BACKGROUND:Huanglian Wendan decoction (HLWD) is traditionally used to treat a syndrome characterized by symptoms such as insomnia, irritability, and digestive disturbances. Its historical application in addressing phlegm-heat-induced mental and emotional disorders offers both a cultural and clinical basis for investigating its potential mechanisms in alleviating depressive symptoms via gut-brain axis. PURPOSE:To explore the potential therapeutic mechanisms of HLWD in improving depression. METHODS:Behavioral outcomes were assessed using the SPT, TST, OFT, and SIT. Neurogenesis was evaluated by measuring dendritic length and neuronal intersections. Allopregnanolone levels were measured using ELISA. Inflammatory signaling pathways (TLR4, MyD88, NF-κB) and cytokines (IL-1β, TNF-α, IL-10, IL-4) in the hippocampus were analyzed via WB. The integrity of the intestinal barrier was further validated through immunofluorescence and histological examination. Finally, GW6471 was employed to investigate whether PPAR-α mediates the effects of HLWD. RESULTS:The UPLC analysis identified 42 constituents, primarily comprising flavonoids, alkaloids, and coumarins. Behavioral assays demonstrated that HLWD effectively ameliorated depressive-like behaviors in mice. Mechanistically, HLWD elevated the levels of DCX-positive neurogenesis markers, inhibited microglial activation, protected the intestinal mucosal barrier, and reduced inflammatory responses in both the colon and hippocampus. The RNA-seq results indicated an enrichment of the PPAR signaling pathway in colon. Consistent with this finding, HLWD significantly upregulated both the protein and mRNA levels of PPAR-α in the colon. Meanwhile, it increased the concentration of allopregnanolone in hippocampal via peripheral circulation. Notably, the administration of the PPAR-α antagonist GW6471 reversed these neuroprotective effects and the associated protein changes, thereby underscoring the critical role of PPAR-α in the therapeutic mechanism of HLWD. CONCLUSION:HLWD can elevate the levels of PPAR-α and allopregnanolone in the colon, subsequently influencing the levels of allopregnanolone in the hippocampus via peripheral circulation. This process may enhance neurological function and alleviate depressive symptoms.

ETHNOPHARMACOLOGICAL RELEVANCE:Paris polyphylla, a prominent traditional Chinese medicinal herb known for its heat-clearing and detoxifying properties, is widely utilized to relieve pain and treat sores, snake bites, and traumatic injuries. Recent pharmacological investigations have revealed its marked anti-tumor activity. However, as research continues to advance, its potential organ toxicity has been identified, presenting certain limitations for related studies. PURPOSE:This study aimed to compare the toxic components, toxic doses, and organ-specific toxic responses of the cultivated and wild varieties of two P. polyphylla cultivars, and to elucidate potential mechanisms underlying variety-specific hepatotoxicity. METHODS:Using ultra-performance liquid chromatography-tandem mass spectrometry, we identified the major active components in cultivated and wild varieties of P. polyphylla cultivars: P. polyphylla Smith var. yunnanensis (Franch.) Hand.-Mazz, referred to as PY, and P. polyphylla Smith var. chinensis (Franch.) Hara, referred to as PC. A comparative analysis was conducted to assess the differences in their contents. Additionally, we evaluated both the acute and subchronic toxicity of these varieties in mice to determine the differences in organ damage caused by the cultivated and wild varieties of PY and PC across various doses. This evaluation was based on the changes in mouse body weight, organ coefficients, and serum biochemical indicator levels, as well as histopathological alterations. Focusing on cultivated PY, we investigated its potential hepatotoxicity targets and the underlying mechanisms using a combination of network toxicology and transcriptomic techniques. The findings were validated through western blotting, terminal deoxynucleotidyl transferase dUTP nick end labeling, and transmission electron microscopy. RESULTS:Quantitative analysis revealed that PY contained higher levels of active components than PC, with wild varieties exceeding cultivated ones. Acute toxicity test revealed that the maximum tolerated doses of the extracts from both cultivated and wild PY and PC varieties exceeded 80 g/kg body weight in mice. In the subchronic toxicity test, when the doses of PY and PC exceeded 1.95 g/kg body weight, significant increases were observed in the levels of liver and heart function biomarkers. Pathological examinations primarily revealed inflammatory changes in the liver and heart in several cases. Notably, wild varieties elicited more pronounced organ damage than cultivated ones. Comprehensive network toxicology and transcriptomic analyzes revealed that P. polyphylla intervention disrupted hepatic metabolic homeostasis through pathways that impair mitochondrial structure and function, while simultaneously activating inflammatory response pathways and promoting hepatocyte apoptosis. Enrichment analysis revealed several key targets, including STAT3. Further experimental results demonstrated that cultivated PY significantly elevated inflammatory factor levels in mice. In liver tissue, there was an aberrant activation of apoptosis and mitochondrial autophagy, accompanied by abnormal expression of related molecules, such as STAT3, Bcl-2, and BNIP3. These research findings indicate that c-PY extract stimulates abnormal mitochondrial autophagy activation, induces apoptosis and inflammatory responses in liver tissue, and ultimately leads to liver damage, potentially associated with the activation of the STAT3/BNIP3 axis. Our study also highlights the efficacy and potential of integrating network toxicology and transcriptomic analyzes in toxicological studies. CONCLUSION:In this study, we compared the composition and toxic effects of cultivated and wild PY and PC varieties. Using transcriptomics and network toxicology, we revealed potential mechanisms of cultivated PY-induced hepatotoxicity. This research lays the foundation for determining the quality standards of P. polyphylla, evaluating the safety of its medicinal use, and elucidating the mechanisms underlying its toxicity.

