Medicinal Plant Research 2025, Vol.15, No.3, 110-118 http://hortherbpublisher.com/index.php/mpr 110 Research Insight Open Access Synergistic Effects of Ganoderma lucidum with Other TCM Herbs: An Analysis of Pharmacological Interactions Guangman Xu, Jiayi Wu Traditional Chinese Medicine Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: guangman.xu@cuixi.org Medicinal Plant Research, 2025, Vol.15, No.3 doi: 10.5376/mpr.2025.15.0012 Received: 20 Mar., 2025 Accepted: 25 Apr., 2025 Published: 25 May, 2025 Copyright © 2025 Xu and Wu, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Xu G.M., and Wu J.Y., 2025, Synergistic effects of Ganoderma lucidum with other TCM herbs: an analysis of pharmacological interactions, Medicinal Plant Research, 15(3): 110-118 (doi: 10.5376/mpr.2025.15.0012) Abstract Ganoderma lucidum (Lingzhi) occupies a prominent position not only in traditional Chinese medicine (TCM) but also in contemporary pharmacological investigation, due to its multifarious biological activities like immunomodulatory, anti-inflammatory, and antioxidant properties. Lingzhi in TCM practice is usually used in combination with other herbal drugs to ensure synergistic potentiation. This review systematically discusses the principal bioactive compounds of G. lucidum, namely, triterpenoids, polysaccharides, phenolic compounds, and sterols, and their pharmacological activities. Special emphasis is laid to the type of interaction of Lingzhi with other classic traditional herbal drugs, such as synergistic augmentation, antagonism, and pharmacokinetic/pharmacodynamic interactions. Particular pairs-Lingzhi and Astragalus, Ginseng, Lycium, Salvia miltiorrhiza, and Angelica sinensis—are addressed to mirror their role in immunoregulation, anti-tumor activities, neuroprotection, cardiovascular augmentation, and anti-aging. Besides, molecular mechanisms of such synergistic effects are described, such as regulation of signal transduction pathways (e.g., NF-κB, MAPK, PI3K-Akt), modulation of immune cell activity, regulation of oxidative stress and inflammation processes, and the role of metabolomics and gut microbiota. Progress in in vitro and animal model research, clinical application, and evidence from evidence-based medicine is presented. In addition, pertinent issues relating to safety assessment, potential herb-drug interaction, and quality control challenges of herbal medicines are discussed. Overall, this review encourages the scientific merit and application value of synergistic actions of G. lucidum with other medicinal herbs, and provides theoretical basis and practical reference for TCM modernization and exploration of new herbal medicines. Keywords Ganoderma lucidum; Synergistic effects; Chinese herbal medicine; Pharmacological interactions; Herbal formulations 1 Introduction Ganoderma lucidum (Lingzhi) has been at the heart of traditional Chinese medicine (TCM) for more than two thousand years, considered the "herb of immortality" due to its wide-ranging health benefits. It was conventionally prescribed to tonify qi, calm the spirit, and promote vitality. Modern pharmacological research has substantiated many of the traditional assertions, demonstrating that G. lucidum contains a rich array of bioactive constituents, including triterpenoids, polysaccharides, phenolic compounds, and sterols. These compounds contribute to its immunomodulatory, anti-inflammatory, antioxidant, anti-tumor, and hepatoprotective activities. The dual validation of Lingzhi by traditional practice and contemporary biomedicine testifies to its unique status as a nexus between ancient empirical knowledge and contemporary pharmacological science (Chiu et al., 2017). A feature of TCM is multi-herb prescriptions, i.e., the use of botanicals in combination in the form of formulae according to synergy, balance, and mutual potentiating. The purpose of these herbal formulae is to maximize therapeutic effect with fewer side effects. Synergy between herbs can be due to a number of mechanisms, including additive or potentiated pharmacological effects, increased bioavailability, and modification of pharmacokinetic and pharmacodynamic processes (Ye et al., 2023). However, hostile or opposite interactions can also happen, and this explains the need for systematic research. As one of the most valued tonic herbs, G. lucidum is commonly combined in formula with other TCM herbs such as Astragalus, Ginseng, Lycium, and Salvia, where it is believed to enhance immune regulation, sustain cardiovascular function, protect neural function, and decelerate aging processes (Seweryn et al., 2021; Ding et al., 2024).
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