Steamed panax notoginseng mitigates CA-MRSA USA300-induced necroptosis in human neutrophils
BackgroundCommunity-associated methicillin-resistant Staphylococcus aureus (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 pathogenici...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1546652/full |
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| author | Lulu Zhang Xiaoyu Feng Hongsa An Weifeng Yang Yuwen Xia Bo Wen Haoran Zheng Yihuan Chen Yungchi Cheng Chunyan Jiang Cheng Lu Yong Tan |
| author_facet | Lulu Zhang Xiaoyu Feng Hongsa An Weifeng Yang Yuwen Xia Bo Wen Haoran Zheng Yihuan Chen Yungchi Cheng Chunyan Jiang Cheng Lu Yong Tan |
| author_sort | Lulu Zhang |
| collection | DOAJ |
| description | BackgroundCommunity-associated methicillin-resistant Staphylococcus aureus (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’s 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.ObjectiveThis 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.MethodsA 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-1β, IL-8, TNF-α. 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.ResultsS-PN significantly inhibited HMGB1, ROS, MCP-1, IL-1β 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 S. aureus 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.ConclusionS-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. |
| format | Article |
| id | doaj-art-c1535511ee0945d6b51bd79fc962f151 |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-c1535511ee0945d6b51bd79fc962f1512025-08-20T02:34:50ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15466521546652Steamed panax notoginseng mitigates CA-MRSA USA300-induced necroptosis in human neutrophilsLulu Zhang0Xiaoyu Feng1Hongsa An2Weifeng Yang3Yuwen Xia4Bo Wen5Haoran Zheng6Yihuan Chen7Yungchi Cheng8Chunyan Jiang9Cheng Lu10Yong Tan11Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaMedical Experimental Center, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT, United StatesDermatological Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaBackgroundCommunity-associated methicillin-resistant Staphylococcus aureus (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’s 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.ObjectiveThis 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.MethodsA 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-1β, IL-8, TNF-α. 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.ResultsS-PN significantly inhibited HMGB1, ROS, MCP-1, IL-1β 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 S. aureus 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.ConclusionS-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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1546652/fullsteamed Panax notoginsengCA-MRSAvirulence factorspolymorphonuclear neutrophilsnecroptosis |
| spellingShingle | Lulu Zhang Xiaoyu Feng Hongsa An Weifeng Yang Yuwen Xia Bo Wen Haoran Zheng Yihuan Chen Yungchi Cheng Chunyan Jiang Cheng Lu Yong Tan Steamed panax notoginseng mitigates CA-MRSA USA300-induced necroptosis in human neutrophils Frontiers in Pharmacology steamed Panax notoginseng CA-MRSA virulence factors polymorphonuclear neutrophils necroptosis |
| title | Steamed panax notoginseng mitigates CA-MRSA USA300-induced necroptosis in human neutrophils |
| title_full | Steamed panax notoginseng mitigates CA-MRSA USA300-induced necroptosis in human neutrophils |
| title_fullStr | Steamed panax notoginseng mitigates CA-MRSA USA300-induced necroptosis in human neutrophils |
| title_full_unstemmed | Steamed panax notoginseng mitigates CA-MRSA USA300-induced necroptosis in human neutrophils |
| title_short | Steamed panax notoginseng mitigates CA-MRSA USA300-induced necroptosis in human neutrophils |
| title_sort | steamed panax notoginseng mitigates ca mrsa usa300 induced necroptosis in human neutrophils |
| topic | steamed Panax notoginseng CA-MRSA virulence factors polymorphonuclear neutrophils necroptosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1546652/full |
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