Polygonatum Sibiricum Polysaccharides Improve Colonic Injury in a Mouse Model of Chronic Obstructive Pulmonary Disease by Regulating Bile Acid Metabolism in the Colon
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2025.0308
- VernacularTitle:黄精多糖通过调控结肠内胆汁酸代谢改善慢性阻塞性肺疾病模型小鼠的结肠损伤
- Author:
Wanrong LI
1
;
Mengting TAO
1
;
Yuanfeng ZOU
1
;
Dan HE
1
;
Nengyuan TANG
1
;
Xin TAN
1
;
Lixia LI
2
;
Dandan CHEN
3
Author Information
1. Research Center for Natural Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 610000, China
2. Sichuan Key Laboratory of Animal Diseases and Human Health, Chengdu 610000, China
3. Guangxi Health Vocational and Technical College, Nanning 530000, China
- Publication Type:Journal Article
- Keywords:
Polygonatum sibiricum polysaccharides;
colonic bile acid metabolism;
chronic obstructive pulmonary disease;
colonic microbiota;
in vitro bile acid binding
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2025;46(3):431-443
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect and mechanism of Polygonatum neutral polysaccharides from sibiricum (PSP-NP) on colon injury in mice with chronic obstructive pulmonary disease (COPD). MethodsMale C57BL/6J mice were randomly divided into a control group, a COPD model group, and a PSP-NP group. The COPD model was established using smoke exposure combined with intranasal LPS administration. The PSP-NP group was simultaneously treated daily with 200 mg/kg of PSP-NP via intragastric gavage, while the other groups received an equal volume of saline. HE staining was used to observe the pathological changes in the colon. ELISA was employed to detect the levels of LPS in serum and the expressions of ZO-1, Occludin, IL-6, and TNF-α in colon tissue. UPLC-MS was used to detect the types and contents of bile acids in colonic content, and to screen for differential bile acids. Differential microbial flora were identified using 16S rRNA gene sequencing, and correlation analysis was conducted with differential bile acids. PSP-NP was combined with the differential bile acids cholic acid (CA), and deoxycholic acid (DCA) in vitro to analyze the binding capacity of PSP-NP for CA and DCA. PSP-NP was applied to NCM460 normal colonic epithelial cells cultured in CA and DCA. Cell migration ability was assessed using the scratch assay, and the mRNA expression levels of inflammatory cytokines TNF-α, IL-6, and NF-κB were measured by RT-qPCR. ResultsPSP-NP effectively improved colonic damage in COPD model mice, enhanced mechanical barrier function, alleviated inflammatory response, and regulated abnormal changes in colonic flora and bile acid metabolism. Correlation analysis further revealed that PSP-NP regulated colonic bile acid metabolism and reduced the redundancy of secondary bile acids by increasing the relative abundance of Bacteroidota, Verrucomicrobiota, Bacteroides, and Akkermansia, while decreasing the relative abundance of Lactobacillus and Bifidobacterium. Notably, in vitro binding assays demonstrated that PSP-NP bound to differential bile acids DCA and CA, with the strongest binding capacity for DCA at 58.2%. In cellular functional studies, DCA inhibited the migration ability of colonic epithelial cells NCM460 and significantly increased the relative mRNA expression levels of inflammatory factors TNF-α, IL-6, and NF-κB. Importantly, co-treatment with PSP-NP significantly ameliorated the impact of DCA on NCM460 cells. ConclusionsPSP-NP may significantly improve colonic damage in COPD model mice. The mechanism may involve the regulation of colonic bile acid metabolism and bile acid profiles through both microbial modulation and direct binding, thereby reducing the damage caused by secondary bile acids such as DCA to colonic epithelial cells.