Integrated network pharmacology and clinical study to reveal the efficacy and tolerability of Huoxue Tongjiang decoction for the treatment of non-erosive reflux disease-related symptoms.

BACKGROUND AND

OBJECTIVES

Non-erosive reflux disease (NERD), a common gastrointestinal disorder, often responds poorly to acid suppressants. This study evaluated the efficacy and safety of Huoxue Tongjiang Decoction (HTD), a patented traditional Chinese medicine (TCM), for NERD with Qi stagnation-blood stasis syndrome, integrating network pharmacology and clinical trials.

METHODS

Network pharmacology identified HTD's active components and targets using TCMSP and GeneCards databases. A "drug-component-target" network was constructed, followed by protein interaction analysis, Gene body analysis (GO), and KEGG pathway enrichment via DAVID. A randomized, double-blind, placebo-controlled trial enrolled 64 NERD patients with Qi stagnation-blood stasis syndrome, randomized to HTD (n = 32) or placebo (n = 32) for 4 weeks, with 2-week follow-up. Outcomes included reflux/heartburn severity (Visual Analog Scale [VAS], gastroesophageal reflux disease questionnaire [GERD-Q]), TCM syndrome scores, SF-36 quality-of-life, HAD scores, and recurrence rates.

RESULTS

Network analysis revealed 20 core HTD components (e.g., quercetin, luteolin, baicalin) and 11 key targets (TNF, IL6, TP53), primarily modulating HIF-1 and TNF signaling pathways. Clinically, 30 HTD and 31 placebo patients completed the study. After 2/4 weeks and follow-up, HTD showed significantly higher overall symptom remission (43.3%, 73.3%, 73.3%) versus placebo (16.1% at all timepoints; P < 0.05). Reflux response rates for HTD were 30.0%, 66.7%, 66.7% vs. 12.9% (placebo; P < 0.0001). Heartburn response rates in HTD were 43.3%, 63.3%, 76.7% vs. 16.1% (P < 0.05). VAS reflux scores decreased from 3.75 ± 1.599 to 1.98 ± 1.292 (HTD) vs. minimal changes in placebo; heartburn scores improved similarly (3.33 ± 1.724 to 1.81 ± 1.471; P < 0.05 post-2 weeks). GERD-Q scores were lower in HTD (7.9 ± 2.29, 6.2 ± 2.07, 6.8 ± 2.40) . placebo (9.4 ± 2.83, 8.9 ± 2.55, 8.9 ± 2.59; P < 0.05). TCM syndrome improvement rates in HTD were 56.7%, 86.7%, 76.7% vs. 16.1%, 25.8%, 41.9% (P < 0.05). SF-36 physical pain, energy, and mental health scores improved in HTD (P < 0.05). Recurrence rates were 27.3% (HTD) vs. 40.0% (placebo; P < 0.05). No adverse events occurred.

CONCLUSIONS

HTD significantly alleviates reflux, heartburn, and retrosternal pain in NERD, improves quality of life, reduces recurrence, and demonstrates duration-dependent efficacy. Its anti-inflammatory mechanisms may involve TNF and HIF-1 pathways, with no safety concerns observed.