Chlovalicin B, a Chlorinated Sesquiterpene Isolated from the Marine Mushroom Digitatispora marina.

As part of our search for bioactive metabolites from understudied marine microorganisms, the new chlorinated metabolite chlovalicin B (1) was isolated from liquid cultures of the marine basidiomycete Digitatispora marina, which was collected and isolated from driftwood found at Vannøya, Norway. The structure of the novel compound was elucidated by spectroscopic methods including 1D and 2D NMR and analysis of HRMS data, revealing that 1 shares its molecular scaffold with a previously isolated compound, chlovalicin. This represents the first compound isolated from the Digitatispora genus, and the first reported fumagillin/ovalicin-like compound isolated from Basidiomycota. Compound 1 was evaluated for antibacterial activities against a panel of five bacteria, its ability to inhibit bacterial biofilm formation, for antifungal activity against Candida albicans, and for cytotoxic activities against malignant and non-malignant human cell lines. Compound 1 displayed weak cytotoxic activity against the human melanoma cell line A2058 (~50% survival at 50 µM). No activity was detected against biofilm formation or C. albicans at 50 µM, or against bacterial growth at 100 µM nor against the production of cytokines by the human acute monocytic leukemia cell line THP-1 at 50 µM.

Anticancer potential of rhizome extract and a labdane diterpenoid from Curcuma mutabilis plant endemic to Western Ghats of India.

Zingiberaceae plants are well known for their use in ethnomedicine. Curcuma mutabilis Skornick., M. Sabu & Prasanthk., is an endemic Zingiberaceae species from Western Ghats of Kerala, India. Here, we report for the first time, the anticancer potential of petroleum ether extract from C. mutabilis rhizome (CMRP) and a novel labdane diterpenoid, (E)-14, 15-epoxylabda-8(17), 12-dien-16-al (Cm epoxide) isolated from it. CMRP was found to be a mixture of potent bioactive compounds including Cm epoxide. Both the extract and the compound displayed superior antiproliferative activity against several human cancer cell lines, without any display of cytotoxicity towards normal human cells such as peripheral blood derived lymphocytes and erythrocytes. CMRP treatment resulted in phosphatidylserine externalization, increase in the levels of intracellular ROS, Ca2+, loss of mitochondrial membrane potential as well as fragmentation of genomic DNA. Analyses of transcript profiling and immunostained western blots of extract-treated cancer cells confirmed induction of apoptosis by both intrinsic and extrinsic pathways. The purified compound, Cm epoxide, was also found to induce apoptosis in many human cancer cell types tested. Both CMRP and the Cm epoxide were found to be pharmacologically safe in terms of acute toxicity assessment using Swiss albino mice model. Further, molecular docking interactions of Cm epoxide with selected proteins involved in cell survival and death were also indicative of its druggability. Overall, our findings reveal that the endemic C. mutabilis rhizome extract and the compound Cm epoxide isolated from it are potential candidates for development of future cancer chemotherapeutics.

Triptolide: reflections on two decades of research and prospects for the future.

Covering: 2000 to 2020 Triptolide is a bioactive diterpene triepoxide isolated from Tripterygium wilfordii Hook F, a traditional Chinese medicinal plant whose extracts have been used as anti-inflammatory and immunosuppressive remedies for centuries. Although triptolide and its analogs exhibit potent bioactivities against various cancers, and inflammatory and autoimmune diseases, none of them has been approved to be used in the clinic. This review highlights advances in material sourcing, molecular mechanisms, clinical progress and new drug design strategies for triptolide over the past two decades, along with some prospects for the future course of development of triptolide.

Investigation on the Epoxidation of Piperitenone, and Structure-activity Relationships of Piperitenone Oxide for Differentiation-inducing Activity.

