{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:38:08Z","timestamp":1787319488585,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences","award":["CI2021A04009"],"award-info":[{"award-number":["CI2021A04009"]}]},{"name":"the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences","award":["L2022046"],"award-info":[{"award-number":["L2022046"]}]},{"name":"the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences","award":["ZZ15-YQ-041"],"award-info":[{"award-number":["ZZ15-YQ-041"]}]},{"name":"the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences","award":["ZXKT21029"],"award-info":[{"award-number":["ZXKT21029"]}]},{"name":"Qihang Talent Program","award":["CI2021A04009"],"award-info":[{"award-number":["CI2021A04009"]}]},{"name":"Qihang Talent Program","award":["L2022046"],"award-info":[{"award-number":["L2022046"]}]},{"name":"Qihang Talent Program","award":["ZZ15-YQ-041"],"award-info":[{"award-number":["ZZ15-YQ-041"]}]},{"name":"Qihang Talent Program","award":["ZXKT21029"],"award-info":[{"award-number":["ZXKT21029"]}]},{"name":"Fundamental Research Funds for the Central Public Welfare Research Institutes","award":["CI2021A04009"],"award-info":[{"award-number":["CI2021A04009"]}]},{"name":"Fundamental Research Funds for the Central Public Welfare Research Institutes","award":["L2022046"],"award-info":[{"award-number":["L2022046"]}]},{"name":"Fundamental Research Funds for the Central Public Welfare Research Institutes","award":["ZZ15-YQ-041"],"award-info":[{"award-number":["ZZ15-YQ-041"]}]},{"name":"Fundamental Research Funds for the Central Public Welfare Research Institutes","award":["ZXKT21029"],"award-info":[{"award-number":["ZXKT21029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Agarwood, a highly valuable resin\/wood combination with diverse pharmacological activities but scarce supply, has a long history of being used as a medicine in several medical systems. Grafted Kynam agarwood (GKA) has been cultivated successfully recently and has the qualities meeting the definition of premium Kynam agarwood. However, there are few comprehensive comparisons between GKA and normal agarwood in terms of traits, global composition, and activity, and some key issues for GKA to be adopted into the traditional Chinese medical (TCM) system have not been elaborated. The two types of agarwood samples were evaluated in terms of trait characteristics, physicochemical indicators, key component groups, and global compositional profile. Furthermore, a molecular docking was performed to investigate the active ingredients. In vitro activity assays were performed to evaluate the activation of adenosine 5\u2019-monophosphate (AMP)-activated protein kinase (AMPK) by GKA and normal agarwood. The results revealed that, overall, the traits, microscopic characteristics, chemical composition types, and bioactivity between GKA and normal agarwood were similar. The main differences were the content of resin (ethanolic extract content), the content of key component groups, and the composition of the different parent structural groups of 2-(2-phenethyl) chromones (PECs). The contents of total PEC and ethanol extract content of GKA were significantly higher than those of normal agarwood. The MS-based high-throughput analysis revealed that GKA has higher concentrations of sesquiterpenes and flindersia-type 2-(2-phenylethyl) chromones (FTPECs) (m\/z 250-312) than normal agarwood. Molecular docking revealed that parent structural groups of FTPECs activated multiple signaling pathways, including the AMPK pathway, suggesting that FTPECs are major active components in GKA. The aim of this paper is to describe the intrinsic reasons for GKA as a high-quality agarwood and a potential source for novel drug development. We combined high-throughput mass spectrometry and multivariate statistical analysis to infer the different components of the two types of agarwood. Then we combined virtual screening and in vitro activity to construct a component\/pharmacodynamic relationship to explore the causes of the activity differences between agarwood with different levels of quality and to identify potentially valuable lead compounds. This strategy can also be used for the comprehensive study of other TCMs with different qualities.