ArticleChinese medicine2025
Ganoderma lucidum spore oil alleviates psychological stress-evoked tumor progression by enhancing FcγR-mediated macrophage phagocytosis.
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Dong-Dong Li *State Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Zi-Xuan Li *State Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Yang-Fan Zhou *State Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Ling Jin *State Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Wan-Li LiangState Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Wen-Dong XuNational Engineering Research Center of Pharmaceutical Processing Technology of Traditional Chinese Medicine and Drug Innovation/Guangdong Provincial Key Laboratory of Medicinal Lipids, Guangzhou HanFang Pharmaceutical Company Limited, Guangzhou, 510240, China.
Xiang LuoState Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Guan-Di XiaoState Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Qi-Jun ChenState Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Ting XieSchool of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, 650500, China.
Hui XuState Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Yang LiuState Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Hong-Fei CaiNational Engineering Research Center of Pharmaceutical Processing Technology of Traditional Chinese Medicine and Drug Innovation/Guangdong Provincial Key Laboratory of Medicinal Lipids, Guangzhou HanFang Pharmaceutical Company Limited, Guangzhou, 510240, China.
Yun-Feng CaoNHC Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shang Hai, 200032, China.
Wan-Yang SunState Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Yi-Fang LiState Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Lei LiangState Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Ju-Yan LiuNational Engineering Research Center of Pharmaceutical Processing Technology of Traditional Chinese Medicine and Drug Innovation/Guangdong Provincial Key Laboratory of Medicinal Lipids, Guangzhou HanFang Pharmaceutical Company Limited, Guangzhou, 510240, China. maoyk@byshf.com.
Yan-Ping WuState Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China. wuyanping@jnu.edu.cn.
Rong-Rong HeState Key Laboratory of Bioactive Molecules and Druggability Assessment/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/The First Affiliated Hospital/The Sixth Affiliated Hospital/Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/College of Pharmacy/School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China. rongronghe@jnu.edu.cn.ORCID http://orcid.org/0000-0001-5505-5672
Funding
China Association of Chinese Medicine 2024-QNRC2-B23Guangdong Basic and Applied Basic Research Foundation 2021A1515011297Guangdong Basic and Applied Basic Research Foundation 2023B1515040016Guangdong Basic and Applied Basic Research Foundation 2024A1515011423Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine 2023LSYS002Guangdong Provincial Key Laboratory of Medicinal Lipids 2023B1212070030Guangzhou Basic and Applied Basic Research Foundation 2024A04J4020Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility 2024A03J090National Natural Science Foundation of China 81973718National Natural Science Foundation of China 82305063National Natural Science Foundation of China 82321004National Natural Science Foundation of China 82374327National Natural Science Foundation of China 82474359National Natural Science Foundation of China T2341004The Fundamental Research Funds for the Central Universities 21623116
Abstract
backgroundGanoderma lucidum (G. lucidum), has been documented as a medicinal herb in classical texts and officially recognized in both Eastern and Western pharmacopeias. G. lucidum spore oil (GLSO), a lipid substance extracted from sporoderm-broken spores, has shown potential in enhancing immune function and prolonging the survival of tumor patients. However, the mechanisms underlying GLSO's immunomodulatory effects remain poorly unknown.
methodsThe effect of psychological stress on tumor progression and macrophage phagocytosis was analyzed by an in vivo small animal imaging system and flow cytometry. The effect of psychological stress on phospholipid composition in mice was investigated by LC-MS/MS based lipidomic analysis. The effectiveness of GLSO in tumor-bearing mice subjected to restraint stress was observed by tumor burden and phagocytosis of macrophages. Finally, the underlying mechanism of GLSO on macrophage phagocytosis in mice subjected to psychological stress was explored by RNA-seq, and the FcγR/SYK-mediated macrophage phagocytosis pathway was confirmed by qPCR, Western blotting, and confocal laser technology.
resultsOur study discovered that psychological stress-triggered tumor progression is contributed to by liposoluble components-impaired macrophage phagocytosis. Lipidomics analysis further identified lysophosphatidylinositol [LPI (18:0)] as a key factor suppressing macrophage phagocytic capacity under psychological stress. GLSO was shown to mitigate psychological stress-evoked tumor progression by enhancing macrophage-mediated phagocytosis of tumor cells in vivo. Mechanistically, transcriptomics analysis revealed that the LPI-mediated FcγR phagocytosis pathway is a crucial axis driving the therapeutic effect of GLSO under psychological stress.
conclusionOur findings illustrate that psychological stress-promoted cancer progression is contributed by the critical liposoluble components LPI (18:0)-mediated FcγR phagocytosis signaling inhibition. GLSO alleviates the dampened phagocytosis of macrophages caused by stress through regulating LPI/FcγR-mediated phagocytosis-related pathways, underscoring its potential as a therapeutic intervention for stress-related tumor progression.
Indexed as
Ganoderma lucidum spore oilLysophosphatidylinositolMacrophagesPhagocytosisPsychological stress
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