Phenolic-enriched ethanol-soluble fraction of Codonopsis pilosula attenuates LPS-induced acute lung injury in mice via the gut-lung axis
4 affiliations
- 1College of Life Sciences, Sichuan Normal University
- 2School of Pharmacy, Chengdu Medical College
- 3Shanxi Zhendong Wuhe Yi Yang Tang Co., Ltd.
- 4Shanxi Key Laboratory of Medicinal and Edible Homology Functional Food
Abstract
Background: Codonopsis pilosula (Dangshen), a traditional Chinese medicine targeting the Lung Meridian, is commonly steeped in 50% (alcohol by volume) distilled spirits (Baijiu) in China as a medicinal liquor for protecting against lung diseases, including acute lung injury (ALI). This alcohol-steeping preparation yields an ethanol-soluble fraction with a distinct phytochemical profile from conventional aqueous extracts. However, its bioactive compounds and the underlying protective mechanisms against ALI remain unclear.
Objective: This study aimed to characterize the bioactive compounds of the ethanol-soluble fraction of C. pilosula (designated as CPPP) and investigate its protective mechanisms against lipopolysaccharide (LPS)-induced ALI in mice.
Methods: CPPP was characterized by non-targeted metabolomic profiling and targeted quantitative analysis using UPLC-ESI-MS/MS, performed sequentially to achieve comprehensive metabolite coverage and precise quantification of identified constituents. Male C57BL/6J mice were pretreated with CPPP for 30 days prior to intraperitoneal injection of LPS to induce ALI. Comprehensive assessments included 16S rRNA sequencing of the gut microbiota, untargeted metabolomic profiling of feces and serum, enzyme-linked immunosorbent assay (ELISA) quantification of serum inflammatory factors and LPS, histological evaluation and immunohistochemistry (IHC) analysis of gut and lung tissues.
Results: CPPP was enriched in phenolic acids and derivatives (25.3%, w/w). Compared to the normal control, CPPP significantly (P < 0.05) enriched beneficial gut bacteria Clostridium, Bifidobacterium and Akkermansia . CPPP increased fecal levels of butyric acid, serotonin and spermidine, elevated serum level of serotonin, and reduced serum levels of trimethylamine N-oxide, phenylacetylglycine, and phenylacetylglutamine. CPPP significantly (P < 0.001) decreased the levels of LPS-induced pro-inflammatory factors in serum (CRP, TNF-α, IL-6) and lung tissue (MPO, TNF-α, IL-1β, IL-6, IL-18), while increasing the level of anti-inflammatory IL-10 in serum (P < 0.001) and lung tissue (P < 0.01). These anti-inflammatory effects of CPPP, together with the microbiota-derived metabolic alterations, correlated strongly with the CPPP-mediated preservation of intestinal barrier parameters (villus height, goblet cell density, and tight junction protein expression) and attenuation of lung injury parameters (pulmonary inflammation, edema, and histopathological damage).
Conclusion: CPPP attenuated LPS-induced ALI in mice by remodeling gut microbiota, reprogramming key metabolites and suppressing pro-inflammatory factors along the gut-lung axis. These findings validate the lung-protective potential of phenolic compounds from traditional alcohol-steeping preparation of C. pilosula and provide mechanistic insights for developing microbiota-targeted interventions in inflammatory lung diseases.
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BibTeX
@article{li2026phenolicenriched,
title = {{Phenolic-enriched ethanol-soluble fraction of Codonopsis pilosula attenuates LPS-induced acute lung injury in mice via the gut-lung axis}},
author = {Jiao Li and Qian Xiao and Yi Ran Sun and Si Yu Zhang and Xun Gou and Jie Xie and Ying Li and Jia Hui Yuan and Ling Ling Zeng and Guang Bin Meng and Jian Xin Chai and Xiao Yu Zhang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1863500},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1863500/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Phenolic-enriched ethanol-soluble fraction of Codonopsis pilosula attenuates LPS-induced acute lung injury in mice via the gut-lung axis
AU - Jiao Li
AU - Qian Xiao
AU - Yi Ran Sun
AU - Si Yu Zhang
AU - Xun Gou
AU - Jie Xie
AU - Ying Li
AU - Jia Hui Yuan
AU - Ling Ling Zeng
AU - Guang Bin Meng
AU - Jian Xin Chai
AU - Xiao Yu Zhang
PY - 2026
DA - 2026/10/07
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1863500
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1863500/full
AB - Background: Codonopsis pilosula (Dangshen), a traditional Chinese medicine targeting the Lung Meridian, is commonly steeped in 50% (alcohol by volume) distilled spirits (Baijiu) in China as a medicinal liquor for protecting against lung diseases, including acute lung injury (ALI). This alcohol-steeping preparation yields an ethanol-soluble fraction with a distinct phytochemical profile from conventional aqueous extracts. However, its bioactive compounds and the underlying protective mechanisms against ALI remain unclear. Objective: This study aimed to characterize the bioactive compounds of the ethanol-soluble fraction of C. pilosula (designated as CPPP) and investigate its protective mechanisms against lipopolysaccharide (LPS)-induced ALI in mice. Methods: CPPP was characterized by non-targeted metabolomic profiling and targeted quantitative analysis using UPLC-ESI-MS/MS, performed sequentially to achieve comprehensive metabolite coverage and precise quantification of identified constituents. Male C57BL/6J mice were pretreated with CPPP for 30 days prior to intraperitoneal injection of LPS to induce ALI. Comprehensive assessments included 16S rRNA sequencing of the gut microbiota, untargeted metabolomic profiling of feces and serum, enzyme-linked immunosorbent assay (ELISA) quantification of serum inflammatory factors and LPS, histological evaluation and immunohistochemistry (IHC) analysis of gut and lung tissues. Results: CPPP was enriched in phenolic acids and derivatives (25.3%, w/w). Compared to the normal control, CPPP significantly (P < 0.05) enriched beneficial gut bacteria Clostridium, Bifidobacterium and Akkermansia . CPPP increased fecal levels of butyric acid, serotonin and spermidine, elevated serum level of serotonin, and reduced serum levels of trimethylamine N-oxide, phenylacetylglycine, and phenylacetylglutamine. CPPP significantly (P < 0.001) decreased the levels of LPS-induced pro-inflammatory factors in serum (CRP, TNF-α, IL-6) and lung tissue (MPO, TNF-α, IL-1β, IL-6, IL-18), while increasing the level of anti-inflammatory IL-10 in serum (P < 0.001) and lung tissue (P < 0.01). These anti-inflammatory effects of CPPP, together with the microbiota-derived metabolic alterations, correlated strongly with the CPPP-mediated preservation of intestinal barrier parameters (villus height, goblet cell density, and tight junction protein expression) and attenuation of lung injury parameters (pulmonary inflammation, edema, and histopathological damage). Conclusion: CPPP attenuated LPS-induced ALI in mice by remodeling gut microbiota, reprogramming key metabolites and suppressing pro-inflammatory factors along the gut-lung axis. These findings validate the lung-protective potential of phenolic compounds from traditional alcohol-steeping preparation of C. pilosula and provide mechanistic insights for developing microbiota-targeted interventions in inflammatory lung diseases.
SN - 1663-9812
ER -