<\/jats:p>","DOI":"10.3390\/molecules28041667","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T01:35:29Z","timestamp":1675992929000},"page":"1667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Comprehensive Comparisons between Grafted Kynam Agarwood and Normal Agarwood on Traits, Composition, and In Vitro Activation of AMPK"],"prefix":"10.3390","volume":"28","author":[{"given":"Fengming","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Georgetown University Medical Center, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaochu","family":"Wang","sequence":"additional","affiliation":[{"name":"Georgetown University Medical Center, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanxi","family":"Huang","sequence":"additional","affiliation":[{"name":"Georgetown University Medical Center, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5525-4740","authenticated-orcid":false,"given":"Zhijie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.jep.2016.06.055","article-title":"Aquilaria spp. (agarwood) as source of health beneficial compounds: A review of traditional use, phytochemistry and pharmacology","volume":"189","author":"Hashim","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chen, X., Liu, Y., Yang, Y., Feng, J., Liu, P., Sui, C., and Wei, J. (2018). Trunk surface agarwood-inducing technique with Rigidoporus vinctus: An efficient novel method for agarwood production. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198111"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Shivanand, P., Arbie, N.F., Krishnamoorthy, S., and Ahmad, N. (2022). Agarwood-The Fragrant Molecules of a Wounded Tree. Molecules, 27.","DOI":"10.3390\/molecules27113386"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1039\/C8RA09409H","article-title":"Overview of sesquiterpenes and chromones of agarwood originating from four main species of the genus Aquilaria","volume":"9","author":"Gao","year":"2019","journal-title":"RSC Adv."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1002\/pca.2944","article-title":"Rapid authentication of agarwood by using liquid extraction surface analysis mass spectrometry (LESA-MS)","volume":"31","author":"Xie","year":"2020","journal-title":"Phytochem. Anal."},{"key":"ref_6","unstructured":"National Pharmacopoeia Committee (2020). Pharmacopoeia of the People\u2019s Republic of China, China Medical Science Press."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.phytol.2014.03.003","article-title":"Fragrant agarofuran and eremophilane sesquiterpenes in agarwood \u2018Qi-Nan\u2019 from Aquilaria sinensis","volume":"8","author":"Yang","year":"2014","journal-title":"Phytochem. Lett."},{"key":"ref_8","first-page":"41","article-title":"The textual research of Chinese herbal medicine qinan and its historical origin","volume":"1","author":"Huang","year":"2021","journal-title":"China Trop. Agric."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1080\/23802359.2021.1914210","article-title":"Molecular identification of Aquilaria species with distribution records in China using DNA barcode technology","volume":"6","author":"Kang","year":"2021","journal-title":"Mitochondrial DNA Part B"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104493","DOI":"10.1016\/j.fitote.2020.104493","article-title":"Characterization of the incense ingredients of cultivated grafting Kynam by TG-FTIR and HS-GC-MS","volume":"142","author":"Chen","year":"2020","journal-title":"Fitoterapia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5593730","DOI":"10.1155\/2021\/5593730","article-title":"Remarkable phytochemical characteristics of Chi-Nan Agarwood induced from new-found Chi-Nan germplasm of Aquilaria sinensis compared with ordinary Agarwood","volume":"2021","author":"Yu","year":"2021","journal-title":"Int. J. Anal. Chem."},{"key":"ref_12","first-page":"432","article-title":"Quality analysis and evaluation of agarwood produced by \u201cChi-nan\u201d germplasm based on standard of Chinese Pharmacopoeia","volume":"24","author":"Feng","year":"2022","journal-title":"Mod. Chin. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kao, W.Y., Hsiang, C.Y., Ho, S.C., Ho, T.Y., and Lee, K.T. (2018). Chemical Profiles of Incense Smoke Ingredients from Agarwood by Headspace Gas Chromatography-Tandem Mass Spectrometry. Molecules, 23.","DOI":"10.3390\/molecules23112969"},{"key":"ref_14","first-page":"5720","article-title":"Comparative analysis of chemical constituents and anti-oxidant and anti-inflammatory activities of six representative agarwood essential oils","volume":"18","author":"Chen","year":"2022","journal-title":"Chin. Tradit. Herb. Drugs"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"265","DOI":"10.2147\/DDDT.S348028","article-title":"Discovery of Biomarkers and Potential Mechanisms of Agarwood Incense Smoke Intervention by Untargeted Metabolomics and Network Pharmacology","volume":"16","author":"Dong","year":"2022","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"123056","DOI":"10.1016\/j.jchromb.2021.123056","article-title":"An integrated chemical characterization based on FT-NIR, GC-MS and LC-MS for the comparative metabolite profiling of wild and cultivated agarwood","volume":"1188","author":"Yao","year":"2022","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Liao, G., Dong, W.H., Yang, J.L., Li, W., Wang, J., Mei, W.L., and Dai, H.F. (2018). Monitoring the Chemical Profile in Agarwood Formation within One Year and Speculating on the Biosynthesis of 2-(2-Phenylethyl)Chromones. Molecules, 23.","DOI":"10.3390\/molecules23061261"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"114397","DOI":"10.1016\/j.ejmech.2022.114397","article-title":"Occurrence, synthesis and biological activity of 2-(2-phenyethyl)chromones","volume":"237","author":"Fan","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.fitote.2017.02.009","article-title":"Anti-inflammatory 2-(2-phenylethyl)chromone derivatives from Chinese agarwood","volume":"118","author":"Huo","year":"2017","journal-title":"Fitoterapia"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Liu, Y.Y., Chen, D.L., Wei, J.H., Feng, J., Zhang, Z., Yang, Y., and Zheng, W. (2016). Four New 2-(2-Phenylethyl)chromone Derivatives from Chinese Agarwood Produced via the Whole-Tree Agarwood-Inducing Technique. Molecules, 21.","DOI":"10.3390\/molecules21111433"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"105177","DOI":"10.1016\/j.fitote.2022.105177","article-title":"Seven new 2-(2-phenylethyl) chromone derivatives from agarwood of Aquilaria agallocha with inhibitory effects on nitric oxide production","volume":"159","author":"Zhang","year":"2022","journal-title":"Fitoterapia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20912","DOI":"10.3390\/molecules201119736","article-title":"New Flavones, a 2-(2-Phenylethyl)-4H-chromen-4-one Derivative, and Anti-Inflammatory Constituents from the Stem Barks of Aquilaria sinensis","volume":"20","author":"Wang","year":"2015","journal-title":"Molecules"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1055\/s-0033-1350647","article-title":"2-(2-phenylethyl)chromone derivatives in Chinese agarwood \u201cQi-Nan\u201d from Aquilaria sinensis","volume":"79","author":"Yang","year":"2013","journal-title":"Planta Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1080\/10286020.2017.1379998","article-title":"Two new 2-(2-Hydroxy-2-phenylethyl)chromens from agarwood originating from Aquilaria crassna","volume":"20","author":"Wang","year":"2018","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1080\/10286020.2016.1268602","article-title":"Qinanmer, a new compound from Chinese agarwood \u2018Qi-Nan\u2019 originating from Aquilaria sinensis","volume":"19","author":"Shao","year":"2017","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_26","first-page":"205","article-title":"New chromone and triglyceride from Cucumis melo seeds","volume":"9","author":"Ibrahim","year":"2014","journal-title":"Nat. Prod. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1080\/14786419.2019.1672066","article-title":"Three new 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones and one new dimeric 2-(2-phenylethyl)chromone from agarwood of Aquilaria crassna Pierre ex Lecomte in Laos","volume":"35","author":"Zhao","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1080\/14786419.2018.1528591","article-title":"New 2-(2-phenylethyl)chromone derivatives from agarwood and their inhibitory effects on tumor cells","volume":"34","author":"Liu","year":"2020","journal-title":"Nat. Prod. Res."