BACKGROUND:Arbutin (AR), a natural glycoside compound widely distributed in botanical sources, exerts neuroprotective properties. Nevertheless, the pharmacological effect of AR on depression and its underlying mechanism remain undefined. METHODS:The mice were induced by chronic unpredictable mild stress (CUMS) procedure 16S rRNA sequencing and metabolomic analyses were conducted. The in vitro neuroinflammatory model was established using lipopolysaccharide (LPS) stimulated BV2 microglia. RESULTS:The present study found that AR alleviated the depressive-like behaviors, inflammatory reaction, oxidative stress, restored neurotrophic factors and gut tight junction proteins. TLR4/NF-κB/IRAK1 signaling was involved in these alterations. 16S rRNA sequencing and metabolomics showed that AR enriched muribaculaceae and tryptophan metabolism. Muribaculum intestinale and AR ameliorated depressive-like behaviors, inflammation and 5-HT content, Tryptophan Hydroxylase 1 (TPH1) and Indoleamine 2,3-Dioxygenase 1 (IDO1) expressions, tryptophan metabolism and kynurenine route. The molecular docking and molecular dynamic suggested that AR might bind to TPH1 and IDO1. CONCLUSION:In conclusion, AR alleviated depressive-like behavior in mice by reducing neuroinflammation, modulating gut microbiota, and TPH1/IDO1-mediated serotonin synthesis.

