Anti-hypertensive and composition as well as pharmacokinetics and tissues distribution of active ingredients from Alpinia zerumbet.

Alpinia zerumbet is a food flavor additive and a traditional medicine herb around the world. Several studies have reported that A. zerumbet has excellent effects on a variety of cardiovascular diseases, but its potential hypertensive applications, and pharmacokinetic features of main active substances have not been fully investigated. The mechanism of anti-hypertension with ethyl acetate extracts of A. zerumbet fruits (AZEAE) was evaluated by L-NNA-induced hypertensive rats and L-NAME-injured human umbilical vein endothelial cells (HUVECs). Blood pressure, echocardiographic cardiac index and H&E staining were used to preliminary evaluate the antihypertensive effect of AZEAE, the levels of TNF-α, IL-6, and IL-1ß were evaluated by ELISA, and the proteins expression of IL-1ß, IL-18, AGTR1, VCAM, iNOS, EDN1 and eNOS were also evaluated. In addition, isolation, identification, and activity screening of bioactive compounds were carried ou. Next, pharmacokinetics and tissues distribution of dihydro-5,6-dehydrokavain (DDK) in vivo were measured, and preliminary absorption mechanism was conducted with Caco-2 cell monolayers. AZEAE remarkably enhanced the state of hypertensive rats. Twelve compounds were isolated and identified, and five compounds were isolated from this plant for the first time. The isolated compounds also exhibited good resistance against injury of HUVECs. Moreover, pharmacokinetics and Caco-2 cell monolayers demonstrated AZEAE had better absorption capacity than DDK, and DDK exhibited differences in tissues distribution and gender difference. This study was the first to assess the potential hypertensive applications of A. zerumbet in vivo and vitro, and the first direct and concise study of the in vivo behavior of DDK and AZEAE.

Long non­coding RNA SNHG1 promotes breast cancer progression by regulation of LMO4.

Long non­coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) was reported to be a critical regulator of tumorigenesis and is frequently deregulated in several cancer types. However, the exact mechanism by which SNHG1 contributes to breast cancer progression has not been fully elucidated. The identification of the molecular mechanism of SNHG1 is important for understanding the development of breast cancer and for improving the prognosis of the patients with this disease. In the present study, increased expression levels of SNHG1 were noted in breast cancer tumors following analysis of differentially expressed lncRNAs between 1,063 tumor and 102 normal tissues derived from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA­BRCA) dataset. This finding was further validated using 50 pairs of normal and tumor tissues that were collected from patients with breast cancer. Notably, SNHG1 expression was significantly correlated with estrogen receptor (ER)/progesterone receptor (PR) negative status (ER­/PR­) and advanced clinical stage in breast cancer tissues. Knockdown of SNHG1 led to cell growth arrest, cell cycle redistribution and cell migration inhibition of breast cancer cells. The miRDB database predicted that miR­573 interacts with SNHG1. RT­PCR confirmed the negative regulation of miR­573 levels by SNHG1 in breast cancer cells and the Dual­luciferase reporter assay confirmed their complementary binding. The repression of miR­573 by SNGH1 decreased LIM domain only 4 (LMO4) mRNA and protein expression levels in the breast cancer cell lines tested and induced the expression of cyclin D1 and cyclin E. In vitro experiments indicated that LMO4 overexpression could reverse siSNHG1­induced cell growth arrest, cell cycle redistribution and inhibition of cell migration in breast cancer cells. Moreover, the tumor xenograft model indicated that SNHG1 knockdown inhibited MDA­MB­231 growth in vivo and LMO4 overexpression reversed the tumor growth inhibition induced by SNHG1 knockdown. The present study demonstrated that SNHG1 acts as a novel oncogene in breast cancer via the SNHG/miR­573/LMO4 axis and that it could be a promising therapeutic target for patients with breast cancer.

Interleukin-4 signalling pathway underlies the anxiolytic effect induced by 3-deoxyadenosine.

