Plumbagin (Plumbago zeylanica L.) has a wide spectrum of anticancer activity with a relatively lower toxicity. The molecular mechanisms of proliferation inhibition and apoptosis induction by plumbagin on esophageal squamous carcinoma cell lines may be important for the structure modification and clinical application of plumbagin. After treatment of KYSE-30, KYSE-70 and KYSE-140 cells with 0-20 μmol·L^-1 of plumbagin for 24, 48, 72 h, CCK8 was used to examine the proliferation, Annexin V and PI immunofluorescence staining for apoptosis, real-time PCR and Western blot for FoxM1 mRNA and protein expression, dual-luciferase reporter gene assay for the transcriptional activity of FoxM1, respectively. In addition, the relationship between anti-tumor effect of plumbagin and FoxM1 was investigated in vivo. Plumbagin significantly inhibited proliferation and induced apoptosis of esophageal squamous carcinoma cell in vitro and in vivo. Moreover, plumbagin down-regulated the expression of FoxM1 through suppression of its gene transcription. Our findings suggest that plumbagin may inhibit the proliferation of esophageal squamous carcinoma cell in vivo and in vitro through down-regulating the expression of FoxM1.

This study was aimed to construct a "drug-target-pathway" network of Xuebijing injection for sepsis treatment in an effort to explore the "multi-components, multi-targets, multi-pathways" mechanism based on "system-system" research mode. Active ingredients of Xuebijing injection were used to predict the potential targets according to reversed pharmacophore matching method. The pathway information was acquired from DAVID and KEGG database. The Cytoscape software was used to construct the "ingredient-target-pathway" network of Xuebijing injection for sepsis treatment. The results showed that 21 major active ingredients of Xuebijing injection regulated 550 targets (HRAS, GSK3B, BTK, AK, et al) and affected 10 inflammation and immune-related pathways, such as B cell receptor signaling pathway, VEGF signaling pathway, natural killer cell mediated cytotoxicity, Toll-like receptor signaling pathway. The sepsis therapeutic effect of Xuebijing injection reflected the action features of traditional Chinese medicine as multi-ingredients, multi-targets, multi-pathways. This research clarifies the material basis of Xuebijing injection for anti-inflammation and immunoregulation, providing a scientific basis for elucidation the mechanism of Xuebijing injection in the treatment of sepsis.

Vascular endothelial growth factor receptor (VEGFR-2), a member of the super family of protein tyrosine kinase receptors, plays a vital role in the regulation of tumor metastasis and angiogenesis. Several VEGFR-2 inhibitors have been marketed as antitumor drugs and a range of inhibitors are undergoing clinical or preclinical studies. According to the principle of multi-targeted pharmacolgy, in the field of tumor treatment, nonselective drugs targeting on more than one kinase to inhibit different cell pathways can be more effective than drugs specific for one kinase. Multi-target treatment does not mean abandonment of selectivity, but a precise selectivity for several kinases related to tumor, which is also a big challenge in the development of small molecular antitumor drugs. This paper reviews briefly the advances in research of the VEGFR-2 inhibitors and selectivity strategy in recent years.

The aim of this research is to investigate the inhibitory effects of calpain inhibitors (ALLN and calpain inhibitor Ⅳ) on mammary epithelial-mesenchymal transition (EMT) of MCF-10A cells induced by fibronectin (FN). After FN treatment of MCF-10A cells for 48 h, cell migration and invasion were determined by scratch repair assay and matrigel coated transwell assay, respectively. Vimentin, E-cadherin, snail and calpain-2 protein expression were measured by Western blot. The results suggest that FN induced morphological changes in MCF-10A cells, significantly increased the migration and invasion abilities of MCF-10A cells, upregulated the expression of calpain-2, vimentin and snail, and downregulated the expression of E-cadherin. All such changes by FN were reversed with ALLN and calpain inhibitor Ⅳ. In conclusion, the upregulation of calpain-2 was involved in FN-induced EMT of MCF-10A mammary epithelial cells, which may be inhibited by ALLN and calpain inhibitor Ⅳ.

HSP90 is widely expressed in cells with the main function in assisting the maturation of other proteins that are called clients. Many clients play critical roles in the occurrence and development of cancer. Inhibition of HSP90 can lead to degradation of the oncogenic proteins, and result in potent anti-cancer effects. HSP90-HOP interaction is critical for the chaperone function of HSP90, thereby disruption of the HSP90-HOP interaction is a novel strategy in the inhibition of HSP90. Based on the technology of homogeneous time-resolved fluorescence (HTRF), we developed a new assay for the identification of new inhibitors of HSP90-HOP interaction. This method was evaluated in the study of the HSP90-HOP inhibition activity of the pentapeptide MEEVD from HSP90 C-terminal and its derivatives. This study can provide a basis for the screening and discovery of novel HSP90-HOP disruptors.

