1.Intervention Effect and Molecular Mechanism of Dabufei Decoction in Dunhuang Formula Combined with Cisplatin on Lewis Lung Adenocarcinoma in Mice
Mengyong XIAO ; Yali LUO ; Xiaofeng QI ; Jing LUO ; Linna MA ; Linfeng RUAN ; Nini LIAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):95-104
ObjectiveTo explore the intervention effect and molecular mechanism of Dabufei decoction in Dunhuang formula combined with cisplatin on Lewis lung adenocarcinoma-bearing mice. MethodFifty C57BL/6J mice were used, with 10 randomly assigned to the blank group (without modeling), and 40 subcutaneously inoculated with Lewis cells to establish a Lewis lung adenocarcinoma-bearing mouse model. These 40 mice were randomly divided into the following four groups (with 10 mice in each group): Model group (equal volume of physiological saline), cisplatin group (5 mg·kg-1), Dabufei decoction group (14.35 g·kg-1·d-1), and Dabufei decoction combined with cisplatin group (Dabufei decoction 14.35 g·kg-1·d-1 + cisplatin 5 mg·kg-1). Each group was treated continuously for 14 days. The general condition of the mice was observed, body weight changes were recorded, and the tumor inhibition rate, spleen index, and thymus index were calculated. Peripheral blood white blood cell (WBC), platelet (PLT), and hemoglobin (HGB) were detected by routine blood tests. Flow cytometry was used to detect the expression of CD4+CD25+FoxP3+ regulatory T cells (Treg) and natural killer (NK) cells in the spleen. Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were used to determine the expression of proteins and mRNA related to the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in tumor tissues. ResultCompared with the blank group, the model group showed decreased body weight (P<0.05), spleen index, and thymus index (P<0.05), decreased percentage of NK cells in the spleen (P<0.05), increased percentage of Treg cells (P<0.05), and decreased counts of WBC, PLT, and HGB (P<0.05). Compared with the model group, the Dabufei decoction group exhibited significant tumor growth inhibition, increased body weight, and reduced tumor weight (P<0.05), increased percentage of NK cells (P<0.05), decreased proportion of Treg cells (P<0.05), and increased counts of WBC, PLT, and HGB (P<0.05). In the cisplatin group, tumor growth was significantly inhibited, body weight significantly decreased (P<0.05), and tumor weight significantly reduced (P<0.05). The spleen index and thymus index decreased (P<0.05), and the percentage of Treg cells significantly decreased (P<0.05). The counts of WBC, PLT, and HGB significantly decreased (P<0.05). In the Dabufei decoction combined with cisplatin group, tumor growth was significantly inhibited, and tumor weight significantly reduced (P<0.05). The levels of phosphorylated PI3K, Akt, and mTOR proteins and mRNA in tumor tissues were significantly reduced in all medication groups (P<0.05). Compared with the cisplatin group, the Dabufei decoction combined with cisplatin group showed significantly inhibited tumor growth, reduced tumor weight (P<0.05), increased body weight (P<0.05), increased spleen index and thymus index (P<0.05), increased percentage of NK cells (P<0.05), decreased percentage of Treg cells (P<0.05), significantly increased counts of WBC, PLT, and HGB (P<0.05), and reduced levels of phosphorylated PI3K, Akt, and mTOR and their mRNA (P<0.05). ConclusionDabufei decoction combined with cisplatin has a synergistic effect with reduced toxicity, effectively regulating immune function, increasing the proportion of NK cells, reducing the proportion of Treg cells, improving bone marrow suppression, and downregulating the PI3K/Akt/mTOR signaling pathway to inhibit tumor growth in Lewis lung adenocarcinoma-bearing mice.