Background: Abnormal tumor blood vessels can significantly promote the malignant progression of tumors, prompting researchers to focus on drugs that normalize these vessels for clinical treatment. The combination of the Qi-tonifying drug Astragali Radix and the blood-activating drug Curcumae Rhizoma, referred to as AC, exhibited significant anti-tumor metastasis effects. However, the association between the anti-tumor metastasis effect of AC and its potential role in regulating tumor vascular remodeling warrants further exploration. Purpose: This study aimed to elucidate the mechanism through which AC induces tumor blood vessel normalization in colon cancer (CC). Methods: The potential active components of AC were identified through UPLC-MS/MS. An orthotopic transplantation model of CC was established in BALB/c mice using the CT26-Lucifer cell line, and the effects of AC were evaluated using IVIS imaging, hematoxylin and eosin (H&E) staining, and immunohistochemistry. Network pharmacology and molecular biology analyses were employed to identify the potential direct targets of AC. Subsequently, RT-PCR and Western blotting techniques were utilized to validate the findings obtained from network pharmacology. Furthermore, ELISA and other methodologies were used to investigate glycolysis-related indicators, along with immunofluorescence technology to demonstrate changes in vascular leakage and perfusion characteristics associated with blood vessel normalization. Results: We identified HIF-1 alpha as a potential direct target of AC. This interaction influences the glycolytic processes in both tumor cells and tumor-associated endothelial cells (TECs) by directly binding to HIF-1 alpha and modulating its nuclear translocation, thereby determining the integrity of TEC junctions. Mechanistically, AC directly regulates the key enzyme PFKFB3 in glycolysis by modulating HIF-1 alpha expression and inhibiting its nuclear translocation. This action reduces tumor glycolytic flux, decreases the internalization of VE-cad, and influences the expression of downstream matrix metalloproteinases (MMPs), thereby strengthening the adherens and tight junctions between TECs and restoring vascular integrity. Conclusion: This study presents novel findings that AC can regulate glycolysis through the inhibition of HIF-1 alpha nuclear translocation, thereby promoting the normalization of tumor blood vessels and effectively inhibiting tumor metastasis. These results suggested that AC may serve as an effective therapeutic agent for normalizing tumor blood vessels.

Ethnopharmacological relevance: Bupleurum chinense DC.-Scutellaria baicalensis Georgi (BS) is a classic drug pair that has good clinical effects on depression and many tumors. However, the concurrent targeting mechanism of how the aforementioned drug pair is valid in the two distinct diseases, has not been clarified yet. Aim of the study: The components of BS were detected by LC-MS, combined with network pharmacology to explore the active ingredients and common targeting mechanism of its multi-pathway regulation of BS in treating depression and CRC, and to validate the dual effects of BS using the CUMS mice model and orthotopic transplantation tumor mice model of CRC. Results: Twenty-nine components were screened, 84 common gene targets were obteined, and the top 5 key targets including STAT3, PIK3R1, PIK3CA, AKT1, IL-6 were identified by PPI network. GO and KEGG analyses revealed that PI3K/AKT and JAK/STAT signaling pathways might play a crucial role of BS in regulating depression and CRC. BS significantly modulated CUMS-induced depressive-like behavior, attenuated neuronal damage, and reduced serum EPI and NE levels in CUMS model mice. BS improved the pathological histological changes of solid tumors and liver tissues and inhibited solid tumors and liver metastases in tumor-bearing mice. BS significantly decreased the proteins' expression of IL-6, p-JAK2, p-STAT3, p-PI3K, p-AKT1 in hippocampal tissues and solid tumors, and regulated the levels of IL-2, IL-6 and IL-10 in serum of two models of mice. Conclusion: BS can exert dual antidepressant and anti-CRC effects by inhibiting the expression of IL-6/JAK2/ STAT3 and PI3K/AKT pathway proteins and regulating the release of inflammatory cytokines.

The global diagnosis rate and mortality of gastric cancer (GC) are among the highest. Ferroptosis and iron-metabolism have a profound impact on tumor development and are closely linked to cancer treatment and patient’s prognosis. In this study, we identified six PRDEGs (prognostic ferroptosis- and iron metabolism-related differentially expressed genes) using LASSO-penalized Cox regression analysis. The TCGA cohort was used to establish a prognostic risk model, which allowed us to categorize GC patients into the high- and the low-risk groups based on the median value of the risk scores. Our study demonstrated that patients in the low-risk group had a higher probability of survival compared to those in the high-risk group. Furthermore, the low-risk group exhibited a higher tumor mutation burden (TMB) and a longer 5-year survival period when compared to the high-risk group. In summary, the prognostic risk model, based on the six genes associated with ferroptosis and iron-metabolism, performs well in predicting the prognosis of GC patients.

