Manpixiao Decoction Halted the Malignant Transformation of Precancerous Lesions of Gastric Cancer: From Network Prediction to In-Vivo Verification

Abstract

Manpixiao decoction (MPX), a traditional Chinese medicine formula, is mainly used to improve the gastric mucosal pathology and stomach discomfort in patients with gastric precancerous lesions. Precancerous lesion of gastric cancer (PLGC) refers to intestinal metaplasia and/or dysplasia based on gastric mucosal atrophy. Effective prevention and treatment of PLGC is of great significance to reduce the incidence of gastric cancer. Because of the complexity of the etiology and pathogenesis of PLGC, there is no unified and effective treatment plan in western medicine. In recent years, traditional Chinese medicine has shown obvious advantages in the treatment of PLGC and the prevention of its further progression to gastric cancer, relying on its multi-approach and multi-target comprehensive intervention characteristics. This study is designed to examine the protective effect of MPX against PLGC and further to reveal the engaged mechanism via integrating network pharmacology and in vivo experimental evidence. Network pharmacology results demonstrated that inflammation, immune responses, and angiogenesis might be associated with the efficacy of MPX in the treatment of PLGC, in which the PI3K-Akt, cellular senescence, P53 and protein processing in endoplasmic reticulum were involved. Then, we established a rat model of PLGC using a combination of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), sodium salicylate, irregular fasting, and ranitidine, and observed the effects after MPX treatment. Our result showed that MPX improved the pathological condition of gastric mucosa in PLGC rats and reduced the incidence of gastric cancer. Next, the analysis of serum inflammatory cytokines showed that MPX reduced the inflammation-related cytokines (such as IL-1α, IL-7, CSF-1, and CSF-3) in the serum. Additionally, MPX also had a regulation effect on the “protein/protein phosphorylation-signaling pathway” network in the core region of the PLGC rats. It is showed that MPX can inhibit the phosphorylation of PI3K-AKT, and downregulates the EGFR, β-catenin, and N-cadherin protein levels. These results indicate that MPX halted the PLGC progression through inhibiting EGFR-PI3K-AKT related epithelial-mesenchymal transition process.

The effect of phytochemicals in N-methyl-N-nitro-N-nitroguanidine promoting the occurrence and development of gastric cancer

“…SHPPB2 could significantly promote the proliferation of spleen cells in gastric cancer rats induced by ConA or LPS, improve anti-inflammatory cytokines secretion, and reduce pro-inflammatory cytokines ( Han et al, 2018 ). The research results of Li et al (2022) indicated that Manpixiao decoction reduces inflammatory cytokines such as IL-1α, IL-7, CSF-1 and CSF-3 in serum of precancerous lesion of gastric cancer rats induced by MNNG.…”

Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer: A critical review

“…The Manpixiao Decoction is a compound used in Chinese medicine. Li et al [ 69 ] confirmed that this compound could inhibit the progression of PLGC by reducing the occurrence of systemic inflammatory reactions in the local gastric mucosa and inhibiting the EGFR-PI3K-AKT related EMT pathway.…”

Gastric precancerous lesions:occurrence, development factors, and treatment

“…In rats with chronic atrophic gastritis and precancerous lesions, weiqi decoction can reduce COX-2 and increase PGE2, inhibiting gastric inflammation ( 113 ). Manpixiao Decoction can prevent the progress of GPL by improving systemic inflammation in local gastric mucosa and inhibiting EGFR-PI3K-AKT-related EMT pathways ( 114 ). Banxia Xiexin decoction can hinder the signaling path of the toll-like receptors (TLRs)/nuclear factors- κ B(NF- κ B).…”