Piperitenone oxide, a major chemical constituent of the essential oil of spearmint, Mentha spicata, induces differentiation in human colon cancer RCM-1 cells. In this study, piperitenone oxide and trans-piperitenone dioxide were prepared as racemic forms by epoxidation of piperitenone. The relative configuration between two epoxides in piperitenone dioxide was determined to be trans by 1H NMR analysis and nuclear Overhauser effect spectroscopy (NOESY) in conjunction with density functional theory (DFT) calculations. Optical resolution of (±)-piperitenone oxide by high-performance liquid chromatography (HPLC) using a chiral stationary phase (CSP) afforded both enantiomers with over 98% enantiomeric excess (ee). Evaluation of the differentiation-inducing activity of the synthetic compounds revealed that the epoxide at C-1 and C-6 in piperitenone oxide is important for the activity, and (+)-piperitenone oxide has stronger activity than (-)-piperitenone oxide. The results obtained in this study provide new information on the application of piperitenone oxide and spearmint for differentiation-inducing therapy. Furthermore, natural piperitenone oxide was isolated from M. spicata. The enantiomeric excess of the isolated natural piperitenone oxide was 66% ee. Epoxidation of piperitenone with hydrogen peroxide proceeded in a phosphate buffer under weak basic conditions to give (±)-piperitenone oxide. These results suggest that the nonenzymatic epoxidation of piperitenone, which causes a decrease in the enantiomeric excess of natural piperitenone oxide, is accompanied by an enzymatic epoxidation in the biosynthesis of piperitenone oxide.

Two new 5,6-epoxysterols from calcareous marine sponge Leucetta chagosensis.

Chemical investigation on CH2Cl2 extract of the marine sponge Leucetta chagosensis, collected from the South China Sea, afforded two new 5,6-epoxysterols, 5α,6α-epoxycholesta-8(14),22(E)-diene-3ß,7α-diol (1) and (24R)-24-ethyl-5α,6α-epoxycholesta-8(14),22(E)-diene-3ß,7α-diol (2) along with ten known related steroid analogs (3-12). Their structures were elucidated on the basis of NMR spectroscopic analyses, and comparison with the literature. All isolates were tested for cytotoxicity against three tumor cell lines only known compounds 11 and 12 exhibited notable cytotoxic activity against A549 (IC50: 3.0 and 5.6 µM), PC9 (2.0 and 15.6 µM), and MCF-7 (9.4 and 11.8 µM) cell lines, respectively.

New 9α-Hydroxy-5α,6α-epoxyhydroxysterols from the Vietnamese Marine Sponge Ircinia echinata.

Chemical investigation of the methanol extract of the Vietnamese marine sponge Ircinia echinata led to the isolation of six new 9α-hydroxy-5α,6α-epoxysterols: 5α,6α-epoxycholesta-7,22(E)-dien-3ß,9α-diol (1), 5α,6α-epoxycholesta-7,24(28)-dien-3ß,9α-diol (2), (24R)-5α,6α-epoxy-24-ethyl-cholesta-7-en-3ß,9α-diol (3), 5α,6α-epoxycholesta-7-en-3ß,9α-diol (4), (24S)-5α,6α-epoxyergosta-7,22-dien-3ß,9α-diol (5), and (24R)-5α,6α-epoxy-24-methyl-cholesta-7-en-3ß,9α-diol (6) along with the known 5α-6α-epoxysterols: 5α,6α-epoxystigmasta-7-en-3ß-ol (7), 5α,6α-epoxystigmasta-7,22-dien-3ß-ol (8), and 5α,6α-epoxyergosta-7-en-3ß-ol (9). Their structures and their configurations were established on the basis of high resolution mass spectra and extensive 1D and 2D NMR spectroscopic data and by comparison with the literature. Their cytotoxic activity, evaluated against three human cancer cell lines, MCF-7, Hep-G2 and LU-1, revealed that only compounds 3 and 4 exhibited significant antiproliferative activity and compound 3 showed a selective inhibition towards the MCF-7 human breast cancer cells.

Preparation and Improved Physical Characteristics of Propylene Oxide Rubber Composites.

