{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:45:17Z","timestamp":1792518317490,"version":"4.5.0"},"reference-count":92,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Autonomous University of Aguascalientes","award":["PIBT23-1"],"award-info":[{"award-number":["PIBT23-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The guava tree (Psidium guajava L.) is a tropical plant from the Myrtaceae family. Leaf extracts from this plant have been used in traditional medicine to treat gastrointestinal disorders and exhibit several functional activities that benefit human health. Different varieties of guava trees produce fruits in colors ranging from white to red and present a characteristic metabolic profile in both their leaves and fruits. This study presents a metabolomic characterization of the leaves from two guava varieties: the Caxcana cultivar with yellow fruits and the S-56 accession with pink fruits. Metabolite profiling was conducted using Gas Chromatography\u2013Mass Spectrometry (GC\u2013MS) on methanol extracts, followed by multivariate statistical analysis, including Principal Component Analysis (PCA), and a heat map visualization of compound concentrations in the two varieties. The results identified \u03b2-caryophyllene as the major secondary metabolite present in both varieties, with a relative abundance of 16.46% in the Caxcana variety and 23.06% in the S-56 cultivar. Furthermore, in silico analyses, such as network pharmacology and molecular docking, revealed key interactions with proteins such as CB2, PPAR\u03b1, BAX, BCL2, and AKT1, suggesting potential therapeutic relevance. These findings highlight the pharmacological potential of guava leaf metabolites in natural product chemistry and drug discovery.<\/jats:p>","DOI":"10.3390\/ijms26062530","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T07:31:42Z","timestamp":1741764702000},"page":"2530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Metabolomic Characterization and Bioinformatic Studies of Bioactive Compounds in Two Varieties of Psidium guajava L. Leaf by GC\u2013MS Analysis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4593-5582","authenticated-orcid":false,"given":"Ana","family":"Valdivia-Padilla","sequence":"first","affiliation":[{"name":"Centro de Ciencias B\u00e1sicas, Departamento de Qu\u00edmica, Universidad Aut\u00f3noma de Aguascalientes, Aguascalientes 20131, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9000-1378","authenticated-orcid":false,"given":"Ashutosh","family":"Sharma","sequence":"additional","affiliation":[{"name":"Centre of Bioengineering, NatProLab, School of Engineering and Sciences, Tecnologico de Monterrey, Quer\u00e9taro 76130, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6925-5445","authenticated-orcid":false,"given":"Jorge","family":"Zegbe","sequence":"additional","affiliation":[{"name":"Campo Experimental Pabell\u00f3n, Instituto Nacional de Investigaciones Forestales, Agr\u00edcolas y Pecuarias, Km 32.5 Carretera Aguascalientes-Zacatecas, Pabell\u00f3n de Arteaga, Aguascalientes 20668, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3418-6416","authenticated-orcid":false,"given":"Jos\u00e9","family":"Morales-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Centro de Ciencias B\u00e1sicas, Departamento de Qu\u00edmica, Universidad Aut\u00f3noma de Aguascalientes, Aguascalientes 20131, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Marrelli, M. (2021). Medicinal Plants. Plants, 10.","DOI":"10.3390\/plants10071355"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/pca.2883","article-title":"Metabolomics Analysis and Biological Investigation of Three Malvaceae Plants","volume":"31","author":"Abdelhafez","year":"2020","journal-title":"Phytochem. Anal."