{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T19:55:34Z","timestamp":1788551734961,"version":"build-2803163510"},"reference-count":99,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Abdullah International Medical Research Center (KAIMRC)","award":["SP19.271.R"],"award-info":[{"award-number":["SP19.271.R"]}]},{"name":"Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia","award":["SP19.271.R"],"award-info":[{"award-number":["SP19.271.R"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Myrrh extract is a well-known medicinal plant with significant therapeutic benefits attributed to the activity of its diverse metabolites. It has promising activity against cancer and inflammatory diseases, and could serve as a potential therapeutic alternative since most therapeutic agents have severe side effects that impair quality of life. Method: The current study identified the active metabolites from the myrrh resin methanolic extract. Then, the extracts were tested for in vitro anti-inflammatory and anti-cancer activity using cancer cell lines and Tamm-Horsfall Protein 1 (Thp-1)-like macrophage cell lines. Furthermore, using an in vivo rat model, the extracts\u2019 anti-inflammatory and wound-healing activity was investigated. In addition, in silico predictions of the myrrh constituents highlighted the pharmacokinetic properties, molecular targets, and safety profile, including cytochrome P 450 (CYP) inhibition and organ toxicity. Results: Nine secondary metabolites were identified, and computational predictions suggested a good absorption profile, anticancer, anti-inflammatory, and wound-healing effects. The myrrh extract had moderate cytotoxic activity against both HL60 and K562 leukemia cell lines and the KAIMRC1 breast cancer cell line. Myrrh caused a dose-dependent effect on macrophages to increase the reactive oxygen species (ROS) levels, promote their polarization to classically activated macrophages (M1) and alternatively activated macrophages (M2) phenotypes, and consequently induce apoptosis, highlighting its ability to modulate macrophage function, which could potentially aid in several desired therapeutic processes, including the resolution of inflammation, and autophagy which is an important aspect to consider in cancer treatment. The topical application of myrrh improved wound healing, with no delayed inflammatory response, and promoted complete re-epithelization of the skin, similar to the positive control. In conclusion, we provide evidence for the methanolic extract of myrrh having cytotoxic activity against cancer cells and anti-inflammatory wound-healing properties, which may be attributed to its role in modulating macrophage function. Furthermore, we suggest the active constituents responsible for these properties, which warrants further studies focusing on the precise roles of the active metabolites.<\/jats:p>","DOI":"10.3390\/ph15080944","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T04:04:00Z","timestamp":1659326640000},"page":"944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["The Role of Myrrh Metabolites in Cancer, Inflammation, and Wound Healing: Prospects for a Multi-Targeted Drug Therapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6323-0781","authenticated-orcid":false,"given":"Rasha Saad","family":"Suliman","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Fatima College of Health Sciences, Abu Dhabi 3798, United Arab Emirates"},{"name":"College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11461, Saudi Arabia"},{"name":"Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2770-218X","authenticated-orcid":false,"given":"Sahar Saleh","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11461, Saudi Arabia"},{"name":"Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2475-0258","authenticated-orcid":false,"given":"Rizwan","family":"Ali","sequence":"additional","affiliation":[{"name":"Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimah","family":"Aljatli","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norah Abdulaziz","family":"Aljammaz","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Huwaizi","sequence":"additional","affiliation":[{"name":"Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7153-4112","authenticated-orcid":false,"given":"Rania","family":"Suliman","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Sciences, Prince Sultan Military College of Health Sciences, Dahran 31448, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khawla Mohammed","family":"Kahtani","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5657-4650","authenticated-orcid":false,"given":"Ghadeer M.","family":"Albadrani","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tlili","family":"Barhoumi","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulelah","family":"Altolayyan","sequence":"additional","affiliation":[{"name":"Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6530-1504","authenticated-orcid":false,"given":"Ishrat","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Basic