Sealing rubbers employed in cold climates such as the Siberian Arctic must be able to withstand temperatures as low as -50 °C while still exhibiting specific relaxation, strength, tribological characteristics, and a resistance to aggressive media. Previous investigations of propylene oxide rubber (SKPO, Tg = -73 °C) modified with polytetrafluoroethylene (PTFE) have revealed that, while the rubber composite materials exhibit double the wear resistance compared to unmodified polypropylene oxide rubber, they have poor frost resistance. In the present study, we developed materials based on SKPO and ultrafine PTFE (UPTFE), which can be characterized by its smaller particle size, low molecular weight, high tribo-technical characteristics, and resistance to aggressive media. The properties of the rubber composites were evaluated using the standard methods. The structures of the materials were investigated by electron microscopy and XRD analysis. It was shown that the materials have excellent wear resistance, resistance to aggressive media, compression set, and low-temperature resistance. The addition of UPTFE is preferable to the addition of PTFE because the desired positive effects can be attained with only 0.5⁻1 parts per hundred parts of rubber (phr) UPTFE while 20 phr PTFE would be necessary.

Plagiochiline A Inhibits Cytokinetic Abscission and Induces Cell Death.

We previously reported on the isolation and biological activities of plagiochiline A (1), a 2,3-secoaromadendrane-type sesquiterpenoid from the Peruvian medicinal plant, Plagiochila disticha. This compound was found to have antiproliferative effects on a variety of solid tumor cell lines, as well as several leukemia cell lines. Other researchers have also noted the cytotoxicity of plagiochiline A (isolated from different plant species), but there are no prior reports regarding the mechanism for this bioactivity. Here, we have evaluated the effects of plagiochiline A on cell cycle progression in DU145 prostate cancer cells. A cell cycle analysis indicated that plagiochiline A caused a significant increase in the percentage of cells in the G2/M phase when compared with control cells. When cells were stained and observed by fluorescence microscopy to examine progress through the mitotic phase, we found a significant increase in the proportion of cells with features of late cytokinesis (cells connected by intercellular bridges) in the plagiochiline A-treated samples. These results suggest that plagiochiline A inhibits cell division by preventing completion of cytokinesis, particularly at the final abscission stage. We also determined that plagiochiline A reduces DU145 cell survival in clonogenic assays and that it induces substantial cell death in these cells.

Antimutagenic constituents from Monanthotaxis caffra (Sond.) Verdc.

OBJECTIVES: Monanthotaxis caffra (Sond.) Verdc. (Annonaceae) has been reported to possess antitumoural properties. Preliminary screening showed that the crude methanolic leaf extract had strong antimutagenic effects against aflatoxin B1 -induced mutagenicity. The aim of this study was to isolate and evaluate the antimutagenic properties of the active constituents from M. caffra. METHODS: Different chromatographic, spectroscopic and spectrometric techniques were used for the isolation and identification of the antimutagenic constituents. The antimutagenic effect of the extract and compounds was evaluated using Ames, Vitotox and Comet assays. KEY FINDINGS: Bioassay-guided fractionation of the methanolic leaf extract yielded two antimutagenic compounds identified as (+)-crotepoxide and 5,6-diacetoxy1-benzoyloxymethyl-1,3-cyclohexadiene. Crotepoxide had strong antimutagenicity in the Vitotox assay with an IC50 value of 131 µg/ml. 5,6-Diacetoxy-1-benzoyloxymethyl-1,3-cyclohexadiene showed strong antimutagenic activity in the Ames assay with an IC50 value of 348.9 µg/plate and no antimutagenic activity in the Vitotox test. Furthermore, the compound was able to inhibit, block or prevent biotransformation of aflatoxin B1 by repressing the proteins involved in transcription. CONCLUSIONS: Crotepoxide and 5,6-diacetoxy-1-benzoyloxymethyl-1,3-cyclohexadiene have the potential to mitigate the risks arising from consumption of aflatoxin B1 -contaminated food and feed.

Halogenated Compounds from Directed Fermentation of Penicillium concentricum, an Endophytic Fungus of the Liverwort Trichocolea tomentella.

