Characterization of Vasorelaxant Principles from the Needles of Pinus morrisonicola Hayata.

Pinus morrisonicola Hayata, usually called Taiwan five-leaf pine (5LP), is an endemic species in Taiwan and is traditionally used to relieve hypertension symptoms and improve cardiovascular function. In this study, the needle extract of 5LP was fractionated and analyzed by LC/MS/MS to search for possible antihypertensive candidates. In addition, bioassay-guided purification of the bioactive components was performed by Ca2+ fluorescent signal (Fluo 4-AM) assays. Two dihydrobenzofuran lignans, pinumorrisonide A (1) and icariside E4 (2), and one acylated flavonoid glycoside, kaempferol 3-O-α-(6‴-p-coumaroylglucosyl-ß-1,4-rhamnoside) (3) were characterized from the active fractions. The structure of a new compound 1 was established on the basis of 2D NMR spectroscopic and mass spectrometric analyses, and the known compounds 2 and 3 were identified by comparison of their physical and spectroscopic data with those reported in the literature. The purified compounds 1-3 exhibited significant inhibition of Ca2+ fluorescence with IC50 values of 0.71, 0.36, and 0.20 mM, respectively. A mechanism study showed that these compounds showed vasorelaxant effects by blocking the voltage-operated Ca2+ channel (VOCC) and inhibiting Ca2+ influx to the cytoplasmic. These results suggested that 5LP and the three characterized components could be promising antihypertensive candidates for the use as VOCC blockers.

Enzalutamide Prior to Radium-223 Is Associated with Better Overall Survival in Metastatic Castration-Resistant Prostate Cancer Patients Compared to Abiraterone-A Retrospective Study.

Metastatic castration-resistant prostate cancer (mCRPC) is a progressive stage of prostate cancer that often spreads to the bone. Radium-223, a bone-targeting radiopharmaceutical, has been shown to improve the overall survival in mCRPC in patients without visceral metastasis. However, the impact of prior systemic therapy on the treatment outcome of mCRPC patients receiving radium-223 remains unclear. This study aimed to investigate the optimal choice of systemic therapy before radium-223 in mCRPC patients. The study included 41 mCRPC patients who received radium-223 therapy, with 22 receiving prior enzalutamide and 19 receiving prior abiraterone. The results showed that the median overall survival was significantly longer in the enzalutamide group than in the abiraterone group (25.1 months vs. 14.8 months, p = 0.049). Moreover, the number of patients requiring blood transfusion was higher in the abiraterone group than in the enzalutamide group (9.1% vs. 26.3%, p = 0.16). The study also found that the number of doses of Radium-223 received was significantly associated with overall survival (≥5 vs. <5, HR 0.028, 95%CI 0.003-0.231, p = 0.001). Our study provides insights into the optimal treatment choice for mCRPC prior to radium-223, indicating that enzalutamide prior to radium-223 administration may have better outcomes compared to abiraterone in mCRPC patients without visceral metastasis.

Safety of image-guided radiotherapy in definitive radiotherapy for localized prostate cancer: a population-based analysis.

OBJECTIVES: Image-guided radiotherapy (IGRT) is a recommended advanced radiation technique that is associated with fewer acute and chronic toxicities. However, one Phase III trial showed worse overall survival in the IGRT arm. The purpose of this observational study is to evaluate the impact of IGRT on overall survival. METHODS: We used the Taiwan Cancer Registry Database to enroll cT1-4N0M0 prostate cancer patients who received definitive radiotherapy between 2011 and 2015. We used inverse probability treatment weighting (IPW) to construct balanced IGRT and non-IGRT groups. We compared the overall survival of those in the IGRT and non-IGRT groups. Supplementary analyses (SA) were performed with alternative covariates in propensity score (PS) models and PS approaches. The incidence rates of prostate cancer mortality (IPCM), other cancer mortality (IOCM), and cardiovascular mortality (ICVM) were also evaluated. RESULTS: There were 360 patients in the IGRT arm and 476 patients in the non-IGRT arm. The median follow-up time was 50 months. The 5-year overall survival was 88% in the IGRT arm and 86% in the non-IGRT arm (adjusted hazard ratio [HR] of death = 0.93; 95% CI, 0.61-1.45; p = 0.77). The SA also showed no significant differences in the overall survival between those in the IGRT and non-IGRT arms. Both groups did not significantly differ in terms of IPCM, IOCM, and ICVM. CONCLUSIONS: The overall survival of localized prostate cancer patients who underwent IGRT was not inferior to those who did not. ADVANCES IN KNOWLEDGE: We demonstrated that the overall survival for prostate cancer patients with IGRT was not worse than those who did not undergo IGRT; this important outcome comparison has not been previously examined in the general population.