Parthenolide is a sesquiterpene lactone derived from the plant feverfew (Tanacetum parthenium) that possesses multiple anti-inflammatory and anti-cancer properties. A specific, sensitive, accurate and precise LC-MS/MS method was developed and validated in the quantitative analysis of parthenolide in rat plasma. A liquid-liquid extraction method was used to separate the analyte and the internal standard (IS, costunolide) from plasma. A water-methanol mobile phase system was utilized in the gradient chromatographic separation. The calibration curve with good linearity (r² > 0.99) was established between 2 and 128 ng·mL^-1 with accuracy and precision within acceptable limits at different QC levels. High extraction recovery was achieved for both parthenolide (89.55%-95.79%) and IS (96.87%). Based on this LC-MS/MS method, the plasma stability and pharmacokinetics of parthenolide were assessed in rats. Parthenolide was proved to be very unstable in rat plasma, and was distributed and eliminated quickly in vivo, with a half-life less than 90 min. A high dose of parthenolide (80 mg·kg^-1) resulted in a very low initial concentration (138.86±21.07 ng·mL^-1). The systemic exposure of parthenolide (area under the curve) increased disproportionally from 40 mg·kg^-1 dose group to 80 mg·kg^-1 dose group. The present study may provide helpful information for the development of parthenolide as a drug candidate.

A new phomapyrone derivative (1), and 9 known compounds were isolated from the ethyl acetate fraction of solid fermentation of Fusarium redolens, the endophytic fungus from Edgeworthia chrysantha, by using various isolation techniques such as Sephadex LH-20, MCI GEL and Semi pre-HPLC, etc. Their structures were identified by spectroscopic analysis, including MS, UV, CD, specific rotation, IR, 1D and 2D NMR, as (+)-7S-4-deoxy-9-hydroxyphomapyrone C (1), uracil (2), uridine (3), 2'-deoxyuridine (4), adenosine (5), 2'-deoxyadenosine (6), cordysinin B (7), ergosterol (8), ergosta-5α, 8β-epidioxy-6, 22-dien-3β-ol (9), and (22E, 24S)-3α-hydroxy-24-methylcholesta-5, 8, 22-trien-7-one (10).

Persicae semen has been used for years as a traditional Chinese medicine to treat diseases. Because of their similar morphologies, Persicae semen was commonly inadvertently mixed with Armeniacae semen amarum (a toxic herbal seed). Development of a reliable method for discriminating Persicae semen from its adulterant is necessary to reduce confusion for the drug safety in clinical practices. This study evaluates the efficiency of high-resolution melting (HRM) combined with internal transcribed spacer 2 (ITS2) to analyze Persicae semen. Our findings show that HRM allows not only the identification of adulteration but also the quantification of the most common admixture. HRM sensitivity in adulterant detection was assessed through the analysis of mixing samples with different proportions of Prunus persica and Prunus armeniaca control. The results are presented as a linear regression with r of 0.96 and imply the capability of the method to detect adulteration. In particular, HRM detected seeds of Prunus persica in Prunus armeniaca at concentrations as low as 1%, and commercial products labeled as 'Persicae semen' were purchased from markets and could rapid authenticated by HRM analyses. This study is significant in the verification of the authenticity in the quality control of herbal medicine. In the near future, it is promising to be the main trend for identifying traditional Chinese medicinal materials.

Tianlongtongxin (TLTX) formula is composed of six Chinese herbs including Rhodiola rosea L., Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma and so on. It has been mainly used in the treatment of chest-Bi syndrome in the clinics. To investigate the material foundation and provide reference for clinical dosage regimen, the pharmacokinetics of seven components in the rat plasma were studied after oral administration of TLTX. A high sensitive method was established to determine the seven active components from TLTX in rat plasma based on the LC-MS/MS technique. The method met the requirements of preclinical pharmacokinetic study, through the investigation of linearity, specificity, recovery, accuracy, precision and stability. After administration of TLTX at 4.5 g·kg^-1 dose, all of the components were detectable in the plasma after 5 min. The concentration peaks were observed at 0.11-4.67 h respectively after administration with great difference in levels. The AUC of salidroside was significantly higher than other components, suggesting it as a main active component in TLTX formula. The observations provide scientific evidence for the rationality of salidroside as monarch drug in the formula.

In this study, we developed a qualitative analytical method based on liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) for identification of multi-constituents of raw Fructus Arctii (RFA) and processed Fructus Arctii (PFA). We established a UHPLC-UV analytical method for simultaneously determining 6 major compounds in Fructus Arctii. UHPLC-Q-TOF-MS/MS qualitative analysis was performed under negative and positive ion modes and a total of 23 chemical compounds were identified. The analysis data were subjected to a principle component analysis with a t-test. Ten peaks were found to be the main difference (P < 0.05) between RFA and PFA. HPLC-UV quantitative method result showed the contents of 6 constituents were different between RFA and PFA. The results indicated that there was less arctiin, chlorogenic acid, isochlorogenic acid A in PFA than in RFA. However, there were higher levels of arctigenin, isochlorogenic acid B, isochlorogenic acid C in the PFA than RFA, which may be the main reason for different clinical efficacy of RFA and PFA.