Objective: To study the effects of Radix Scutellariae on neurogenesis in chronic corticosterone-induced depression mouse and explore its possible mechanism. Methods: Fifty female C57BL/6J mice were randomly divided into control group, model group, escitalopram group, Radix Scutellariae low-dose group and high-dose group. Chronic corticosterone was injected subcutaneously for 6 weeks to induce depression model mice. After 3 weeks, the other three groups except the control group were treated with escitalopram 10 mg/kg, Radix Scutellariae 0.75 and 1.5 g/kg for 3 weeks. The sucrose preference test,tail suspension test, forced swimming test, open field test, novelty-suppressed feeding tests were used to evaluate the depressivelike behaviors after the administration. ELISA was used to detect serum corticosterone content. Immunohistochemistry was used to detect the number of Ki-67 and BrdU positive cells in the hippocampal dentate gyrus. Western Blot was used to detect PI3K/AKT/GSK3β/β-catenin pathway proteins expression. Results: Compared with the control group, the mice’s sucrose preference rate decreased（P＜0.01）, the immobility time in the tail suspension and forced swimming experiment was prolonged（P＜0.01）,the incubation period increased（P＜0.01）, the feeding rate decreased in the novel feeding experiment（P＜0.01）, and the serum corticosterone content increased（P＜0.01） after 6 weeks corticosterone injecting. The number of Ki-67 and BrdU positive cells in the hippocampal dentate gyrus were also significantly reduced（P＜0.01）, and the protein expressions of p-PI3K, p-AKT, p-GSK3β and β-catenin in hippocampus tissue were significantly down-regulated（P＜0.01）. Compared with model group, the behaviors indicators of sucrose preference test, tail suspension test, forced swimming test, novelty-suppressed feeding tests in escitalopram group and Radix Scutellariae high-dose group were significantly improved（P＜0.01, P＜0.05）, the tail suspension test, forced swimming test and incubation period in the Radix Scutellariae low-dose group were significantly improved（P＜0.01, P＜0.05）. The protein expressions of p-PI3K, p-AKT, p-GSK3β and β-catenin were significantly up-regulated in escitalopram group and Radix Scutellariae high-dose group（P＜0.01, P＜0.05）, and p-AKT and β-catenin were up-regulated in Radix Scutellariae low-dose group（P＜0.01, P＜0.05）. Conclusion: Radix Scutellariae can alleviate chronic corticosterone-induced depressive-like behaviors and promote neurogenesis of adult-born hippocampal granule cells. Its mechanism may be closely related to the PI3K/AKT/GSK3β/β-catenin signaling pathway.

Objective: To establish a quantitative analysis of multi-components by single marker (QAMS) method for the determination of lovastatin and lovastatin acid for the quality control of Hongqu Fuling tablets. Methods: Lovastatin as a control, the RP-HPLC method was used to establish the relationship between the correction factor of lovastatin and lovastatin acid, and to simultaneously quantify both lovastatin and lovastatin acid in the Hongqu Fuling tablets by QAMS. Results: The negative sample had no interference, the specificity of the sample detection method was good, the linear relationship between lovastatin and lovastatin acid was good within the corresponding linear range, R2>0.9999, the precision and repeatability RSD values were less than 3%, and the recovery was 98.43%～103.18%. The relative correction factor of lovastatin acid and lovastatin was 0.9000, and the repeatability was good. The average content of lovastatin acid was 0.3563 mg/g determined by QAMS, and the average content of lovastatin acid determined by external standard method was 0.3668 mg/g, and the average content of lovastatin was 1.1113 mg/g, which indicated that the constructed QAMS method could be used for the multi-component quality evaluation research of Hongqu Fuling Tablets. Conclusion: The QAMS method established in this study was stable, accurate and specific, and would provide a scientific basis for the quality control and in-depth development of Hongqu Fuling tablets.

