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polarization. Mechanistically, TLR4-, TLR2-specific inhibitors, and TLR4-knockout cells confirmed TLR4 as the primary receptor for CPP-3a, with TLR2 playing a secondary role in cytokine modulation. CPP-3a activated NF-\u03baB and p38 MAPK signaling pathways via the MyD88-dependent pathway, evidenced by phosphorylation of NF-\u03baB\/p65 with its nuclear translocation and increased phosphorylation of p38 MAPK, with these signaling activations further validated by specific pathway inhibitors that abolished M1 polarization phenotypes. Collectively, CPP-3a emerges as a potent TLR4-targeted immunomodulator with adjuvant potential for inflammatory and infectious diseases.<\/jats:p>","DOI":"10.3390\/md23070290","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T15:48:22Z","timestamp":1752680902000},"page":"290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Chlorella pyrenoidosa Polysaccharide CPP-3a Promotes M1 Polarization of Macrophages via TLR4\/2-MyD88-NF-\u03baB\/p38 MAPK Signaling Pathways"],"prefix":"10.3390","volume":"23","author":[{"given":"Yihua","family":"Pi","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8023-3944","authenticated-orcid":false,"given":"Qingxia","family":"Yuan","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Marine Drugs, University Engineering Research Center of High-Efficient Utilization of Marine Traditional Chinese Medicine Resources, Institute of Marine Drugs, University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoting","family":"Qin","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chundie","family":"Lan","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingdong","family":"Nong","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxia","family":"Yun","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Tang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Leng","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Marine Drugs, University Engineering Research Center of High-Efficient Utilization of Marine Traditional Chinese Medicine Resources, Institute of Marine Drugs, University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9482-6054","authenticated-orcid":false,"given":"Lifeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1080\/10408399109527556","article-title":"Microalgae as food and supplement","volume":"30","author":"Kay","year":"1991","journal-title":"Crit. 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