Dental Sciences, College of Dentistry, Princess Nourah Bint Abdulrahman University, Riyadh 40886, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/j.1472-765X.2012.03216.x","article-title":"The additive and synergistic antimicrobial effects of select frankincense and myrrh oils\u2014A combination from the pharaonic pharmacopoeia","volume":"54","author":"Kamatou","year":"2012","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_2","first-page":"153","article-title":"Essential oils of some Boswellia spp., Myrrh and Opopanax","volume":"18","author":"Demirci","year":"2003","journal-title":"Undefined"},{"key":"ref_3","unstructured":"US Food and Drug Administration (2021, May 25). CFR\u2014Code of Federal Regulations Title 21. New Hampshire Ave, Available online: https:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfcfr\/cfrsearch.cfm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.tox.2004.01.027","article-title":"Safety evaluation of food flavorings","volume":"198","author":"Schrankel","year":"2004","journal-title":"Toxicology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.jsps.2016.10.011","article-title":"Analysis of inorganic and organic constituents of myrrh resin by GC-MS and ICP-MS: An emphasis on medicinal assets","volume":"25","author":"Ahamad","year":"2017","journal-title":"Saudi Pharm. J."},{"key":"ref_6","first-page":"163","article-title":"Components, therapeutic value and uses of myrrh","volume":"58","author":"Rashed","year":"2003","journal-title":"Die Pharm. Int. J. Pharm. Sci."},{"key":"ref_7","unstructured":"(2022, January 16). NCI Dictionary of Cancer Terms-National Cancer Institute, Available online: https:\/\/www.cancer.gov\/publications\/dictionaries\/cancer-terms\/."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"730","DOI":"10.3892\/etm.2016.3398","article-title":"Myrrh attenuates oxidative and inflammatory processes in acetic acid-induced ulcerative colitis","volume":"12","author":"Fatani","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3804356","DOI":"10.1155\/2017\/3804356","article-title":"A pilot study on bioactive constituents and analgesic effects of MyrLiq\u00ae, a Commiphora myrrha extract with a high furanodiene content","volume":"2017","author":"Germano","year":"2017","journal-title":"BioMed Res. Int."},{"key":"ref_10","unstructured":"Daniel, M. (2006). Medicinal Plants: Chemistry and Properties, Science Publishers."},{"key":"ref_11","first-page":"32","article-title":"Antibacterial activity of Commiphora molmol in wound infections","volume":"2","author":"Mohamed","year":"2017","journal-title":"J. Diagn. Pathol. Oncol."},{"key":"ref_12","first-page":"639","article-title":"Antibacterial activity of Commiphora molmol in wound infections","volume":"17","author":"Hassan","year":"2017","journal-title":"Biochem. Cell. Arch."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1053\/gast.2003.50008","article-title":"Protective association of aspirin\/NSAIDs and esophageal cancer: A systematic review and meta-analysis","volume":"124","author":"Corley","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.3892\/ol.2013.1520","article-title":"Composition and potential anticancer activities of essential oils obtained from myrrh and frankincense","volume":"6","author":"Chen","year":"2013","journal-title":"Oncol. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1042\/BSR20192372","article-title":"Myrrh induces the apoptosis and inhibits the proliferation and migration of gastric cancer cells through down-regulating cyclooxygenase-2 expression","volume":"40","author":"Sun","year":"2020","journal-title":"Biosci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Alqahtani, A.S., Nasr, F.A., Noman, O.M., Farooq, M., Alhawassi, T., Qamar, W., and El-Gamal, A. (2020). Cytotoxic evaluation and anti-angiogenic effects of two furano-sesquiterpenoids from Commiphora myrrh resin. Molecules, 25.","DOI":"10.3390\/molecules25061318"},{"key":"ref_18","unstructured":"(2022, January 16). Corticosteroid Adverse Effects-PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/30285357\/."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1024\/0040-5930\/a000230","article-title":"Immunsuppressiva-Wirkungen, nebenwirkungen und interaktionen","volume":"68","author":"Stucker","year":"2011","journal-title":"Ther. Umsch."