Ganoderma lucidum spore powder alleviates rheumatoid arthritis-associated pain hypersensitivity through inhibiting accumulation, N1 polarization, and ROS production of neutrophils in mice
IntroductionRheumatoid arthritis (RA) is a chronic condition characterized by joint pain that significantly impairs patients’ work and daily lives. The limited understanding of the pathological mechanisms underlying RA-related pain poses challenges for effective clinical pain management. Ganoderma l...
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Frontiers Media S.A.
2025-04-01
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| author | Sen Huang Sen Huang Zhaochun Zhan Zhaochun Zhan Fei Xu Xiaolin Liu Zhenning Fang Wenbo Wu Zhile Liang Zhile Liang Guoguo Liu Mengyuan Wang Helena Soares da Silva Xin Luo Xin Luo Xin Luo Xin Luo Kai Mo Kai Mo |
| author_facet | Sen Huang Sen Huang Zhaochun Zhan Zhaochun Zhan Fei Xu Xiaolin Liu Zhenning Fang Wenbo Wu Zhile Liang Zhile Liang Guoguo Liu Mengyuan Wang Helena Soares da Silva Xin Luo Xin Luo Xin Luo Xin Luo Kai Mo Kai Mo |
| author_sort | Sen Huang |
| collection | DOAJ |
| description | IntroductionRheumatoid arthritis (RA) is a chronic condition characterized by joint pain that significantly impairs patients’ work and daily lives. The limited understanding of the pathological mechanisms underlying RA-related pain poses challenges for effective clinical pain management. Ganoderma lucidum spore powder (GLSP) has demonstrated therapeutic benefits in various diseases, with no reported toxicity or adverse effects.MethodsThis study investigates the role of neutrophils in the pathological mechanisms of RA-related pain using collagen-induced arthritis (CIA) mice and an ex vivo neutrophil model. A combination of techniques, including animal models, flow cytometry, behavioral testing, cell adoptive transfer, and network pharmacology analysis, was employed to evaluate the effects and targets of GLSP on pain symptoms and neutrophil activity in CIA mice.ResultsFlow cytometric analysis revealed the accumulation and activation of neutrophils in the paws of CIA mice. Furthermore, the levels of pro-inflammatory CD95+ neutrophil subpopulations (N1 state) and ROS+ cells in the affected paws were positively correlated with the severity of mechanical allodynia and heat hyperalgesia observed in these mice. Our findings indicate that oral administration of GLSP significantly alleviates joint destruction, paw swelling, and pain hypersensitivity in CIA mice. Notably, GLSP reversed CIA-induced neutrophil accumulation, N1 polarization, and reactive oxygen species (ROS) production. Both network pharmacology target prediction and in vivo/in vitro experimental validation indicated that GLSP inhibits N1 polarization and ROS production in neutrophils by modulating the TNF-α signaling pathway, thus exerting RA-specific analgesic effects.DiscussionIn summary, this study offers new insights into the pathological mechanisms of RA-related pain and demonstrates that neutrophil accumulation, N1 polarization, and ROS production contribute to RA-related pain. GLSP alleviates RA-related pain by inhibiting the pro-inflammatory phenotype of neutrophils, highlighting its potential for clinical translation in the treatment of RA. |
| format | Article |
| id | doaj-art-07658aa586dc48229a30dbcc7fda3d52 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-07658aa586dc48229a30dbcc7fda3d522025-08-20T03:53:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15692951569295Ganoderma lucidum spore powder alleviates rheumatoid arthritis-associated pain hypersensitivity through inhibiting accumulation, N1 polarization, and ROS production of neutrophils in miceSen Huang0Sen Huang1Zhaochun Zhan2Zhaochun Zhan3Fei Xu4Xiaolin Liu5Zhenning Fang6Wenbo Wu7Zhile Liang8Zhile Liang9Guoguo Liu10Mengyuan Wang11Helena Soares da Silva12Xin Luo13Xin Luo14Xin Luo15Xin Luo16Kai Mo17Kai Mo18Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaKey Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaKey Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Shunde Hospital, Southern Medical University, Foshan, ChinaKey Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaKey Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaKey Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Shunde Hospital, Southern Medical University, Foshan, ChinaInstitute of Perioperative Medicine and Organ Protection, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaInstitute of Perioperative Medicine and Organ Protection, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaIntroductionRheumatoid arthritis (RA) is a chronic condition characterized by joint pain that significantly impairs patients’ work and daily lives. The limited understanding of the pathological mechanisms underlying RA-related pain poses challenges for effective clinical pain management. Ganoderma lucidum spore powder (GLSP) has demonstrated therapeutic benefits in various diseases, with no reported toxicity or adverse effects.MethodsThis study investigates the role of neutrophils in the pathological mechanisms of RA-related pain using collagen-induced arthritis (CIA) mice and an ex vivo neutrophil model. A combination of techniques, including animal models, flow cytometry, behavioral testing, cell adoptive transfer, and network pharmacology analysis, was employed to evaluate the effects and targets of GLSP on pain symptoms and neutrophil activity in CIA mice.ResultsFlow cytometric analysis revealed the accumulation and activation of neutrophils in the paws of CIA mice. Furthermore, the levels of pro-inflammatory CD95+ neutrophil subpopulations (N1 state) and ROS+ cells in the affected paws were positively correlated with the severity of mechanical allodynia and heat hyperalgesia observed in these mice. Our findings indicate that oral administration of GLSP significantly alleviates joint destruction, paw swelling, and pain hypersensitivity in CIA mice. Notably, GLSP reversed CIA-induced neutrophil accumulation, N1 polarization, and reactive oxygen species (ROS) production. Both network pharmacology target prediction and in vivo/in vitro experimental validation indicated that GLSP inhibits N1 polarization and ROS production in neutrophils by modulating the TNF-α signaling pathway, thus exerting RA-specific analgesic effects.DiscussionIn summary, this study offers new insights into the pathological mechanisms of RA-related pain and demonstrates that neutrophil accumulation, N1 polarization, and ROS production contribute to RA-related pain. GLSP alleviates RA-related pain by inhibiting the pro-inflammatory phenotype of neutrophils, highlighting its potential for clinical translation in the treatment of RA.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1569295/fullrheumatoid arthritispainneutrophilsGanoderma lucidum spore powderreactive oxygen species |
| spellingShingle | Sen Huang Sen Huang Zhaochun Zhan Zhaochun Zhan Fei Xu Xiaolin Liu Zhenning Fang Wenbo Wu Zhile Liang Zhile Liang Guoguo Liu Mengyuan Wang Helena Soares da Silva Xin Luo Xin Luo Xin Luo Xin Luo Kai Mo Kai Mo Ganoderma lucidum spore powder alleviates rheumatoid arthritis-associated pain hypersensitivity through inhibiting accumulation, N1 polarization, and ROS production of neutrophils in mice Frontiers in Immunology rheumatoid arthritis pain neutrophils Ganoderma lucidum spore powder reactive oxygen species |
| title | Ganoderma lucidum spore powder alleviates rheumatoid arthritis-associated pain hypersensitivity through inhibiting accumulation, N1 polarization, and ROS production of neutrophils in mice |
| title_full | Ganoderma lucidum spore powder alleviates rheumatoid arthritis-associated pain hypersensitivity through inhibiting accumulation, N1 polarization, and ROS production of neutrophils in mice |
| title_fullStr | Ganoderma lucidum spore powder alleviates rheumatoid arthritis-associated pain hypersensitivity through inhibiting accumulation, N1 polarization, and ROS production of neutrophils in mice |
| title_full_unstemmed | Ganoderma lucidum spore powder alleviates rheumatoid arthritis-associated pain hypersensitivity through inhibiting accumulation, N1 polarization, and ROS production of neutrophils in mice |
| title_short | Ganoderma lucidum spore powder alleviates rheumatoid arthritis-associated pain hypersensitivity through inhibiting accumulation, N1 polarization, and ROS production of neutrophils in mice |
| title_sort | ganoderma lucidum spore powder alleviates rheumatoid arthritis associated pain hypersensitivity through inhibiting accumulation n1 polarization and ros production of neutrophils in mice |
| topic | rheumatoid arthritis pain neutrophils Ganoderma lucidum spore powder reactive oxygen species |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1569295/full |
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