Low curcumin concentration enhances the anticancer effect of 5-fluorouracil against colorectal cancer.

BACKGROUND: Colon cancer treatments include surgery, radiotherapy, and chemotherapy. Chemotherapy using 5-fluorouracil (5-FU) has been widely applied to treat colorectal cancer (CRC). However, it is important to explore the use of chemotherapy drugs in combination with other agents to decrease severe adverse effects. PURPOSE: This study aimed to investigate the effects of curcumin in combination with 5-FU on the proliferation, migration, and apoptosis of CRC SW620 cell line both in vitro and in vivo. METHODS: Flow cytometry was used to study the effect of curcumin on chemotherapy-induced apoptosis in CRC cells. The mechanism of curcumin's enhanced antitumor effect in vivo was investigated using gene knockdown, TUNEL, western blot, qRT-PCR and immunohistochemistry. RESULTS: The results showed a synergistic effect of the two compounds on CRC cells. Considerable reduction in the proliferation and migration of SW620 cells was observed in the combination treatment group. Significantly increased apoptosis rate extended the survival of immunodeficient mice in the combination group as compared to that of the 5-FU group (p < 0.05). The results showed that curcumin significantly inhibited pERK signaling and downregulated L1 expression in SW620 cells. CONCLUSIONS: We conclude that curcumin promotes chemosensitivity of CRC cells to 5-FU by downregulating L1 expression. Our findings provide experimental evidence for the synergism between curcumin and 5-FU, which can be utilized in clinical applications for reducing the toxicity and adverse effects of 5-FU.

Botrychium schaffneri Underw. extract acts via DIABLO to induce apoptosis and inhibit proliferation of non-small cell lung carcinoma in vitro and in vivo.

BACKGROUND: Botrychium schaffneri Underw. has been popularly consumed since ancient times as a traditional medicine in China to treat whooping cough, bronchial asthma, and febrile convulsive twitch disease. This led us to investigate whether Botrychium schaffneri Underw. extract (BSE) may be effective against lung cancer, especially non-small cell lung carcinoma (NSCLC). METHODS: In this study, we extracted the ethanolic root extract of the grass, Botrychium schaffneri Underw. In vitro study, the change of NCI-H1299 cell proliferation was observed with CCK8 and MTT assays. Cell apoptosis was assessed using a kit based on staining with FITC-conjugated annexin V. In vivo study, we establish a stable animal model of NSCLC in nude mice, tumor volume and weight was measured twice a week. We conduct gene microarray screened for differentially expressed genes (DEGs), between NCI-H1299 cells treated by BSE or not. Then the DEGs were functionally annotated and path enriched. RESULTS: It was revealed that BSE significantly suppressed NSCLC cell proliferation (IC50 134 µg/mL) and induced apoptosis. It also slowed tumor growth without affecting body weight, and a dose of 25 g/kg led to significantly smaller tumors than in control animals (13.85±3.36 vs. 23.40±6.05, P=0.044). Apoptosis-related protein direct IAP Binding protein with low PI (DIABLO) expression was up-regulated by BSE, and DIABLO knockdown significantly attenuated the anti-tumor effects of the extract. CONCLUSIONS: In conclusion, BSE reduces the viability of NSCLC cells and promotes apoptosis, and these effects may be mediated by DIABLO.

Investigation of sugars, organic acids, phenolic compounds, antioxidant activity and the aroma fingerprint of small white apricots grown in Xinjiang.

Small white apricot is well known as a famous fresh fruit and even a folk medicine in Xinjiang. To investigate nutritive value, antioxidant activity, and flavor of small white apricot, sugars, organic acids, total flavonoids, phenolic compounds, antioxidant activities, and volatile compounds in five apricot cultivars were examined by high-performance liquid chromatography (HPLC) and headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results showed that sucrose (32.94% to 42.49%), malic acid (69.21% to 76.75%), and quercetin-3-rutinoside (72.84% to 74.05%) were the dominant sugar, organic acid, and phenolic compounds in small white apricot, respectively. The antioxidant activity reached up to 61.72 to 135.52 mg TEs 100 g-1 . Furthermore, the aroma fingerprint of the small white apricot consisted of 1-octen-3-ol, 1-dodecanol, pentanal, hexanal, (E)-2-hexenal, (E)-2-heptenal, 6-methyl-5-hepten-2-one, (E)-2-nonenal, 1-octen-3-one, ß-myrcene, and linalool, providing clear green, grassy, and fatty notes. Apricots from different cultivars possessed a similar flavor, while linalool and (E)-2-hexenal had been identified as the characteristic aroma compounds in small white apricot. The results provide a complete chemical characterization of the taste, functional ingredients and aroma of the small white apricot. PRACTICAL APPLICATION: The nutritive value, antioxidant activity and flavor of small white apricot were investigated in this study. The results will provide a theoretical basis for developing characteristic variety aroma, nutritive value, and medicinal value of small white apricot.

[Effect of ear point embedding on plasma and effect site concentrations of propofol-remifentanil in elderly patients after target-controlled induction].