Traditional Chinese drug effects are a highly generalized function of drug treatment and health care under the guidance of the theory of Chinese medicine. The identification of each drug effect has experienced a long historical evolution. Throughout the records and applications in ancient and modern herbal literature， there are different degrees of expression， which may be attributed to the differences in geographical space， the understanding of doctors， the inheritance of academic schools， and the selection of compatible environments. The redefinition of traditional Chinese drug effects merits an in-depth discussion. Clarifying the "source" and "flow" of the drug effects， considering the combination of basic effects and prescription， and evaluating the dosage of drugs should be the main principles of the research. On the basis of inheritance and innovation， it is proposed that we attach importance to the collation of traditional Chinese drug effects in ancient and modern literature， strengthen the inheritance of the clinical medication experiences of famous historical Chinese medicines， introduce modern clinical and pharmacological research， and use the phylogenetic theory of medicinal plants as the main approaches to study traditional Chinese drug effects. This has far-reaching significance for unifying and standardizing traditional Chinese drug effects， improving clinical efficacy， and broadening the clinical application scope of traditional Chinese drugs.

BACKGROUND:Colorectal cancer (CRC) is a common malignancy that can significantly diminish patients' quality of life. Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (AC) is an ancient Chinese medicinal combination used for the treatment of CRC. However, the core ingredients and targets involved in regulating lipid and amino acid metabolism in CRC remain unknown. We aimed to explore the key components and pharmacological mechanisms of AC in the treatment of CRC through a comprehensive analysis of network metabolomics, network pharmacology, molecular docking, and biological methods.METHODS:Ultra-performance liquid chromatography/mass spectrometry (MS) was used for quality control. Gas chromatography/MS and liquid chromatography/MS were used to detect metabolites in the feces and serum of CRC mice. A network pharmacology approach and molecular docking were used to explore the potential genes involved in the CRC-target-component network. The effect of AC on tumor immunity was investigated using flow cytometry and polymerase chain reaction.RESULTS:AC, high-dose AC, and 5-fluorouracil treatment reduced liver metastasis and tumor mass. Compared with the CRC group, 2 amino acid metabolites and 14 lipid metabolites (LPC, PC, PE) were upregulated and 15 amino acid metabolites and 9 lipid metabolites (TG, PE, PG, 12-HETE) were downregulated. Subsequently, through network analysis, four components and six hub genes were identified for molecular docking. AC can bind to ALDH1B1, ALDH2, CAT, GOT2, NOS3, and ASS1 through beta-Elemene, canavanine, betaine, and chrysanthemaxanthin. AC promoted the responses of M1 macrophages and down-regulated the responses of M2 macrophages, Treg cells, and the gene expression of related factors.CONCLUSION:Our research showed that AC effectively inhibited the growth and metastasis of tumors and regulated metabolism and immunity in a CRC mouse model. Thus, AC may be an effective alternative treatment option for CRC.

巴西人参Hebanthe eriantha(Poir)Pedersen是中南美洲地区一种应用广泛的药用植物.本文查阅国内外相关研究文献及资料,在中医药理论的指导下,探究巴西人参的中药药性.巴西人参性微温,味甘、微苦;归肾、脾、肝经.功效为补肾助阳,益气健脾,养血疏肝.可用于肾虚阳痿,精血不足,性欲淡漠,阳痿早泄;脾气虚弱,神疲乏力;血虚不寐;肝气郁结;癌病.药用部位为根及根茎,日用量为1～3 g,研粉冲服.概括归纳巴西人参的性味归经、功效主治及用法用量,以期为巴西人参在中医临床应用奠定理论基础,促进新外来中药的研究应用.

