Anti-Inflammatory Potential of Ganoderma lucidum Triterpenes: A Systematic Review and Meta-Analysis of Preclinical Evidence.

Background: Ganoderma lucidum triterpenes are bioactive compounds with recognized anti-inflammatory, antitumor, and immunomodulatory properties. This systematic review synthesizes evidence regarding the anti-inflammatory activity of these triterpenes based on studies from the last two decades. Methods: A systematic search was performed in PubMed, Medline, and Embase (2003-2025) for original in vitro and in vivo (non-clinical) studies evaluating G. lucidum triterpene extracts or isolated compounds. Clinical trials, reviews, and multi-species extracts were excluded. The review is registered on PROSPERO (CRD42024510982), and animal study quality was assessed using the SYRCLE Risk of Bias tool. Findings: From over 3000 records, 23 articles were included. Studies utilized diverse models, including macrophages, human PBMCs, and various animal strains (mice, rats, chickens). All studies reported significant anti-inflammatory effects via reduction in pro-inflammatory markers (TNF-α, IL-1β, IL-6), primarily through downregulation of MAPK and TLR-4/NF-κB signaling pathways. Meta-analysis of in vitro data confirmed significant reductions in NO levels (-3.29 [95% CI: -5.21, -1.37]; p = 0.0008), IL-6 (-3.51 [-4.73, -2.29]; p < 0.00001), and TNF-α (-2.20 [-2.93, -1.48]; p < 0.00001). Similar anti-inflammatory profiles were observed in vivo across hepatic and splenic tissues. Interpretation: Evidence consistently demonstrates the potent anti-inflammatory activity of G. lucidum triterpenes, highlighting their potential as therapeutic candidates for inflammatory diseases. However, the structural complexity and isomer diversity of these compounds remain significant barriers to pharmacological standardization. Future research must prioritize clinical translation by investigating compound synergism, bioavailability, and long-term toxicity profiles, which were notably absent in current non-clinical literature.