OBJECTIVE: To observe the clinical effect of ear point embedding on plasma and effect site concentrations of propofol-remifentanil in elderly patients who underwent abdominal external hernia surgery at the time of consciousness and pain disappearing by target-controlled infusion (TCI) and bispectral index (BIS). METHODS: Fifty patients who underwent elective abdominal hernia surgery were randomly assigned into an observation group and a control group, 25 cases in each one. In the observation group, 30 minutes before anesthesia induction, Fugugou (Extra), Gan (CO12), Pizhixia (AT4), and Shenmen (TF4) were embedded by auricular needles until the end of surgery, 10 times of counter press each point. In the control group, the same amount of auricular tape was applied until the end of surgery at the same points without stimulation 30 minutes before anesthesia induction. Patients in the two groups were given total intravenous anesthesia, and BIS was monitored by BIS anesthesia depth monitor. Propofol was infused by TCI at a beginning concentration of 1.5µg/L and increased by 0.3µg/L every 30s until the patients lost their consciousness. After that, remifentanil was infused by TCI at a beginning concentration of 2.0µg/L and increased by 0.3µg/L every 30s until the patients had no body reaction to pain stimulation (orbital reflex). Indices were recorded, including mean arterial pressure (MAP), heart rate (HR) and the BIS values, at the time of T0 (entering into the operation room), T1 (losing consciousness) and T2 (pain relief), the plasma and effect site concentrations of propofol at T1, the plasma and effect site concentrations of remifentanil at T2. After surgery we recorded the total amounts of propofol and remifentanil, surgery time and anesthesia time. RESULTS: At T1 and T2, MAP and HR of the observation group were higher than those of the control group (P<0.05, P<0.01). At T1, the plasma and effect site concentrations of propofol in the observation group were significantly lower than those in the control group (P<0.05, P<0.01). At T2, the plasma and effect site concentrations of remifentanil in the observation group were significantly lower than those in the control group (P<0.05, P<0.01). There was no significant difference in BIS values at T1 and T2 between the two groups (bothP>0.05). There was no significant difference in operation time and anesthesia time between the two groups (bothP>0.05). The total amount of remifentanil in the observation group was significantly lower than that in the control group (P<0.01). There was no significant difference in the total amount of propofol between the two groups (P>0.05). CONCLUSIONS: Ear points embedding combined with propofol-remifentanil TCI could reduce the plasma and effect site concentrations of propofol and remifentanil and the total amount of remifentanil in elderly patients with extra-abdominal hernia surgery, and had the effect of assisting sedation and analgesia.

Salvianolate Blocks Apoptosis During Myocardial Infarction by Down Regulating miR-122-5p.

BACKGROUND: Recent studies have provided evidence that microRNAs (miRNAs), as a potential biomarker, were involved in the regulation of gene expression in Myocardial Infarction (MI). This study aimed to highlight the role of salvianolate on cardiomyocyte apoptosis in MI. METHODS: Anterior descending branch of left coronary artery was ligated to set up MI model. MiR- 122-5p mimic was transfected into cardiomyocytes and verified by quantitative real-time PCR (qRT-PCR). Cell viability and apoptotic rate were measured by MTT assay and flow cytometry together with TUNEL method, respectively. Changes in the expression of caspase-3, Bax and Bcl-2 were quantified by qRT-PCR and western blot. RESULTS: After treatment with salvianolate, miR-122-5p expression and caspases-3 activity significantly decreased in rat myocardial tissues. Furthermore, cardiomyocytes apoptosis rate was obviously suppressed while cell viability dramatically increased in H9C2 cardiomyocytes. However, overexpression of miR-122-5p reversed the aforementioned trends. Simultaneously, it could also mitigate the anti-apoptosis effect of salvianolate on the upregulation of caspases-3 viability and Bax expression and downregulation of Bcl-2 expression. CONCLUSION: Salvianolate induces the anti-apoptosis mechanism of cardiomyocytes via downregulation of miR-122-5p, Bax expression and caspases-3 as well as upregulation of Bcl-2 expression. In contrast, overexpression of miR-122-5p inhibits the effect of salvianolate.

Determination of asiatic acid in beagle dog plasma after oral administration of Centella asiatica extract by precolumn derivatization RP-HPLC.

A novel precolumn derivatization reversed-phase high-performance liquid chromatography (RP-HPLC) method with UV-vis detection for the quantitative determination of total concentration of asiatic acid (AA) in beagle dog plasma is described. AA was extracted with n-hexane-dichloromethane-2-propanol (20:10:1, v/v/v) from plasma, which had been hydrolyzed by acid and derivatized with p-Toluidine. Chromatographic separation was achieved on a C(18) column using gradient elution in a water-methanol system. Detection was set at UV wavelength of 248nm. A calibration curve ranging from 0.01 to 1.5microg/mL was shown to be linear, and the lower limit of quantification (LLOQ) was 0.01microg/mL. The intra- and inter-day precisions which were determined by three different concentrations (0.05, 0.2 and 0.8microg/mL) ranged from 4.4% to 13.1% and 4.6% to 14.2%, respectively. Mean extraction recoveries were no less than 65% for AA and ursolic acid (IS). Plasma samples containing asiatic acid were stable for 30 days at -20 degrees C. The method was successfully applied to a pharmacokinetic study in beagle dogs after oral administration of Centella asiatica extract, and the main pharmacokinetic parameters obtained were: T(1/2), 4.29h; T(max), 2.70h; C(max), 0.74microg/mL; AUC(0-t) and AUC(0-infinity), 3.74 and 3.82microgh/mL, respectively.