Background: Colorectal cancer (CRC) is one of the most common malignancies that can diminish patients’ quality of life. Astragalus mongholicus Bunge–Curcuma aromatica Salisb. (AC) is an ancient Chinese medication combination used for the treatment of many malignancies. However, its core components and targets involved in regulating lipid and amino acid metabolism in CRC remain unknown. In this study, we aimed to explore the key components and pharmacological mechanisms of AC in the treatment of CRC through a comprehensive analysis of network metabolomics, network pharmacology, molecular docking, and biological methods. Methods: Ultra-performance liquid chromatography/mass spectrometry (MS) was used for quality control. Gas chromatography/MS and liquid chromatography/MS were used to detect metabolites in CRC murine feces and serum. A network pharmacology approach and molecular docking were used to explore the potential genes involved in the CRC–target–component network. The effect of AC on tumor immunity was investigated using flow cytometry and polymerase chain reaction.Results: AC treatment reduced liver metastasis and tumor volume. Compared with the CRC group, 14 lipid metabolites were upregulated and 15 amino acid metabolites and 9 lipid metabolites were downregulated. Subsequently, through network analysis, four components and six hub genes were identified for molecular docking. AC can bind to ALDH1B1, ALDH2, CAT, GOT2, NOS3, and ASS1 through beta-elemene, canavanine, betaine, and chrysanthemaxanthin. AC promoted the responses of M1 macrophages and down-regulated the responses of M2 macrophages, Treg cells, and the gene expression of related factors.Conclusion: Our research showed that AC effectively inhibited the growth and metastasis of tumors and regulated metabolism and immunity in a CRC mouse model. Thus, AC may be an effective alternative treatment option for CRC.

中医历代肿瘤治疗屡用活血类药,但学界对此频有争议.究其原因,大抵以肿瘤转移为完全"动态"过程认识为前提,认为其运用有助扩散转移之虞.受《黄帝内经》"传舍"理论启示,根据文献及前期课题研究成果,认为肿瘤转移是动静结合的过程,而癌栓黏附血管内壁的"静态"过程更为关键.补气活血药可改善血瘀状态,调控肿瘤转移,并一定程度加强同质肿瘤细胞之间的黏附,起到有利抗肿瘤转移的双相作用.于此,用补气活血药进行抗肿瘤治疗当为常态.

缺氧存在于肿瘤发生、发展全过程,且加速肿瘤细胞侵袭、转移;而改善肿瘤缺氧状况能有效提高药物敏感性,延长肿瘤患者生存期.缺氧诱导因子(HIF)-1α是缺氧主要表达的基因,且与缺氧环境下肿瘤糖代谢异变及血管结构异常密切相关.笔者结合课题组前期研究结果及肿瘤的病理特征,认为肿瘤缺氧的基本病机是气虚血瘀、本虚标实,提出补气活血药(黄芪、莪术配伍)可改善肿瘤缺氧,进而抑制肿瘤生长和转移的构想,为进一步揭示补气活血药抗肿瘤作用机制提供研究思路.

Introduction Colorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients. Methods To identify patients who may benefit from immunotherapy using immune checkpoint inhibitors, we constructed an immune-related gene prognostic index (IRGPI) for predicting the efficacy of immunotherapy in patients with CRC. Transcriptome datasets and clinical information of patients with CRC were used to identify differential immune-related genes between tumor and para-carcinoma tissue. Using weighted correlation network analysis and Cox regression analysis, the IRGPI was constructed, and Kaplan–Meier analysis was used to evaluate its predictive ability. We also analyzed the molecular and immune characteristics between IRGPI high-and low-risk subgroups, performed sensitivity analysis of ICI treatment, and constructed overall survival-related receiver operating characteristic curves to validate the IRGPI. Finally, IRGPI genes and tumor immune cell infiltration in CRC model mice with orthotopic metastases were analyzed to verify the results. Results The IRGPI was constructed based on the following 11 hub genes: ADIPOQ, CD36, CCL24, INHBE, UCN, IL1RL2, TRIM58, RBCK1, MC1R, PPARGC1A, and LGALS2. Patients with CRC in the high-risk subgroup showed longer overall survival than those in the low-risk subgroup, which was confirmed by GEO database. Clinicopathological features associated with cancer progression significantly differed between the high- and low-risk subgroups. Furthermore, Kaplan–Meier analysis of immune infiltration showed that the increased infiltration of naïve B cells, macrophages M1, and regulatory T cells and reduced infiltration of resting dendritic cells and mast cells led to a worse overall survival in patients with CRC. The ORC curves revealed that IRGPI predicted patient survival more sensitive than the published tumor immune dysfunction and rejection and tumor inflammatory signature Discussion Thus, the low-risk subgroup is more likely to benefit from ICIs than the high-risk subgroup. CRC model mice showed higher proportions of Tregs, M1 macrophages, M2 macrophages and lower proportions of B cells, memory B cell immune cell infiltration, which is consistent with the IRGPI results. The IRGPI can predict the prognosis of patients with CRC, reflect the CRC immune microenvironment, and distinguish patients who are likely to benefit from ICI therapy.

