskelettal activity>
	Antioxidant											o								o						o
	Anti-Arthritis	o
	Anti-osteoporosis			o
	Muscle hypertrophic						o
8	<Immunomodulatory activity>
	Anti-anaphylactic schock			o
	Anti-Rheumatoid arthritis			o
	Immunomodulatory													o
-	<Others>
9	Respiratory protective		o	o					o								o
10	Gastroprotective	o			o				o						o
11	Analgesic	o		o						o						o
12	Insecticidal		o	o						o
13	Nephroprotective		o											o
14	Intoxication																		o
15	Sepsis								o

Components: 1, β-Caryophyllene; 2, Nootkatone; 3, Cedrol; 4, d-Limonene; 5, Elemol; 6, α-Cedrene; 7, α-Santalol; 8, β-Patchoulene; 9, Longifolene; 10, Nerolidol; 11, Alloaromadendrene; 12, β-Dihydroagarofuran; 13, β-Elemene; 14, α-Humulene; 15, γ-Eudesmol; 16, Spathulenol; 17, Valencene; 18, β-Eudesmol; 19, α-Selinene; 20, β-Selinene; 21, δ-Cadinene; 22, α-Copaene; 23, α-Curcumene; 24, Dehydrofukinone; 25, 7-epi-γ-Eudesmol(epi-γ-Eudesmol); 26, α-Agarofuran; 27,Cyperene; 28, Germacrene D; 29, Baimuxinal; 30, γ-Selinene; 31, Agarospirol; 32, α-Cyperone; 33, trans-Calamenene; 34, α-Eudesmol; 35, Hinesol; 36, δ-Guaiene(α-Bulnesene); 37, Valerenol; 38, Valerianol.

Table 6.

Factor analysis (principal component extraction) of peak areas

Categories		Components			Communalities
Categories		Factor 1	Factor 2	Factor 3	Communalities
Peak area	Group 1	-0.062	-0.061	0.946	0.903
	Group 2	-0.006	0.807	-0.184	0.686
	Group 3	0.838	0.263	-0.021	0.772
	Group 4	0.257	0.668	0.348	0.633
	Group 5	0.579	0.435	0.054	0.527
	Group 6	0.313	0.687	-0.06	0.573
	Group 7	0.898	0.012	-0.053	0.809
Eigenvalue		2.012	1.832	1.060
Variance explained(%)		28.745	26.174	15.140
Cumulative variance explained (%)		28.745	54.920	70.059
KMO=0.667, Bartlett’s Test of Sphericity χ²=135.542 (p<0.001)

Table 7.

Sesquiterpenes and monoterpenes identified from agarwood (GC–MS) and their biological activities reported in the literature

No.	Compound	Peak area (%) by sample (1-7) (%)							Primary bioactivities	Study type	Abstract	Ref.
No.	Compound	1	2	3	4	5	6	7	Primary bioactivities	Study type	Abstract	Ref.
1	a-Agarofuran	0.154	0.129	15.808	0.841	3.358	0.936	10.784	Anti-inflammatory	in vitro	α-Agarofuran induces apoptosis by a mitochondrial dysfunction in MCF-7, PC9, C4-2B	(Alizadeh et al., 2020)
2	7-epi-γ Eudesmol (epi-γ-Eudesmol)	0.566	0.537	5.21	0.95	5.668	1.136	10.528	Antioxidant	in vitro	Bauhinia ungulata’s major constituent, epi-γ-eudesmol (13.6%), contributes to strong antioxidant activity	(Nunes de Andrade Medeiros et al., 2024)
3	Agarospirol	-	1.748	1.265	2.842	11.888	2.72	0.558	Antipsychotic	in vivo	Jinkoh-eremol and agarospirol, isolated from agarwood benzene extract, showed positive effects on the central nervous system.	(Okugawa et al., 1996)
4	Baimuxinal	0.565	-	0.346	0.923	2.166	0.374	0.667	Antimicrobial	in vitro	Essential oils of A. sinensis had better inhibition activities towards Bacillus subtilis and Staphyloccus aureus	(Chen et al., 2011)
5	Cedrol	-	1.132	0.081	0.302	-	1.699	3.692	Anticancer	in vitro/in vivo	Cedrol-treated mice exhibited no significant differences in body weight and improved TMZ-induced liver damage	(Chang et al., 2020)
									Neurologic	clinical study	Hippocampal rCBF(Regional Cerebral Blood Flow) was bilaterally increased during cedrol inhalation	(Hori et al., 2012)
									Respiratory protective	clinical study	• Cedrol enhances parasympathetic, suppresses sympathetic outflow	(Kagawa et al., 2003; Umeno et al., 2008)
									Respiratory protective	in vivo	• Cedrol inhalation induces sedation, affects autonomic activity	(Kagawa et al., 2003; Umeno et al., 2008)
									Neurologic	clinical study	Aromatherapy inhalation improves sleep disturbance symptoms in elderly individuals with dementia	(Takeda et al., 2017)
									Anti-obesity	in vivo	Cedrol in the diet can prevent HFD-induced obesity and related metabolic syndrome	(Zhao et al., 2023b)
									Analgesic	clinical study	Cedrol has a sedative effect in people, impacting the autonomic nervous system	(Yada et al., 2007)
									Insecticidal	in vitro	Cedrol caused dose-dependent death of black-legged tick nymphs and was repellent to red imported fire ants	(Eller et al., 2014)
									Anti-anaphylactic schock	in vivo	Cedrol suppressed mast cell degranulation and inhibited histamine release	(Chakraborty et al., 2017)
									Anti-rheumatoid arthritis	in vivo	Cedrol dose-dependently alleviates chronic inflammation and pain, inhibiting p-JAK3 expression	(Zhang et al., 2021)
									Anti-osteoporosis	in vitro	Cedrol inhibits RANKL-induced osteoclastogenesis by suppressing ROS, NFATc1, NF-κB, and MAPK pathways	(Xu et al., 2023)
									Dermatoprotective	in vitro	• Cedrol enhances fibroblast growth in a dose-dependent manner	(Jin et al., 2012; Ryu et al., 2015; Yoon et al., 2009>)
										Clinical study	• Cedrol has been shown to possess anti-aging effects on the skin (Cedrol promotes fibroblast, collagen, elastin production)
