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The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.
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Objective To design and synthesize the conjugate (compound 1) of chlorin e6 (compound 3) with fluorouracil (5-Fu) as novel pH-responsive dual-mode antitumor photosensitizer by acyl hydrazone bond coupling, based on literature reports that combination of 5-Fu and photosensitizer possess synergistic anti-tumor effect, and investigate its photodynamic antitumor activity and mechanism. Methods Lead compound 3 was obtained by alkali degradation with 25% KOH-CH3OH on pheophorbide a (compound 4) which was prepared through acid hydrolysis of chlorophyll a in crude chlorophyll extracts from silkworm excrement. Reflux reaction of 5-Fu with P2S5 in pyridine formed crude 4-thio-5-fluorouracil which was followed to react with hydrazine hydrate (N2H4·H2O) in CH3OH to give 5-fluorouracil-4-hydrazone (compound 2). Then, treatment of compound 3 i.e. acid alkali degradation product of chlorophyll a in silkworm excrement with EDC·HCl generated its 171- and 152 cyclic anhydride which was followed to directly react with intermediate compound 2 to successfully get title compound 1. In addition, its pH-responsive 5-Fu release and photodynamic antitumor activity and their mechanisms in vitro were investigated. Results Compound 1 could responsively release 5-Fu at pH 5.0, with a cumulative release rate of 60.3% within 24 h. It exhibited much higher phototoxicity against melanoma B16-F10 and liver cancer HepG2 cells than talaporfin and its precursor compound 3, with IC50 value being 0.73 μmol/L for B16-F10 cells and 0.90 μmol/L for HepG2 cells, respectively. Upon light irradiation, it also could significantly induce cell apoptosis and intracellular ROS level and block cell cycle in S phase. Its structure was confirmed by UV, 1H-NMR, ESI-MS and elemental analysis data. Conclusion The conjugate compound 1 of compound 3 and 5-Fu has the advantages of strong PDT anticancer activity, high therapeutic index (i.e. dark toxicity/phototoxicity ratio) and responsively release 5-Fu at pH 5.0 etc. which shows “unimolecular” dual antitumor effects of PDT and chemotherapy and is worthy of further research and development.
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A sesquiterpene natural substance called artemisinin was discovered in Artemisia annua. One of its derivatives， artesunate （ART）， has the properties of economy， immediate effect， low toxicity， and good tolerance. Since it has a quick and powerful killing effect on plasmodium in the erythrocyte phase and can quickly handle clinical seizure and symptoms， it is currently mostly utilized to treat cerebral malaria and other severe instances of malaria. In addition， it has antitumor， antivirus， anti-hepatic fibrosis， anti-inflammatory， antibacterial， hepatocyte protection， immunological modulation， and other pharmacological properties and can inhibit cell proliferation， induce cell apoptosis， and reduce the incidence of sepsis. In many countries， artemisinin-based combination therapies （ACTs）， such as artemether-benflumetol， artesunate-amodiaquine， and artemether-lumefantrine， are the first-line treatments for malaria. Recent research on artesunate by Chinese and international scholars has revealed that compared with monotherapy， artesunate combination therapy offers more benefits in terms of improving pharmacological effects， shortening the duration of medicine， and minimizing adverse effects. Through systematic retrieval of Web of Science Core Collection and integration through CiteSpace （6.2.1） software， this article reviewed the mechanism of artesunate combined with other medications with regard to antimalarial， antitumor， antibacterial， and antiviral features in the previous five years， so as to provide some theoretical basis for rational development and utilization of ART and new drug research and development.