},{"key":"ref_29","first-page":"300","article-title":"Phenylethylchromones with In Vitro Antitumor Promoting Activity from Aquilaria filaria","volume":"83","author":"Suzuki","year":"2017","journal-title":"Planta Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1021\/acs.jnatprod.8b00635","article-title":"Adiponectin-secretion-promoting phenylethylchromones from the agarwood of Aquilaria malaccensis","volume":"82","author":"Ahn","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1080\/14756366.2019.1576657","article-title":"Sesquiterpenoids and 2-(2-phenylethyl)chromones respectively acting as \u03b1-glucosidase and tyrosinase inhibitors from agarwood of an Aquilaria plant","volume":"34","author":"Yang","year":"2019","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1021\/np0503808","article-title":"Neuroprotective 2-(2-phenylethyl)chromones of Imperata cylindrica","volume":"69","author":"Yoon","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4292","DOI":"10.1016\/j.tetlet.2013.06.006","article-title":"An efficient procedure for the preparation of natural products bearing the 2-(2-phenylethyl)chromone skeleton","volume":"54","author":"Williams","year":"2013","journal-title":"Tetrahedron Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"112578","DOI":"10.1016\/j.phytochem.2020.112578","article-title":"2-(2-Phenylethyl)chromone derivatives: Promising \u03b1-glucosidase inhibitors in agarwood from Aquilaria filaria","volume":"181","author":"Mi","year":"2021","journal-title":"Phytochemistry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s11418-020-01410-z","article-title":"Five new 2-(2-phenylethyl)chromone derivatives from agarwood","volume":"74","author":"Shibata","year":"2020","journal-title":"J. Nat. Med."},{"key":"ref_36","first-page":"795","article-title":"New 2-(2-Phenylethyl)chromone Derivatives and Inhibitors of Phosphodiesterase (PDE) 3A from Agarwood","volume":"11","author":"Sugiyama","year":"2016","journal-title":"Nat. Prod. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e202200490","DOI":"10.1002\/cbdv.202200490","article-title":"Chemical and Bioactivity Diversity of 2-(2-Phenylethyl)chromones in Agarwood: A Review","volume":"19","author":"Yu","year":"2022","journal-title":"Chem. Biodivers"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41586-022-04431-8","article-title":"Low-dose metformin targets the lysosomal AMPK pathway through PEN2","volume":"603","author":"Ma","year":"2022","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"707399","DOI":"10.3389\/fphar.2021.707399","article-title":"Trimetazidine Attenuates Heart Failure by Improving Myocardial Metabolism via AMPK","volume":"12","author":"Shu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Khaliq, H.A., Alhouayek, M., Quetin-Leclercq, J., and Muccioli, G.G. (2022). 5\u2019AMP-activated protein kinase: An emerging target of phytochemicals to treat chronic inflammatory diseases. Crit. Rev. Food Sci. Nutr., 1\u201326.","DOI":"10.1080\/10408398.2022.2145264"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Xia, C., Wang, G., Chen, L., Geng, H., Yao, J., Bai, Z., and Deng, L. (2022). Trans-gnetin H isolated from the seeds of Paeonia species induces autophagy via inhibiting mTORC1 signalling through AMPK activation. Cell Prolif., e13360.","DOI":"10.1111\/cpr.13360"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.stem.2020.03.006","article-title":"A Metformin-Responsive Metabolic Pathway Controls Distinct Steps in Gastric Progenitor Fate Decisions and Maturation","volume":"26","author":"Miao","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.sbi.2017.10.010","article-title":"Protein structure-based drug design: From docking to molecular dynamics","volume":"48","author":"Caflisch","year":"2018","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/hep.32221","article-title":"Breviscapine alleviates NASH by inhibiting TGF-\u03b2-activated kinase 1-dependent signaling","volume":"76","author":"Lan","year":"2021","journal-title":"Hepatology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1158\/0008-5472.CAN-10-1899","article-title":"The role of calcium in the activation of estrogen receptor-alpha","volume":"71","author":"Divekar","year":"2011","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1002\/ijc.33745","article-title":"Role of calcium in