Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2023

Open Access 01-12-2023 | Gastric Cancer | Research

Elian granules alleviate precancerous lesions of gastric cancer in rats by suppressing M2-type polarization of tumor-associated macrophages through NF-κB signaling pathway

Authors: Zhirong Yi, Qingling Jia, Yujiao Wang, Yuqin Zhang, Tianyi Xie, Jianghong Ling

Published in: BMC Complementary Medicine and Therapies | Issue 1/2023

Login to get access

Abstract

Background

Precancerous lesions of gastric cancer (PLGC) refer to a kind of histopathological changes in the gastric mucosa that can progress to gastric cancer. Elian granules (ELG), a Chinese medicinal prescription, have achieved satisfactory results in the treatment of PLGC. However, the exact mechanism underlying the therapeutic effect of ELG remains unclear. Here, this study aims to explore the mechanism of ELG alleviating PLGC in rats.

Methods

The chemical ingredients of ELG were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Specific Pathogen Free SD rats were randomly assigned to 3 groups: the control, model, and ELG groups. The 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) integrated modeling method was adopted to construct the PLGC rat model in groups except for the control group. Meanwhile, normal saline was used as an intervention for the control and model groups, and ELG aqueous solution for the ELG group, lasting 40 weeks. Subsequently, the stomach of rats was harvested for further analysis. Hematoxylin-eosin staining of the gastric tissue was conducted to assess the pathological changes. Immunofluorescence was carried out for the expression of CD68, and CD206 proteins. Real-time quantitative PCR combined with Western blot was conducted to analyze the expression of arginase-1(Arg-1), inducible nitric oxide synthase (iNOS), p65, p-p65, nuclear factor inhibitor protein-α (IκBα), and p-IκBα in gastric antrum tissue.

Results

Five chemical ingredients including Curcumol, Curzerenone, Berberine, Ferulic Acid, and 2-Hydroxy-3-Methylanthraquine were identified in ELG. The gastric mucosal glands of rats treated with ELG were orderly arranged, with no intestinal metaplasia and no dysplasia. Furthermore, ELG decreased the percentage of M2-type TAMs marked with CD68 and CD206 proteins, and the ratio of Arg-1 to iNOS in the gastric antrum tissue of rats with PLGC. In addition, ELG could also down-regulate the protein and mRNA expression of p-p65, p65, and p-IκBα, but up-regulate the expression of IκBα mRNA in rats with PLGC.