Background One of the most challenging aspects of colon cancer (CC) prognosis and treatment is liver-tropic metastasis. Astragalus mongholicus Bunge— Curcuma aromatica Salisb. (AC) is a typical medication combination for the therapy of many malignancies. Our previous studies found that AC intervention inhibits liver metastasis of colon cancer (LMCC). Nevertheless, the comprehensive anti-metastasis mechanisms of AC have not been uncovered. Methods In bioinformatics analysis, RNA-seq data of CC and LMCC patients were collected from TCGA and GEO databases, and differentially expressed genes (DEGs) were identified. The biological processes and signaling pathways involved in DEGs were enriched by GO and KEGG. The protein–protein interaction (PPI) network of DEGs was established and visualized using the Cytocape software, followed by screening Hub genes in the PPI network using Degree value as the criterion. Subsequently, the expression and survival relevance of Hub gene in COAD patients were verified. In the experimental study, the effects of AC on the inhibition of colon cancer growth and liver metastasis were comprehensively evaluated by cellular and animal models. Finally, based on the results of bioinformatics analysis, the possible mechanisms of AC inhibition of colon cancer EMT and liver metastasis were explored by in vivo and in vitro pharmacological experiments. Results In this study, we obtained 2386 DEGs relevant to LMCC from the COAD (colon adenocarcinoma) and GSE38174 datasets. Results of GO gene function and KEGG signaling pathway enrichment analysis suggested that cellular EMT (Epithelial-mesenchymal transition) biological processes, Cytokine-cytokine receptor interaction and PI3K/Akt signaling pathways might be closely related to LMCC mechanism. We then screened for CXCL8, the core hub gene with the highest centrality within the PPI network of DEGs, and discovered that CXCL8 expression was negatively correlated with the prognosis of COAD patients. In vitro and in vivo experimental evidence presented that AC significantly inhibited colon cancer cell proliferation, migration and invasion ability, and suppressed tumor growth and liver metastasis in colon cancer orthotopic transplantation mice models. Concomitantly, AC significantly reduced CXCL8 expression levels in cell supernatants and serum. Moreover, AC reduced the expression and transcription of genes related to the PI3K/AKT pathway while suppressing the EMT process in colon cancer cells and model mice. Conclusions In summary, our research predicted the potential targets and pathways of LMCC, and experimentally demonstrated that AC might inhibit the growth and liver metastasis in colon cancer by regulating EMT via the CXCL8/CXCR2 axis and PI3K/AKT/mTOR signaling pathway, which may facilitate the discovery of mechanisms and new therapeutic strategies for LMCC.

目的:挖掘中医药治疗非小细胞肺癌(NSCLC)的成方规律,以期为临床遣方用药及新药研发提供一定的理论依据.方法:以中国知网(CNKI)中近40年来中医药治疗中晚期NSCLC的临床研究文献作为数据来源,通过筛选后建立方剂数据库,再运用数据挖掘软件进行频数统计、关联规则分析、系统聚类、因子分析及复杂网络构建等.结果:经过纳排标准筛选出307篇临床文献,包含方剂483首.中晚期NSCLC常见证候以气阴两虚为主,证候要素以气虚、阴虚、痰、血瘀、热(火)邪、毒邪、湿邪多见.使用的药物类别以补虚药、清热药、化痰止咳平喘药、利水渗湿药和活血化瘀药较为集中.使用高频次药物为黄芪、甘草、麦冬、浙贝母、茯苓等,其中四气以寒性最为常见,五味以苦、甘、辛味居多,归经主要集中在肺、脾、胃经.关联规则分析发现关联强度较高的规则有17条,因子分析中可提取公因子数为10个,系统聚类分析得出5大类.复杂网络分析提示核心中药处方为六君子汤合益气养阴解毒方加减.结论:益气养阴、健脾化痰、清热解毒、活血化瘀是中医药治疗中晚期NSCLC的基本治则,数据挖掘的核心组合和新方具有重要的指导借鉴意义,但仍需与中医理论相结合,有待进一步的临床及实验研究给予验证.