hormone-independent and -resistant breast cancer","volume":"149","author":"Cyrus","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40203-015-0008-z","article-title":"A molecular docking study of phytochemical estrogen mimics from dietary herbal supplements","volume":"3","author":"Powers","year":"2015","journal-title":"Silico Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"815891","DOI":"10.3389\/fendo.2021.815891","article-title":"Exploration of the Molecular Mechanism of Polygonati Rhizoma in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking","volume":"12","author":"Zhao","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_49","first-page":"400","article-title":"Determination of Chromones Content in Agarwood by Using UV Spectrophotometry","volume":"4","author":"Yang","year":"2014","journal-title":"J. Trop. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/s41467-022-27971-z","article-title":"Identification of a diarylpentanoid-producing polyketide synthase revealing an unusual biosynthetic pathway of 2-(2-phenylethyl)chromones in agarwood","volume":"13","author":"Wang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4395","DOI":"10.1016\/j.tetlet.2005.04.072","article-title":"Three novel diepoxy tetrahydrochromones from agarwood artificially produced by intentional wounding","volume":"46","author":"Yagura","year":"2005","journal-title":"Tetrahedron Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/ffj.2034","article-title":"The volatile and semi-volatile constituents of agarwood, the infected heartwood of Aquilaria species: A review","volume":"26","author":"Naef","year":"2011","journal-title":"Flavour Fragr. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1039\/D0NP00042F","article-title":"Natural products in agarwood and Aquilaria plants: Chemistry, biological activities and biosynthesis","volume":"38","author":"Li","year":"2021","journal-title":"Nat. Prod. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10265","DOI":"10.1016\/S0040-4020(01)88332-0","article-title":"Preparation of (\u2212)-guaia-1 (10), 11-dien-15, 2-olide and (\u2212)-2\u03b1-hydroxyguaia-1 (10), 11-dien-15-oic acid, fragrant sesquiterpenes in agarwood (Aquilaria agallocha Roxb.)","volume":"48","author":"Ishihara","year":"1992","journal-title":"Tetrahedron"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"115799","DOI":"10.1016\/j.ces.2020.115799","article-title":"Engineered Saccharomyces cerevisiae for the de novo synthesis of the aroma compound longifolene","volume":"226","author":"Hassan","year":"2020","journal-title":"Chem. Eng. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13020-019-0248-7","article-title":"Simultaneous UPLC-TQ-MS\/MS determination of six active components in rat plasma: Application in the pharmacokinetic study of Cyclocarya paliurus leaves","volume":"14","author":"Ning","year":"2019","journal-title":"Chin. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.addr.2015.01.009","article-title":"The application of in silico drug-likeness predictions in pharmaceutical research","volume":"86","author":"Tian","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/mp.2016.225","article-title":"Role of the adipose PPAR\u03b3-adiponectin axis in susceptibility to stress and depression\/anxiety-related behaviors","volume":"22","author":"Guo","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3547","DOI":"10.1002\/jcb.24232","article-title":"Promotion of adiponectin multimerization by emodin: A novel AMPK activator with PPAR\u03b3-agonist activity","volume":"113","author":"Chen","year":"2012","journal-title":"J. Cell Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1080\/09168451.2017.1336923","article-title":"WSF-P-1, a novel AMPK activator, promotes adiponectin multimerization in 3T3-L1 adipocytes","volume":"81","author":"Wang","year":"2017","journal-title":"Biosci. Biotechnol. Biochem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1667\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:28:41Z","timestamp":1760120921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,9]]},"references-count":61,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["molecules28041667"],"URL":"https:\/\/doi.org\/10.3390\/molecules28041667","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,9]]}}}