										in vitro	• Elemol (10.88%), γ-eudesmol (9.41%), and sabinene (8.86%) were the major components in Cryptomeria japonica essential oil (CJE). CJE exhibited strong antibacterial activity against the acne-causing bacteria
									Preventive effect against alopecia	in vivo	• Cedrol prevents chemo-induced hair loss in mice.	(Chen et al., 2016; Zhang et al., 2016a)
									Preventive effect against alopecia	in vivo	• Cedrol stimulates hair growth, increases hair follicle length, and enhances hair follicle cycling in mice	(Chen et al., 2016; Zhang et al., 2016a)
6	α-Curcumene	1.007	0.259	0.275	-	0.18	0.206	-	Anticancer	in vitro	• α-Curcumene significantly inhibited migration and invasion of MDA-MB-231 breast cancer cells.	(Al-Amin et al., 2023; Shin & Lee, 2013)
									Anticancer	in vitro	• α-Curcumene exhibits anticancer activity by inducing apoptosis in SiHa cells	(Al-Amin et al., 2023; Shin & Lee, 2013)
									Antimicrobial	in vitro	The synergistic effect of α-curcumene with imipenem enhances antibiotic efficacy against E. cloacae	(da Silva et al., 2015)
7	β-Dihydroagarofuran	0.983	-	3.44	2.014	2.997	1.862	-	Anticancer	in vitro	β-Dihydroagarofuran sesquiterpenes induce apoptosis via mitochondrial dysfunction in Maytenus disticha	(González-Chavarría et al., 2020)
									Antimicrobial	in vitro	Dihydroagarofuran sesquiterpenes show antitumor-promoting activity.	(Takaishi et al., 1992)
									Neurologic	in vitro	β-Dihydroagarofuran compounds improve scopolamine-impaired cognition	(Ning et al., 2015)
8	δ-Guaiene (α-Bulnesene)	0.242	0.289	1.615	1.18	0.519	-	-	Cardiovascular protective	in vitro	δ-Guaiene(α-bulnesene) competitively inhibited PAF receptor	(Hsu et al., 2006)
9	Dehydrofukinone (Dihydrokaranone)	14.73	-	0.1	3.137	-	0.132	-	Neurologic	in vivo	• DHF exhibits sedative and anesthetic effects in fish by interacting with GABAergic and cortisol pathways	(Garlet et al., 2015; Garlet et al., 2017)
9	Dehydrofukinone (Dihydrokaranone)	14.73	-	0.1	3.137	-	0.132	-	Neurologic	in vivo	• β-Dihydroagarofuran compounds improve scopolamine-impaired cognition	(Garlet et al., 2015; Garlet et al., 2017)
10	β-Eudesmol	-	6.667	-	1.446	1.555	1.618	-	Anticancer	in vitro	• α-, β-, and γ-eudesmol isomers exhibit cytotoxic effects against various tumor cell lines	(Bomfim et al., 2013; Ma et al., 2008; Tsuneki et al., 2005)
											• β-eudesmol inhibited the proliferation of human umbilical vein endothelial cells (HUVEC)
											• β-eudesmol inhibits both the proliferation and migration of HUVEC
									Intoxication	in vivo	β-eudesmol as an antidote for intoxication from organophosphorus anticholinesterase agents	(Chiou et al., 1995)
11	γ-Eudesmol	-	1.214	-	-	0.51	0.222	0.068	Anticancer	in vitro	Sesquiterpene-rich C. schoenanthus oil exhibits cytotoxicity in multiple cancer cell lines (HT29, HCT116, MCF7, and MDA-MB231)	(Yagi et al., 2016)
									Antimicrobial	in vitro	Litsea kostermansii leaf oil rich in eudesmols exhibits strong antibacterial activity	(Ho et al., 2009)
									Analgesic	in vivo	Jatropha pelargoniifolia root oil demonstrates potent analgesic activity in vivo models	(Aati et al., 2019)
12	δ-Cadinene	-	0.179	-	-	0.886	-	0.088	Anticancer	in vitro	δ-Cadinene inhibits ovarian cancer cell growth via apoptosis and cell cycle arrest	(Hui et al., 2015)
									Antimicrobial	in vitro	δ-Cadinene showed antibacterial activity against Streptococcus pneumoniae.	(Pérez-López et al., 2011)
13	β-Caryophyllene	0.086	-	0.142	0.685	-		0.118	Anticancer	in vitro	• β-Caryophyllene (BCP) induces apoptosis and caspase-3 activation in tumor cell lines	(Amiel et al., 2012; Dahham et al., 2015; Fidyt et al., 2016)
											• BCP exhibited selective antibacterial activity against S. aureus
											• BCP is a phytocannabinoid with strong affinity to cannabinoid receptor type 2 (CB2)
									Antimicrobial	in vitro	• BCP exhibited antibacterial activity against Bacillus cereus.	(Moo et al., 2020; Yoo & Jwa, 2019)
									Antimicrobial	in vitro	• BCP exhibited strong antimicrobial activity against periodontopathogens	(Moo et al., 2020; Yoo & Jwa, 2019)
									Anti-inflammatory	in vivo	• BCP exerts significant inhibitory effects on carrageenan-induced paw oedema in mice and rats	(Fernandes et al., 2007; Picciolo et al., 2020)
									Anti-inflammatory	in vitro	• BCP has a marked efficacy in a preclinical in vitro model of oral mucositis	(Fernandes et al., 2007; Picciolo et al., 2020)
									Dyslipidemia	in vivo	• BCP increases antioxidant potential and elevates HDL via CB2 receptors	(Baldissera et al., 2017; Jung et al., 2015; Youssef et al., 2019)
											• BCP inhibits lipid accumulation and suppression of HFD-stimulated melanoma progression
											• BCP reduced cholesterol, triglycerides, and LDL levels, comparable to simvastatin.
