Ganoderma lucidum (Lingzhi) is traditionally recognized for its potential to delay aging, although its precise molecular mechanisms remain unclear. This study employed network pharmacology and molecular docking to investigate the material basis and mechanisms underlying the anti-aging effects of Ganoderma lucidum. Active components of Ganoderma lucidum and their potential targets were identified using the TCMSP database. Aging-related targets were retrieved from the GeneCards, OMIM, and Disgenet databases. The Venny 2.1 online tool was utilized to obtain common targets shared between the drug and the disease (aging). A “Drug-Components-Aging-Targets” network was constructed using Cytoscape 3.8.2, and a Protein-Protein Interaction (PPI) network was generated via the STRING database. Functional enrichment analysis of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for the drug-disease intersection targets was performed using the DAVID database, with results visualized via the Weishengxin website. Finally, molecular docking validation of the binding affinity between key active components and core targets was conducted using SYBYL-X 2.1.1 software. The results identified 29 active components in G. lucidum, 819 aging-related targets, and 98 overlapping targets. Molecular docking demonstrated strong binding activity between core anti-aging components (including ganoderic acid, ganoderenic acid, and ganodermanondiol) and key targets (such as CYP19A1, NR3C1, and HMGCR). This study indicates that the anti-aging effects of Ganoderma lucidum involve synergistic actions through multiple components, targets, and pathways. These findings provide a theoretical foundation for further exploration of its anti-aging mechanisms.
References
[1]
Ghanem, A.S., Nguyen, C.M., Mansour, Y., Fábián, G., Rusinné Fedor, A., Nagy, A., et al. (2023) Investigating the Association between Sociodemographic Factors and Chronic Disease Risk in Adults Aged 50 and above in the Hungarian Population. Healthcare, 11, Article 1940. https://doi.org/10.3390/healthcare11131940
[2]
Dong, B. and Ding, Q. (2009) Aging in China: A Challenge or an Opportunity? JournaloftheAmericanMedicalDirectorsAssociation, 10, 456-458. https://doi.org/10.1016/j.jamda.2009.06.007
[3]
Shan, J., Mo, J., An, C., Xiang, L. and Qi, J. (2024) β-Cyclocitral from Lavandulaangustifolia Mill. Exerts Anti-Aging Effects on Yeasts and Mammalian Cells via Telomere Protection, Antioxidative Stress, and Autophagy Activation. Antioxidants, 13, Article 715. https://doi.org/10.3390/antiox13060715
[4]
Gleichmann, U., Gleichmann, U. and Gleichmann, S. (2011) Von der kardiovaskulären Prävention zur Anti-Aging-Medizin: Einfluss auf Telomere und Zellalterung. DMW—DeutscheMedizinischeWochenschrift, 136, 1913-1916. https://doi.org/10.1055/s-0031-1286363
[5]
Liu, J., Zhang, B., Wang, L., Li, S., Long, Q. and Xiao, X. (2024) Bioactive Components, Pharmacological Properties and Underlying Mechanism of Ganoderma lucidum Spore Oil: A Review. ChineseHerbalMedicines, 16, 375-391. https://doi.org/10.1016/j.chmed.2023.09.007
[6]
Wang, J., Cao, B., Zhao, H. and Feng, J. (2017) Emerging Roles of Ganoderma lucidum in Anti-Aging. Aginganddisease, 8, 691-707. https://doi.org/10.14336/ad.2017.0410
[7]
Ding, W., Zhang, X., Yin, X., Zhang, Q., Wang, Y., Guo, C., etal. (2022) Ganoderma lucidum Aqueous Extract Inducing PHGPx to Inhibite Membrane Lipid Hydroperoxides and Regulate Oxidative Stress Based on Single-Cell Animal Transcriptome. ScientificReports, 12, Article No. 3139. https://doi.org/10.1038/s41598-022-06985-z
[8]
Kumar, H., Bansal, S., Chaudhary, R., Sharma, S., Gupta, S. and Choudhary, S. (2024) Amelioration of Neuronal Deficits in Aged Rats via Ganoderma lucidum Extract Alone and Combination with α Lipoic Acid. JournalofPharmacologyandPharmacotherapeutics, 16, 77-91. https://doi.org/10.1177/0976500x241288673
[9]
Wang, A., Xiao, C., Zheng, J., Ye, C., Dai, Z., Wu, Q., etal. (2020) Terpenoids of Ganoderma lucidum Reverse Cognitive Impairment through Attenuating Neurodegeneration via Suppression of PI3K/Akt/mTOR Expression inVivo Model. JournalofFunctionalFoods, 73, Article ID: 104142. https://doi.org/10.1016/j.jff.2020.104142
[10]
Cuong, V.T., Chen, W., Shi, J., Zhang, M., Yang, H., Wang, N., etal. (2019) The Anti-Oxidation and Anti-Aging Effects of Ganoderma lucidum in Caenorhabditiselegans. ExperimentalGerontology, 117, 99-105. https://doi.org/10.1016/j.exger.2018.11.016