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.bpg.2009.11.005","article-title":"Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract","volume":"24","author":"Sostres","year":"2010","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.3892\/or.2015.3725","article-title":"Cycloartan-24-ene-1\u03b1,2\u03b1,3\u03b2-triol, a cycloartane-type triterpenoid from the resinous exudates of Commiphora myrrha, induces apoptosis in human prostatic cancer PC-3 cells","volume":"33","author":"Gao","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1021\/np070442p","article-title":"Cycloartane-type triterpenoids from the resinous exudates of Commiphora opobalsamum","volume":"71","author":"Shen","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1080\/0972060X.2019.1574611","article-title":"Essential oil constituents and biological activities of the halophytic plants, Suaeda vermiculata Forssk and Salsola cyclophylla Bakera growing in Saudi Arabia","volume":"22","author":"Mohammed","year":"2019","journal-title":"J. Essent. Oil Bear. Plants"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1186\/s12885-017-3812-5","article-title":"Isolation and characterization of a new naturally immortalized human breast carcinoma cell line, KAIMRC1","volume":"17","author":"Ali","year":"2017","journal-title":"BMC Cancer"},{"key":"ref_25","unstructured":"(2021, May 25). Way2Drug-Main. Available online: http:\/\/way2drug.com\/PassOnline\/."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1093\/bioinformatics\/16.8.747","article-title":"PASS: Prediction of activity spectra for biologically active substances","volume":"16","author":"Lagunin","year":"2000","journal-title":"Bioinformatics"},{"key":"ref_27","unstructured":"(2021, December 26). Molinspiration Cheminformatics. Available online: https:\/\/www.molinspiration.com\/."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13321-016-0130-x","article-title":"Improving chemical similarity ensemble approach in target prediction","volume":"8","author":"Wang","year":"2016","journal-title":"J. Cheminform"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"W357","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules","volume":"47","author":"Daina","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_30","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_31","unstructured":"(2021, December 26). SwissADME. Available online: http:\/\/www.swissadme.ch\/."},{"key":"ref_32","unstructured":"(2021, October 21). ProTox-II-Prediction of TOXicity of Chemicals. Available online: https:\/\/tox-new.charite.de\/protox_II\/."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4760","DOI":"10.1038\/s41598-021-83556-8","article-title":"Investigation of biological activity of soil fungal extracts and LC\/MS-QTOF based metabolite profiling","volume":"11","author":"Mohammed","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s10495-009-0332-z","article-title":"Furano-sesquiterpene from soft coral, Sinularia kavarittiensis: Induces apoptosis via the mitochondrial-mediated caspase-dependent pathway in THP-1, leukemia cell line","volume":"14","author":"Arepalli","year":"2009","journal-title":"Apoptosis"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2174\/1385272820666161018130431","article-title":"Furanodienone: An emerging bioactive furanosesquiterpenoid","volume":"21","author":"Messina","year":"2017","journal-title":"Curr. Org. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1002\/chin.200517187","article-title":"Absolute Stereostructures of Polypodane-Type Triterpenes, Myrrhanol A and Myrrhanone A, from Guggul-Gum Resin (the Resin of Balsamodendron mukul)","volume":"36","author":"Matsuda","year":"2005","journal-title":"ChemInform"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.canlet.2008.01.049","article-title":"Anti-tumor effect of beta-elemene in glioblastoma cells depends on p38 MAPK activation","volume":"264","author":"Yao","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_38","first-page":"161","article-title":"Frankincense and myrrh resources of Ethiopia: II. Medicinal and industrial uses","volume":"26","author":"Lemenith","year":"2003","journal-title":"SINET Ethiop. J. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bai, Z., Yao, C., Zhu, J., Xie, Y., Ye, X.Y., Bai, R., and Xie, T. (2021). Anti-tumor drug discovery based on natural product \u03b2-elemene: Anti-tumor mechanisms and structural modification. Molecules, 26.","DOI":"10.3390\/molecules26061499"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"108812","DOI":"10.1016\/j.biopha.2019.108812","article-title":"Molecular targets of \u03b2-elemene, a herbal extract used in traditional Chinese medicine, and its potential role in cancer therapy: A review","volume":"114","author":"Zhai","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e2815","DOI":"10.1038\/cddis.2017.220","article-title":"Furanodienone induces G0\/G1 arrest and causes apoptosis via the ROS\/MAPKs-mediated caspase-dependent pathway in human colorectal cancer cells: A study in vitro and in vivo","volume":"8","author":"Jiang","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_42","first-page":"1207","article-title":"Nuclear Receptors: Recent Drug Discovery for Cancer Therapies","volume":"40","author":"Zhao","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1055\/s-2006-959594","article-title":"Anti-inflammatory activity of resins from some species of the plant family Burseraceae","volume":"59","author":"Duwiejua","year":"1993","journal-title":"Planta Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7479518","DOI":"10.1155\/2019\/7479518","article-title":"The protective effect of dietary phytosterols on cancer risk: A systematic meta-analysis","volume":"2019","author":"Jiang","year":"2019","journal-title":"J. