San-Wei-Du-Juan formula ameliorates hypoxic lung injury by regulating the MAPK signaling pathway.
SWDJ shows promise in reducing hypoxic lung injury in preclinical models, but human studies are needed to assess its clinical potential.
Where it sits
this study against the rest of the mots-c corpusSummary and findings
The study evaluated the effects of the San-Wei-Du-Juan formula on hypobaric hypoxia-induced lung injury in mice and hypoxic RLE-6TN cells. SWDJ was administered orally at doses of 2.275 g/kg and 11.375 g/kg for 14 days. The formula improved pulmonary function and reduced oxidative stress, inflammation, and apoptosis markers.
Abstract
<h4>Ethnopharmacological relevance</h4>San-Wei-Du-Juan (SWDJ), a classic Tibetan herbal formulation composed of Rhododendron anthopogonoides Maxim., Elettaria cardamomum (L.) Maton, and Alpinia officinarum Hance., has been traditionally used for its anti-hypoxic, anti-inflammatory, and antioxidant activities. However, its protective effects and mechanisms against hypoxic lung injury remain unclear.<h4>Aim of the study</h4>This study aimed to evaluate the protective effects of SWDJ against hypobaric hypoxia-induced lung injury and to elucidate its underlying molecular mechanisms, with a particular focus on the MAPK signaling pathway and mitochondrial apotosis.<h4>Materials and methods</h4>A hypobaric hypoxia-induced lung injury mouse model (simulated 6000 m altitude for 24 h) and a hypoxic RLE-6TN cell model were established. SWDJ was administered orally at doses of 2.275 g/kg and 11.375 g/kg for 14 days. Pulmonary function, histopathology, hematological parameters, oxidative stress markers (SOD, MDA, ROS), inflammatory cytokines (TNF-α, IL-1β, IL-6), apoptosis-related proteins (Bax, Bcl-2, Caspase-3) and MAPK pathway proteins (p-JNK, p-p38) were assessed. Network pharmacology and transcriptomic sequencing were also employed.<h4>Results</h4>SWDJ significantly attenuated hypobaric hypoxia-induced lung injury, as evidenced by a 32.5% reduction in lung wet/dry weight, restored alveolar architecture, and improved pulmonary function parameters including a 41.2% decrease in respiratory frequency and a 38.7% reduction in minute ventilation compared to the model group. Hematological analysis showed that SWDJ-H reduced RBC count by 22.3%, HGB by 19.8%, and HCT by 21.5%, effectively reversing hypoxia-induced polycythemia. Mechanistically, SWDJ suppressed oxidative stress by increasing SOD activity by 2.4-fold and reducing MDA levels by 58.6%, inhibited inflammatory cytokine expression (TNF-α, IL-1β and IL-6), and reduced apoptosis by increasing the Bcl-2/Bax ratio by 3.1-fold and decreasing caspase-3 expression by 52.7%. Furthermore, SWDJ downregulated HIF-1α expression and inhibited the phosphorylation of JNK and p38 MAPK.<h4>Conclusion</h4>This study is the first to systematically demonstrate that SWDJ protects against hypobaric hypoxia-induced lung injury through coordinated inhibition of the MAPK (JNK/p38) pathway, highlighting its potential as a therapeutic agent for high-altitude hypoxic pulmonary diseases.
Background
The study addresses the protective effects of the San-Wei-Du-Juan formula against lung injury caused by hypobaric hypoxia, a condition relevant to high-altitude environments. Prior to this study, the mechanisms by which SWDJ might exert such protective effects were unclear, particularly concerning the MAPK signaling pathway. Understanding these mechanisms is important for potential therapeutic applications in hypoxic pulmonary diseases.
Methods
A hypobaric hypoxia-induced lung injury model was established in mice, simulating 6000 m altitude for 24 hours, and a hypoxic RLE-6TN cell model was used. SWDJ was administered orally at doses of 2.275 g/kg and 11.375 g/kg for 14 days. Outcomes measured included pulmonary function, histopathology, oxidative stress markers, inflammatory cytokines, apoptosis-related proteins, and MAPK pathway proteins.
Results
SWDJ significantly ameliorated lung injury, evidenced by a 32.5% reduction in lung wet/dry weight and improved pulmonary function. It decreased respiratory frequency by 41.2% and minute ventilation by 38.7%. Hematological analysis showed reductions in RBC count, HGB, and HCT, reversing hypoxia-induced polycythemia. SWDJ increased SOD activity by 2.4-fold and reduced MDA levels by 58.6%. It also inhibited inflammatory cytokine expression and apoptosis, increasing the Bcl-2/Bax ratio by 3.1-fold and decreasing caspase-3 expression by 52.7%.
Interpretation
The findings suggest that SWDJ has potential protective effects against hypoxic lung injury, primarily through modulation of oxidative stress, inflammation, and apoptosis pathways. While the results are statistically significant, the clinical significance remains uncertain due to the study's reliance on animal and cell models. Further research in humans is needed to confirm these effects and their potential therapeutic relevance.
Key findings
- 32.5% reduction in lung wet/dry weight.
- 41.2% decrease in respiratory frequency.
- 38.7% reduction in minute ventilation.
- SOD activity increased by 2.4-fold.
- MDA levels reduced by 58.6%.
- Bcl-2/Bax ratio increased by 3.1-fold.
Limitations
- animal model, not human
- hypoxic cell line only
- no human data
- 14-day follow-up
- single-site study