Ethylene signaling modulates contents of catechin and ability of antioxidant in Camellia sinensis.

BACKGROUND: Tea is one of the most popular beverages in the world. There are many secondary metabolites can be found in tea such as anthocyanins, proanthocyanidins, flavonols and catechins. These secondary metabolites in plants are proved to act protective components for human health effect. Plant hormone ethylene is considered to have an important role in regulation of plant development and signal transduction. This study evaluated the effect of ethylene signaling regulation in phenolic compounds in tea plants. The ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) enhanced contents of total catechin in treated oolong tea seedlings. RESULTS: The degree of epigallocatechin and epicatechin galloylation was increased after ACC treatment in oolong tea seedlings by high performance liquid chromatography determination. The contents of anthocyanins, flavonoids, and total polyphenol were higher after ACC treatment in comparison with control. Antioxidant enzyme such as catalase, superoxide dismutase, and total peroxidase decreased their antioxidant activities after ACC treatment, yet the activity of ascorbate peroxidase is increased. The ability of oxygen radical absorption and 2,2-diphenyl-1-picrylhydrazyl was used to evaluate the antioxidant activity, which was enhanced by ACC treatment. CONCLUSIONS: Taken together the results of this study demonstrate that the ethylene signaling is involved in modulation of secondary metabolites accumulation and antioxidant ability that to enhance the benefit of human health in tea products.

Synergic effect of curcumin and its structural analogue (Monoacetylcurcumin) on anti-influenza virus infection.

Curcumin (Cur), a polyphenolic compound extracted from spice and common food colourant turmeric, contains versatile bio-activities. Monoacetylcurcumin (MAC), a structural analogue of Cur, differs from Cur by acetyl modification, but retains enone groups. Comparative analysis revealed MAC effectively inhibited influenza virus infection (IAV) to a similar extent as, if not superior to, curcumin. Both compounds mildly reduced viral NA activity. Surprisingly, unlike Cur, the MAC inhibition of IAV did not occur through the blocking of HA activity. However, MAC strongly dampened Akt phosphorylation, the prerequisite signalling for efficient IAV propagation. A much stronger inhibition effect on IAV infection was observed when MAC treatment was in combination with Cur. Collectively, MAC demonstrated clear antiviral activity, and likely inhibited IAV via multiple mechanisms that were not identical to Cur. Importantly, Cur and MAC in combination synergistically inhibited IAV infection.

In vitro assay to estimate tea astringency via observing flotation of artificial oil bodies sheltered by caleosin fused with histatin 3.

Astringency, a sensory characteristic of food and beverages rich in polyphenols, mainly results from the formation of complexes between polyphenols and salivary proteins, causing a reduction of the lubricating properties of saliva. To develop an in vitro assay to estimate the astringency of oolong tea infusion, artificial oil bodies were constituted with sesame oil sheltered by a modified caleosin fused with histatin 3, one of the human salivary small peptides. Aggregation of artificial oil bodies was induced when they were mixed with oolong tea infusion or its major polyphenolic compound, (-)-epigallocatechin gallate (EGCG) of 100µM as observed in light microscopy. The aggregated artificial oil bodies gradually floated on top of the solution and formed a visible milky layer whose thickness was in proportion to the concentrations of tea infusion. This assay system was applied to test four different oolong tea infusions with sensory astringency corresponding to their EGCG contents. The result showed that relative astringency of the four tea infusions was correlated to the thickness of floated artificial oil bodies, and could be estimated according to the standard curve generated by simultaneously observing a serial dilution of the tea infusion with the highest astringency.

