Medicinal Plant Research 2025, Vol.15, No.3, 110-118 http://hortherbpublisher.com/index.php/mpr 114 cornerstone of immunoregulatory and antitumor benefits in multi-herb formulations (Lu et al., 2020; Luo et al., 2021). 5.3 Regulation of oxidative stress and inflammatory responses Ganoderma lucidum and their formulational blends with other herbs exert strong antioxidant actions by scavenging free radicals and stimulating endogenous antioxidant enzymes. They also suppress inflammatory responses through inflammasome blockage and downregulating pro-inflammatory cytokine transcription, normally through the NF-κB and NLRP3 pathways. These mechanisms also provide protective functions against oxidative insult and chronic inflammation (Lu et al., 2020; Ding et al., 2024). 5.4 Roles of metabolomics and gut microbiota Current evidence highlights the involvement of metabolomics and gut microbiota in mediating synergistic action of Ganoderma lucidum with other TCM herbs. GLPs can regulate the composition of gut microbiota, which has a ripple effect on immune and metabolic pathways. Metabolomic profiling shows that such combinations can influence the levels of key metabolites, resulting in their therapeutic effects, such as neuroprotection and metabolic regulation (Jiang et al., 2024). 6 Advances in Clinical and Experimental Studies of Ganoderma lucidum with TCM Herbs 6.1 Findings from in vitro and animal studies A large number of in vitro and animal experiments have shown that G. lucidum, especially its polysaccharides and triterpenoids, have obvious antioxidant, anti-inflammatory, immunomodulatory and anti-tumor effects. For instance, G. lucidum polysaccharides alleviate cognitive dysfunction in animal models, by inhibiting neuroinflammation mediated by the NLRP3/NF-κB signaling pathway, and regulating the composition of the gut microbiota (Cadar et al., 2023; Jiang et al., 2024). In cardiovascular research, G. lucidum polysaccharides can regulate lipid metabolism, reduce oxidative stress, and improve endothelial function in animal models of atherosclerosis. Co-culture studies with traditional Chinese medicines, like ginseng, have shown that the combination of G. lucidum with other medicinal materials, can promote the degradation of plant cell wall components, and enhance the bioavailability of active ingredients (Figure 2). 6.2 Clinical applications and examples of herbal formulae Although the number of clinical studies is relatively small, there is already evidence that G. lucidum supplements can enhance the body's antioxidant capacity, reduce oxidative stress and support liver health. A randomized, double-blind, placebo-controlled trial found that G. lucidum, is rich in triterpenoids and polysaccharides could improve plasma antioxidant indicators, and reverse mild fatty liver status in healthy volunteers (Chiu et al., 2017). In addition, supplementation of G. lucidum dry extract can regulate T lymphocyte function, and promote anti-inflammatory immune response in elderly women (Iser-Bem et al., 2024). Though G. lucidum is often included in traditional Chinese medicine prescriptions for metabolic, liver and immune-related diseases, standardized clinical evidence for specific combinations remains limited. 6.3 Evidence and limitations from evidence-based medicine In vitro and some clinical studies support the therapeutic potential of G. lucidum and its combination with traditional Chinese medicine, but there is still a lack of large-scale and high-quality clinical trial evidence. Studies have pointed out that, the health benefits observed in animal and in vitro experiments, are not always consistently replicated in human trials, which may be related to differences in formulations, dosages and study populations (Chan et al., 2021; Swallah et al., 2023). Besides, methodological limitations, small sample sizes, and the lack of standardization in TCM preparations are common problems. More rigorously designed and well-sample clinical studies, are needed in the future to confirm the efficacy, and safety of G. lucidum compound in different patient populations (Wu et al., 2023).
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