One new chlorinated xanthone, 6-chloro-3,8-dihydroxy-1-methylxanthone (1), a new 2-bromo-gentisyl alcohol (2), and a mixture of 6-epimers of 6-dehydroxy-6-bromogabosine C (3a and 3b), together with 19 previously identified compounds, epoxydon (4), norlichexanthone (5), 2-chlorogentisyl alcohol (6), hydroxychlorogentisyl quinone (7), 6-dehydroxy-6α-chlorogabosine C (8a), 6-dehydroxy-6ß-chlorogabosine C (8b), gentisyl alcohol (9), gentisyl quinone (10), (R,S)-1-phenyl-1,2-ethanediol (11), dehydrodechlorogriseofulvin (12), dechlorogriseofulvin (13), dehydrogriseofulvin (14), griseofulvin (15), ethylene glycol benzoate (16), alternariol (17), griseoxanthone C (18), drimiopsin H (19), griseophenone C (20), and griseophenone B (21), were isolated from cultures of Penicillium concentricum, a fungal endophyte of the liverwort Trichocolea tomentella. The structures of the new compounds (1, 2, 3a, and 3b) were elucidated by interpretation of spectroscopic data including one- and two-dimensional NMR techniques. Among these, compounds 2-4 displayed modest cytotoxicity to the MCF-7 hormone-dependent breast cancer cell line with IC50 values of 8.4, 9.7, and 5.7 µM, respectively, whereas compound 9 exhibited selective cytotoxicity against the HT-29 colon cancer cell line with an IC50 value of 6.4 µM. During this study we confirmed that the brominated gentisyl alcohol (2) was formed by chemical conversion of 4 during bromide salt addition to culture media.

OSMAC approach leads to new fusarielin metabolites from Fusarium tricinctum.

Using the OSMAC (One Strain MAny Compounds) approach, the fungal endophyte Fusarium tricinctum was cultivated on fruit and vegetable juice-supplemented solid rice media. This led to an up to 80-fold increase in the accumulation of the new natural product fusarielin J (1), as well as to the induction of two new natural products fusarielin K (2) and fusarielin L (3) and the known derivatives fusarielins A (4) and B (5). Compounds 2-5 were not detected when the fungus was grown on rice media lacking either fruit or vegetable juice. The highest increase in the accumulation of compound 1 was observed in the presence of apple and carrot juice, whereas the stimulating effect was weaker for banana juice. Compound 1 exhibited cytotoxicity against the human ovarian cancer cell line A2780, with an IC50 value of 12.5 µM.

[Determination of glycidyl methacrylate in the air of workplace captured adsorbent tube by gas chromatography].

Objective: To develop a new solid sorbent tube for capturing glycidyl methacrylate (GMA) in workplace air, and establish a complete set of method. Methods: GMA in workplace air was captured by the new solid sorbent tube filled with carbon aerogel adsorbent, desorbed with solution of 50% (V/V) dimethylformamide-carbon disulfide, separated through capillary chromatographic column, and then analyzed by gas chromatography-flame ionization detector. Results: The linear range of GMA was 0.38-604.80 mg/L, and the related coefficient was 0.999 82. The within-run and the between-run precision were 1.11%-2.80% and 2.53%-4.84% respectively. The average desorption efficiency was 93.20%-94.97%. The minimum quantification concentration and The minimum quantification concentration were 0.02 and 0.07 mg/m(3) respectively (3.00 L sample) . Samples could be stored for at least 8 days at room temperature. Conclusion: The newly developed solid sorbent tube and its complete set of gas chromatography method is simple, and has high sensitivity and precision, so it can be used for sampling and quantitative detection of GMA in workplace air.

New cytotoxic furan from the marine sediment-derived fungi Aspergillus niger.