									Cardiovascular protective	in vivo	BCP showed protective effects against doxorubicin-induced inflammation in the myocardium	(Meeran et al., 2019)
									Antidiabetic	in vivo	Oral BCP and glibenclamide dose-dependently reduced blood glucose and increased plasma insulin	(Basha & Sankaranara-yanan, 2014)
									Neurologic	in vivo	• BCP reduced astrocyte increase and DNA oxidation.	(Chávez-Hurtado et al., 2020; de Oliveira et al., 2016)
									Neurologic	in vivo	• BCP displays anticonvulsant activity against seizures induced by PTZ in mice	(Chávez-Hurtado et al., 2020; de Oliveira et al., 2016)
									Analgesic	in vivo	BCP effectively attenuated PINP, possibly through CB2-activation in the CNS	(Segat et al., 2017)
									Atopic dermatitis	in vitro	BCP alleviated DNCB-induced atopic dermatitis in mice	(Ahn et al., 2022)
									Anti-arthritis	in vivo	BCP monotherapy reduced paw swelling, improved joint histology, and decreased oxidative stress and TNF-α in arthritic rats	(El-Sheikh et al., 2019)
									Dermatoprotective	in vivo	• BCP treatment enhanced re-epithelialization and collagen content, with increased laminin-γ2 and desmoglein-3 expression	(Gushiken et al., 2022; Koyama et al., 2019)
									Dermatoprotective	in vivo	• BCP enhanced re-epithelialization in mouse skin wounds	(Gushiken et al., 2022; Koyama et al., 2019)
									Gastroprotective	in vivo	BCP effectively alleviated H. pylori infection and its related gastroduodenal symptoms	(Woo et al., 2020)
									Cardiovascular protective	in vivo	BCP attenuated ischemic stroke injury via ferroptosis regulation	(Hu et al., 2022)
									Hepatoprotective	in vivo	BCP protects against liver injury through down-regulation of the TLR4 and RAGE signaling	(Cho et al., 2015)
14	β-Elemene	0.919	-	-	-	-	0.083	0.165	Anticancer	in vitro	• β-Elemene can effectively inhibit proliferation and induce apoptosis in hepatoma HepG2 cells	(Dai et al., 2013; Li et al., 2010; Wang et al., 2005)
											• β-Elemene inhibits t the growth of various carcinoma cells, including brain, breast, cervical, colon, and lung.
											• β-Elemene induced apoptosis in NSCLC cells via caspase activation and mitochondrial pathway
									Immunomodulatory	in vitro	• β-Elemene induces apoptosis and suppresses inflammation in psoriatic keratinocytes	(Wang et al., 2022; Zhang et al., 2011)
									Immunomodulatory	in vitro	• β-Elemene significantly delayed the onset of experimental autoimmune encephalomyelitis (EAE)	(Wang et al., 2022; Zhang et al., 2011)
									Nephroprotective	in vivo	β-elemene inhibited the synthesis of extracellular matrix-related proteins in mice with unilateral ureteral obstruction (UUO)	(Sun et al., 2022)
15	β-Selinene	-	-	0.167	0.059	0.07	-	-	Antimicrobial	in vitro	Platycladus orientalis containing β-caryophyllene (13.4%), β-selinene (6.5%), shows moderate antibacterial effects against E. coli	(Kim & Lee, 2015)
									Anti-inflammatory	in vivo	The essential oil from C. macrophylla leaves containing β-selinene exhibited anti-inflammatory, analgesic, and antipyretic activities in mice	(Chandra et al., 2017)
16	trans-Calamenene		0.036				0.132	0.024	Anticancer	in vitro	Myristica fatua leaf extract rich in trans-calamenene (17.75%), caryophyllene (7.49%), demonstrates significant anticancer activity against MCF-7 cells	(Fajriah et al., 2017)
17	α-Copaene		0.017	0.38		0.199	-	0.153	Anticancer	in vitro	α-Copaene exhibited cytotoxic activity against rat neurons and N2a neuroblastoma cell lines	(Turkez et al., 2014)
									Antimicrobial	in vitro	a-Copaene exhibits antibacterial activity and inhibits four foodborne pathogens	(Chen et al., 2024)
18	Cyperene	0.347	-	-	-	0.071	-	-	Antimicrobial	in vitro	Cyperus rotundas rhizome oil demonstrates antioxidant, cytoprotective, and antibacterial activities in vitro	(Hu et al., 2017)
19	Elemol	-	-	0.454	-	-	0.375	-	Anticancer	in vitro	Canarium commune essential oil demonstrates potent anticancer activity against A549 lung cancer cells in vitro	(Kurban et al., 2023)
									Antimicrobial	in vitro	• Elemol and eudesmol exhibited potent antifungal activity against Trichophyton rubrum	(Kim et al., 2016; Rahman et al., 2017)
									Antimicrobial	in vitro	• A. polystachya leaf extracts showed strong antibacterial activity, with elemol (5.76%), one of the major compounds, contributing to this effect	(Kim et al., 2016; Rahman et al., 2017)
									Anti-inflammatory	in vivo	L. lacunosa essential oil exhibits notable antiinflammatory and analgesic activities in vivo	(Ladeira et al., 2023)
									Anti-alzheimer	in vitro	Elemol inhibits AChE, potentially enhancing brain acetylcholine for Alzheimer’s therapy	(Amat-Ur-Rasool & Ahmed, 2015)
									Atopic dermatitis	in vivo/in vitro	Elemol modulates multiple immune and inflammatory responses associated with atopic dermatitis in an animal model	(Yang et al. 2015)
									Dermatoprotective	in vitro	• NAE, containing 9.5% elemol, shows antibacterial and anti-inflammatory effects against acne pathogens	(Kim et al., 2011; Yoon et al., 2009)