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ObjectiveTo clarify the scientific validity of in vivo pharmacokinetic determination of the whole drug composition in Shenbai nanosuspension in rats， and to provide methodological guidance and theoretical basis for the in vivo study of multi-component complex system of traditional Chinese medicine（TCM） preparations. MethodThe concentration of the overall components， mainly total saponins and total polysaccharides in Shenbai decoction and Shenbai nanosuspension， was determined in rat plasma at different times by area under the absorbance-wavelength curve method（AUAWC）， and the concentration of individual ginsenoside Rg1 was determined by high performance liquid chromatography（HPLC）， and the methodology was verified. The pharmacokinetic parameters of the whole component were compared with those of ginsenoside Rg1 to evaluate the in vivo operational characteristics of the two preparations. ResultThe methodological investigations of AUAWC and HPLC were in accordance with the requirements. AUAWC analysis showed that the overall components in both the decoction group and the nanosuspension group showed a one-compartment model， with half-life（t1/2） of 2.43 h and 2.04 h， respectively. The relative bioavailability of Shenbai nanosuspension was 138.99%. HPLC assay showed that ginsenoside Rg1 in the decoction group and the nanosuspension group showed a two-compartment model， with distribution half-life（t1/2α） of 0.13 h and 2.55 h， and elimination half-life（t1/2β） were 14.28 h and 3.85 h， respectively. The relative bioavailability of Shenbai nanosuspension was 127.49%. Compared with Shenbai decoction， the time to peak（tmax）， peak concentration（Cmax） and area under the drug-time curve（AUC） of the overall components and ginsenoside Rg1 in Shenbai nanosuspension were increased. ConclusionThe established AUAWC can be used for the pharmacokinetic study of the overall components of TCM preparations， which is complementary to the results of individual components measured by HPLC， and can provide useful reference for the in vivo study of new dosage forms of TCM.
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Paridis Rhizoma possesses the functions of clearing heat and detoxifying， alleviating swelling and relieving pain， cooling the liver and calming the convulsion. Saponins are the main active components of Paridis Rhizoma. Studies have shown that total saponins in Paridis Rhizoma have obvious inhibitory effect on solid tumors such as breast cancer， lung cancer， gastric cancer， and liver cancer and non-solid tumors such as leukemia. The saponins may exert the anti-tumor effects by inhibiting the proliferation， migration， and invasion of tumor cells， regulating cell cycle， inducing apoptotic and non-apoptotic death pathways， and regulating metabolism and tumor microenvironment. Furthermore， total saponins in Paridis Rhizoma showed anti-inflammatory， antioxidant， antimicrobial， hemostatic， and uterus-contracting activities. At the same time， they may induce apoptosis of normal cells， inflammation and oxidative stress， and metabolic disorders. In recent years， the reports of liver injury， reproductive injury， gastrointestinal injury， hemolysis， and other adverse reactions caused by total saponins in Paridis Rhizoma have been increasing. Pharmacokinetic studies have shown that there are significant differences in the metabolism of total saponins in Paridis Rhizoma administrated in different ways. Injection has a fast clearance rate， while oral administration may have hepatoenteric circulation. Meanwhile， due to the low solubility and activation of P-glycoprotein （P-gp） molecular pump， the prototype absorption， intestinal permeability， and recovery rate of total saponins in Paridis Rhizoma are poor， which affects the bioavailability. The bioavailability can be improved to some extent by preparing new dosage forms or new drug delivery systems with advanced technology. This paper reviews the pharmacological effect， pharmacokinetics， and adverse reactions of Rhizoma Paridis total saponins by searching the China National Knowledge Infrastructure （CNKI）， VIP， and Web of Science with ''Rhizoma Paridis total saponins'' as the keywords， hoping to provide references for the research， development， and clinical application of such components.
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@#Apoptosis is an important means to regulate cell proliferation and maintain homeostasis. Recent researches have shown that the B-cell lymphoma-2 (BCL-2) family not only plays a dominant role in the regulation of normal cell apoptosis, but also plays a crucial role in the formation of tumor genesis, progression and subsequent drug resistance mediated by the escape mode of apoptosis. The phenomenon that BCL-2 family antagonized the apoptosis induced by antitumor drugs and then acquired drug resistance has been reported in the clinical treatment of hematologic lymphatic system tumors, breast cancer, lung cancer, gastric cancer and other diseases. Thus, specific inhibitors targeting anti-apoptotic members of the BCL-2 family have emerged with the development of research. In this paper, we systematically reviewed the regulation of apoptosis mediated by BCL-2 family and the drug resistance mediated by BCL-2 family. Meanwhile, we summarized the research advances of BCL-2 family specific inhibitors to provide new strategy for solving the problems on tumor therapeutic resistance and for finding new therapeutic targets in the future.