A fungal strain of Aspergillus niger was recovered from sediments collected in the Northeast coast of Brazil (Pecém's offshore port terminal). Cultivation in different growth media yielded a new ester furan derivative, 1, along with malformin A1, malformin C, cyclo (trans-4-hydroxy-L-Pro-L-Leu), cyclo (trans-4-hydroxy-L-Pro-L-Phe), cyclo (L-Pro-L-Leu), cyclo (L-Pro-L-Phe), pseurotin D, pseurotin A, chlovalicin, cyclo (L-Pro-L-Tyr) and cyclo (L-Pro-L-Val). Compound 1 was cytotoxic against HCT-116 cell line, showing IC50 = 2.9 µg/mL (CI 95% from 1.8 to 4.7 µg/mL).

Extraction and Liquid Chromatography-Tandem Mass Spectrometry Detection of 3-Monochloropropanediol Esters and Glycidyl Esters in Infant Formula.

A method was developed for the extraction of fatty acid esters of 3-chloro-1,2-propanediol (3-MCPD) and glycidol from infant formula, followed by quantitative analysis of the extracts using liquid chromatography-tandem mass spectrometry (LC-MS/MS). These process-induced chemical contaminants are found in refined vegetable oils, and studies have shown that they are potentially carcinogenic and/or genotoxic, making their presence in edible oils (and processed foods containing these oils) a potential health risk. The extraction procedure involves a liquid-liquid extraction, where powdered infant formula is dissolved in water and extracted with ethyl acetate. Following shaking, centrifugation, and drying of the organic phase, the resulting fat extract is cleaned-up using solid-phase extraction and analyzed by LC-MS/MS. Method performance was confirmed by verifying the percent recovery of each 3-MCPD and glycidyl ester in a homemade powdered infant formula reference material. Average ester recoveries in the reference material ranged from 84.9 to 109.0% (0.6-9.5% RSD). The method was also validated by fortifying three varieties of commercial infant formulas with a 3-MCPD and glycidyl ester solution. Average recoveries of the esters across all concentrations and varieties of infant formula ranged from 88.7 to 107.5% (1.0-9.5% RSD). Based on the validation results, this method is suitable for producing 3-MCPD and glycidyl ester occurrence data in all commercially available varieties of infant formula.

Comparative analysis of four terpenoids in root and cortex of Tripterygium wilfordii Radix by different drying methods.

BACKGROUND: Tripterygium wilfordii Radix, a well-known traditional medicine in china which is used for treatment of inflammation, pain, tumor and immune regulation for centuries in china, accompany with the serious toxic side effects. This study was carried out for simultaneously analyzing the four main components (triptolide, triptophenolide, demethylzeylasteral and celastrol) in Tripterygium wilfordii Radix under different drying processes, which was important for reducing the toxicity and quality control of Tripterygium wilfordii Radix in future. METHODS: The terpenes were extracted by using ultrasonic method with ethyl acetate from root or cortex of Tripterygium wilfordii Radix, and the sensitive and rapid HPLC-PDA method was developed for simultaneous quantification of triptolide, triptophenolide, demethylzeylasteral and celastrol in root and cortex of Tripterygium wilfordii Radix for evaluation of the impacts by different drying processes. RESULTS: The four compounds in their respective determined arrange had good linearity of 0.9998≦R2≦0.9999 and the average recoveries were range from 94.69 to 100.28%, RSDs were within 0.27 to 2.42%, respectively. The contents of triptolide, triptophenolide, demethylzeylasteral and celastrol in different Tripterygium wilfordii Radix individuals were varied greatly at different drying temperatures. Under different temperatures, the contents of triptolide, triptophenolide, demethylzeylasteral, and celastrol were 37.94-70.31 mg/g, 0-1.807 mg/g, 0.3513-9.205 mg/g, 3.202-15.31 mg/g, respectively. The suitable drying temperature of terpenoids in root of wild and cultivate are 80 °C and 60 °C, the suitable drying temperature of terpenoids in cortex is 40 °C. CONCLUSIONS: The method established is high sensitivity, accuracy, reliability and suitable for the simultaneous analysis of terpenoids in Tripterygium wilfordii Radix. The data provide a scientific basis and reference for the quality control of herb and preparations related to Tripterygium wilfordii Radix.

