Mechanism of Anti-tumor Effects of Viola Medicinal Materials Based on Network Pharmacology and Molecular Docking

[Objectives]To explore the relationship between anti-tumor components,targets,and pathways involved in Viola medicinal materials,study its main active components,and evaluate its inhibitory activity.[Methods]Through network pharmacological analysis,molecular docking simulation experiments and in vitro experiments,the main components and corresponding targets of Viola were screened out,and their anti-tumor signaling pathways were confirmed.MTT colorimetric assay was used to investigate the inhibitory effect of different extraction layers of Viola on the growth of tumor cells.[Results]18 anti-tumor active components such as 2α,19α-Dihydroxyursolic acid,Corlumine,Madolin U,Trifolirhizin and etc.,and 52 action targets such as PTGS2,PTGS1,P2RX7,MMP1,and GABRB3,and anti-tumor signaling pathways were confirmed.The results of molecular docking showed that all the selected Viola compounds had good binding activity.The results of MTT colorimetric assay showed that the petroleum ether layer and n-butanol layer had a good inhibitory effect on the growth of tumor cell lines.[Conclusions]Viola medicinal materials have the potential of anti-tumor,triterpenoids and flavonoids may be the main active components,and the petroleum ether layer and n-butanol layer have better inhibitory effect on the growth of tumor cells.

Research Progress in Anti-tumor Effects of Traditional Chinese Medicine and Its Extracts

Traditional Chinese medicine and its extracts have received widespread attention due to their significant anti-tumor effects and low adverse reactions.Many traditional Chinese medicine and its extracts have been applied in clinical tumor treatment.In this paper,the research progress in anti-tumor effects of plant-based traditional Chinese medicine and its extracts,animal-based traditional Chinese medicine and its extracts,and traditional Chinese medicine compound is reviewed.

Anti-tumor effect of statin on pancreatic adenocarcinoma:From concept to precision medicine

A statin is a cholesterol-lowering agent,which inhibits HMG-CoA(3-hydroxy-3-methylglutaryl-coenzyme A)reductase and subsequently reduces the cholesterol precursor,and was first used commercially in 1987.The concept of cholesterol restriction leading to cancer cell dysfunction was proposed in 1992.The interruption of different signaling pathways has been proved in preclinical experiments to elucidate the anti-tumor mechanism of statins in pancreatic adenocarcinoma.Observational studies have shown that the clinical use of statins is beneficial in patients with pancreatic adenocarcinoma,including a chemoprevention effect,post-surgical resection follow-up and therapeutic prognosis of advanced cancer stage.Arrest of the cancer cell cycle by the combined use of gemcitabine and statin was observed in a cell line study.The effect of microbiota on the tumor microenvironment of pancreatic adenocarcinoma is a new therapeutic approach as statins can modulate the gut microbiota.Hence,further randomized trials of statins in pancreatic adenocarcinoma treatment will be warranted with application of precision medicine from microbiota-derived,cell cycle-based and signaling pathway-targeted research.

Clinical Observation on the Improved Short-Term Effects of Anti-Tumor Purified Chinese Medicine Injection Ai-Jing for 138 Cases with Malignant Tumors

The subjects of this study were to observe the improved short-term effects of anti-tumor purified Chinese medicine injection Ai-Jing for 138 cases with malignant tumors. This was a multi-center clinical study, and a total of 138 patients included 96 males and 42 females, with the age from 60 to 76 years. Ai-Jing has obtained the Chinese invention patent since 2008 (ZL991-03528.3). A novel technique acupoint injection method was adopted. Except for lung cancer, patients with other malignant tumors were injected once every other day, 2 ml each time. A course of treatment needs 6 Ai-Jing injections, lung cancer patients need 10 - 20 Ai-Jing injections. At the same time, patients were treated with traditional medicine decoction. Due to the limited number of cases, cure rate, recovery rate and remission rate were calculated as a whole, respectively 18.12%, 44.20% and 32.15%. All the invalid patients were lung cancer, accounting for 16.67% of the patients treated with lung cancer, and the total treatment inefficiency was 6.52%. Conclusion: Chinese Medicine Injection Ai-Jing extracts the effective components of anti-cancer and tumorigenesis, and has the effects of anti-cancer and tumorigenesis, anti-inflam-matory and analgesic, and repairing body damage, with small toxic and side effects and low cost.

Research progress on fluorescence analysis of antitumor Chinese medicine components

This paper classifies the anti-tumor traditional Chinese medicine's fluorescence analysis and finds that its research content mainly includes two aspects:the application of fluorescence analysis in the determination of the effective component content of anti-tumor traditional Chinese medicine;the study of the combined use of fluorescence imaging technology and the drug.According to literature analysis,it is found that although the research on the fluorescence analysis of anti-tumor Chinese medicine components is in a good state of development,it still needs to explore further in the identification of unknown components and deeper research on known components.Therefore,it can provide a certain basis for clinical guidance of tumor patients.

