Hydrogen improves the efficacy of tetrandrine in the treatment of silicosis by inhibiting vascular endothelial mesenchymal transition caused by oxidative stress
Xiao K, Li M, Mu Y, Sun Y, Wang S, Chen S, Ma J, Cao M, Yang Y, Shao H, Ding X, Cui G, Du Z. · Frontiers in Bioengineering and Biotechnology. 2026;13:1668524.
What kind of evidence is this?
Preclinical
Randomized controlled mouse silicosis experiment with mechanistic assays and single-cell RNA sequencing
Respiratory health
Inhaled H₂
Not reported in this record.
Not reported in this record.
Methods at a glance
Male C57BL/6 mice, aged 6–8 weeks, with silicosis induced by one intratracheal instillation of silica; treatment began 28 days later.
The H₂/tetrandrine experiment randomized 50 mice to five groups (n=10 each): control, silicosis, H₂, tetrandrine and H₂+tetrandrine. Most histology, imaging and molecular analyses used n=3 per group, hydroxyproline used n=4–6, and single-cell sequencing used one mouse per group.
Eight weeks of treatment after the 28-day silicosis-model establishment period.
Mice inhaled the hydrogen/oxygen mixture for 2 hours/day, 6 days/week. In the combination group, inhalation was added to tetrandrine 20 mg/kg by gavage twice daily, 6 days/week.
Inhaled hydrogen–oxygen mixture: 66% H₂ and 33% O₂ — Brown's-gas-type oxyhydrogen mixture, not H₂ alone.
Shanghai Asclepius Meditec AMS-H-03 generator; the article reports 66% H₂, 33% O₂ and 3 L/min total output. The percentages sum to 99%, consistent with rounded source values; Hydrogenology does not silently change them to 66.666%/33.333%.
Approximately 1,980 mL/min H₂, calculated from the reported 3,000 mL/min total flow × 66%; the article does not state a separately measured H₂ flow.
33% O₂; approximately 990 mL/min O₂, calculated from 3,000 mL/min × 33%. The remaining 1% of total flow is unresolved because the published percentages are rounded and sum to 99%.
Normal control, untreated silicosis, H₂ alone and tetrandrine alone; additional separate cohorts examined tetrandrine distribution and N-acetylcysteine.
Outcomes and reported result
Lung injury and fibrosis histology, CT density, respiratory resistance, hydroxyproline, lung tetrandrine concentration, oxidative-stress and mitochondrial-autophagy markers, apoptosis, vascular EndMT markers, immunofluorescence and single-cell RNA-sequencing analyses of APP/CD74 signaling.
The Results section reports lung tetrandrine concentration of 38±6.1 ng/mg with tetrandrine alone and 73.4±11 ng/mg with H₂+tetrandrine; the abstract instead summarizes an increase from about 50 to 80 ng/mg. The combination group also showed lower histological injury/fibrosis and changes in oxidative-stress, apoptosis, EndMT and APP/CD74 measures versus the silicosis model, with several comparisons favoring combination over monotherapy.
The complete open-access publisher article, methods, group allocation, gas composition and total flow, assay-level sample sizes, positive findings, internal numerical/statistical inconsistencies, limitations, funding and conflict statement were checked.
A reported association, difference or mechanism is not automatically a clinical benefit. Null findings, outcome type, study design and precision all matter.
Cautions and applicability
Preclinical mouse evidence only. The authors report no power calculation, small assay subsets and no long-term clinical efficacy or safety validation. Single-cell sequencing used one mouse per condition. The paper contains differing tetrandrine values between abstract and Results and reports p=0.042 with a 95% CI of −60.44 to 0.78 for one concentration comparison, an interval that includes zero; Hydrogenology preserves this inconsistency rather than resolving it. No dedicated adverse-event analysis is reported. Public Chinese grants funded the work; authors declared no commercial or financial conflicts.
Experimental silicosis in male mice; it does not establish efficacy or safety in people with silicosis.
Not reported in this record.
Not reported in this record.
Not reported in this record.
No single-study GRADE certainty rating is assigned. Certainty is assessed by important outcome across a complete eligible evidence set, not by attaching a final grade to one source.
Sources and record status
PMID: 41561355 · DOI: 10.3389/fbioe.2025.1668524
Open-access publisher article and PubMed Central copy.
Frontiers publisher full article, PubMed metadata and PubMed Central record; full-text extraction checked 8 August 2026.
2026-08-10