Multi-residue methods for the determination of over four hundred pesticides in solid and liquid high sucrose content matrices by tandem mass spectrometry coupled with gas and liquid chromatograph.

For the first time three methods: matrix solid phase dispersion (MSPD), original and modified QuEChERS, with and without clean up step were studied in order to evaluate the extraction efficiency of various classes of pesticides from solid and liquid high sucrose content matrices. Determinations over four hundred pesticides were performed by gas and liquid chromatography with triple quadrupole mass spectrometry (GC/LC/MS/MS) using multiple reaction monitoring. The proposed methods were validated on sugar beets and their technological product beet molasses. In general, the recoveries obtained for the original QuEChERS and MSPD method were lower (<70%) than for the modified QuEChERS without clean up in sugar beet and with clean up in beet molasses. Among these methods, high extraction yields were achieved as recommended in SANCO/12571/2013, with repeatability of 4.4-19.2% and within-laboratory reproducibility of 7.1-18.4% for citrate QuEChERS, whereas greater ruggedness were observed for MSPD. The limit of quantification (LOQ) at (the lowest MRL=0.01mgkg(-1)e.g. for oxamyl()) or below (0.005mgkg(-1)) the regulatory maximum residue level for the pesticides were achieved. The expanded measurement uncertainty was not higher than 30% for all target analytes. Matrix effects were compared and observed for both matrices at both gas and liquid chromatography. The most compounds showed signal enhancement and it was compensated by using matrix-matched calibration and modified QuEChERS characterized lower matrix effects. The confirmation of suitability citrate QuEChERS optimized method was to use for routine testing of several dozen samples determination and residue of epoxiconazole and tebuconazole (both at 0.01mgkg(-1)) in the samples of beet molasses and cyfluthrin (0.06mgkg(-1)) in sugar beet were found.

Synergistic anticancer effects of triptolide and celastrol, two main compounds from thunder god vine.

Triptolide and celastrol are two main active compounds isolated from Thunder God Vine with the potent anticancer activity. However, the anticancer effect of triptolide in combination with celastrol is still unknown. In the present study, we demonstrated that the combination of triptolide with celastrol synergistically induced cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the increased intracellular ROS accumulation in cancer cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine dramatically blocked the apoptosis induced by co-treatment with triptolide and celastrol. Treatment with celastrol alone led to the decreased expressions of HSP90 client proteins including survivin, AKT, EGFR, which was enhanced by the addition of triptolide. Additionally, the celastrol-induced expression of HSP70 and HSP27 was abrogated by triptolide. In the nude mice with xenograft tumors, the lower-dose combination of triptolide with celastrol significantly inhibited the growth of tumors without obvious toxicity. Overall, triptolide in combination with celastrol showed outstanding synergistic anticancer effect in vitro and in vivo, suggesting that this beneficial combination may offer a promising treatment option for cancer patients.

O discurso do excesso sexual como marca da brasilidade: revisitando o pensamento social brasileiro das décadas de 1920 e 1930 / The discourse of sexual excess as a hallmark of Brazilianness: revisiting Brazilian social thinking in the 1920s and 1930s

O objetivo deste trabalho é analisar o discurso do excesso sexual produzido pelo pensamento social brasileiro das décadas de 1920 e 1930 na sua interlocução com o discurso médico da época. De inspiração foucaultiana, o texto inscreve-se no campo da história dos saberes e está subsidiado por documentos sociológicos e médicos do período de referência. No quadro da recodificação vintecentista sobre o imaginário da brasilidade, o tema do excesso sexual foi revisitado pelo pensamento sociológico local, forjando-o ora como um perturbador do projeto civilizatório nacional, ora como um traço que deveria ser positivado por ter sido a condição de possibilidade da hibridização cultural de suas matrizes identitárias.