									Dermatoprotective	in vitro	• The major components of 8 essential oil—kaurene, elemol, and γ-eudesmol—effectively inhibit the growth of drug-resistant skin pathogens	(Kim et al., 2011; Yoon et al., 2009)
20	Germacrene D	1.483	-	-	-	-	-	-	Antimicrobial	in vitro	• Essential oils isolated from the leaves of Cosmos bipinnatus and their antibacterial activity.	(Olajuyigbe & Ashafa, 2014; Şahin et al.,2004)
20	Germacrene D	1.483	-	-	-	-	-	-	Antimicrobial	in vitro	• Caryophyllene and spathulenol are the main constituents of Origanum vulgare ssp. vulgare essential oil, which shows potent antibacterial activity	(Olajuyigbe & Ashafa, 2014; Şahin et al.,2004)
21	α-Humulene	-	-	-	0.107	-	-	1.044	Anticancer	in vivo	α-Humulene and transcaryophyllene isolated from S. officinalis essential oil inhibited the growth of MCF-7 breast cancer and HCT-116 colon cancer cells	(Hadri et al., 2010)
									Anti-inflammatory	in vivo	•α-Humulene and (–)-transcaryophyllene were effective in reducing paw edema in mice and exhibited antiinflammatory activity	(Medeiros et al., 2007; Rogerio et al., 2009)
									Anti-inflammatory	in vivo	• Both α-humulene and trans-caryophyllene inhibit the LPS-induced NF-κB activation and neutrophil migration	(Medeiros et al., 2007; Rogerio et al., 2009)
									Gastroprotective	in vivo	α-Humulene may attenuate HCl/ethanol-induced gastritis by inhibiting histamine release and NF-κB activation	(Yeo et al., 2021)
22	Longifolene	-	-	7.648	-	-	1.857	-	Anticancer	in vitro	Longifolene/Junipene demonstrated cytotoxicity against prostate cancer (DU-145) and oral cancer (SCC-29B) cell lines	(Grover et al., 2022)
									Antimicrobial	in vitro	Oxidized longifolene derivatives show strong antifungal activity	(Mukai et al., 2018)
									Analgesic	in vivo	Caryophyllene and longifolene exhibited anti-neuropathic pain activity in a mouse model	(Sukmawan et al., 2023)
									Insecticidal	in vitro	Longifolene exhibited anti-Reticulitermes speratus (Japanese subterranean termite) activity	(Mukai et al., 2017)
23	Nootkatone	0.253	-	-	-	0.131	-	-	Antimicrobial	in vitro	(+)-Nootkatone prevented S.aureus biofilm formation	(Farha et al., 2020)
									Anti-inflammatory	in vivo	Nootkatone reduces inflammation by suppressing cytokines and leukocyte recruitment	(Bezerra Rodrigues Dantas et al., 2020)
									Anti-alzheimer	in vivo	Nootkatone improves cognitive function in Y-maze and water maze	(Wang et al., 2018c)
									Neurologic	in vivo	Nootkatone alleviated depressive-like behaviors induced by chronic unpredictable mild stress (CUMS)	(Zhao et al., 2023a)
									Anti-obesity	in vivo	Nootkatone activates AMPK, boosts metabolism, prevents obesity, improves performance	(Murase et al., 2010)
									Insecticidal	in vitro	Nootkatone and derivatives show strong insecticidal and acaricidal effects	(Galisteo Pretel et al., 2019)
									Atopic dermatitis	in vitro	Nootkatone downregulates pro-inflammatory chemokine expression in HaCaT cells	(Choi et al., 2014b)
									Respiratory protective	in vivo	Nootkatone reduces Th2 cytokines in bronchoalveolar lavage fluid	(Gai et al., 2023)
									Cardiovascular protective	in vivo	Nootkatone elevated cardiac antioxidant proteins and attenuated oxidative stress in mice	(Al-Salam et al., 2022)
									Hepatoprotective	in vivo	Nootkatone confers hepatoprotection by reducing oxidative stress, inflammation, and apoptosis	(Kurdi et al., 2018)
									Respiratory protective	in vivo	Nootkatone prevents DEP-induced airway resistance and lung inflammatory cell infiltration	(Nemmar et al., 2018)
									Nephroprotective	in vivo	Nootkatone modulates NOX4, NF-κB, and Nrf2/HO-1 pathways in kidney tissues	(Dai et al., 2023)
									Anti-alzheimer	in vivo	Nootkatone reduces inflammatory cytokines via TLR4/NF-κB/NLRP3 inhibition	(Qi et al., 2019)
									Anti-inflammatory	in vivo	Nootkatone attenuates smoke-induced inflammation and oxidative stress in testes.	(Ali et al., 2019)
24	α-Santalol	2.255	-	-	1.075	-	-	-	Anticancer	in vivo	• Topical α-santalol dose-dependently inhibits UVB-induced skin tumorigenesis in mice	(Bommareddy et al., 2007; Bommareddy et al., 2018; Bommareddy et al., 2012; Kaur et al., 2005; Santha et al., 2013)
										in vitro	• α-Santalol inhibits breast cancer cell migration via Wnt/β-catenin pathway
											• α-Santalol induces apoptosis in PC-3 and LNCaP prostate cancer cells
											•α-Santalol induces apoptosis through caspase activation and mitochondrial disruption
											• α-Santalol exhibits potent anti-neoplastic effects in diverse breast cancer cells
									Anti-inflammatory	in vitro	Santalol inhibits COX-mediated prostaglandin production and inflammatory cytokine secretion	(Sharma et al., 2014)
									Neurologic	Clinical study	• α-Santalol and β-santalol exhibited central nervous system activity in mouse model	(Hongratanaworakit et al., 2004; Okugawa et al., 1995; Okugawaet al., 2000; Satou et al., 2015)
											• α-Santalol and β-santalol exhibited central nervous system activity in mouse model
											• α-Santalol induces analgesia and modulates dopamine and serotonin receptor activity