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Objective:To analyze and explore the possible mechanism of anti-tumor metastasis of Notoginseng Radix et Rhizoma using Internet pharmacology. Methods:The active components and targets of Notoginseng Radix et Rhizoma were screened by retrieving Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). GeneCards database was used to screen the anti-tumor metastasis-related targets, and compounds and disease targets were under mapping analysis. Key targets of Notoginseng Radix et Rhizoma for anti-tumor metastasis were screened through Venn map. With the help of Cytoscape 3.7.2 software, a compound-disease network diagram was constructed. String platform was used to build a PPI network. Bioconductor was used to enrich the target genes for KEGG signaling pathway and GO biological process analysis. Results:Totally 119 active components were selected from Notoginseng Radix et Rhizoma. There were 8 eligible active components, corresponding to 162 related targets, 121 targets related to anti-tumor metastasis, and 30 key targets screened by PPI network, including AKT1, MAPK1, JUN, RELA, IL6, etc. GO enrichment analysis mainly involved biological processes such as cytokine receptor binding, heme binding, RNA polymerase Ⅱ transcription factor binding, ubiquitin protein ligase binding, and steroid hormone receptor activity. 149 signal pathways related to Notoginseng Radix et Rhizoma anti-tumor metastasis were obtained by KEGG enrichment analysis, mainly involving multiple signal pathways, such as AGE-RAGE and PI3K-Akt, and hepatitis B, Kaposi's sarcoma-associated herpes virus infection, human cytomegalovirus infection and other viral infections and various tumors. Conclusion:Notoginseng Radix et Rhizoma can pass multiple active components, such as ginsenoside f2, ginsenoside rh2 β-, sitosterol, stigmasterol and quercetin, and multiple targets, such as AKT1, MAPK1, JUN, RELA and IL6, acting on multiple pathways such as PI3K-Akt, thereby playing the role of anti-tumor metastasis.
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2-cyano-3，12-dioxooleana-1，9 （11）-dien-28-oic acid （CDDO） is a compound synthesized by taking oleanolic acid， a natural triterpene， as a precursor or precursor， and transforming three modifiable functional groups in the molecule through a series of chemical structure modification. In order to improve its anti-tumor activity， CDDO derivatives are further synthesized. In this paper， the research results of anti-tumor effects and mechanisms of CDDO and its derivatives in recent years are summarized. It is found that CDDO and its derivatives have a wide range of anti-tumor effects， and can show significant anti-tumor effects on breast cancer， pancreatic cancer， lung cancer and ovarian cancer at low concentrations such as micromole or even nanomole， among which CDDO methyl ester compound （CDDO-Me） and CDDO imidazolidinone compound （CDDO-Im） have the most obvious effects. CDDO and its derivatives exert anti-tumor activity mainly by inducing tumor cell apoptosis， and regulating metabolic reprogramming and immune microenvironment. The involved pathways mainly include Janus protein tyrosine kinase （JAK）/ signal transduction and transcription activation protein 3（STAT3） signal pathway， nuclear factor E2-related factor 2 （NRF2） signal pathway， phosphatidylinositol 3 kinase （PI3K）/protein kinase B （also known as Akt）/mammalian rapamycin target protein （mTOR） signal pathway， Wnt/β-catenin signal pathway， nuclear factor κB signal pathway.