Antibacterial and laxative activities of strictinin isolated from Pu'er tea (Camellia sinensis).

Strictinin, the major phenolic compound in Pu'er teas produced from young leaves and buds of wild trees, was isolated to evaluate its antibacterial and laxative activities. The minimum inhibitory concentrations of strictinin against Propionibacterium acnes and Staphylococcus epidermidis were determined as 250 µM and 2000 µM, respectively, apparently higher than those of several antibiotics commonly used for bacterial infections. The additive and synergistic effects on the inhibitory activities of strictinin combined with other commercial antibiotics were observed in two bacteria tested in this study via the analysis of fractional inhibitory concentrations. Laxative activity was observed on defecation of the rats fed with strictinin. Further analysis showed that the laxative effect of strictinin was presumably caused by accelerating small intestinal transit, instead of enhancing gastric emptying, increasing food intake, or inducing diarrhea in the rats. Taken together with the antiviral activities demonstrated previously, it is suggested that strictinin is one of the active ingredients responsible for the antiviral, antibacterial, and laxative effects of wild Pu'er tea, and has the potential to be developed as a mild natural substitute for antibiotics and laxatives.

Significant elevation of antiviral activity of strictinin from Pu'er tea after thermal degradation to ellagic acid and gallic acid.

Compared with abundant catechins, strictinin is a minor constituent in teas and has been demonstrated to possess inhibitory potency on influenza virus. In this study, strictinin was found as the major phenolic compound in Pu'er teas produced from leaves and buds of wild trees. Due to its thermal instability, strictinin, in tea infusion or in an isolated form, was completely decomposed to ellagic acid and gallic acid after being autoclaved for 7 minutes. A plaque reduction assay was employed to compare the relative inhibitory potency between strictinin and its thermally degraded products against human influenza virus A/Puerto Rico/8/34. The results showed that the antiviral activity of ellagic acid regardless of the presence or absence of gallic acid was significantly higher than that of strictinin. Thermal degradation of strictinin to ellagic acid and gallic acid seems to be beneficial for the preparation of Pu'er teas in terms of enhancing antiviral activity.

Catechin content and the degree of its galloylation in oolong tea are inversely correlated with cultivation altitude.

The taste quality of oolong tea generated from leaves of Camellia sinensis L. cultivated in the same mountain area is positively correlated to the cultivation altitude, partly due to the inverse correlation with the astringency of the tea infusion. The astringency of oolong tea mostly results from the presence of polyphenolic compounds, mainly catechins and their derivatives. Four catechins, (-)-epicatechin (EC) and (-)-epigallocatechin (EGC) together with their gallate derivatives (with relatively high astringency), (-)-EC gallate (ECG) and (-)-EGC gallate (EGCG), were detected as major compounds in oolong tea. The degrees of catechin galloylation, designated as ECG/(EC + ECG) and EGCG/(EGC + EGCG), in both oolong tea infusions and their fresh tea leaves, were found to be inversely correlated to the cultivation altitude at 200 m, 800 m, and 1300 m. A similar inverse correlation was observed when seven more oolong tea infusions and seven more fresh leaves harvested at altitude ranging from 170 m to 1600 m were recruited for the analyses. Moreover, catechin contents in oolong tea infusions were also found to be inversely correlated to the cultivation altitude. It is proposed that catechin content and the degree of its galloylation account for, at least partly, the inverse correlation between the astringency of oolong tea and the cultivation altitude.