1.Traditional Chinese Medicine Treats Chronic Atrophic Gastritis via Multiple Pathways
Sici WANG ; Yuan LI ; Ping LI ; Haocheng ZHENG ; Weiyu CHEN ; Xia DING
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(19):193-202
ObjectiveTo mine the compatibility rules of patented traditional Chinese medicine (TCM) compound prescriptions for treating chronic atrophic gastritis (CAG) by systems pharmacology and molecular docking methods, and predict the targets and molecular mechanisms of Chinese medicinals with different efficacy in the treatment of CAG. MethodThe TCM compound prescriptions for treating CAG were extracted from the patent system of the China National Intellectual Property Administration. The active components and targets of the prescriptions were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrative Database (TCMID), and UniProt. The candidate targets and pathways of CAG were obtained from GeneCards, DisGeNet, Online Mendelian Inheritance in Man (OMIM), MalaCards, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome. The gene ontology (GO) functional annotation and KEGG pathway enrichment were realized by R Studio 4.1.2. STRING11.0 was employed to build the protein-protein interaction (PPI) network, and AutoDock Vina 4.2.6 was used for the docking between key targets and components. ResultA total of 228 TCM compound prescriptions for treating CAG were extracted. The medicinals used in these prescriptions mainly had warm or cold nature, bitter or sweet taste, tropism to the spleen, stomach, and liver meridians, and the efficacy of tonifying Qi, regulating Qi movement, clearing heat, and activating and toniying blood. The prescriptions mainly treated CAG via p53, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), forkhead box protein O (FoxO), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1 (HIF-1) signaling pathways. Molecular docking results confirmed that the active components in the prescriptions had docking activities with key receptor proteins. ConclusionThis study preliminarily analyzed the compatibility rules of TCM compound prescriptions in the treatment of CAG. The medicinals with different efficacy treat CAG by regulating cell proliferation, apoptosis, and oxidative stress response, preventing carcinogen production, promoting gastric acid secretion, and improving local microcirculation in a multi-target, multi-pathway, multi-link manner. The findings facilitate the research on the TCM treatment of CAG.
2.Evolutionary Law of Syndrome and Syndrome Elements during the Malignant Transformation of Chronic Hepatitis B
Simiao YU ; Xia DING ; Ping LI ; Sici WANG ; Jiahui LI ; Jing JING ; Tingting HE ; Yongqiang SUN ; Liping WANG ; Aozhe ZHANG ; Jie LIN ; Yuan LI ; Ruilin WANG
Journal of Traditional Chinese Medicine 2023;64(23):2427-2434
ObjectiveTo clarify the evolutionary laws of syndromes and syndrome elements at different stages during the malignant transformation of chronic hepatitis B (CHB). MethodsA total of 671 patients with hepatitis B virus infection, who were admitted to the outpatient and inpatient departments of Dongzhimen Hospital of Beijing University of Chinese Medicine and The Fifth Medical Center of Chinese PLA General Hospital from July 1st, 2020 to June 30th, 2021, were included, involving 120 cases of CHB, 340 cases of hepatitis B liver cirrhosis (HBLC), 64 cases of precancerous lesions with hepatitis B liver cirrhosis (PLHC), and 147 cases of hepatitis B liver cirrhosis with hepatocellular carcinoma (HCC). A Survey form of traditional Chinese medicine syndrome during malignant transformation of chronic hepatitis B was designed, and the general information, auxiliary examination and the four examinations results were collected. Factor analysis and K-means clustering were used to determine and statistically analyze the syndrome and syndrome elements. ResultsFive traditional Chinese medicine (TCM) syndrome types were identified in CHB patients, while there were six TCM syndrome types in HBLC, PLHC and HCC stages. Among CHB patients, the main syndromes were liver constraint and spleen deficiency (53.33%) and liver-gallbladder damp-heat (21.67%), and the dominant syndrome elements were qi stagnation (27.60%), heat (17.71%) and qi deficiency (17.71%). In the HBLC stage, the syndromes were mainly blood stasis obstructing the collaterals (23.83%) and liver constraint and spleen deficiency (22.35%), with dominant syndrome elements being blood stasis (19.25%), dampness (17.46%), and qi deficiency (15.01%). For the PLHC stage, the primary syndrome types were blood stasis obstructing the collaterals (29.68%) and liver-kidney yin deficiency (20.31%), and the leading syndrome elements were blood stasis (22.12%), yin deficiency (15.93%), and qi deficiency (15.04%). In the HCC stage, the syndrome was dominated by blood stasis obstructing the collaterals (33.34%) and liver-kidney yin deficiency (19.73%), with the main syndrome elements being blood stasis (24.52%), yin deficiency (16.09%), and qi deficiency (15.33%). During the progression of CHB to malignancy, there was a gradual decrease in excess syndromes including liver-gallbladder damp-heat and water-dampness internal obstruction from 21.67% to 19.04%. In contrast, deficiency syndromes including liver-kidney yin deficiency and spleen-kidney yang deficiency increased from 15.83% to 31.97%. Additionally, excess syndrome elements including qi stagnation, heat and dampness decreased from 59.89% to 34.48%, while deficiency syndrome elements including qi deficiency, yin deficiency and yang deficiency increased from 32.30% to 41.00%. ConclusionDuring the malignant transformation of CHB, there exists a progression of syndrome and syndrome elements, shifting from qi stagnation, heat and qi deficiency to blood stasis (predominantly excess), dampness and qi deficiency, and then to blood stasis (predominantly deficiency), yin deficiency and qi deficiency, characterized by “deficiency-excess complex, and shift from excess to deficiency”.