Conclusions

The results showed that ELG attenuates PLGC in rats by suppressing the M2-type polarization of tumor-associated macrophages (TAMs) through NF-κB signaling pathway.
Literature
5.
go back to reference Xu J, Yu Y, He X, Niu N, Li X, Zhang R, et al. Tumor-associated macrophages induce invasion and poor prognosis in human gastric cancer in a cyclooxygenase-2/MMP9-dependent manner. Am J Transl Res. 2019;11:6040–54.PubMedPubMedCentral Xu J, Yu Y, He X, Niu N, Li X, Zhang R, et al. Tumor-associated macrophages induce invasion and poor prognosis in human gastric cancer in a cyclooxygenase-2/MMP9-dependent manner. Am J Transl Res. 2019;11:6040–54.PubMedPubMedCentral
11.
go back to reference Cong J, Liao LJ, Zhu MP, Cai G, Zhang ZL. Clinical efficacy of Elian granule in patients with chronic atrophic gastritis. J Anhui Tradit Chin Med Coll. 2015;34:27–30. Cong J, Liao LJ, Zhu MP, Cai G, Zhang ZL. Clinical efficacy of Elian granule in patients with chronic atrophic gastritis. J Anhui Tradit Chin Med Coll. 2015;34:27–30.
12.
go back to reference Yang S, Zhuang Y, Guo L, Cong J, Cen R. Effect of Elian granules on precancerous lesions of chronic atrophic gastritis and its influence on patients’ immune function. Chin J Integr Trad West Med Dig. 2021;29:638–41. Yang S, Zhuang Y, Guo L, Cong J, Cen R. Effect of Elian granules on precancerous lesions of chronic atrophic gastritis and its influence on patients’ immune function. Chin J Integr Trad West Med Dig. 2021;29:638–41.
14.
go back to reference Cui RT, Cai G, Cheng Y, Wang SP, Yang QH, Tian T. Effect of Leweijian (LWJ) on experimentally induced dysplasia of gastric epithelial cell apoptosis and regulation gene. Chin J Integr Tradit West Med Gastrospleen. 2000;8:67–9. Cui RT, Cai G, Cheng Y, Wang SP, Yang QH, Tian T. Effect of Leweijian (LWJ) on experimentally induced dysplasia of gastric epithelial cell apoptosis and regulation gene. Chin J Integr Tradit West Med Gastrospleen. 2000;8:67–9.
15.
go back to reference Yi Z, Lin Y, Wang Y, Jia Q, Zhang Y, Xie T, et al. Effect of Elian Granule on Autophagy and PI3K/Akt/mTOR signaling pathway in gastric tissue of rats with gastric Cancer. Chin J Exp Trad Med Formul. 2021;27:84–91. Yi Z, Lin Y, Wang Y, Jia Q, Zhang Y, Xie T, et al. Effect of Elian Granule on Autophagy and PI3K/Akt/mTOR signaling pathway in gastric tissue of rats with gastric Cancer. Chin J Exp Trad Med Formul. 2021;27:84–91.
16.
go back to reference Gu ZJ, Tang RY, Lin J, Li YM, Zhang ZL, Cai G. Elian Granules” for the treatment of chronic atrophic gastritis of spleen deficiency and heat stagnation pattern accompanied with intestinal metaplasia: a randomized controlled clinical trial. Shanghai J Tradit Chin Med. 2015;49:40–3. Gu ZJ, Tang RY, Lin J, Li YM, Zhang ZL, Cai G. Elian Granules” for the treatment of chronic atrophic gastritis of spleen deficiency and heat stagnation pattern accompanied with intestinal metaplasia: a randomized controlled clinical trial. Shanghai J Tradit Chin Med. 2015;49:40–3.
17.
go back to reference Shu WN, Yang Q, Zhong H, Hu XZ, Liu Y, Ma MZ. Establishment and evaluation of a rat model of chronic atrophic gastritis. Hunan J Tradit Chin Med. 2017;33:139–42. Shu WN, Yang Q, Zhong H, Hu XZ, Liu Y, Ma MZ. Establishment and evaluation of a rat model of chronic atrophic gastritis. Hunan J Tradit Chin Med. 2017;33:139–42.
18.
go back to reference Zheng JY, Zhao ZM, Pan HF, Li SY, Cai TT, Zhang CZ. Study on the pathologic structure and ultrastructure of stomach mucosal disease in precancerous lesions of gastric carcinoma rats with spleen-deficiency syndrome. China J Tradit Chin Med Pharm. 2018;33:1730–5. Zheng JY, Zhao ZM, Pan HF, Li SY, Cai TT, Zhang CZ. Study on the pathologic structure and ultrastructure of stomach mucosal disease in precancerous lesions of gastric carcinoma rats with spleen-deficiency syndrome. China J Tradit Chin Med Pharm. 2018;33:1730–5.
22.
go back to reference Zhang P, Zhang LN, Yang Y, Ma XR. Curcumol induces apoptosis in tongue squamous cell carcinoma Tca-8113 cells by activating p38 MAPK mediated-mitochondrial apoptotic pathway. J Oral Sci Res. 2021;37:509–13. Zhang P, Zhang LN, Yang Y, Ma XR. Curcumol induces apoptosis in tongue squamous cell carcinoma Tca-8113 cells by activating p38 MAPK mediated-mitochondrial apoptotic pathway. J Oral Sci Res. 2021;37:509–13.
23.
go back to reference Zheng T, Xiao H, Shen Y, Zhang X, Jiang K, Liu L, et al. Anticancer effects of curzerenone against drug-resistant human lung carcinoma cells are mediated via programmed cell death, loss of mitochondrial membrane potential, ROS, and blocking the ERK/MAPK and NF-κB signaling pathway. J BUON. 2019;24:907–12.PubMed Zheng T, Xiao H, Shen Y, Zhang X, Jiang K, Liu L, et al. Anticancer effects of curzerenone against drug-resistant human lung carcinoma cells are mediated via programmed cell death, loss of mitochondrial membrane potential, ROS, and blocking the ERK/MAPK and NF-κB signaling pathway. J BUON. 2019;24:907–12.PubMed
25.
go back to reference Han Y, Xu Z, Zhang F, Ji H. Effect of Hedyotis Diffusa on proliferation, telomerase activity, and Ki-67 gene expression in cervical cancer cells. Mod J Integr Tradit Chin West Med. 2019;28:3914–8. Han Y, Xu Z, Zhang F, Ji H. Effect of Hedyotis Diffusa on proliferation, telomerase activity, and Ki-67 gene expression in cervical cancer cells. Mod J Integr Tradit Chin West Med. 2019;28:3914–8.
27.
go back to reference Liu N, Jiang CX, Liu L, Long CC, Yang BL, Zhang A. Effect of Berberine on proliferation and apoptosis of human ovarian cancer cells. Matern Child Health Care China. 2018;33:911–4. Liu N, Jiang CX, Liu L, Long CC, Yang BL, Zhang A. Effect of Berberine on proliferation and apoptosis of human ovarian cancer cells. Matern Child Health Care China. 2018;33:911–4.
39.
go back to reference Chen Z, An J, Wei Y, Yang J, Wang R, Xing E. Studies on molecular signaling pathways of gastric cancer and its precancerous lesions. Mod J Integr Tradit Chin West Med. 2018;27:4098–101. Chen Z, An J, Wei Y, Yang J, Wang R, Xing E. Studies on molecular signaling pathways of gastric cancer and its precancerous lesions. Mod J Integr Tradit Chin West Med. 2018;27:4098–101.
40.
go back to reference Li M, Xu L, Shan Z. Study on therapeutic effect and mechanism of Qi-Zhu Er-Zhu Er-Cao Tang in treatment of chronic atrophic gastritis precancerous lesion based on pathway of NF-κB (p65) and CyclinE. World Sci Technol / Mod Tradit Chin Med Mater Med. 2015;17:2119–24. Li M, Xu L, Shan Z. Study on therapeutic effect and mechanism of Qi-Zhu Er-Zhu Er-Cao Tang in treatment of chronic atrophic gastritis precancerous lesion based on pathway of NF-κB (p65) and CyclinE. World Sci Technol / Mod Tradit Chin Med Mater Med. 2015;17:2119–24.
41.
go back to reference Pan Z, Zhang S, Zheng L. A review on treating gastric precancerous lesions in TCM based on NF-κB signaling pathway. Clin J Chin Med. 2021;13:146–8. Pan Z, Zhang S, Zheng L. A review on treating gastric precancerous lesions in TCM based on NF-κB signaling pathway. Clin J Chin Med. 2021;13:146–8.
Metadata
Title
Elian granules alleviate precancerous lesions of gastric cancer in rats by suppressing M2-type polarization of tumor-associated macrophages through NF-κB signaling pathway
Authors
Zhirong Yi
Qingling Jia
Yujiao Wang
Yuqin Zhang
Tianyi Xie
Jianghong Ling
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2023
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-023-04015-7

Other articles of this Issue 1/2023

BMC Complementary Medicine and Therapies 1/2023 Go to the issue