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@#Phosphatidylinositol-3-kinase (PI3K) inhibitors can increase the sensitivity of tumor cells to Poly ADP-ribose polymerase-1 (PARP-1) inhibitors. Therefore, the simultaneous inhibition of the PARP-1 and PI3K activities are expected to overcome the drug resistance of PARP-1 inhibitors.In our previous work, two compounds XW-1 and WZ-1 with excellent activities against PARP-1 and PI3K were obtained with the limitation to further study due to their poor water solubility.Therefore, XW-1 and WZ-1 were chosen as lead compounds to optimize their solubility by introducing a salt-forming site via a urea group, and 11 novel compounds were designed and synthesized. The structure of all target compounds was confirmed by 1H NMR, 13C NMR, and HRMS.The enzyme activities of the compounds against PARP-1 and PI3K were measured, and the results showed that most of the compounds demonstrated good inhibitory activities against PARP-1 and PI3K.Based on the above result, the inhibitory activities of compounds 8b, 8e, and 8f against MDA-MB-231, MDA-MB-468, HCC1937, HCT116, and olaparib-resistant HCT116R were determined by MTT, respectively.Additionally, the structure-activity relationship was discussed. The results showed that these compounds displayed excellent antiproliferation activity.Among them, compound 8f demonstrated antiproliferation remarkably against all five tumor cells, which was more potent than that of olaparib, and was comparable to that of BKM120.Furthermore, the solubility of hydrochloride salts of compound 8b and 8f was significantly improved compared to the lead compounds.The results of this study will provide a theoretical basis for the further development of PARP-1 and PI3K dual-target inhibitors with good pharmaceutical properties and strong inhibitory activities.
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OBJECTIVE@#To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer.@*METHODS@#TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed.@*RESULTS@#The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05).@*CONCLUSION@#Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.
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Animals , Humans , Mice , Apoptosis , Dendritic Cells/immunology , Glycyrrhizic Acid/pharmacology , HMGB1 Protein , Lung Neoplasms/immunologyABSTRACT
Objective To explore the antitumor small molecules targeting the ubiquitin–proteasome system (UPS) on the basis of active molecules from traditional Chinese medicine. Methods UbG76V-GFP stably expressing cell line was constructed to screen novel small molecule inhibitors targeting UPS. The fluorogenic substrates of Suc-LLVY-AMC, Z-LLE-AMC, and Boc-LRR-AMC were used to assess the effect of dioscin on the 20S proteasome hydrolase activity. The Ub-AMC substrate was used to evaluate the effect of dioscin on the intracellular deubiquitinating enzyme activity. Western blot was used to detect the effect of dioscin on intracellular ubiquitination levels. CCK-8 and colony formation assays were used to detect the inhibitory effect of dioscin on the tumor cell proliferation. Results Dioscin is a UPS inhibitor discovered through the UbG76V-GFP reporter system. It enhances intracellular ubiquitination and inhibits tumor cell proliferation and colony formation by targeting deubiquitinating enzymes. Conclusion Dioscin could significantly inhibit tumor cell proliferation by targeting ubiquitin–proteasome.
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Photothermal therapy (PTT) has attracted significant attention due to minimal side effects and high treatment specificity. However, it often requires very high temperature to achieve complete tumor ablation under a single PTT. Such high temperature brings obvious thermal damage and inflammatory response to the body, affecting the therapeutic effect. In recent years, nitric oxide (NO) has been used to significantly inhibit tumor growth and enhance the sensitivity of tumor cells of temperature and drugs, thus enhancing the therapeutic effect. However, compounds as NO donors often have some disadvantages such as poor biocompatibility and untargeted delivery, etc., therefore, this medical application based on NO therapy is limited. In conclusion, the organic combination of NO donors and photothermal agents (PTAs) is expected to overcome the shortcomings of single therapy and achieve the antitumor effect of "1 + 1 > 2". In view of the rapid development of NO combining with PTT in tumor therapy, this review firstly introduces the antitumor mechanisms of different types of NO donors. Then the treatment strategy based on NO combined with PTT is discussed. Finally, the prospects and challenges of this combination therapy strategy in the clinical treatment of cancer are discussed.
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Polysaccharides is one of the main bioactive components of Cordyceps species, because of the potential clinical value with stronger anti-tumor, such as anti-neuroblastoma, anti-melanoma, anti-lung cancer, anti-colon cancer and so on, its have received widespread attention in biomedical field and increasing research in last decades. According to structural elucidation, this review gives a systematic literature overview on antitumor mechanism of Cordyceps species-derived polysaccharides from three aspects, including inhibition of tumor cell growth, enhancement of immunomodulatory activity and reduction of tumor metastasis. Finally, it also puts forward some scientific problems for follow up research.