The objective of this article is to analyze the discourse of sexual excess produced by Brazilian social thinking in the 1920s and 1930s and its dialog with the medical discourse at the time. Inspired by Foucault, it is within the field of the history of knowledge and is supported by sociology and medical documents from the period in question.Within the framework of the twentieth century re-codification of the imagery of Brazilianness, the topic of sexual excess was revisited by local thinkers in the field of sociology and seen either as disturbing the national civilizing project, or as a trait that should be seen in a positive light because it permitted the cultural hybridization of its sources of identity.

Triptolide: progress on research in pharmacodynamics and toxicology.

ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii Hook. f. (Tripterygium wilfordii), also known as Huangteng and gelsemium elegan, is a traditional Chinese medicine that has been marketed in China as Tripterygium wilfordii glycoside tablets. Triptolide (TP), an active component in Tripterygium wilfordii extracts, has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. This review summarizes recent developments in the research on the pharmacodynamics, pharmacokinetics, pharmacy and toxicology of TP, with a focus on its novel mechanism of reducing toxicity. This review provides insight for future studies on traditional Chinese medicine, a field that is both historically and currently important. MATERIALS AND METHODS: We included studies published primarily within the last five years that were available in online academic databases (e.g., PubMed, Google Scholar, CNKI, SciFinder and Web of Science). RESULTS: TP has a long history of use in China because it displays multiple pharmacological activities, including anti-rheumatism, anti-inflammatory, anti-tumor and neuroprotective properties. It has been widely used for the treatment of various diseases, such as rheumatoid arthritis, nephritic syndrome, lupus, Behcet׳s disease and central nervous system diseases. Recently, numerous breakthroughs have been made in our understanding of the pharmacological efficacy of TP. Although TP has been marketed as a traditional Chinese medicine, its multi-organ toxicity prevents it from being widely used in clinical practice. CONCLUSIONS: Triptolide, a biologically active natural product extracted from the root of Tripterygium wilfordii, has shown promising pharmacological effects, particularly as an anti-tumor agent. Currently, in anti-cancer research, more effort should be devoted to investigating effective anti-tumor targets and confirming the anti-tumor spectrum and clinical indications of novel anti-tumor pro-drugs. To apply TP appropriately, with high efficacy and low toxicity, the safety and non-toxic dose range for specific target organs and diseases should be determined, the altered pathways and mechanisms of exposure need to be clarified, and an early warning system for toxicity needs to be established. With further in-depth study of the efficacy and toxicity of TP, we believe that TP will become a promising multi-use drug with improved clinical efficacy and safety in the future.

Traditional Chinese medicine: a treasured natural resource of anticancer drug research and development.

To discover and develop novel natural compounds, active ingredients, single herbs and combination formulas or prescriptions in traditional Chinese medicine (TCM) with therapeutic selectivity that can preferentially kill cancer cells and inhibit the amplification of cancer without significant toxicity is an important area in cancer therapy. A lot of valuable TCMs were applied as alternative or complementary medicines in the United States and Europe. But these TCMs, as one of the main natural resources, were widely used to research and develop new drugs in Asia. In TCMs, some specific herbs, animals, minerals and combination formulas were recorded and exploited due to their active ingredients and specific natural compounds with antitumor activities. The article focused on the antitumor properties of natural compounds and combination formulas or prescriptions in TCMs, described its influence on tumor progression, angiogenesis, metastasis, and revealed its mechanisms of antitumor and inhibitory action. Among the nature compounds, triptolide, berberine, matrine, oxymatrine, kurarinone and deoxypodophyllotoxin (DPT) with specific molecular structures have been separated, purified, and evaluated their antitumor properties in vitro and in vivo. Cancer is a multifactorial and multistep disease, so the treatment effect of combination formulas and prescriptions in TCMs involving multi-targets and multi-signal pathways on tumor may be superior than that of agents targeting a single molecular target alone. Shi Quan Da Bu Tang and Yanshu injection, as well known combination formulas and prescriptions in TCMs, have shown an excellent therapeutic effect on cancer.