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Angulo-L\u00f3pez, J.E., Flores-Gallegos, A.C., Torres-Le\u00f3n, C., Ram\u00edrez-Guzm\u00e1n, K.N., Mart\u00ednez, G.A., and Aguilar, C.N. (2021). Guava (Psidium Guajava L.) Fruit and Valorization of Industrialization By-Products. Processes, 9.","DOI":"10.3390\/pr9061075"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s40816-018-0093-8","article-title":"The Phytochemistry and Medicinal Value of Psidium Guajava (Guava)","volume":"4","author":"Naseer","year":"2018","journal-title":"Clin. Phytoscience"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kumar, M., Tomar, M., Amarowicz, R., Saurabh, V., Nair, M.S., Maheshwari, C., Sasi, M., Prajapati, U., Hasan, M., and Singh, S. (2021). Guava (Psidium Guajava L.) Leaves: Nutritional Composition, Phytochemical Profile, and Health-Promoting Bioactivities. Foods, 10.","DOI":"10.3390\/foods10040752"},{"key":"ref_6","first-page":"1233","article-title":"Caracterizaci\u00f3n de La Guayaba Cultivada En M\u00e9xico","volume":"13","year":"2022","journal-title":"Rev. Mex. Cienc. Agric."},{"key":"ref_7","first-page":"4","article-title":"Caracterizaci\u00f3n Morfol\u00f3gica de Fruto de la Colecci\u00f3n Ex Situ de Psidium Guajava L.","volume":"9","year":"2016","journal-title":"Agro Product."},{"key":"ref_8","first-page":"198","article-title":"Fenolog\u00eda, productividad y calidad de fruto de guayaba pulpa crema y rosa en clima tropical en M\u00e9xico","volume":"40","year":"2015","journal-title":"Interciencia"},{"key":"ref_9","unstructured":"Padilla Ram\u00edrez, J.S., Gonz\u00e1lez Gaona, E., and Perales de la Cruz, M.\u00c1. (2010). Nuevas variedades de guayaba (Psidium guajava L.). Folleto T\u00e9cnico 42, Instituto Nacional de Investigaciones Forestales, Agr\u00edcolas y Pecuarias."},{"key":"ref_10","first-page":"393","article-title":"Caracterizaci\u00f3n de Germoplasma Sobresaliente de Guayabo de la Regi\u00f3n Calvillo-Ca\u00f1ones, M\u00e9xico","volume":"25","year":"2002","journal-title":"Rev. Fitotec. Mex."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, S., Liu, G., Xie, C., Zhou, Y., Yang, R., Wu, J., Xu, J., and Tu, K. (2024). Metabolomics Analysis of Different Quinoa Cultivars Based on UPLC-ZenoTOF-MS\/MS and Investigation into Their Antioxidant Characteristics. Plants, 13.","DOI":"10.3390\/plants13020240"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hill, C.B., and Roessner, U. (2013). Metabolic Profiling of Plants by GC\u2013MS. The Handbook of Plant Metabolomics, Wiley Online Books.","DOI":"10.1002\/9783527669882.ch1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1111\/pce.14407","article-title":"Exact Mass GC-MS Analysis: Protocol, Database, Advantages, and Application to Plant Metabolic Profiling","volume":"45","author":"Abadie","year":"2022","journal-title":"Plant Cell Environ."},{"key":"ref_14","first-page":"81","article-title":"A Review: Uses of Gas Chromatography-Mass Spectrometry (GC-MS) Technique for Analysis of Bioactive Natural Compounds of Some Plants","volume":"9","author":"Hameed","year":"2017","journal-title":"Int. J. Toxicol. Pharmacol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104103","DOI":"10.1016\/j.arabjc.2022.104103","article-title":"Untargeted GC-MS Metabolomics Applied to Wild Leaves and Callus Produced by Plant Tissue Culture of Hibiscus Sabdariffa L.","volume":"15","author":"Sobrinho","year":"2022","journal-title":"Arab. J. Chem."},{"key":"ref_16","first-page":"3","article-title":"Study of GC-MS and HPLC Characterized Metabolic Compounds In Guava (Psidium guajava L.) Leaves","volume":"56","author":"Afzal","year":"2019","journal-title":"Pak. J. Agric. Sci."},{"key":"ref_17","first-page":"11","article-title":"Leaf essential oil composition and bioactivity of Psidium guajava from Kathmandu, Nepal","volume":"3","author":"Satyal","year":"2015","journal-title":"Am. J. Essent. Oils Nat. Prod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1080\/14786419.2019.1648462","article-title":"Chemical composition and antimicrobial activity of the essential oil of senescent leaves of guava (Psidium guajava L.)","volume":"35","author":"Chaturvedi","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1080\/0972060X.2017.1417746","article-title":"Gas Chromatography-Mass Spectrometry (GC-MS) Analysis of Volatile Components from Guava Leaves","volume":"20","author":"Xu","year":"2017","journal-title":"J. Essent. Oil Bear. Plants"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/jxb\/erab487","article-title":"Volatile-Mediated Plant\u2013Plant Interactions: Volatile Organic Compounds as Modulators of Receiver Plant Defence, Growth, and Reproduction","volume":"73","author":"Brosset","year":"2022","journal-title":"J. Exp. Bot."