											• Santalol crosses the blood-brain barrier and exerts central sedative effects in mice
									Dyslipidemia in diabetics	in vivo	Oral administration significantly lowers glucose, TC, LDL, and TG in diabetic rats	(Kulkarni et al., 2012)
									Hepatoprotective in diabetics	in vivo	Treatment normalized body weight, glucose, bilirubin, glycogen, and lipid peroxidation in diabetic mice	(Misra & Dey, 2013)
25	α-Selinene	-	-	-	4.846	-	0.978	-	Anticancer	In silico	In silico analysis implicates α-selinene as an aromatase P450 antagonist in breast cancer.	(Alakanse et al., 2019)
									Antioxidant	in vitro	Essential oil containing α/β-selinene exhibits antibacterial activity against E. coli and S. aureus	(Keawsa-ard et al., 2012)
26	γ-Selinene	0.381	-	0.414	0.109	-	-	-	Antimicrobial	in vitro	Agarwood oil rich in γ-selinene exhibits antimicrobial activity against S. aureus and C. albicans	(Wetwitayaklung et al., 2009)
27	Spathulenol	0.143	-	-	-	0.17	-	-	Anticancer	in vitro	• Volatile oil rich in spathulenol exhibits anticancer activity against K-562 cells	(Brito et al., 2018; do Nascimento et al., 2018)
27	Spathulenol	0.143	-	-	-	0.17	-	-	Anticancer	in vitro	• Essential oil rich in spathulenol shows antioxidant and anticancer activity against ovarian cells	(Brito et al., 2018; do Nascimento et al., 2018)
									Anti-inflammatory	in vivo	Spathulenol-rich extract alleviates cutaneous inflammation and pain in mouse models	(Ladeira et al., 2023)
									Respiratory protective	in vitro	Spathulenol isolated from Azorella compacta exhibits antimycobacterial activity against M. tuberculosis	(Dzul-Beh et al., 2019)
28	Valerenol	0.156		0.193		0.072	-	-	Neurologic	in vivo	Valerenic acid and valeranol exhibited strong anxiolytic activity in wild-type mice	(Benke et al., 2009)
29	Alloaromadendrene	-	-	-	-	0.139	-	-	Anti-inflammatory	in vitro	Essential oil rich in alloaromadendrene mitigates inflammation-associated fungal infections	(Piras et al., 2022)
									Antimicrobial	in vitro	Alloaromadendrene exhibits potent antifungal activity against yeast (Cryptococcus neoformans) and dermatophytes	(Sawant et al., 2007)
									Antioxidant	in vivo	Alloaromadendrene exhibit potential as sources of antioxidants and anti-aging agents	(Yu et al., 2014)
30	α-Cedrene	0.068	0.015	-	-	0.0345			Antimicrobial	in vitro	Essential oil rich in α/β-cedrene exhibits notable antimicrobial activity	(Johnston et al., 2001)
									Antidiabetic	in vivo	α-Cedrene activates MOR23, enhancing glucose uptake and improving glucose intolerance	(Kang et al., 2020)
									Anti-obesity	in vivo	Oral administration of α-cedrene improved obesity and metabolic dysfunction via Adcy3-dependent mechanisms	(Tong et al., 2019)
									Hepatoprotective	in vivo	α-Cedrene activates OR10j5/cAMP–PKA signaling, reducing hepatic lipid accumulation in vitro and in vivo	(Tong et al., 2017)
									Muscle hypertrophic	in vivo	α-Cedrene induced the expression of mouse olfactory receptor 23 (MOR23) and increased muscle mass and strength	(Tong et al., 2018)
31	Hinesol	-	-	0.42	-	-		0.46	Anticancer	in vitro	Hinesol was responsible for the apoptosis-inducing activity in these human leukemia HL-60 cells	(Masuda et al., 2015)
32	Nerolidol	-	-	-	-	0.39	-	-	Anticancer	in vivo	Nerolidol treatment significantly reduces the incidence of colon adenomas in rats.	(Wattenberg, 1991)
									Antimicrobial	in vitro	• Nerolidol has antioxidant, antibacterial, and antibiofilm activities	(de Moura et al., 2021; Park et al., 2009)
									Antimicrobial	in vitro	• Citral, eugenol, nerolidol, and α-terpineol exhibit antifungal activity against T. mentagrophytes	(de Moura et al., 2021; Park et al., 2009)
									Anti-inflammatory	in vivo	Nerolidol exhibits antinociceptive and anti-inflammatory effects via GABAergic and cytokine modulation	(Fonsêca et al., 2016)
									Dermatoprotective	in vitro	Nerolidol safely enhances 5-FU dermal penetration as a transdermal permeation enhancer.	(Cornwell & Barry, 1994)
33	Valerianol				2.737		1.916		Antimicrobial	in vitro	10-epi-γ-eudesmol exhibited strong antioxidant activity.	(Mei et al., 2008)
34	Limonene (d-Limonene)	-	0.092	-	-	-	0.14		Antimicrobial	in vitro	Natural limonene inhibits Gram-negative, Gram-positive bacteria and yeast fungi.	(Wróblewska et al., 2019)
									Anticancer	in vivo	d-Limonene exhibits antiangiogenic and proapoptotic effects on gastric cancer	(Lu et al., 2004)
									Anti-inflammatory	in vitro/in vivo	• (+)-Limonene epoxide exhibits antioxidant, anxiolytic, and neuroprotective potential for anxiety regulation	(de Almeida et al., 2014; Yoon et al., 2010; Yu et al., 2017)
											• d-Limonene suppresses inflammatory mediators and cytokine production, exhibiting anti-inflammatory effects
											• d-limonene attenuates inflammation and oxidative stress, protects mucosa, and modulates immunity in UC rats
									Neurologic	in vitro	Limonene reduces anxiety-related behaviors via activation of the dopamine and GABA neurotransmitter systems	(Song et al., 2021)