3.Dayuanyin Regulates TLR/MAPK/NF-κB Pathway for Preventing and Treating Acute Lung Injury Induced by H1N1 Infection
Chengze LI ; Fuhao CHU ; Yuan LI ; Yunze LIU ; Haocheng ZHENG ; Sici WANG ; Yixiao GU ; Wanhong ZHU ; Ruoshi ZHANG ; Xingjian SONG ; Cong GAI ; Xia DING
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):52-60
ObjectiveTo investigate the therapeutic effect of Dayuanyin on acute lung injury induced by H1N1 infection and decipher the potential mechanism. MethodThe constituents in Dayuanyin were analyzed by ultra-high performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS). Forty-eight female BALB/c mice were randomized into normal, model, oseltamivir (19.5 mg·kg-1), and low-, medium-, and high-dose (2.73, 5.46, 10.92 g·kg-1) Dayuanyin groups. The normal and model groups were administrated with deionized water by gavage, and the other groups were administrated with the corresponding drugs by gavage. On day 3 of drug administration, the normal group received nasal inhalation of normal saline, and the other groups were inoculated intranasally with A/RP/8/34 (H1N1) for the modeling of influenza virus infection. Mice were administrated with drugs continuously for 7 days and weighed daily. Sampling was performed 12 h after the last administration, and the lung tissue was weighed to calculate the lung index. Hematoxylin-eosin staining was performed to observe the pathological and morphological changes of the lung tissue and bronchi. The cytometric bead array (CBA) was used to measure the serum levels of interferon-gamma (IFN-γ), C-X-C motif ligand 1 (CXCL1), tumor necrosis factor-alpha (TNF-α), chemokine ligand 2 (CCL2), interleukin-12p70 (IL-12p70), chemokine ligand 5 (CCL5), interleukin-1β (IL-1β), chemokine (C-X-C motif) ligand 10 (CXCL10), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-10 (IL-10), interferon-beta (IFN-β), interferon-alpha (IFN-α), and interleukin-6 (IL-6). According to the results of mass spectrometry and network pharmacology, we analyzed the mechanism of Dayuanyin in treating acute lung injury caused by H1N1. The protein levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor-kappa B (NF-κB), and their phosphorylated forms were determined by Western blot. The mRNA levels of myeloid differentiation factor 88 (MyD88), Toll-like receptor 3 (TLR3), Toll-like receptor 7 (TLR7), and Toll-like receptor 8 (TLR8) in the lung tissue were measured by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultA total of 57 compounds, including paeoniflorin and baicalein, were detected in Dayuanyin. Compared with the normal group, the model group showed decreased body weight (P<0.01), lung edema and hemorrhage, increased lung index (P<0.01), and elevated levels of IFN-γ, IL-12p70, CCL5, IL-1β, CXCL10, GM-CSF, IFN-β, and IL-6 (P<0.01). Compared with the model group, Dayuanyin attenuated alveolar wall thickening, capillary congestion, and immune cell infiltration, reduced the alterations in body weight and lung index (P<0.01), and down-regulated the protein levels of IFN-γ, IL-12p70, CCL5, IL-1β, CXCL10, GM-CSF, IFN-β, and IL-6 (P<0.01). A total of 57 key genes were predicted by network pharmacological analysis, of which the MAPK signaling pathway was the main target signaling pathway. Compared with the normal group, the model group showed up-regulation in the protein levels of phosphorylation (p)-ERK1/2, p-p38 MAPK, and p-NF-κB (P<0.01) and the mRNA levels of TLR7, TLR8, MyD88, and TLR3 (P<0.05, P<0.01). Compared with the model group, Dayuanyin lowered the phosphorylation levels of ERK1/2, p38 MAPK, and NF-κB p65 in a dose-dependent manner (P<0.01) and down-regulated the mRNA levels of TLR3, TLR7, TLR8, and MyD88 (P<0.01). ConclusionDayuanyin can prevent and control H1N1 infection-induced acute lung injury by inhibiting the TLR/MAPK/NF-κB signaling pathway.