Weipiling decoction alleviates N-methyl-N-nitro-N'-nitrosoguanidine-induced gastric precancerous lesions via NF-κB signalling pathway inhibition

Penghui Yang; Hongmei Yang; Hengli Zhou; Qiuyue Li; Sufen Wei; Qi Wang; Yan Yan; Yongqiang Liu; Huafeng Pan; Siyi Li

doi:10.1186/s13020-022-00663-y

Weipiling decoction alleviates N-methyl-N-nitro-N'-nitrosoguanidine-induced gastric precancerous lesions via NF-κB signalling pathway inhibition

Chin Med. 2022 Sep 9;17(1):104. doi: 10.1186/s13020-022-00663-y.

Authors

Penghui Yang¹, Hongmei Yang^{1

2}, Hengli Zhou¹, Qiuyue Li¹, Sufen Wei³, Qi Wang¹, Yan Yan⁴, Yongqiang Liu⁵, Huafeng Pan⁶, Siyi Li^{7

8

9}

Affiliations

¹ Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
² Department of Emergency Ward, The First Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, 550001, China.
³ Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
⁴ Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
⁵ Research Center of Chinese Herbal Resources Science and Engineering, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
⁶ Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. gzphf@gzucm.edu.cn.
⁷ Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Guangzhou, 510405, China. lisiyi@gzucm.edu.cn.
⁸ International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. lisiyi@gzucm.edu.cn.
⁹ Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, 523808, China. lisiyi@gzucm.edu.cn.

Abstract

Aim of the study: We aimed to explore how weipiling (WPL) decoction WPL alleviates gastric precancerous lesions (GPLs) and uncover its anti-inflammatory roles in GPL treatment.

Materials and methods: The anti-GPL action mechanisms of WPL were analysed using a network pharmacological method. The WPL extract was prepared in a traditional way and evaluated for its major components using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). BALB/c mice were exposed to N-methyl-N-nitro-N-nitrosoguanidine (MNNG) (150 μg/mL) for 6 weeks to induce GPLs. GPL mice were administered WPL (3.75 g/kg/day and 15 g/kg/day) for an additional 8 weeks. Haematoxylin and eosin (H&E) staining was used to investigate histological alterations in gastric tissues. Expression of the T helper 1 (Th1) cell markers CD4⁺ and interferon-gamma (INF-γ) were tested using immunohistochemistry (IHC). Inflammatory protein and mRNA levels in the nuclear factor kappa B (NF-κB) pathway were detected using western blotting and a quantitative reverse transcription polymerase chain reaction (RT-qPCR), respectively.

Results: We identified and selected 110 active compounds and 146 targets from public databases and references. Four representative components of WPL were established and quantified by HPLC-MS/MS analysis. WPL attenuated MNNG-induced GPLs, including epithelial shedding, cavity fusion, basement membranes with asymmetrical thickness, intestinal metaplasia, dysplasia, pro-inflammatory Th1-cell infiltration, and INF-γ production, indicating that WPL prevents inflammation in the gastric mucosa. Furthermore, WPL reversed MNNG-induced activation of the IκB/NF-κB signalling pathway and subsequently attenuated the upregulation of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase (NOX)) family members NOX2 and NOX4.

Conclusion: WPL attenuated GPLs by controlling the generation of pro-inflammatory elements and inhibiting the NF-κB signalling pathway in vivo.

Keywords: Gastric precancerous lesion; Inflammation; N-methyl-N-nitro-N-nitrosoguanidine; NF-κB; Weipiling decoction.

Abstract

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