[11]
Ji, C., Yang, Y., Fu, Y., Pu, X. and Xu, G. (2022) Improvement of Ganoderma lucidum Water Extract on the Learning and Memory Impairment and Its Mechanism in D-Galactose-Induced Aging Mice. JournalofFunctionalFoods, 99, Article ID: 105322. https://doi.org/10.1016/j.jff.2022.105322
[12]
Zhang, G., Xue, P., Zhao, H., Guan, T. and Ma, Z. (2024) Network Pharmacology and Molecular Docking Reveal the Antioxidant Potential of Mangiferin from Mango Peel. LettersinDrugDesign&Discovery, 21, 1263-1273. https://doi.org/10.2174/1570180820666230403090658
[13]
Furth, P.A., Wang, W., Kang, K., Rooney, B.L., Keegan, G., Muralidaran, V., etal. (2023) ESR1 but Not CYP19A1 Overexpression in Mammary Epithelial Cells during Reproductive Senescence Induces Pregnancy-Like Proliferative Mammary Disease Responsive to Anti-Hormonals. TheAmericanJournalofPathology, 193, 84-102. https://doi.org/10.1016/j.ajpath.2022.09.007
[14]
Appleton, A.A. (2025) A Polyepigenetic Glucocorticoid Exposure Score and HPA Axis-Related DNA Methylation Are Associated with Gestational Epigenetic Aging. Epigenetics, 20, Article ID: 2471129. https://doi.org/10.1080/15592294.2025.2471129
[15]
Zhang, X., Ji, C., Fu, Y., Yang, Y. and Xu, G. (2024) Screening of Active Components of Ganoderma lucidum and Decipher Its Molecular Mechanism to Improve Learning and Memory Disorders. BioscienceReports, 44, Article No. 7. https://doi.org/10.1042/bsr20232068
[16]
Wang, S., Wang, L., Shangguan, J., Jiang, A. and Ren, A. (2024) Research Progress on the Biological Activity of Ganoderic Acids in Ganoderma lucidum over the Last Five Years. Life, 14, Article 1339. https://doi.org/10.3390/life14101339
[17]
Chen, L., Wu, B., Mo, L., Chen, H., Yin, X., Zhao, Y., etal. (2025) High-Content Screening Identifies Ganoderic Acid a as a Senotherapeutic to Prevent Cellular Senescence and Extend Healthspan in Preclinical Models. NatureCommunications, 16, Article No. 2878. https://doi.org/10.1038/s41467-025-58188-5
[18]
Li, S., Li, L., Zhang, C., Fu, H., Yu, S., Zhou, M., etal. (2023) PM2.5 Leads to Adverse Pregnancy Outcomes by Inducing Trophoblast Oxidative Stress and Mitochondrial Apoptosis via KLF9/CYP1A1 Transcriptional Axis. eLife, 12, e85944. https://doi.org/10.7554/elife.85944
[19]
Wang, Q., Zhang, L., Han, X., Wang, D., Ding, M., Cheng, D., etal. (2023) 2,3’,4,4’,5-pentachlorobiphenyl Induces Mitochondria-Dependent Apoptosis Mediated by AhR/Cyp1a1 in Mouse Germ Cells. JournalofHazardousMaterials, 445, Article ID: 130547. https://doi.org/10.1016/j.jhazmat.2022.130547
Gong, P., Wang, D., Cui, D., Yang, Q., Wang, P., Yang, W., etal. (2021) Anti-Aging Function and Molecular Mechanism of Radixastragali and Radixastragali Preparata via Network Pharmacology and PI3K/Akt Signaling Pathway. Phytomedicine, 84, Article ID: 153509. https://doi.org/10.1016/j.phymed.2021.153509
He, D., Wu, H., Xiang, J., Ruan, X., Peng, P., Ruan, Y., etal. (2020) Gut Stem Cell Aging Is Driven by mTORC1 via a P38 MAPK-p53 Pathway. NatureCommunications, 11, Article No. 37. https://doi.org/10.1038/s41467-019-13911-x
[24]
Yuan, W., Weaver, Y.M., Earnest, S., Taylor, C.A., Cobb, M.H. and Weaver, B.P. (2023) Modulating P38 MAPK Signaling by Proteostasis Mechanisms Supports Tissue Integrity during Growth and Aging. NatureCommunications, 14, Article No. 4543. https://doi.org/10.1038/s41467-023-40317-7
[25]
Ding, L., Shangguan, H., Wang, X., Liu, J., Shi, Y., Xu, X., etal. (2025) Extraction, Purification, Structural Characterization, Biological Activity, Mechanism of Action and Application of Polysaccharides from Ganoderma lucidum: A Review. InternationalJournalofBiologicalMacromolecules, 288, Article ID: 138575. https://doi.org/10.1016/j.ijbiomac.2024.138575
[26]
Wang, T., Xie, Z., Huang, Z., Li, H., Wei, A., Di, J., etal. (2015) Total Triterpenoids from Ganoderma lucidum Suppresses Prostate Cancer Cell Growth by Inducing Growth Arrest and Apoptosis. JournalofHuazhongUniversityofScienceandTechnology [MedicalSciences], 35, 736-741. https://doi.org/10.1007/s11596-015-1499-x
[27]
Rahman, M.A., Hossain, S., Abdullah, N. and Aminudin, N. (2020) Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes) Ameliorates Spatial Learning and Memory Deficits in Rats with Hypercholesterolemia and Alzheimer’s Disease. InternationalJournalofMedicinalMushrooms, 22, 93-103. https://doi.org/10.1615/intjmedmushrooms.2020033383