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dunki\u0107, V., Nazli\u0107, M., Ru\u0161\u010di\u0107, M., Vuko, E., Akrap, K., Topi\u0107, S., Milovi\u0107, M., Vuleti\u0107, N., Puizina, J., and Grube\u0161i\u0107, R.J. (2022). Hydrodistillation and Microwave Extraction of Volatile Compounds: Comparing Data for Twenty-One Veronica Species from Different Habitats. Plants, 11.","DOI":"10.3390\/plants11070902"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Montejano-Ram\u00edrez, V., \u00c1vila-Oviedo, J.L., Campos-Mendoza, F.J., and Valencia-Cantero, E. (2024). Microbial Volatile Organic Compounds: Insights into Plant Defense. Plants, 13.","DOI":"10.3390\/plants13152013"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/tpj.15453","article-title":"Volatile Terpenes\u2013Mediators of Plant-to-plant Communication","volume":"108","author":"Rosenkranz","year":"2021","journal-title":"Plant J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s11101-013-9331-3","article-title":"The Evolution of Foliar Terpene Diversity in Myrtaceae","volume":"13","author":"Padovan","year":"2014","journal-title":"Phytochem. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1007\/s10886-012-0149-z","article-title":"Mosaic Eucalypt Trees Suggest Genetic Control at a Point That Influences Several Metabolic Pathways","volume":"38","author":"Padovan","year":"2012","journal-title":"J. Chem. Ecol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Portillo-Estrada, M. (2024). Limitations of Plant Stress Tolerance upon Heat and CO2 Exposure in Black Poplar: Assessment of Photosynthetic Traits and Stress Volatile Emissions. Plants, 13.","DOI":"10.3390\/plants13081165"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1080\/14786419.2015.1068772","article-title":"Chemical Composition and Insecticidal Activities of Essential Oils against Diamondback Moth, Plutella Xylostella (L.) (Lepidoptera: Yponomeutidae)","volume":"30","author":"Reddy","year":"2016","journal-title":"Nat. Prod. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10383","DOI":"10.1007\/s11356-017-9490-7","article-title":"High Toxicity of Camphene and \u03b3-Elemene from Wedelia Prostrata Essential Oil against Larvae of Spodoptera litura (Lepidoptera: Noctuidae)","volume":"25","author":"Benelli","year":"2018","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1016\/j.csbj.2021.04.015","article-title":"Multiblock Metabolomics: An Approach to Elucidate Whole-Body Metabolism with Multiblock Principal Component Analysis","volume":"19","author":"Tanabe","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"113681","DOI":"10.1016\/j.phytochem.2023.113681","article-title":"A New Sesquiterpene Synthase Catalyzing the Formation of (R)-\u03b2-Bisabolene from Medicinal Plant Colquhounia Coccinea Var. Mollis and Its Anti-Adipogenic and Antibacterial Activities","volume":"211","author":"Li","year":"2023","journal-title":"Phytochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1002\/ptr.5543","article-title":"\u03b2-Bisabolene, a Sesquiterpene from the Essential Oil Extract of Opoponax (Commiphora Guidottii), Exhibits Cytotoxicity in Breast Cancer Cell Lines","volume":"30","author":"Yeo","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.phymed.2010.06.018","article-title":"Synergistic Properties of the Terpenoids Aromadendrene and 1,8-Cineole from the Essential Oil of Eucalyptus Globulus against Antibiotic-Susceptible and Antibiotic-Resistant Pathogens","volume":"17","author":"Mulyaningsih","year":"2010","journal-title":"Phytomedicine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.lfs.2018.01.029","article-title":"Aromadendrene