{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:13:22Z","timestamp":1753892002944,"version":"3.41.2"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Community-associated methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (CA-MRSA) disrupts innate immunity by inducing necroptosis in polymorphonuclear neutrophils (PMNs), a process linked to excessive inflammation and tissue damage. CA-MRSA releases virulence factors that enhance its pathogenicity by disrupting the host\u2019s innate immune response, particularly impairing the phagocytic function of PMNs. Steamed Panax notoginseng (S-PN), a traditional Chinese medicine (TCM), has demonstrated immune-regulatory and anti-inflammatory properties, showing promising therapeutic effects in alleviating the severe inflammatory responses induced by pathogenic microbial infections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aims to investigate the pharmacological effects and mechanisms of S-PN alleviating CA-MRSA-induced PMN necroptosis by suppressing MRSA virulence factors and inhibiting the RIPK1\/RIPK3\/MLKL signaling pathway, thereby attenuating inflammatory damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A co-culture model of MRSA USA300 strain and PMNs isolated from healthy human blood was established to observe the changes in necroptosis marker HMGB1, PMNs counts, ROS, chemokine MCP-1 and pro-inflammatory cytokines IL-1\u03b2, IL-8, TNF-\u03b1. RNA-seq was employed to analyze the effects of S-PN on the transcriptional expression of pathogenesis-related genes of MRSA. RT-PCR was utilized to validate the expression of S-PN on MRSA virulence factors and PMNs necroptosis related genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>S-PN significantly inhibited HMGB1, ROS, MCP-1, IL-1\u03b2 and IL-8 in MRSA-PMN co-cultures, the PMN count in the S-PN group was higher than that in the model group. S-PN downregulated MRSA pathogenic-associated <jats:italic>S. aureus<\/jats:italic> infection and quorum sensing signaling pathways, and significantly reduced the virulence factors PSM and PVL. S-PN suppressed the expression of genes associated with necroptosis ripk1, ripk3, and mlkl in PMNs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>S-PN alleviates CA-MRSA infection-induced immune damage through dual mechanisms: suppression of bacterial virulence factors (PSM and PVL) and inhibition of PMNs necroptosis. These findings underscore its potential as a complementary therapeutic strategy against CA-MRSA infections, providing a theoretical foundation for integrating TCM into adjuvant treatments for drug-resistant bacterial infections.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1546652","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T05:45:35Z","timestamp":1748583935000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Steamed panax notoginseng mitigates CA-MRSA USA300-induced necroptosis in human neutrophils"],"prefix":"10.3389","volume":"16","author":[{"given":"Lulu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongsa","family":"An","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weifeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuwen","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoran","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yungchi","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"677","DOI":"10.3390\/toxins13100677","article-title":"Staphylococcus aureus toxins: an update on their pathogenic properties and potential treatments","volume":"13","author":"Ahmad-Mansour","year":"2021","journal-title":"Toxins (Basel)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1139\/y11-057","article-title":"Ginseng aqueous extract attenuates the production of virulence factors, stimulates twitching and adhesion, and eradicates biofilms of Pseudomonas aeruginosa","volume":"89","author":"Alipour","year":"2011","journal-title":"Can. 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