Comparative Evaluation of Antitumor Chinese Patent Medicine Injections Based on Evidence-Based Medicine and Markov Model

Objective: The objective of this study was to explore the safety, efficacy, economy, and other aspects of frequently-used antitumor Chinese patent medicine injections through a comprehensive evaluation of evidence-based medical research to provide scientific information and decision-making basis for drug selection, rational drug use, public awareness of safe drug use, and medical insurance. Materials and Methods: The names of five frequently used antitumor Chinese patent medicine injections were used as search terms, including the compound Sophora flavescens injection, Kangai injection, Aidi injection, Kanglaite injection, and Brucea javanica oil emulsion injection. Relevant evidence-based medical research was extracted from the databases. A descriptive evaluation was conducted, and the Markov model was used for the cost-benefit analysis. Finally, the above injections are ranked by comprehensive scores using the multi-criteria decision analysis and Delphi method. Results: The five injections had their own advantages in enhancing the effectiveness of anti-tumor treatments, improving the quality of life for cancer patients, and reducing the incidence of adverse reactions. From the perspective of economy and other attributes, compound S. flavescens was superior to B. javanica oil, Aidi, Kangai, and Kanglaite. After a comprehensive evaluation of the above five injections, the compound S. flavescens injection received the highest score. Conclusions: Compound S. flavescens, Kangai, Aidi, B. javanica oil, and Kanglaite have their own advantages in effectiveness and no significant difference in safety. Compound S. flavescens injection has the highest comprehensive score. Clinical attention should be paid to monitoring the initial stage of medication and special groups.

肺癌细胞株中NVB和Doc药物敏感性关联基因的研究

目的:筛选小细胞肺癌(SCLC)和非小细胞肺癌(NSCLC)细胞株中与诺维苯(NVB)、泰索帝(Doc)药物感受性相关的基因。方法:采用MTT比色分析法测定4株SCLC细胞株和6株NSCLC细胞株对NVB、Doc的药物感受性,同时应用cDNAmacroarray技术检测10株肺癌细胞株中1291个药物感受性关联基因的表达状态,分析二者之间的相关性。结果:与NVB和Doc药物敏感性关联(r≥±0.4)的基因共有56个。1)与NVB药物敏感性相关联的基因有36个,SCLC+NSCLC组与NSCLC组共同表达的基因有20个,其中,SCLC+NSCLC组表达的基因有27个,特异表达的有7个,NSCLC组为29个基因,9个基因特异表达。2)与Doc药物敏感性相关联的基因有50个,其中,SCLC+NSCLC组与NSCLC组共同表达的基因有12个,SCLC+NSCLC组表达的基因有24个,12个基因特异表达,NSCLC组为38个基因,26个基因特异表达。3)肺癌细胞株中与NVB、Doc药物感受性相关联基因的分类主要分布于:信号转导分子﹑代谢酶类及其抑制剂、细胞因子和转录因子等4类。结论:SCLC和NSCLC细胞株中NVB、Doc药物敏感性相关联基因存在明显差异,但分类基本相同。

Experimental Research on Anti-tumor Metastasis Effect of Basil Polysaccharide in vivo

Objective: To study the effects of basil polysaccharide (BP) in inhibiting tumor growth and metastasis in vivo. Methods: One hundred and fifty mice were randomly divided into five groups to observe the effect on tumor growth after H22 cancer cells had been transplanted subcutaneously into their right armpit region and treated with different dosages (5 mg/kg, 2. 5 mg/kg and 1. 25 mg/kg) of BP for 14 days, with Mi-tomycin (Mit-C) used as control. Another 150 mice were randomly divided into three groups, models of tumor metastasis in the lung by various paths (lymphatic, blood circulatory and spontaneous) were established respectively. They were treated with BP or Mit-C to observe the influence of treatments on tumor metastasis by various paths. Results: BP of various dosages showed no effect on tumor growth, but in high and middle dosage, it could significantly reduce the number or metastasis nodules ( P<0. 05). Conclusion: BP has a tumor metastasis inhibitory effect, which might be one of the candidates for new anti-tumor metastasis agents. Its mechanism may be blocking the function of platelets in the tumor metastasis progress.

Screening the active constituents of Chinese medicinal herbs as potent inhibitors of Cdc25 tyrosine phosphatase, an activator of the mitosis-inducing p34^(cdc2) kinase

Objective: To screen and evaluate the active constituents of Chinese medicinal herbs as potent inhibitors of Cdc25phosphatase. Methods: The affinity chromatography purified glutashione-S-transferase/Cdc25A phosphatase fusion protein and Cdc2/cyclin B from the extracts of starfish M phase oocytes are used as the cell cycle-specific targets for screening the antimitotic constituents. We tested 9 extracts isolated from the Chinese medicinal herbs and vegetables including the agents currently used in cancer treatment by measuring the inhibition of Cdc25A phosphatase and Cdc2 kinase activity. The antitumor activity of the extracts was also evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry.Results: Cdc25A inhibitory activity and antitumor activity are detected in the extracts isolated from three Chinese medicinal herbs Agrimonapilosa; Herba solani lyrati; Galla chinesis. Conclusion: We found three extracts isolated from Chinese medicinal herbs have potential inhibitory activity of Cdc25 phosphatase using a highly specific mechanism-based screen assay for antimitotic drug discovery.

Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10,MC38 and Hep1-6 Tumor Models

Objective To investigate the anti-tumor effects of Pien Tze Huang(PZH)in mouse models of B16–F10 melanoma,MC38 colorectal cancer,Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model.Methods Various tumor models,including B16–F10,MC38 and Hep1-6 tumor hypodermic inoculation models,B16–F10 and Hep1-6 pulmonary metastasis models,Hep1-6 orthotopic implantation model,and chemically induced hepatocellular carcinoma model,were utilized to evaluate the anti-tumor function of PZH.Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice.For cell proliferation and death of tumor cells in vitro,as well as T cell activation markers,cytokine production and immune checkpoints analysis,single-cell suspensions were prepared from mouse spleen,lymph nodes,and tumors after PZH treatment.Results PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth(P<0.01).Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16–F10 melanoma models,and decreased pulmonary metastasis of B16–F10 melanoma and Hep1-6 hepatoma(P<0.01).However,in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells(P>0.05).Nevertheless,PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma,tumor necrosis factor alpha,and interleukin 2 in CD4^(+)T cells in vitro(P<0.01 or P<0.05).Importantly,PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8^(+)T cells(P<0.01 or P<0.05).Conclusion This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity,indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

Targeting Tumor-Associated Macrophages by Anti-tumor Chinese Materia Medica

Tumor-associated macrophages（TAMs） play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica（CMM） is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine（CM） and its practice, some prescriptions of CM regulate the body＇s internal environment possibly including the remodeling the tumor microenvironment（TME）. Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasisand immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM＇s dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy.

Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill

Cancer still has elevated morbidity and mortality,which undoubtedly impacts the life quality of affected individuals.Remarkable advances have been made in cancer therapy,although the toxicities of traditional therapies remain an obvious challenge.Dahuang Zhechong Pill(DHZCP),developed by Zhongjing Zhang in the Synopsis of the Golden Chamber,represents an effective anticancer traditional Chinese medicine(TCM).In this review,it was found that DHZCP is therapeutically utilized in liver,lung,gastric,pancreatic and other cancers in clinic.Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest,apoptosis and autophagy,as well as suppressed tumor cell proliferation,obstructed angiogenesis and metastasis,enhanced immunity,and reversal of multidrug resistance.The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.

人肺癌细胞中去甲长春新碱和泰索帝药物敏感性基因的比较分析

目的筛选人肺癌细胞株中与去甲长春新碱(NVB)、泰索帝(Doc)药物敏感性相关的基因。方法采用MTT比色分析法,测定4株小细胞肺癌(SCLC)细胞株和6株非小细胞肺癌(NSCLC)细胞株对NVB、Doc的药物敏感性;应用cDNA macroarray技术检测10株肺癌细胞株中1291个药物敏感性关联基因的表达状态,聚类分析二者间的相关性。结果(1)NVB对10株肺癌细胞株的作用效果明显优于Doc。(2)10株肺癌细胞株中,与Doc呈正相关的药物敏感性关联基因多于NVB,而与NVB呈负相关的多于Doc;而在6株NSCLC中,与Doc和NVB呈正相关、负相关一致的基因较多。(3)10株肺癌细胞株中,有51个基因与Doc、NVB药物敏感性相关联,占全部候选基因的3.95%(51/1291)。与NVB药物敏感性呈显著相关的基因27个,其中负相关24个,正相关3个;与Doc药物敏感性关联的基因24个,其中负相关13个,正相关11个。6株NSCLC株中,有67个基因与药物敏感性相关,占全部实验基因的5.19%(67/1291)。与NVB药物敏感性呈显著相关的基因29个,其中负相关25个,正相关4个;与Doc药物敏感性关联的基因38个,其中负相关34个,正相关4个。(4)Rab1、Rab3、Rho B、Rho C、Rac1、Rac2、Gho GDIβ、CD44、Integrinα5、Integrinα6、Integrinβ5、Vinculin等细胞骨架关联基因在SCLC、NSCLC中的表达存在差异。结论SCLC和NSCLC细胞株中,NVB、Doc药物敏感性相关联基因表达存在明显差异。

Bioactive metabolites from macrofungi: ethnopharmacology, biological activities and chemistry

Exploration of natural sources for novel bioactive compounds has been an emerging field of medicine over the past decades,providing drugs or lead compounds of considerable therapeutic potential.This research has provided exciting evidence on the isolation of microbe-derived metabolites having prospective biological activities.Mushrooms have been valued as traditional sources of natural bioactive compounds for many centuries and have been targeted as promising therapeutic agents.Many novel biologically active compounds have been reported as a result of research on medicinal mushrooms.In this review,we compile the information on bioactive structure-elucidated metabolites from macrofungi discovered over the last decade and highlight their unique chemical diversity and potential benefits to novel drug discovery.The main emphasis is on their anti-Alzheimer,antidiabetic,anti-malarial,anti-microbial,anti-oxidant,antitumor,anti-viral and hypocholesterolemic activities which are important medicinal targets in terms of drug discovery today.Moreover,the reader’s attention is brought to focus on mushroom products and food supplements available in the market with claimed biological activities and potential human health benefits.