									Antidiabetic	in vivo	Limonene prevents diabetic complications via antioxidant activity and improved hepatic lipid metabolism	(Bacanlı et al., 2017)
									Gastroprotective	in vivo	Limonene promotes gastric mucosal healing and regeneration, enhancing gastroprotection	(Moraes et al., 2013)
35	α-Eudesmol	-	1.543	-	-	-	-	-	Cardiovascular protective	in vivo	α-Eudesmol inhibits glutamate release and alleviates post-ischemic brain injury in rats	(Asakura et al., 2000)
36	Valencene	0.174	-	-	-	-	-	-	Anticancer	in vitro	In HeLa cells, valencene demonstrated significant anticancer effects	(Liu et al., 2012)
									Dermatoprotective	in vitro	Valencene suppresses UVB-induced melanogenesis and signaling in B16F10 melanoma cells	(Nam et al., 2016)
									Cardiovascular protective	in vivo	(+)-Nootkatone and (+)-valencene improve sepsis survival via HO-1-mediated anti-inflammatory effects	(Tsoyi et al., 2011)
37	α-Cyperone	-	-	-	-	0.231	-	-	Anti-inflammatory	in vitro	α-Cyperone exhibited anti-inflammatory activity through the inhibition of NF-κB signaling	(Salman et al., 2011)
38	β-Patchoulene	-	0.086	-	-	-	-	-	Anticancer	in vitro/in vivo	β-Patchoulene inhibits hypoxia-induced hepatocellular carcinoma growth, proliferation, migration, EMT, and promotes apoptosis by suppressing the NF-κB/HIF-1α pathway	(Tu et al., 2022)
									Anti-inflammatory	in vivo	β-Patchoulene reduces inflammation by inhibiting cytokines, oxidative stress, and NF-κB activation in vivo	(Zhang et al., 2016b)
									Gastroprotective	in vivo	β-Patchoulene exhibits gastroprotective effects by reducing gastric ulcers, oxidative stress, inflammation, apoptosis, and regulating NF-κB and ERK1/2 pathways	(Liu et al., 2017)
									Sepsis	in vivo / ex vivo	β-Patchoulene improved cognitive function and survival in SAE mice by reducing inflammation, oxidative stress, microglial activation, and apoptosis, likely via Sirt1/Nrf2/HO-1 pathway	(Tian et al., 2023)
									Respiratory protective	in vivo	β-Patchoulene (10 mg/ kg) reduced lung edema, neutrophil infiltration, oxidative stress, and pro-inflammatory cytokines in LPS-induced ALI, demonstrating strong anti-inflammatory and protective effects comparable to DEX	(Chen et al., 2017)
39	Italicene ether	1.473	2.1	4.923	16.242	6.771	1.165	3.46	-	-	-	-

Sample 1, Vietnamese agarwood (A. crassna); Sample 2, Indonesian agarwood; Sample 3, Malaysian agarwood; Sample 4, Myanmar agarwood; Sample 5, Cambodian agarwood; Sample 6, Laitian agarwood; Sample 7, Thai agarwood. When the same compound was detected at multiple retention times, the peak areas were summed and expressed as total peak area (%).

Table 8.

Summary of studies on major sesquiterpenes from agarwood with experimentally validated anti-inflammatory activity and related molecular mechanisms

Compound	Activity	Study model	Concentration	Outcomes	Ref.
Cedrol	Anti-anaphylactic shock	in vitro study on compound 48/80-induced BALB/c mice	• Cedrol 50, 100, 200 mg/kg, p.o.	Reducing mast cell degranulation and blocking histamine release	(Chakraborty et al., 2017)
	Anti-anaphylactic shock	in vitro study on compound 48/80-induced BALB/c mice	• Cedrol-loaded nanostructured lipid carriers (NLCs) 12.5, 25, 50, 100, 200 mg/kg cedrol as NLC (7.23% and 14% cedrol loading)		(Chakraborty et al., 2017)
	Anti-rheumatoid arthritis	in vitro study on adjuvant-induced arthritis (AIA) in rat	Cedrol 20, 40, 80 mg/kg	Dose-dependent alleviation of chronic inflammation and pain by cedrol, accompanied by inhibition of p-JAK3 expression	(Zhang et al., 2021)
	Anti-osteoporosis	• in vitro study on BMM (bone marrow monocytes) cells were extracted from mouse femur and tibia	• Cedrol 0, 10, 20 μM	Inhibition of RANKL-induced osteoclastogenesis by cedrol through suppression of ROS, NFATc1, NF-κB, and MAPK pathways	(Xu et al., 2023)
	Anti-osteoporosis	• in vitro study in ovariectomized female C57BL/6 mice	• Cedrol 20 mg/kg		(Xu et al., 2023)
β-Caryophyllene	Anti-inflammatory	in vitro study on mice with paw edema induced with carrageenan and ovalbumin.	α-Humulene and (−)-trans-caryophyllene were each orally administered at a dose of 50 mg/kg.	Significant reduction of paw edema; inhibition of TNF-α, IL-1β, PGE2, iNOS, and COX-2; anti-inflammatory activity comparable to dexamethasone	(Fernandes et al., 2007)
	Dyslipidemia	in vitro study on Wistar rats fed with HFFD plus β-caryophyllene	β-caryophyllene (30 mg/kg) was orally administered for 4 weeks.	Reduction of visceral fat index, LDL, and VLDL levels	(Youssef et al., 2019)
				Enhancement of antioxidant capacity and elevation of HDL levels via CB2 receptor activation. Attenuation of vascular inflammation through CB2 and PPAR-γ receptor pathways
				Restoration of aortic nitric oxide levels by upregulating eNOS and downregulating iNOS expression
		• in vitro study on mice with HFD-induced melanoma progression	Administration of a high-fat diet (60 kcal% fat) supplemented with 0, 0.15, or 0.3% BCP for 16 weeks.	• Inhibition of HFD-induced body weight gain, fasting blood glucose, tumor growth, LN metastasis, tumor proliferation, angiogenesis, lymphangiogenesis; restoration of apoptotic cell levels	(Jung et al., 2015)