RATIONALE: Converging evidence suggests that neuroimmunity plays an important role in the pathophysiology of anxiety. Interleukin (IL)-4 is a key cytokine regulating neuroimmune functions in the central nervous system. More efficient anxiolytics with neuro-immune mechanisms are urgently needed. OBJECTIVE: To determine whether 3'-deoxyadenosine (3'-dA) exerts an anxiolytic effect and to examine the role of IL-4 in the anxiolytic effect of 3'-dA in mice. METHODS: We investigated the effects of 3'-dA on anxiety-like behaviors using elevated plus maze (EPM) or light-dark box (LDB) tests after 45 min or 5 days of treatment. Expression of IL-4, IL-10, IL-1ß, TNF-α, and IL-6 in the prefrontal cortex (PFC) was detected by Western blot and/or double immunostaining. Intracerebroventricular injection of RIL-4Rα (an IL-4-specific inhibitor) and intraperitoneal injection of 3'-dA or imipramine were co-administered, followed by EPM test. RESULTS: 3'-dA exhibited a stronger and faster anxiolytic effect than imipramine in behavioral tests. Furthermore, 3'-dA enhanced IL-4 expression after 45 min or 5 days, TNF-α and IL-1ß expression decreased significantly after a 5-day treatment with 3'-dA, and IL-10 expression increased after a 5-day treatment with 3'-dA or imipramine in the PFC. IL-4 was expressed in neurons and in some astrocytes and microglia. IL-4 expression showed a strong positive correlation with reduced anxiety behaviors. RIL-4Rα completely blocked the anxiolytic effects induced by 3'-dA and imipramine. CONCLUSIONS: This study identifies a novel and common anxiolytic IL-4 signaling pathway and provides an innovative drug with a novel neuro-immune mechanism for treating anxiety disorder.

Puerarin Induces Hepatocellular Carcinoma Cell Apoptosis Modulated by MAPK Signaling Pathways in a Dose-dependent Manner.

BACKGROUND/AIM: Puerarin possesses a battery of therapeutic values in diverse disorders, including pro-apoptotic actions in multiple cancers. Herein, we investigated the effects of puerarin on hepatocellular carcinoma (HCC) in vitro. MATERIALS AND METHODS: MTT and flow cytometry were carried out to evaluate the viability and apoptosis of SMMC-7721 HCC cells in the presence of different concentrations of puerarin. Moreover, expression levels, as well as phosphorylation status of several canonical components in mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase 1/2 (ERK1/2), c- Jun N-terminal kinase (JNK), p38, were measured by reverse transcription and quantitative real-time polymerase chain reaction (RT-PCR) and western blot analysis at indicated time intervals. RESULTS: Puerarin inhibited proliferation of SMMC-7721 cells and promoted their apoptosis in a dose- and time-dependent fashion (p<0.05). Both the expression and phosphorylation levels of MAPK proteins were dramatically increased on puerarin treatment. CONCLUSION: Puerarin could be employed as a potential anti-carcinogen that exhibits pro-apoptotic effects on HCC cells, in a dose- and time-dependent manner, with emphasis on MAPK pathways whose initiation may contribute to this process.

Efficacy and safety of tenofovir disoproxil fumarate in preventing vertical transmission of hepatitis B in pregnancies with high viral load.

This study was a meta-analysis of the literature on the efficacy and safety of tenofovir disoproxil fumarate (TDF) in preventing vertical transmission of hepatitis B in pregnancies with high viral load. Four observational studies and one randomized controlled trial involving 585 pregnant women and 595 newborns were included in the meta-analysis. TDF was more effective than the placebo in reducing vertical transmission in HBeAg-positive chronic hepatitis B (CHB) pregnancies with high serum HBV-DNA levels (OR = 0.21, 95% CI = 0.07-0.61) at 4-12 months, infant HBV DNA seropositivity at delivery (OR = 0.16, 95% CI = 0.07-0.37), and a severe flair in maternal alanine aminotransferase (ALT) levels (OR = 0.43, 95% CI = 0.19-0.95) during pregnancy. In addition, TDF showed more improvement in HBV DNA suppression at delivery (OR = 254.46, 95% CI = 28.39-2280.79). No significant differences were found in HBeAg seroconversion or ALT normalization; or in rates of cesarean section, emergent cesarean section, postpartum hemorrhage, prematurity, congenital malformations, or infant death. However, TDF induced more drug-related adverse events (OR = 2.33, 95% CI = 1.39-3.89) and elevated creatine kinase (CK) (OR = 9.56, 95% CI = 1.17-78.09) than in controls. The available evidence suggests that TDF is effective and safe in preventing vertical transmission of hepatitis B in pregnancies exhibiting a high viral load.