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

The short version

This systematic review and meta-analysis of 56 randomized controlled trials (4,605 participants) examined whether herbal formulae containing Smilax glabra, known in Chinese as Tufuling, help people with acute gout. Gout is a painful inflammatory arthritis caused by uric acid crystals depositing in joints. In traditional Chinese medicine, many acute flares are classed as dampness-heat accumulation, a pattern defined by red, swollen, hot, painful joints and dark urine, and treated by clearing heat and resolving dampness. The authors also used computer-based network pharmacology to predict which plant compounds and proteins might explain the effects. All 56 trials took place in China and enrolled adults, with ages ranging from 18 to 80 years, diagnosed with gout and the dampness-heat pattern. Participants received a Tufuling-containing herbal formula, sometimes with external applications or acupuncture, either alone or added to standard drugs such as NSAIDs, colchicine, allopurinol or benzbromarone, for 14 days or less. Comparison groups received the standard drugs alone. Pain was measured on a 10-point visual analog scale, and blood uric acid, C-reactive protein and erythrocyte sedimentation rate (inflammation markers) were also tracked. Herbal formulae added to standard drugs reduced pain by 0.94 points on the 10-point scale (a modest but statistically significant gain across 17 trials), raised the chance of a treatment response by 15% (risk ratio 1.15), and lowered blood uric acid by 57 micromoles per litre. Herbal formulae alone did not beat standard drugs for pain (a 0.33-point difference, not significant) but did lower uric acid. Adverse events, mostly stomach and intestinal complaints, totalled 73 in herbal groups versus 161 in comparison groups, all mild to moderate. Certainty of evidence was rated low to moderate, and heterogeneity was very high for pain (I² = 93.2%). Network analysis predicted 49 gout-related protein targets for Tufuling, centred on PTGS2, IL1B, PPARG and TP53 (proteins governing inflammation and metabolism), and docking suggested diosgenin binds PTGS2 strongly (-11.6 kcal/mol). The authors suggest Tufuling-based formulae may be a useful adjunct in acute gout, but the evidence carries clear limits. Most trials lacked blinding and trial registration, all came from China, treatment lasted at most 14 days, a quarter of trials did not report adverse events, and only four reported follow-up. The findings do not extend to chronic gout or other traditional patterns, and the network predictions are untested hypotheses. The authors call for larger, rigorous trials with longer follow-up and laboratory validation of the predicted targets.

Key findings

• Fifty-six randomized trials with 4,605 people in China tested herbal formulae containing Smilax glabra (Tufuling) for acute gout with the traditional Chinese medicine pattern called dampness-heat accumulation (red, swollen, hot, painful joints).
• When the herbal formulae were added to standard gout drugs, pain scores were 0.94 points lower on a 10-point scale, the treatment response rate was 15% higher (risk ratio 1.15), and blood uric acid was 57.02 micromoles per litre lower than with standard drugs alone.
• Herbal formulae used alone did not reduce pain more than standard drugs (0.33-point difference, not statistically significant), although they lowered uric acid by 47.56 micromoles per litre.
• Reported adverse events were mostly digestive and mild to moderate: 73 in the herbal groups versus 161 in the comparison groups, but 25% of trials did not report adverse events and treatment lasted 14 days or less.
• The authors rate the certainty of the evidence as low to moderate, note that most trials were unblinded and unregistered, and describe the network pharmacology and molecular docking results (such as diosgenin binding PTGS2 at -11.6 kcal/mol) as hypotheses that need laboratory testing.

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