		• in vitro study on 3T3-L1 preadipocytes		• Inhibition of lipid accumulation, adipocyte and M2-cell accumulation, and CCL19/21-CCR7 axis activity; suppression of HFD-stimulated melanoma progression	(Jung et al., 2015)
	Cardiovascular protective	in vitro study on doxorubicin-induced myocardial dysfunction in mice	Intraperitoneal administration of BCP (25 mg/kg) was performed six days per week for five weeks.	Protective effect against doxorubicin-induced myocardial inflammation; activation of CB2 and PPARγ receptors	(Meeran et al., 2019)
	Anti-inflammatory	in vitro study on human gingival fibroblasts (GF) and human oral mucosa epithelial cells (EC)	BCP (10 μg/mL)	Decreased TNF-α, IL-1β, IL-6, and IL-17A levels; effect reversed by CB2 antagonist (AM630), indicating CB2-mediated action	(Picciolo et al., 2020)
	Analgesic	in vitro study on paclitaxel (PTX) induced peripheral neuropathy (PINP) in mice	Oral administration of BCP at doses of 12.5, 25, or 50 mg/kg for 10 days.	Attenuation of PTX-induced mechanical allodynia and prevention of PINP development via CB2-dependent mechanisms; reduced spinal p38 MAPK and NF-κB activation; decreased Iba-1 and IL-1β immunoreactivity	(Segat et al., 2017)
	Atopic dermatitis	• in vitro study on BALB/c mice with DNCB-induced AD-like skin inflammation;	• Topical administration of 0.01, 0.1, and 100 μL BCP for 20 days in BALB/c mice	Alleviation of DNCB-induced AD-like skin lesions; inhibition of inflammatory cell infiltration; suppression of IL-4-induced EGR1 and TSLP expression via MAPK pathway	(Ahn et al., 2022)
	Atopic dermatitis	• in vitro study on HaCaT keratinocytes	• 0.1, 0.2 μg/ml BCP		(Ahn et al., 2022)
	Dermoprotective	in vitro study on rats with skin wound excision model	Application of 1% β-caryophyllene emulsion twice daily for 3, 7, or 14 days.	Increased IL-10 and GPx; decreased TNF-α, IFN-γ, IL-1β, and IL-6; enhanced re-epithelialization (increased laminin-γ2 and desmoglein-3); increased collagen content	(Gushiken et al., 2022)
	Hepatoprotective	in vitro study on mice with D-galactosamine and LPS-induced acute hepatic injury	Intraperitoneal injection of BCP (50, 100 and 200 mg/kg).	Attenuation of mortality and serum aminotransferase activity; reduction of TNF-α, IL-6, HMGB1; suppression of TLR4, RAGE, p38, JNK phosphorylation, NF-κB, EGR1, and MIP-2 expression	(Cho et al., 2015)
β-Elemene	Immunomodulatory	in vitro study on C57 mice with EAE (autoimmune encephalomyelitis) (multiple sclerosis model)	β-elemene 20 mg/kg/day by intraperitoneal injection for 15 days.	Delayed EAE onset; dose-dependent suppression of MOG-specific T cell proliferation; reduced IL-17, IL-6, IL-23, RORγt; induced Foxp3 expression in periphery and spinal cord	(Zhang et al., 2011)
	Nephroprotective	• in vitro study on male C57BL/6 mice with unilateral ureteral obstruction (UUO)	Treated intraperitoneally with β-elemene at a dose of 40 mg/kg/d for 7 days.	Inhibition of ECM-related protein synthesis; suppression of α-SMA, vimentin, CTGF expression; blockade of JAK2/STAT3, Smad3 phosphorylation, and MyD88 upregulation	(Sun et al., 2022)
	Nephroprotective	• in vitro study on TGF-β-stimulated rat interstitial fibroblast cells			(Sun et al., 2022)
Guaiol	Anticancer	• in vitro study on NSCLC cell lines A549 and H1299	0, 20, 40, 60, 80, 100 μM of guaiol.	Autophagic cell death induction and targeting of both mTORC1 and mTORC2 signaling pathways by (−)-Guaiol	(Yang et al., 2018a)
α-Humulene	Anti-inflammatory	• in vitro study on female BALB/c mice with ovalbumin-induced airway allergic inflammation;	Oral administration of α-humulene or trans-caryophyllene at 50 mg/kg for 22 days.	Restoration of IFN-γ; reduction of IL-5, CCL11, LTB4 in BALF; decreased IL-5 (in vitro); inhibition of NF-κB and AP-1 activation; reduced P-selectin expression in lung tissue	(Rogerio et al., 2009)
	Anti-inflammatory	• in vitro IL-5 assay			(Rogerio et al., 2009)
	Anti-inflammatory	in vitro study on rats with LPS-induced paw oedema	Oral administration (p.o.) of α-humulene or transcaryophyllene at 50 mg/kg	Inhibition of LPS-induced NF-κB activation and neutrophil migration by α-humulene and transcaryophyllene; prevention of TNF-α and IL-1β production by α-humulene	(Medeiros et al., 2007)
Nootkatone	Anti-inflammatory	in vitro study on mice murine models of paw edema and granuloma	Nootkatone (NTK) (10, 100, or 300 mg/kg) was orally administered	Inhibition of leukocyte recruitment (MPO, IL-1β, TNF-α); reduction of granuloma weight and protein content; suppression of IL-1β and TNF-α production	(Bezerra Rodrigues Dantas et al., 2020)
	Anti-alzheimer (Neurologic)	in vitro study on LPS-induced AD model mice	NKT 10 mg/kg	Improved cognitive performance (Y-maze, Morris water maze); reduced neuronal degeneration and microglial activation in hippocampus; decreased hippocampal IL-1β, IL-6, TNF-α, NLRP3, and NF-κB p65 expression	(Wang et al., 2018c)