2.To Explore the Mechanism of Huayu Xiaopi Decoction in the Intervention of Precancerous Lesions of Gastric Cancer Based on Network Pharmacology and Molecular Docking Technique and in vivo Experiment
Ziyou LIU ; Yongqiang DUAN ; Yaorong AN ; Yanying ZHANG ; Bing SONG ; Min BAI ; Xiaomei YUAN ; Yue PENG ; Mengyong XIAO ; Weiqiang LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(4):1092-1103
Objective To predict the target and molecular mechanism of Huayu Xiaopi decoction in the intervention of Precancerous lesions of gastric cancer(PLGC)based on network pharmacology and molecular docking technology,and to conduct experimental verification.Methods A total of 60 SPF SD male rats were randomly selected as blank control,and the other rats were replicated in PLGC model.After successful modeling,the rats were randomly divided into model group,folic acid group(2 mg·kg-1·d-1),Huayu Xiaopi decoction high,medium and low dose groups(24.8,12.4,6.2 g·kg-1·d-1),which were continuously administered for 90 days.The body mass and food intake of rats at 3 h were recorded,and the gastric histopathology was observed by HE staining.Network pharmacology and molecular docking techniques were used to predict the potential targets of Huayu Xiaopi decoction in PLGC intervention,and the core targets were verified by Western blot technique.Results Compared with the blank group,the body mass and 3 h food intake of rats in the model group were significantly decreased(P<0.05),the gastric mucosa of rats was significantly thinner,the glands were significantly reduced and disordered,and the intestinal metaplasia goblet cells and a large number of inflammatory cells were visible in some areas.Compared with the model group,the body mass and 3 h food intake of rats in each administration group were improved to varying degrees.Huayu Xiaopi Decoction improved significantly in medium and high doses(P<0.05),the gastric mucosa was repaired in different degrees,the glandular arrangement tended to be orderly,and the inflammatory cells in the interstitial were gradually reduced.The results of network pharmacology and molecular docking showed that TP53,JUN and MAPK3/1(ERK1/2)were the core targets of Huayu Xiaopi decoction in the intervention of PLGC.Molecular biological detection results showed that compared with blank group,the protein phosphorylation levels of TP53,c-Jun and ERK1/2 in gastric tissue of model group were significantly increased(P<0.05).Compared with model group,the protein phosphorylation levels of TP53,c-Jun and ERK1/2 in gastric tissue of rats in all administration groups were decreased to different degrees,and significantly decreased in Huayu Xiaopi decoction high-dose and medium-dose groups(P<0.05).Conclusion Huayu Xiaopi Decoction can significantly improve the survival condition of PLGC rats and promote gastric mucosal repair,the specific mechanism of which may be related to the decrease of ERK1/2,c-Jun and TP53 protein phosphorylation levels in gastric tissue of PLGC rats,and then regulate the downstream signaling molecular response.
3. Molecular mechanism and treatment of pulmonary fibrosis
Shiqin ZHOU ; Yali LUO ; Wen ZHOU ; Xiaofeng QI ; Mengyong XIAO ; Yali LUO
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(10):1133-1147
Pulmonary fibrosis (PF) is a chronic progressive interstitial lung disease. The pathogenesis of PF is not yet clear. The two anti fibrosis drugs approved for IPF treatment, nidanib and pirfenidone, have been proved to reduce the decline of pulmonary function of pF, but both have side effects. So far, there is no obvious and effective treatment to prevent the progress of pF. Therefore, this review focuses on the different cells, molecular mechanisms involved in PF and the current treatment progress of PF, so as to provide theoretical support for a better understanding of these cells, molecular mechanisms and drug development and application in PF.
4. Research status of dialectical prevention and treatment of acute lung injury based on the theory of "Wei qi and Ying Xue"
Xiaofeng QI ; Yali LUO ; Mengyong XIAO ; Shiqin ZHOU ; Wen ZHOU ; Fangyu AN ; Ben-Jun WEI ; Yongqi LIU ; Yali LUO ; Yongqi LIU
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(4):429-437
Acute lung injury (ALI) is a common clinical critical respiratory disease. At present, the mechanism of the disease has not been fully elucidated, there is a lack of specific drugs in clinical practice and the mortality rate is high, which is a difficult problem in the medical field. In recent years, traditional Chinese medicine has exerted its unique advantages and efficacy in the prevention and treatment of ALI, which has aroused the attention of domestic and foreign scholars. Based on the theory of "Wei Qi Ying Xue", this paper discusses the current research status of prevention and treatment of ALI by traditional Chinese medicine, and analyzes its pathogenesis, clinical manifestations and corresponding analysis with TCM syndrome. According to the angle of "Wei Qi Ying Xue", the progress of syndrome differentiation and treatment is highly consistent with immune response, inflammatory response, oxidative stress and apoptosis, in order to find new ideas and medication for the prevention and treatment of ALI with integrated traditional Chinese and Western medicine.