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Sphingosine kinase (SphK), sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) are involved in the tumor biological processes such as tumor cell proliferation and migration, and play an important role in the development of cancer. In recent years, researchers have increasingly focused on the interaction between cancer cells and the tumor microenvironment. The tumor microenvironment is genetically stable and can be induced to an antitumor phenotype, which has significant therapeutic advantages. Studies have shown that SphK/S1P/S1PR can regulate multiple aspects of the tumor microenvironment. This review summarizes the effects of SphK and S1P/S1PR signaling on the tumor microenvironment from four perspectives: tumor immune microenvironment, cancer associated fibroblasts, tumor angiogenesis and tumor hypoxic microenvironment, and also outlines potential drug research related to these signal molecules, aiming to elucidate the role of SphK/S1P/S1PR in tumor occurrence and development and provide new ideas for the research of anti-tumor drugs.
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By using computer-aided drug design, the activities group model which CDK4/6 inhibitors on the market were introduced to silybin C-7, and a series of silybin derivatives were designed and synthesized, and the structure was confirmed by MS, 13C NMR and 1H NMR. The in vitro antitumor activity evaluation of the target compound was carried out by MTT method, and the in vitro anti-tumor activity was carried out in human hepatocellular carcinoma cells (HepG-2). Experimental results show that all compounds are higher than the activity of the parent silybin, of which compound I1 has a certain inhibitory effect on human HepG-2 cells, which is worth further study.
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Malignant tumors are major diseases that endanger human health. Due to their complex and variable microenvironment, most anti-tumor drugs cannot precisely reach the focal tissue and be released in a controlled manner. Intelligent responsive nano carriers have become a hot spot in the field of anti-tumor drug delivery systems. As an excellent nano material, mesoporous silica has the advantages of non-toxic, stable, adjustable pore volume and pore diameter, and easy functional modification on the surface. By virtue of its perceptive response to the tumor microenvironment or physiological changes, it can achieve the targeted drug release or controlled drug release of the drug delivery system in the tissue, making it an ideal carrier for intelligent response drug delivery system. In this paper, we review the design strategies and current research status of smart responsive anti-tumor drug delivery systems based on mesoporous silica, in order to provide a reference for the development of anti-tumor drug nanoformulations.
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Objective To explore the anti-tumor mechanism of saffron (Crocus sativus L.) by network pharmacology and reverse molecular docking techniques. Methods The main chemical components of saffron were obtained by searching published literature and TCMSP database. The potential targets of these components were predicted using PharmMapper server. The corresponding target genes were identified from UniProt database. The underlying anti-tumor targets of saffron were obtained by mapping the disease genes of cancer or tumor with GeneCards, OMIM and TTD databases. Cytoscape software was used to construct the action target network of saffron active components. The protein-protein interaction analysis was performed by String database, and the GO function and KEGG pathway enrichment analysis were performed by Metascape platform. Finally, molecular docking was performed to evaluate the binding of main components with their potential targets. Results A total of 9 active ingredients in saffron including quercetin, kaempferol, isorhamnetin, picrocrocin and crocin I, were identified, which might act on 37 key targets including AKT1, CCND1, MMP9, EGFR, TP53, involved in P53, TNF and other signaling pathways. Molecular docking indicated modest binding potency through hydrogen bonding, and hydrophobic interactions. Conclusion The anti-tumor effect of saffron was evaluated via the network of components-targets-pathways, which might provide a foundation for further research.
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OBJECTIVE To promote the standardization and integrity of the informed consent form for clinical trials of registered anti-tumor drugs， and to protect the legitimate rights and interests of the subjects. METHODS The ethical review resolutions of clinical trial projects of registered anti-tumor drugs that were initially reviewed by the Ethics Committee of our hospital from July 1st， 2020 to July 1st， 2022 were summarized to statistically analyze the problematic items according to the “Quality Analysis Form of Informed Consent” prepared by our hospital. RESULTS Of the 316 clinical trials of registered anti- tumor drugs that were initially reviewed， 257 （81.3%） had problems with the contents of informed consent form， mainly domestic multi-center trials and phase Ⅲ trials. The main problems included the vague notification of the test fee bearer （68.5%）， the incomplete notification of the test content （59.1%）， the insufficient notification of rights and interests and risks （58.4%）， the insufficient notification of personal information protection （56.0%）， and the nonstandard expression of the informed consent form （52.5%）. CONCLUSIONS There is still a gap between the informed consent form of the clinical trials of registered anti-tumor drugs in our hospital and the requirements of the new version of Good Clinical Practice for Drugs （GCP）. The parties involved in the test can take a number of measures to improve the standardization and integrity of the informed consent form， and the research team should design the informed consent form in strict accordance with the requirements of the new GCP and pay attention to the comprehensive notification about the test. The Ethics Committee can provide the sponsor and researcher with the template of informed consent form and the key points of writing， continue to strengthen the examination ability， improve the examination quality， and effectively protect the safety and interests of the subjects.