目的:观察黄芩对皮质酮诱导的抑郁模型小鼠的抗抑郁作用及对新生颗粒细胞存活及成熟的影响.方法:50只雌性C57BL/6J小鼠随机分为正常对照组、模型对照组、艾斯西酞普兰10 mg/kg组、黄芩0.75、1.5 g/kg组,皮质酮皮下注射6 w诱导抑郁模型小鼠,造模3 w后给予相应药物治疗3 w.进行糖水偏好、强迫游泳行为学测试,免疫荧光检测海马齿状回5-溴脱氧尿嘧啶核苷(BrdU)阳性细胞数、新生未成熟神经元、新生成熟神经元的数目;高尔基染色检测海马齿状回颗粒细胞的形态、树突棘的数目;Western Blot检测海马突触蛋白1(Synapsin 1)和突触后密度蛋白95(PSD95)的蛋白表达.结果:与正常对照组比较,模型对照组小鼠体质量显著下降(P＜0.01),糖水偏好率降低、强迫游泳试验中不动时间显著延长(P＜0.01),海马齿状回BrdU阳性细胞数、新生未成熟神经元、新生成熟神经元的数目显著降低(P＜0.01),神经元的形态复杂性降低、树突总长度显著降低(P＜0.01),海马组织Synapsin 1和PSD95的蛋白表达显著下调(P＜0.01);与模型对照组比较,艾斯西酞普兰10 mg/kg及黄芩1.5 g/kg组给药后可明显增加小鼠的体质量(P＜0.05或P＜0.01),增加糖水偏好率、缩短强迫游泳中的不动时间(P＜0.01),显著增加海马齿状回新生颗粒细胞、新生未成熟神经元、新生成熟神经元的数目(P＜0.01),增加神经元的形态复杂性及树突总长度(P＜0.01),上调海马组织突触蛋白Synapsin 1和PSD95蛋白的表达(P＜0.05或P＜0.01).结论:黄芩可改善皮质酮诱导的模型小鼠抑郁样行为,促进海马齿状回新生颗粒细胞的存活和成熟.

Based on the research literatures of Passiflora incarnata and the theory of traditional Chinese medicine, the paper discussed the traditional Chinese medicinal properties of P. incarnate, so as to provide a theoretical basis for the compatibility and application of P. incarnata. The literature databases of CNKI, Wanfang, VIP, Web of Science, PubMed and Scopus were selected, and the literatures relating to P. incarnata were reviewed to screen out the scientific research literatures with a high credibility, rational design and reliable conclusions. Foreign pharmacopoeia was consulted, and the listed products were summarized. The traditional Chinese medicine properties of P. incarnata were studied based on 32 clinical trials, 66 pharmacological researches, 64 chemical constituents researches as well as the theory of traditional Chinese medicine. It was preliminarily concluded that the medicinal properties of P. incarnata are sweet, cool, and enter heart, liver channels. The function is mainly to calm the heart and tranquilizing the mind, and calm the liver wind. It is used for hyperactivity of liver-Yang, stagnation of liver-Qi, restlessness of mind, depression, nervousness, insomnia. This paper summarized the source, characteristics of natures, tastes and channel tropism, usage and dosage, function indications of P. incarnata, and defined its clear traditional Chinese medicine property, which lays a theoretical foundation for the compatibility and clinical application of P. incarnata and Chinese medicine.