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e2100238","DOI":"10.1002\/cbdv.202100238","article-title":"Prevalence of diterpenes in essential oil of Euphorbia mauritanica L.: Detailed chemical profile, antioxidant, cytotoxic and phytotoxic activities","volume":"18","author":"Essa","year":"2021","journal-title":"Chem. Biodivers."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1021\/jo00402a040","article-title":"Marine natural products: Cembrene-A and cembrene-C from a soft coral, Nephthea species","volume":"43","author":"Vanderah","year":"1978","journal-title":"J. Org. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0039-128X(01)00189-1","article-title":"Effect of chirality at C-20 of methyl 11\u03b2, 17\u03b1, 20-trihydroxy-3-oxo-1, 4-pregnadien-21-oate derivatives on antiinflammatory activity","volume":"67","author":"You","year":"2002","journal-title":"Steroids"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.jsbmb.2008.06.014","article-title":"In vivo and in vitro effect of novel 4, 16-pregnadiene-6, 20-dione derivatives, as 5\u03b1-reductase inhibitors","volume":"111","author":"Bratoeff","year":"2008","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_49","first-page":"6630","article-title":"Antiandrogenic effects of novel androgen synthesis inhibitors on hormone-dependent prostate cancer","volume":"60","author":"Long","year":"2000","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10407","DOI":"10.7314\/APJCP.2014.15.23.10407","article-title":"\u03b2-elemene induces caspase-dependent apoptosis in human glioma cells in vitro through the upregulation of Bax and Fas\/FasL and downregulation of Bcl-2","volume":"15","author":"Li","year":"2015","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.biopha.2016.12.021","article-title":"Role of protease and protease in-hibitors in cancer pathogenesis and treatment","volume":"86","author":"Eatemadi","year":"2017","journal-title":"Biomed. Pharm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"134","DOI":"10.4103\/0974-8490.110545","article-title":"Isolation and identification of bacterial endophytes from pharmaceutical agarwood-producing Aquilaria species","volume":"5","author":"Bhore","year":"2013","journal-title":"Pharmacogn. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1055\/a-1157-9463","article-title":"Investigation of antiplasmodial effects of terpenoid compounds isolated from myrrh","volume":"86","author":"Greve","year":"2020","journal-title":"Planta Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1055\/s-0031-1280087","article-title":"Sesquiterpenoids from the resinous exudates of Commiphora myrrha and their neuroprotective effects","volume":"77","author":"Xu","year":"2011","journal-title":"Planta Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1016\/j.biopha.2018.07.124","article-title":"\u03b2-elemene against Burkitt\u2019s lymphoma via activation of PUMA mediated apoptotic pathway","volume":"106","author":"Hu","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/978-3-319-41342-6_15","article-title":"Guggulsterone and its role in chronic diseases","volume":"929","author":"Yamada","year":"2016","journal-title":"Drug Discov. Mother Nat."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1002\/ptr.2501","article-title":"Antibacterial terpenes from the oleo-resin of Commiphora molmol (Engl.)","volume":"22","author":"Rahman","year":"2008","journal-title":"Phytother. Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Wang, S., Yu, Z., Wang, C., Wu, C., Guo, P., and Wei, J. (2018). Chemical constituents and pharmacological activity of agarwood and Aquilaria plants. Molecules, 23.","DOI":"10.3390\/molecules23020342"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"294","DOI":"10.2174\/1381612822666151112153117","article-title":"Guggulsterone for Chemoprevention of Cancer","volume":"22","author":"Shishodia","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13277","DOI":"10.3748\/wjg.v21.i47.13277","article-title":"Guggulsterone induces apoptosis of human hepatocellular carcinoma cells through intrinsic mitochondrial pathway","volume":"21","author":"Shi","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_61","first-page":"2033","article-title":"Preparation and characterization of solid lipid nanoparticles loaded with frankincense and myrrh oil","volume":"7","author":"Shi","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e12963","DOI":"10.1111\/jfpp.12963","article-title":"Myrrh as a Functional Food with Therapeutic Properties Against Colon Cancer in Traditional Meals","volume":"41","author":"Hamad","year":"2017","journal-title":"J. Food Process. Preserv."