Proteomics and Metabolomics Unveil Codonopsis pilosula (Franch.) Nannf. Ameliorates Gastric Precancerous Lesions via Regulating Energy Metabolism

Abstract

Objective: This study aimed to systematically evaluate the efficacy of Codonopsis pilosula (Franch.) Nannf. (Codonopsis Radix, CR) and reveal the mechanism of its effects on suppressing Gastric Precancerous Lesions.Methods: First, we established the GPL rat model which was induced by N-methyl-N′-nitro-N-nitrosoguanidine, a disordered diet, and 40% ethanol. The CR’s anti-Gastric Precancerous Lesions effect was comprehensively evaluated by body weight, pathological section, and serum biochemical indexes. Then, quantitative proteomics and metabolomics were conducted to unveil the disturbed protein-network and pharmacodynamic mechanism. Furthermore, serum pharmacology was employed to confirm that CR’s anti-gastritis and anti-cancer phenotype in cell models.Results: In animal models, CR had been shown to control inflammation and ameliorate Gastric Precancerous Lesions. Considering the combination of proteomics and metabolomics, we found that CR could significantly reverse the biological pathways related to energy metabolism which were disturbed by the Gastric Precancerous Lesions model. Furthermore, the results of serum pharmacology indicated that the Codonopsis Radix containing serum could ameliorate gastritis injury and selectively inhibit the proliferation of gastric cancer cells rather than normal cells, which was closely related to ATP production in the above mentioned cells.Conclusion: In summary, CR exerted anti-Gastric Precancerous Lesions effects by ameliorating gastritis injury and selectively inhibiting the proliferation of gastric cancer cells rather than normal cells. Proteomics and metabolomics unveiled that its efficacy was closely related to its regulation of the energy-metabolism pathway. This research not only provided new ideas for exploring the mechanism of complex systems such as Chinese herbals but also benefited the treatment strategy of Gastric Precancerous Lesions via regulating energy metabolism.

Dangshen Huangjiu prevents gastric mucosal injury and inhibits Akt/NF-κB pathway

“…0.04 mol L −1 MNNG solution at 5 mL kg −1 was administered via gavage every three days and irregular diets (2 d satiety, l d starvation, 3 d cycle) were used to develop the CNAG rat model. 10 CNAG is characterized by an infiltration of inflammatory cells ( e.g. neutrophils and monocytes) in the mucosal layer and the degree of inflammation is graded according to the intensity and depth of the infiltration.…”

“…Quantitative proteomics and metabolomics results showed that aqueous extract of Dangshen inhibited the proliferation of gastric cancer cells by regulating energy metabolism, and that serum containing Dangshen inhibited the proliferation of gastric cancer AGS cells without a significant effect on normal gastric mucosal epithelial cells. 10 Further study revealed that polysaccharides of Dangshen could effectively inhibit the proliferation of gastric cancer AGS cells, induce apoptosis and inhibit the secretion of pro-inflammatory factors, the mechanism of which may be related to the regulation of the miR-361-5p/ TLR4/NF-κB pathway. 11 Based on the above study, we propose the hypothesis that DHJ may have a protective effect on the gastric mucosa.…”

A systematic review of the mechanism of action and potential medicinal value of codonopsis pilosula in diseases

“…Alzheimer’s disease (AD) is a gradual progressive neurological disorder, and CP can be used to improve nerve cell function and reduce neurodegeneration, which helps to slow down the development of Alzheimer’s disease ( Xie et al, 2024 ). Colon cancer ( Cao Y. et al, 2019 ), gastric precancerous lesions ( He et al, 2022 ), liver cancer ( Liu Z. et al, 2022 ; Li N. et al, 2024 ), hepatitis ( Zeng et al, 2023 ), and colitis ( Li F. et al, 2024 ) are malignant tumors or inflammatory diseases of the digestive system, and CP plays an important role in preventing and treating these diseases play an important role. Interestingly, CP can also regulate the immune function of sepsis ( Choi et al, 2023 ), rheumatoid arthritis ( Wang Y.-J.…”

A review of the botany, ethnopharmacology, phytochemistry, analysis method and quality control, processing methods, pharmacological effects, pharmacokinetics and toxicity of codonopsis radix

“…Lobetyolin and lobetyol are the main active anti-tumor components of Codonopsis lanceolata , Codonopsis lanceolata Polyacetylenes induces apoptosis in lung cancer cells and ameliorates lung dysfunction by inactivating the Ras/PI3K/AKT pathway ( Wang et al, 2022 ). CPPs inhibit MCF-7 cell proliferation and induce apoptosis through downregulation of CCHE1 expression ( He R. et al, 2022 ).…”