Oxide 2, Induces Apoptosis in Skin Epidermoid Cancer Cells through ROS Mediated Mitochondrial Pathway","volume":"197","author":"Pavithra","year":"2018","journal-title":"Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/j.1742-7843.2009.00467.x","article-title":"Antioxidant Activity of Limonene on Normal Murine Lymphocytes: Relation to H2O2 Modulation and Cell Proliferation","volume":"106","author":"Roberto","year":"2010","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Anandakumar, P., Kamaraj, S., and Vanitha, M.K. (2021). D-limonene: A Multifunctional Compound with Potent Therapeutic Effects. J. Food Biochem., 45.","DOI":"10.1111\/jfbc.13566"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105260","DOI":"10.1016\/j.jff.2022.105260","article-title":"Nutraceuticals: A Source of Benefaction for Neuropathic Pain and Fibromyalgia","volume":"97","author":"Mishra","year":"2022","journal-title":"J. Funct. Foods"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Francomano, F., Caruso, A., Barbarossa, A., Fazio, A., La Torre, C., Ceramella, J., Mallamaci, R., Saturnino, C., Iacopetta, D., and Sinicropi, M.S. (2019). \u03b2-Caryophyllene: A Sesquiterpene with Countless Biological Properties. Appl. Sci., 9.","DOI":"10.3390\/app9245420"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.phymed.2013.08.006","article-title":"The Oral Administration of Trans-Caryophyllene Attenuates Acute and Chronic Pain in Mice","volume":"21","author":"Andersen","year":"2014","journal-title":"Phytomedicine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/14786419.2024.2333053","article-title":"Molecular docking of quercetin: A promising approach for the development of new anti-inflammatory and analgesic drugs","volume":"38","author":"Ettitaou","year":"2024","journal-title":"Nat. Prod. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Reggio, P.H. (2009). Therapeutic applications for agents that act at CB1 and CB2 receptors. The Cannabinoid Receptors, Humana Press. The Receptors.","DOI":"10.1007\/978-1-59745-503-9"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.1007\/s00018-016-2300-4","article-title":"The CB2 receptor and its role as a regulator of inflammation","volume":"73","author":"Turcotte","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.apsb.2017.05.005","article-title":"The potential of natural products for targeting PPAR\u03b1","volume":"7","author":"Rigano","year":"2017","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.bcp.2014.07.018","article-title":"Natural product agonists of peroxisome proliferator-activated receptor gamma (PPAR\u03b3): A review","volume":"92","author":"Wang","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Honda, A., Kamata, S., Akahane, M., Machida, Y., Uchii, K., Shiiyama, Y., Habu, Y., Miyawaki, S., Kaneko, C., and Oyama, T. (2022). Functional and Structural Insights into Human PPAR\u03b1\/\u03b4\/\u03b3 Subtype Selectivity of Bezafibrate, Fenofibric Acid, and Pemafibrate. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094726"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/jcb.30162","article-title":"Thymoquinone and quercetin induce enhanced apoptosis in non-small cell lung cancer in combination through the Bax\/Bcl2 cascade","volume":"123","author":"Alam","year":"2022","journal-title":"J. Cell. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s11010-022-04546-6","article-title":"Molecular docking and in vitro experiments verified that kaempferol induced apoptosis and inhibited human HepG2 cell proliferation by targeting BAX, CDK1, and JUN","volume":"478","author":"Zhang","year":"2023","journal-title":"Mol. Cell. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5208","DOI":"10.1021\/acs.jcim.0c01420","article-title":"Analysis of the Binding Sites on BAX and the Mechanism of BAX Activators through Extensive Molecular Dynamics Simulations","volume":"62","author":"Feng","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s10495-017-1434-7","article-title":"Molecular docking studies of bioactive compounds from Annona muricata Linn as potential inhibitors for Bcl-2, Bcl-w and Mcl-1 antiapoptotic proteins","volume":"23","author":"Rosdi","year":"2018","journal-title":"Apoptosis"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"685","DOI":"10.3109\/14756366.2011.608663","article-title":"Molecular docking studies of anti-apoptotic BCL-2, BCL-XL, and MCL-1 proteins with ginsenosides from Panax ginseng","volume":"27","author":"Sathishkumar","year":"2012","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"217","DOI":"10.2174\/1568011033482459","article-title":"The BCL2-family of protein ligands as cancer drugs: The next generation of therapeutics","volume":"3","author":"Liu","year":"2003","journal-title":"Curr. Med. Chem.-Anti-Cancer Agents"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Mirza, Z., and Karim, S. (2023). Structure-Based Profiling of Potential Phytomolecules with AKT1 a Key Cancer Drug Target. Molecules, 28.","DOI":"10.3390\/molecules28062597"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s11030-019-09924-9","article-title":"Combining ligand- and structure-based in silico methods for the identification of natural product-based inhibitors of Akt1","volume":"24","author":"Mahajan","year":"2020","journal-title":"Mol. Divers."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.tips.2022.06.010","article-title":"Developing the Cannabinoid Receptor 2 (CB2) Pharmacopoeia: Past, Present, and Future","volume":"43","author":"Whiting","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Scandiffio, R., Geddo, F., Cottone, E., Querio, G., Antoniotti, S., Gallo, M.P., Maffei, M.E., and Bovolin, P. (2020). Protective Effects of (E)-\u03b2-Caryophyllene (BCP) in Chronic Inflammation. Nutrients, 12.","DOI":"10.3390\/nu12113273"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"124252","DOI":"10.1016\/j.ijpharm.2024.124252","article-title":"Development of Ophthalmic Nanoemulsions of \u03b2-Caryophyllene for the Treatment of Acanthamoeba Keratitis","volume":"659","author":"Porto","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ricardi, C., Barachini, S., Consoli, G., Marazziti, D., Polini, B., and Chiellini, G. (2024). Beta-Caryophyllene, a Cannabinoid Receptor Type 2 Selective Agonist, in Emotional and Cognitive Disorders. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063203"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"101727","DOI":"10.1016\/j.isci.2020.101727","article-title":"PPAR\u03b1 Ligand-Binding Domain Structures with Endogenous Fatty Acids and Fibrates","volume":"23","author":"Kamata","year":"2020","journal-title":"iScience"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1210\/er.2018-00064","article-title":"Molecular Actions of PPAR\u03b1 in Lipid Metabolism and Inflammation","volume":"39","author":"Bougarne","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1007\/s11064-020-02993-5","article-title":"The Novel Role of PPAR Alpha in the Brain: Promising Target in Therapy of Alzheimer\u2019s Disease and Other Neurodegenerative Disorders","volume":"45","author":"Strosznajder","year":"2020","journal-title":"Neurochem. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jneuroim.2006.04.019","article-title":"Peroxisome Proliferator-Activated Receptor-\u03b1 and Retinoid X Receptor Agonists Inhibit Inflammatory Responses of Astrocytes","volume":"176","author":"Xu","year":"2006","journal-title":"J. Neuroimmunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.it.2007.09.003","article-title":"Anti-Inflammatory Actions of PPAR Ligands: New Insights on Cellular and Molecular Mechanisms","volume":"28","author":"Straus","year":"2007","journal-title":"Trends Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"259","DOI":"10.2217\/fca-2016-0059","article-title":"PPARs: Regulators of Metabolism and As Therapeutic Targets in Cardiovascular Disease. Part I: PPAR-\u03b1","volume":"13","author":"Han","year":"2017","journal-title":"Futur. Cardiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1111\/j.1463-1326.2007.00747.x","article-title":"PPAR-alpha: Therapeutic Role in Diabetes-related Cardiovascular Disease","volume":"10","author":"Cheng","year":"2008","journal-title":"Diabetes Obes. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Al-Harbi, L.N. (2024). Morin Prevents Non-Alcoholic Hepatic Steatosis in Obese Rats by Targeting the Peroxisome Proliferator-Activated Receptor Alpha (PPAR\u03b1). Life, 14.","DOI":"10.3390\/life14080945"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/leu.2012.329","article-title":"PPAR-Alpha Is a Therapeutic Target for Chronic Lymphocytic Leukemia","volume":"27","author":"Spaner","year":"2013","journal-title":"Leukemia"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.tips.2021.11.001","article-title":"Physiological and Pharmacological Modulation of BAX","volume":"43","author":"Spitz","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/med.21379","article-title":"Direct Activation of Bax Protein for Cancer Therapy","volume":"36","author":"Liu","year":"2016","journal-title":"Med. Res. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1016\/j.apsb.2024.02.010","article-title":"Directly Targeting BAX for Drug Discovery: Therapeutic Opportunities and Challenges","volume":"14","author":"Zhang","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1038\/sj.cdd.4401975","article-title":"Proapoptotic Multidomain Bcl-2\/Bax-Family Proteins: Mechanisms, Physiological Roles, and Therapeutic Opportunities","volume":"13","author":"Reed","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/cdd.2008.137","article-title":"Bcl-2 Inhibitors: Small Molecules with a Big Impact on Cancer Therapy","volume":"16","author":"Vogler","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1016\/j.exphem.2006.07.008","article-title":"Bcl-2 Inhibitors Induce Apoptosis in Chronic Lymphocytic Leukemia Cells","volume":"34","author":"Cosialls","year":"2006","journal-title":"Exp. Hematol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1158\/0008-5472.CAN-06-2203","article-title":"Influence of Bcl-2 Family Members on the Cellular Response of Small-Cell Lung Cancer Cell Lines to ABT-737","volume":"67","author":"Tahir","year":"2007","journal-title":"Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"D\u2019Aguanno, S., and Del Bufalo, D. (2020). Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer. Cells, 9.","DOI":"10.3390\/cells9051287"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0163-7258(02)00193-6","article-title":"Inhibition of Protein Kinase B\/Akt. Implications for cancer therapy","volume":"93","author":"Hill","year":"2002","journal-title":"Pharmacol. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"458","DOI":"10.2174\/156802610790980602","article-title":"The Akt\/PKB Family of Protein Kinases: A Review of Small Molecule Inhibitors and Progress Towards Target Validation","volume":"10","author":"Barnett","year":"2010","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12964-019-0450-3","article-title":"Distinct Functions of AKT Isoforms in Breast Cancer: A Comprehensive Review","volume":"17","author":"Hinz","year":"2019","journal-title":"Cell Commun. Signal."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1158\/0008-5472.CAN-18-2738","article-title":"AKT as a Therapeutic Target for Cancer","volume":"79","author":"Song","year":"2019","journal-title":"Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1093\/carcin\/bgn201","article-title":"Plant Flavonoid Apigenin Inactivates Akt to Trigger Apoptosis in Human Prostate Cancer: An in Vitro and in Vivo Study","volume":"29","author":"Kaur","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ijbiomac.2016.12.025","article-title":"Identification of Natural Allosteric Inhibitor for Akt1 Protein through Computational Approaches and in Vitro Evaluation","volume":"96","author":"Lakshmi","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"104270","DOI":"10.1016\/j.phrs.2019.104270","article-title":"The Unconventional Role of Akt1 in the Advanced Cancers and in