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/aps.2010.219","article-title":"Sesquiterpenoids from myrrh inhibit androgen receptor expression and function in human prostate cancer cells","volume":"32","author":"Wang","year":"2011","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12906-020-2874-0","article-title":"Frankincense and myrrh and their bioactive compounds ameliorate the multiple myeloma through regulation of metabolome profiling and JAK\/STAT signaling pathway based on U266 cells","volume":"20","author":"Gao","year":"2020","journal-title":"BMC Complement. Med. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"191","DOI":"10.4103\/0974-8490.132593","article-title":"Screening of anticancer activity from agarwood essential oil","volume":"6","author":"Hashim","year":"2014","journal-title":"Pharmacogn. Res."},{"key":"ref_66","first-page":"1382","article-title":"Cytotoxicity activity of extracts and compounds from Commiphora myrrha resin against human gynecologic cancer cells","volume":"5","author":"Su","year":"2011","journal-title":"J. Med. Plants Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ddtec.2004.11.007","article-title":"Lead- and drug-like compounds: The rule-of-five revolution","volume":"1","author":"Lipinski","year":"2004","journal-title":"Drug Discov. Today Technol."},{"key":"ref_68","first-page":"195727","article-title":"Drug Solubility: Importance and Enhancement Techniques","volume":"5","author":"Savjani","year":"2012","journal-title":"ISRN Pharm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3389\/fimmu.2021.734229","article-title":"Reactive Oxygen Species in Macrophages: Sources and Targets","volume":"12","author":"Canton","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_70","unstructured":"Janeway, C.A., Travers, P., Walport, M., and Shlomchik, M.J. (2001). Principles of innate and adaptive immunity. Immunobiology: The Immune System in Health and Disease, Garland Science. [5th ed.]."},{"key":"ref_71","first-page":"491","article-title":"Macrophage cytokines: Involvement in immunity and infectious diseases","volume":"5","author":"Descoteaux","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Hirayama, D., Iida, T., and Nakase, H. (2017). The phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010092"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3389\/fonc.2012.00171","article-title":"The interplay between autophagy and ROS in tumorigenesis","volume":"2","author":"Kongara","year":"2012","journal-title":"Front. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"282739","DOI":"10.1155\/2011\/282739","article-title":"Macrophage autophagy and oxidative stress: An ultrastructural and immunoelectron microscopical study","volume":"2011","author":"Perrotta","year":"2011","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1038\/s41467-020-16400-8","article-title":"The TSPO-NOX1 axis controls phagocyte-triggered pathological angiogenesis in the eye","volume":"11","author":"Wolf","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1038\/s41467-017-02325-2","article-title":"Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4-MD2 complex","volume":"8","author":"Kim","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"101891","DOI":"10.1016\/j.redox.2021.101891","article-title":"Immune cell-produced ROS and their impact on tumor growth and metastasis","volume":"42","author":"Kennel","year":"2021","journal-title":"Redox Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12943-018-0804-2","article-title":"Kinase-targeted cancer therapies: Progress, challenges and future directions","volume":"17","author":"Bhullar","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2217\/14622416.9.1.105","article-title":"ABC multidrug transporters: Structure, function and role in chemoresistance","volume":"9","author":"Sharom","year":"2008","journal-title":"Pharmacogenomics"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6234","DOI":"10.1016\/j.bmcl.2013.09.093","article-title":"Anti-cancer evaluation of carboxamides of furano-sesquiterpene carboxylic acids from the soft coral Sinularia kavarattiensis","volume":"23","author":"Rajaram","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Eissa, M.A., Hashim, Y.Z.H., El-Kersh, D.M., Abd-Azziz, S.S., Salleh, H.M., Isa, M.L.M., and Abd Warif, N.M. (2020). Metabolite Profiling of Aquilaria malaccensis leaf extract using Liquid Chromatography-Q-TOF-Mass spectrometry and investigation of its potential antilipoxygenase activity in-vitro. Processes, 8.","DOI":"10.3390\/pr8020202"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0031-9422(00)80085-0","article-title":"Two furanoeudesmanes from the essential oil of myrrh","volume":"22","author":"Brieskorn","year":"1983","journal-title":"Phytochemistry"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Kerns, E.H., and Di, L. (2008). Drug-Like Properties: Concepts, Structure Design and Methods: From ADME to Toxicity Optimization, Elsevier.","DOI":"10.1016\/B978-012369520-8.50018-8"},{"key":"ref_84","unstructured":"Zulkifle, N.L.B. (2018). Antidiabetic Activity of Aquilaria Malaccensis (Agarwood) Leaves Extracts. [Ph.D. Thesis, Universiti Malaysia Pahang]."