Multidimensional therapeutic advantages of Smilax glabra (Tufuling)-containing formulae in gout: an integrated Systematic Review and network pharmacology-based prediction.

Authors

Qiaoyun Liu, Xiuming Li, Yuping Lin, Xianyu Tang, Guanjie Fan, Lu Sun

Published in

Frontiers in endocrinology. Volume 17. Pages 1863098. Epub Jul 01, 2026.

Abstract

Gout, an inflammatory form of arthritis triggered by monosodium urate (MSU) crystal deposition, poses a substantial global health burden with increasing prevalence and younger onset, particularly in China. In traditional Chinese medicine (TCM), dampness-heat accumulation is a predominant pattern associated with gout. Smilax glabra (Tufuling), a medicinal and edible herb with a history of use for detoxification and elimination of dampness, is also known to promote joint mobility. It is widely used for these purposes. This study aimed to systematically evaluate the clinical efficacy and safety of Tufuling-containing TCM formulae-typically used in combination with other Chinese herbs and/or Western medicine-for gout patients with dampness-heat accumulation, and to generate testable mechanistic hypotheses using network pharmacology.
A systematic review (SR) and meta-analysis were conducted by searching PubMed, Embase, CNKI, and other databases from inception to June 2025, including randomized controlled trials (RCTs) of formulae containing Tufuling interventions for gout. Network pharmacology was utilized to identify active compounds, target genes, and key pathways involved in gout treatment, followed by molecular docking to generate mechanistic hypotheses.
A total of 56 RCTs involving 4,605 participants were included in this analysis. A meta-analysis revealed that Tufuling-containing formulae, particularly when combined with Western medicine (WM) or administered as comprehensive TCM therapy, were associated with reductions in, visual analog scale (VAS) scores (pain), serum uric acid (UA) levels, C-reactive protein (CRP) levels, and the erythrocyte sedimentation rate (ESR) compared with WM monotherapy. A lower reported incidence of gastrointestinal adverse events was observed (73 vs. 161 cases); however, adverse event reporting was incomplete, treatment durations were short, and the follow-up data were limited. Meta-analysis suggested that simpler interventions may be associated with fewer adverse events. Network pharmacology predicted 11, 3, and 14 active compounds for Tufuling, Huangbo, and Bixie, respectively. Target mapping predicted 49 targets for Tufuling, 81 for the Tufuling-Huangbo pair, and 7 for Bixie-all nested within the Tufuling target set. The Tufuling PPI network (48 nodes, 348 edges) identified four core targets: PTGS2, IL1B, PPARG, and TP53. The Tufuling-Huangbo PPI network (76 nodes, 1,054 edges) yielded seven core targets; four overlapped with Tufuling, while CCL2, BCL2, and CXCL8 were Huangbo-specific. KEGG analysis of 48 Tufuling targets identified 228 pathways, with key enrichment in metabolism, lipid and atherosclerosis, PI3K-Akt, TNF, and IL-17 signaling. The 76 Tufuling-Huangbo targets revealed 233 pathways, showing enhanced enrichment in PI3K-Akt, NOD-like receptor, MAPK, TNF, and IL-17 signaling relative to Tufuling alone. Molecular docking predicted For the Tufuling, diosgenin would bound PTGS2 most strongly (-11.6 kcal/mol), followed by TP53 (-9.8kcal/mol) and IL1B (-8.0kcal/mol); beta-sitosterol would bound PPARG (-9.2kcal/mol). For the Tufuling-Huangbo pair, beta-sitosterol additionally would bound BCL2 (-7.9kcal/mol). For Bixie, diosgenin would bound PLA2G4A (-10.3kcal/mol) and PTGS2 (-9.9kcal/mol), while EINECS 213-897-0 would bound NR3C2 (-8.9kcal/mol).
Tufuling-containing formulae may be associated with symptomatic improvements in acute gout with dampness-heat accumulation, including analgesic, anti-inflammatory, and uric acid-lowering effects, although the certainty of evidence ranges from low to moderate. The safety profile appears promising but remains inadequately characterized due to incomplete reporting and short follow-up. The efficacy of this treatment may be mediated by multiple compounds and multi-target modulation of inflammatory and metabolic pathways. Tufuling-based interventions have been identified as potentially valuable adjunctive therapies for the treatment of gout. However, further rigorous RCTs and experimental studies are needed to validate its long-term efficacy and mechanism of action.
https://www.crd.york.ac.uk/prospero/, identifier CRD420251060498.

PMID:
42460320
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.

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