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This review systematically summarizes the natural resource distribution and biological signaling pathways of PA2, as well as the in vivo metabolic profiles of Sec. It further elaborates on the core physiological and pathological processes co-regulated by PA2 and Sec, including oxidative stress homeostasis, inflammatory immune responses, and metabolic reprogramming. Malignant tumors, severe diseases triggered by disrupted organismal homeostasis, serve as the primary research model for exploring the synergistic regulatory effects of PA2 combined with Sec. Accumulating evidence has validated the independent anti-tumor efficacy of PA2 and Sec in respective research domains; nevertheless, studies investigating their synergistic bioactivities remain scarce. Starting from the natural resource distribution of PA2 and the respective core biological functions of the two agents, this work systematically dissects their individual roles in modulating oxidative stress, inflammatory responses, tumor malignant proliferation and apoptosis, and proposes putative synergistic regulatory mechanisms with hypothetical mechanistic validation. The findings are expected to provide theoretical references and innovative research strategies for developing combinatorial interventions of natural polyphenols and selenocysteine against tumors and related disorders, as well as for constructing antioxidant damage defense systems.<\/jats:p>","DOI":"10.3390\/molecules31142503","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T02:32:08Z","timestamp":1784514728000},"page":"2503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic Effects of Selenium, Selenoproteins, Selenocysteine and Procyanidin A2 Based on Immune Response and Oxidative Stress"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5672-9763","authenticated-orcid":false,"given":"Liang","family":"Yang","sequence":"first","affiliation":[{"name":"School of Chemistry and Pharmaceutical Engineering, Hefei Normal University, Hefei 230601, China"},{"name":"Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyun","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Chemistry and Pharmaceutical Engineering, Hefei Normal University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Chemistry and Pharmaceutical Engineering, Hefei Normal University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinnan","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Chemistry and Pharmaceutical Engineering, Hefei Normal University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Qian","sequence":"additional","affiliation":[{"name":"School of Chemistry and Pharmaceutical Engineering, Hefei Normal University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoxiang","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Pharmaceutical Engineering, Hefei Normal University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2906-0125","authenticated-orcid":false,"given":"Bin","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Chemistry and Pharmaceutical Engineering, Hefei Normal University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmiao","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Chemistry and Pharmaceutical Engineering, Hefei Normal University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134855","DOI":"10.1016\/j.foodchem.2022.134855","article-title":"Characterization and bioactivity of A-type procyanidins from litchi fruitlets at different degrees of development","volume":"405","author":"Xie","year":"2023","journal-title":"Food Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.foodchem.2012.05.102","article-title":"Deconvolution of matrix-assisted laser desorption\/ionization time-of-flight mass spectrometry isotope patterns to determine ratios of A-type to B-type interflavan bonds in cranberry proanthocyanidins","volume":"135","author":"Feliciano","year":"2012","journal-title":"Food Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.jff.2012.09.005","article-title":"Procyanidin A2 purification and quantification of American cranberry (Vaccinium marocarpon Ait.) products","volume":"5","author":"Lee","year":"2013","journal-title":"J. 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