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.Prediction of the anti-inflammatory mechanisms of curcumin by module-based protein interaction network analysis.
Yanxiong GAN ; Shichao ZHENG ; Jan P A BAAK ; Silei ZHAO ; Yongfeng ZHENG ; Nini LUO ; Wan LIAO ; Chaomei FU
Acta Pharmaceutica Sinica B 2015;5(6):590-595
Curcumin, the medically active component from Curcuma longa (Turmeric), is widely used to treat inflammatory diseases. Protein interaction network (PIN) analysis was used to predict its mechanisms of molecular action. Targets of curcumin were obtained based on ChEMBL and STITCH databases. Protein-protein interactions (PPIs) were extracted from the String database. The PIN of curcumin was constructed by Cytoscape and the function modules identified by gene ontology (GO) enrichment analysis based on molecular complex detection (MCODE). A PIN of curcumin with 482 nodes and 1688 interactions was constructed, which has scale-free, small world and modular properties. Based on analysis of these function modules, the mechanism of curcumin is proposed. Two modules were found to be intimately associated with inflammation. With function modules analysis, the anti-inflammatory effects of curcumin were related to SMAD, ERG and mediation by the TLR family. TLR9 may be a potential target of curcumin to treat inflammation.