Diabetes-Promoted Carcinogenesis","volume":"145","author":"Alwhaibi","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1093\/pcp\/pch126","article-title":"Enhanced Triterpene and Phytosterol Biosynthesis in Panax Ginseng Overexpressing Squalene Synthase Gene","volume":"45","author":"Lee","year":"2004","journal-title":"Plant Cell Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.jgeb.2018.06.001","article-title":"In Silico Analysis of Squalene Synthase in Fabaceae Family Using Bioinformatics Tools","volume":"16","author":"Aminfar","year":"2018","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"100403","DOI":"10.1016\/j.plgene.2023.100403","article-title":"Squalene Synthase in Plants\u2013Functional Intricacy and Evolutionary Divergence While Retaining a Core Catalytic Structure","volume":"33","author":"Hazra","year":"2023","journal-title":"Plant Gene"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s11240-015-0778-3","article-title":"Overexpression of Squalene Synthase in Withania somnifera Leads to Enhanced Withanolide Biosynthesis","volume":"122","author":"Patel","year":"2015","journal-title":"Plant Cell Tissue Organ Cult. (PCTOC)"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.phytochem.2005.02.016","article-title":"Overexpression of Squalene Synthase in Eleutherococcus senticosus Increases Phytosterol and Triterpene Accumulation","volume":"66","author":"Seo","year":"2005","journal-title":"Phytochemistry"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Alcalde, M.A., Palazon, J., Bonfill, M., and Hidalgo-Martinez, D. (2023). Enhancing Centelloside Production in Centella asiatica Hairy Root Lines through Metabolic Engineering of Triterpene Biosynthetic Pathway Early Genes. Plants, 12.","DOI":"10.3390\/plants12193363"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"110457","DOI":"10.1016\/j.plantsci.2020.110457","article-title":"Advances in Biosynthesis, Regulation, and Metabolic Engineering of Plant Specialized Terpenoids","volume":"294","author":"Nagegowda","year":"2020","journal-title":"Plant Sci."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Zhang, A., Xiong, Y., Fang, J., Jiang, X., Wang, T., Liu, K., Peng, H., and Zhang, X. (2022). Diversity and Functional Evolution of Terpene Synthases in Rosaceae. Plants, 11.","DOI":"10.3390\/plants11060736"},{"key":"ref_89","unstructured":"Wink, M. (2010). Biochemistry of Terpenoids: Monoterpenes, Sesquiterpenes and Diterpenes. Annual Plant Reviews Volume 40: Biochemistry of Plant Secondary Metabolism, Wiley-Blackwell."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Canal, D., Escudero, F.L.G., Mendes, L.A., da Silva Ferreira, M.F., and Turchetto-Zolet, A.C. (2023). Genome-Wide Identification, Expression Profile and Evolutionary Relationships of TPS Genes in the Neotropical Fruit Tree Species Psidium cattleyanum. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-31061-5"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Canal, D., dos Santos, P.H.D., de Avelar Carpinetti, P., Silva, M.A., Fernandes, M., Brustolini, O.J.B., Ferreira, A., and da Silva Ferreira, M.F. (2024). Exploring the Versatility of Sesquiterpene Biosynthesis in Guava Plants: A Comparative Genome-Wide Analysis of Two Cultivars. Sci. Rep., 14.","DOI":"10.1038\/s41598-023-51007-1"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2174\/157340910791760055","article-title":"Metabolomics of medicinal plants: The importance of multivariate analysis of analytical chemistry data","volume":"6","author":"Okada","year":"2010","journal-title":"Curr. Comput.-Aided Drug Des."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2530\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:51:11Z","timestamp":1760028671000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2530"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,12]]},"references-count":92,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26062530"],"URL":"https:\/\/doi.org\/10.3390\/ijms26062530","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,12]]}}}