	Neurologic	in vitro study on mice with CUMS-induced depression	NKT was administered intragastrically at doses of 6 or 12 mg/kg daily for 21 days	Improvement of CUMSinduced depressive-like behaviors; decreased hippocampal IL-1β, IL-18, IL-6, and TNF-α mRNA and protein levels; inhibition of NF-κB signaling and NLRP3 inflammasome activation	(Zhao et al., 2023a)
	Atopic dermatitis	in vitro study on HaCaT cell	0, 10, 30, 50, 100 μM of nootkatone	Inhibition of TNF-α/IFN-γ-induced TARC/CCL17 and MDC/CCL22 mRNA expression	(Choi et al., 2014b)
	Respiratory protective effect	• in vitro study on mice with ovalbumin-induced allergic asthma;	-	Reduction of Th2 cytokines (IL-4, IL-5, IL-13) in BALF; decreased serum IgE; suppression of oxidative stress and NLRP3 inflammasome activation; inhibition of IL-13–induced ROS and NLRP3-mediated pyroptosis	(Gai et al., 2023)
	Respiratory protective effect	• in vitro study on BEAS-2B bronchial epithelial cells	-		(Gai et al., 2023)
	Nephroprotective	in vitro study on mice with CCl4-induced kidney injury	Pretreatment with NKT at 5, 10, and 20 mg/kg/day was performed for one week	Downregulation of NOX4, IL-1β, IL-6, TNF-α proteins and NO; upregulation of Nrf2 and HO-1 mRNAs; downregulation of NF-κB, IL-1β, IL-6, TNF-α, and iNOS mRNAs; inhibition of NOX4 and NF-κB pathways; activation of Nrf2/HO-1 pathway	(Dai et al., 2023)
	Anti-inflammatory	in vitro study on male mice with water pipe smokeinduced testicular toxicity	Nootkatone was orally administered to mice at 90 mg/kg/day for 30 days	Decreased total NO; increased IL-1β and oxidative stress markers (MDA, cytochrome C, 8-oxo-dG); inhibition of NF-κB expression	(Ali et al., 2019)
α-Santalol	Neurologic	in vitro study on mice with writhing models	Sesquiterpenoids (jinkoh-eremol, agarospirol, α-santalol, β-santalol, dehydrocostus lactone, and costunolide) at 50 mg/kg were administered	Antagonistic activity of α-santalol on dopamine D2 and serotonin 5-HT2A receptor binding. Comparable antipsychotic effect of α-santalol and chlorpromazine	(Okugawa et al., 2000)
α-Santalol	Anti-inflammatory	in vitro study on co-cultured human dermal fibroblasts and neoepidermal keratinocytes	α-Santalol, β-santalol, 45, 90 μM	Suppression of LPSinduced production of arachidonic acid metabolites (PGE2, TBX B2)	(Sharma et al., 2014)
α-Cedrene	Hepatoprotective	• in vitro study on mice with high-fat diet (HFD)	• The HFD was supplemented with 0.2% (w/w) α-cedrene, and the experimental diets were provided ad libitum in the form of pellets for 10 weeks	Identification of α-cedrene as a novel MOR23(mouse olfactory receptor 23) agonist with protective effects against highfat diet-induced hepatic steatosis and its associated lipid-lowering effect in HepG2 cells	(Tong et al., 2017)
α-Cedrene	Hepatoprotective	• in vitro study on HepG2 cell	• α-cedrene 100 μM		(Tong et al., 2017)
Nerolidol	Anti-inflammatory	in vitro study on mice with pain models	Nerolidol (200, 300, and 400 mg/kg) was orally administered	Antinociceptive activity via GABAergic system; reduction of carrageenaninduced paw edema; decreased TNF-α levels; reduced IL-1β production in LPS-stimulated peritoneal macrophages	(Fonsêca et al., 2016)
Limonene	Anti-inflammatory	in vitro study on RAW 264.7 cells	-	Decreased expression of iNOS and COX-2; dosedependent reduction of TNF-α, IL-1β, and IL-6	(Yoon et al., 2010)
Limonene	Anti-inflammatory	in vitro study on ulcerative colitis (UC) rat model	D-limonene (50 or 100 mg/kg) was administered by gastric lavage for 7 days	Reduction of disease activity and colonic mucosa damage; suppression of MMP-2 and MMP-9; increased iNOS and COX-2 protein; decreased PGE2 production and TGF-β gene expression; increased p-ERK1/2 expression	(Yu et al., 2017)
α-Cyperone	Anti-inflammatory	in vitro study on Raw 264.7 cells	Cyperone 12.5, 25, 50, 75 μM	a-cyperone and nootkatone, showed stronger anti-inflammatory and a potent NF-kB inhibitory effect on LPS-stimulated RAW 264.7 cells	(Salman et al., 2011)
β-Patchoulene	Anti-inflammatory	in vitro study on mice with xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema	β-Patchoulene was administered orally once daily at 10, 20, and 40 mg/kg for a duration of 7 days	Reduction of carrageenan-induced production of pro-inflammatory cytokines— including TNF-α, IL-1β, IL-6, PGE2, and nitric oxide (NO)—and significant inhibition of iNOS and COX-2 protein expression by β-PAE pretreatment	(Zhang et al., 2016b)
	Gastroprotective	in vitro study on rats with ethanol-induced gastric injury	Rats were intragastrically administered lansoprazole (30 mg/kg) or β-PAE (10, 20, and 40 mg/kg) prior to intragastric administration of ethanol	Reduction of serum TNF-α, IL-1β, and IL-6 levels by β-PAE pretreatment in a dose-dependent manner (10, 20, 40 mg/kg)	(Liu et al., 2017)
	Respiratory protective Lung injury	in vitro study on LPS-induced ALI (acute lung injury) mice	β-PAE (2.5, 5 or 10 mg/ kg, p.o.), β-PAE or DEX were administrated intragastrically once daily for 7 days	Reduction of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) by β-PAE (10 mg/kg) in LPS-induced ALI (acute lung injury)	(Chen et al., 2017)

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