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s00280-005-0137-x","article-title":"Elemene displays anti-cancer ability on laryngeal cancer cells in vitro and in vivo","volume":"58","author":"Tao","year":"2006","journal-title":"Cancer Chemother. Pharm."},{"key":"ref_86","unstructured":"(2022, January 19). [Beta-Elemene Induces Apoptosis of K562 Leukemia Cells]-PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/11783084\/."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Cao, B., Wei, X.-C., Xu, X.-R., Zhang, H.-Z., Luo, C.-H., Feng, B., Xu, R.-C., Zhao, S.-Y., Du, X.-J., and Han, L. (2019). Seeing the Unseen of the Combination of Two Natural Resins, Frankincense and Myrrh: Changes in Chemical Constituents and Pharmacological Activities. Molecules, 24.","DOI":"10.3390\/molecules24173076"},{"key":"ref_88","first-page":"347","article-title":"Cytochrome P450 enzyme mediated herbal drug interactions (Part 1)","volume":"13","author":"Wanwimolruk","year":"2014","journal-title":"EXCLI J."},{"key":"ref_89","first-page":"391","article-title":"The Effect of Cytochrome P450 Metabolism on Drug Response, Interactions, and Adverse Effects","volume":"76","author":"Lynch","year":"2007","journal-title":"Am. Fam. Physician"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Shankar, K., and Mehendale, H.M. (2014). Cytochrome P450. Encyclopedia of Toxicology, Elsevier.","DOI":"10.1016\/B978-0-12-386454-3.00299-2"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Ismail, F., Wahab, A.Y.A., Isa, M.L.M., Muhammad, H., Ismail, R.A.S.R., and Razak, R.N.H.A. (2019). The effects of Aquilaria malaccensis leaves aqueous extract on sperm of Sprague Dawley Rats towards early embryogenesis. IIUM Med. J. Malays., 18.","DOI":"10.31436\/imjm.v18i2.96"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"366","DOI":"10.22270\/jddt.v9i2-s.2710","article-title":"In vitro ADME studies of TUG-891, a GPR-120 inhibitor using SWISS ADME predictor","volume":"9","author":"Mishra","year":"2019","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3329\/bjp.v13i1.33625","article-title":"Pass and Swiss ADME collaborated in silico docking approach to the synthesis of certain pyrazoline spacer compounds for dihydrofolate reductase inhibition and antimalarial activity","volume":"13","author":"Lohidakshan","year":"2018","journal-title":"Bangladesh J. Pharmacol."},{"key":"ref_94","first-page":"159","article-title":"ADME studies of TUG-770 (a GPR-40 inhibitor agonist) for the treatment of type 2 diabetes using SwissADME predictor: In silico study","volume":"12","author":"Negim","year":"2022","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11095-018-2353-1","article-title":"Computational assessment of pharmacokinetics and biological effects of some anabolic and androgen steroids","volume":"35","author":"Roman","year":"2018","journal-title":"Pharm. Res."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Mazumder, K., Hossain, M., Aktar, A., Mohiuddin, M., Sarkar, K.K., Biswas, B., and Fukase, K. (2021). In Silico Analysis and Experimental Evaluation of Ester Prodrugs of Ketoprofen for Oral Delivery: With a View to Reduce Toxicity. Processes, 9.","DOI":"10.3390\/pr9122221"},{"key":"ref_97","first-page":"2063","article-title":"SwissADME predictions of pharmacokinetics and drug-likeness properties of small molecules present in Ipomoea mauritiana Jacq","volume":"8","author":"Ranjith","year":"2019","journal-title":"J. Pharmacogn. Phytochem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s13721-020-00276-1","article-title":"Estimation of drug-likeness properties of GC-MS separated bioactive compounds in rare medicinal Pleione maculata using molecular docking technique and SwissADME in silico tools","volume":"10","author":"Sympli","year":"2021","journal-title":"Netw. Modeling Anal. Health Inform. Bioinform."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1177\/0091270007312153","article-title":"New era in drug interaction evaluation: US Food and Drug Administration update on CYP enzymes, transporters, and the guidance process","volume":"48","author":"Huang","year":"2008","journal-title":"J. Clin. Pharmacol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/8\/944\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:59:22Z","timestamp":1760140762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/8\/944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,29]]},"references-count":99,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ph15080944"],"URL":"https:\/\/doi.org\/10.3390\/ph15080944","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,29]]}}}