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Malignant tumor poses a threat to human health and life. The incidence and fatality rate of malignant tumor have been on the rise. The currently available therapies are radiotherapy and chemotherapy， which cause severe adverse reactions and irreversible damage and thus influence the quality of life of patients. Therefore， it is urgent to find new， safe and effective antitumor drugs. Chinese medicinals are safe with little adverse reactions and long-lasting effect in the treatment of tumor， which have attracted the attention of scholars. Amid the advancement of medical research， more and more anti-tumor components have been extracted from Chinese medicinals. Phellinus is a valuable Chinese medicinal material， and the chemical components mainly include polysaccharides， flavonoids， triterpenes， and polyphenols， which have anti-inflammatory， hypoglycemic， liver-protecting， and anti-tumor effect. The chemical components of Phellinus can inhibit various malignant tumors such as lung cancer， gastric cancer， colon cancer， and melanoma. It exerts the anti-tumor effect by inhibiting proliferation and metastasis of tumor cells， inducing apoptosis and autophagy of the cells， suppressing tumor angiogenesis， and regulating the immunity. In addition， it can enhance efficacy， reduce toxicity， and boost the sensitivity in the radiotherapy and chemotherapy. In this paper， articles were retrieved from China National Knowledge Infrastructure （CNKI）， Web of Science， Pubmed， and Google Scholar with keywords such as "Phellinus， chemical components， and anti-tumor"， and then the chemical components of Phellinus and the anti-tumor mechanisms were summarized. The findings are expected to lays a basis for further development and clinical application of this medicinal.
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As a rare Chinese medicinal material， Paridis Rhizoma is mainly distributed in Yunnan， Guangxi， and Guizhou in southwestern China， with the effect of clearing heat and detoxifying， alleviating edema and relieving pain， cooling liver and tranquilizing mind. It is particularly effective for injuries from falls， fractures， contusions and strains， snake bites， cold wind-induced convulsion， and other diseases， which has been used for more than 2 000 years. According to modern research， polyphyllin Ⅱ， one of the main active components of Paridis Rhizoma， belongs to diosgenin in structure. It has the anti-tumor， anti-inflammatory， antiviral， antibacterial， immune-regulating， antioxidant， and multidrug resistance-reversing activities， showing good application prospect. Especially， the anti-tumor effect of polyphyllin Ⅱ has attracted wide attention， and the mechanism is inhibiting proliferation， migration， and invasion of tumor cells， inducing cell cycle arrest， apoptosis， and autophagy， suppressing angiogenesis， and modulating tumor microenvironment. However， the pharmacokinetic results show that polyphyllin Ⅱ has low bioavailability in vivo due to the low solubility， poor absorption， unsatisfactory distribution， and slow metabolism， which limit the clinical application. In recent years， there has been an explosion of research on the adverse reactions of polyphyllin Ⅱ， such as the strong hemolytic activity and obvious cytotoxicity to liver， kidney， myocardium and cardiovascular cells. Thus， papers were retrieved from "CNKI"， "VIP"， "Wanfang Data"， "PubMed"， "Web of Science"， and "Elsevier SD" with "Paris saponin Ⅱ"， "Polyphyllin Ⅱ" as the main keywords， and the pharmacological activities and mechanisms， pharmacokinetics， and adverse reactions were summarized. The findings are expected to serve as a reference for the in-depth research， development， and utilization of polyphyllin Ⅱ.