{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:59:04Z","timestamp":1785405544246,"version":"3.56.0"},"reference-count":89,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Imam Mohammad Ibn Saud Islamic University","award":["IMSIU-DDRSP2601"],"award-info":[{"award-number":["IMSIU-DDRSP2601"]}]},{"award":["IMSIU-DDRSP2601"],"award-info":[{"award-number":["IMSIU-DDRSP2601"]}],"id":[{"id":"https:\/\/ror.org\/05gxjyb39","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Redox homeostasis is the balance between oxidative processes and antioxidant defenses and is fundamental to cellular integrity. This review critically synthesizes current evidence on the phytochemical composition, redox-modulating mechanisms, and therapeutic bioactivities of Fagonia cretica L. (F. cretica), with the aim of evaluating its translational potential as a natural antioxidant and anticancer agent. F. cretica has emerged as a phytochemically rich candidate containing highly bioactive secondary metabolite for redox-targeted therapeutic applications. Its diverse secondary metabolite profile, including alkaloids, flavonoids, tannins, saponins, terpenoids, glycosides, and phenolic compounds, confers broad biological activity. Bioactive constituents, particularly kaempferol, catechin, quercetin, and arbutin, directly neutralize reactive oxygen species (ROS) and modulate inflammatory pathways through inhibition of COX-1, COX-2, and nitric oxide production. These compounds influence important major ROS-sensitive redox signaling pathways: activation of the Keap1\/Nrf2\/ARE axis to upregulate cytoprotective genes such as HO-1, NQO1, and GCL, suppression of the NF-\u03baB pathway to attenuate pro-inflammatory cytokine transcription, including TNF-\u03b1, IL-1\u03b2, and IL-6, and interference with the MAPK-PI3K\/Akt cascade to disrupt aberrant cancer cell survival and proliferation. Bioactive compound-rich extracts of F. cretica exhibit anticancer activity in MCF-7 breast cancer cells by inducing DNA damage, cell cycle arrest, and apoptotic signaling through the FOXO3a\/p53 pathways. Similar effects have been reported in colorectal (HCT-116) and prostate (PC-3) cancer cells through DNA (cytosine-5)-methyltransferase 1 (DNMT1) downregulation, oxidative stress induction, and ER-\u03b2 activation. Moreover, these extracts demonstrate cytotoxic effects in HepG2 and Caco-2 intestinal cancer cells, often associated with topoisomerase inhibition and caspase activation. Despite encouraging preclinical evidence, systematic studies encompassing pharmacokinetic profiling, toxicological characterization, and human clinical trials remain essential to translate these findings into safe, evidence-based therapeutic applications.<\/jats:p>","DOI":"10.3390\/ph19071036","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T09:34:11Z","timestamp":1783071251000},"page":"1036","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fagonia cretica L. and Redox Homeostasis: An Integrative Review of Phytochemistry, Redox-Sensitive Signaling, and Pharmacological Potential"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7154-3411","authenticated-orcid":false,"given":"Asad","family":"Abbas","sequence":"first","affiliation":[{"name":"Department of Human Nutrition, Faculty of Food Science and Nutrition, Bahauddin Zakariya University, Multan 60800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7397-1596","authenticated-orcid":false,"given":"Saeed","family":"Vohra","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh 11623, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0931","authenticated-orcid":false,"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hameeza","family":"Mushtaq","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Faculty of Food Science and Nutrition, Bahauddin Zakariya University, Multan 60800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Amjad","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Faculty of Food Science and Nutrition, Bahauddin Zakariya University, Multan 60800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arooma","family":"Tabassum","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Government College University, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shehnshah","family":"Zafar","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Faculty of Food Science and Nutrition, Bahauddin Zakariya University, Multan 60800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1506-7836","authenticated-orcid":false,"given":"Anis Ahmad","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1272-0637","authenticated-orcid":false,"given":"Abdulrahman Mohammed","family":"Alhudhaibi","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1123-2806","authenticated-orcid":false,"given":"Bipindra","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Madan Bhandari Academy of Health Sciences, Hetauda 44107, Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Le Gal, K., Schmidt, E.E., and Sayin, V.I. 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