Salidroside alleviates oxidative stress and apoptosis via AMPK/Nrf2 pathway in DHT-induced human granulosa cell line KGN.

In the past few years, emerging evidence established persistent oxidative stress to be a key player in the pathogenesis of polycystic ovary syndrome (PCOS). Particularly, it damages the function of granulosa cells, and thus hinders the development of follicles. The present study aimed to explore and establish the protective effects of salidroside on dihydrotestosterone (DHT)-induced Granulosa-like tumor cell line (KGN), mediated via antioxidant mechanisms. The study assessed the positive effects of salidroside on DHT-induced apoptosis, reactive oxygen species (ROS) accumulation, damage of antioxidant capacity, and mitochondrial membrane potential depolarization. Interestingly, salidroside partly reversed DHT mediated effects, via stimulation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and the downstream antioxidant proteins heme oxygenase-1(HO-1) and quinine oxidoreductase 1(NQO1). Additionally, the knockdown of Nrf2 partly moderated the antioxidant and anti-apoptosis effects of salidroside in DHT-treated KGN cells. Mechanistically, AMP-activated protein kinase (AMPK) was identified to be the upstream signaling involved in salidroside-induced Nrf2 activation, as silencing of AMPK partly prevented the upregulation of Nrf2 and the downstream proteins HO-1 and NQO1. Altogether, the present study is the first to effectively demonstrate the inhibitory effect of salidroside on DHT-stimulated oxidative stress and apoptosis in KGN cells, which was dependent on Nrf2 activation that involved AMPK.

Prognosis of patients with newly diagnosed glioblastoma treated with molecularly targeted drugs combined with radiotherapy vs temozolomide monotherapy: A meta-analysis.

BACKGROUND: Glioblastoma (GB) is one of the most common malignancies with limited standard therapies such as surgery, radiotherapy (RT) plus temozolomide (TMZ). Molecularly targeted drugs have been investigated among various clinical trials and are expected to develop in the field of tumor therapy, while the efficacy remains uncertain due to limited previous results. Thus, we focus on the evaluation of molecularly targeted drugs to clarify its overall effectiveness in terms of treating newly diagnosed GB. METHODS: Electronic databases were searched for eligible literatures updated to April 2018. Randomized-controlled trials were included to assess the efficacy and safety of molecularly targeted drugs in patients with newly diagnosed GB. The main outcomes were further calculated including the following parameters: PFS (progression-free survival), OS (overall survival) as well as AEs (adverse events). All data were pooled along with their 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were evaluated quantitatively. RESULTS: The combination of molecularly targeted drugs with TMZ + RT had no significant effects on OS (OR = 0.96, 95%CI = 0.89-1.04, P = .36). Meanwhile, the combination regimen significantly improved the PFS of patients with newly diagnosed GB (OR = 0.86 ,95% CI 0.75-0.98, P = .02). The rate of AEs (OR = 1.68,95%CI = 1.44-1.97, P < .00001) was higher in patients receiving molecularly targeted drugs, which was comparable to the contemporary group. CONCLUSION: Longer PFS and a higher rate of AEs were observed with the addition of molecularly targeted drugs to standard chemoradiation in patients harboring newly diagnosed GB. Nevertheless, compared with the control arm, the regimen did not significantly prolong OS.

Antioxidant activities and polyphenol content of Morus alba leaf extracts collected from varying regions.

Morus alba leaf (MAL), also known as Mori folium when used as a herbal medicine, has traditionally been used in Chinese medicine to treat diabetes, protect the liver and lower blood pressure. In the present study, MAL was collected from various regions in Korea and the antioxidant activity, total polyphenol contents and main flavonoid contents was investigated. MAL were collected from various areas in Korea and extracted with methanol. The total polyphenol contents were evaluated based on the Folin-Ciocalteu method using a spectrophotometer. The antioxidant activities were determined by a 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay method. The identification and quantification of three main polyphenol constituents was performed using high-performance liquid chromatography/diode array detection analysis. The total polyphenol contents of the MAL extracts varied between 23.2 and 55.4 mg gallic acid equivalent/g. The radical scavenging activity (SC50) of the MAL extracts ranged between 584 and 139 µg/ml. Three flavonol compounds (rutin, isoquercitrin and astragalin) were identified as main polyphenol constituents. These contents varied from 0.68-12.7, 0.69-9.86 and 0.05-3.55 mg/g, respectively. The average of the total was 9.52 mg/g, which was similar to that of commercial MAL extracts (10.58 mg/g). Among the three flavonol compounds, isoquercitrin showed the highest content (5.68 mg/g) followed by rutin (3.1 mg/g) and astragalin (2.4 mg/g). In the present study, the radical scavenging activity, polyphenol content and flavonol content of MAL were significantly different according to growing area. These three flavonol compounds were identified as main constituents of MAL in this study, and are known to have various biological activities, as well as strong antioxidant activities. Therefore, the sum of these three flavonol compounds was indicated as a good marker for the quality control of Mori folium.

Antiplatelet and antithrombotic effect of Phyllostachys pubescens leaves and Mume Fructus combination.

BACKGROUND: Agents currently used for the treatment and prevention of thrombosis have a number of side effects. We conducted this study to develop antithrombotic agents from herbs that are used in food. METHODS: The 80% (v/v) ethanol extracts of Phyllostachys pubescens leaf (PL) and Mume Fructus (MF) and their combinations-2:1 (PM21), 1:1 (PM11), and 1:2 (PM12)-were evaluated on rat platelet aggregation induced by adenosine diphosphate (ADP) in vitro and on arteriovenous shunt thrombosis after 3 days of oral treatment in rats in vivo. RESULTS: At 100 µg/mL, PM21 and PM11 inhibited in vitro ADP-induced aggregation by 44.0 ± 4.3% and 30.0 ± 3.2%, respectively, whereas PL, MF, and PM12 weakly or scarcely inhibited ADP-induced aggregation by 3.9 ± 3.2%, 13.0 ± 2.7%, and 5.2 ± 1.3%, respectively. The IC50 values of PM21 on ADP-, collagen-, and thrombin-induced platelet aggregations were 135.6 ± 7.4 µg/mL, 142.7 ± 5.8 µg/mL, and 186.5 ± 9.7 µg/mL, respectively. In an in vivo rat arteriovenous-shunt thrombosis model, thrombus weight was significantly decreased after the oral administration of 400 mg/kg PL (27.8 ± 3.0%, p < 0.01) or MF (35.2 ± 2.1%, p < 0.01), and with a good accord to the in vitro results, the combination of PL and MF in the ratio of 2:1, PM21 (60.9 ± 1.2%, p < 0.001), showed a superior antithrombotic effect to those of individual extracts. At dosages of 200 mg/kg, 100 mg/kg, and 50 mg/kg, PM21 dose-dependently decreased thrombosis weight (ED50, 314 mg/kg). CONCLUSION: These results suggest that combination preparations of PL and MF, especially their 2:1 combination, can increase antiplatelet and antithromboticeffects more than PL and MF alone, offering evidence for a potential novel combination antithrombotic therapy.

Cytotoxic lignans from the stem bark of Magnolia officinalis.

Three new lignans, 4'-methoxymagndialdehyde ( 1), 4'-methoxymagnaldehyde B ( 2), and 4'-methoxymagnaldehyde E ( 3), were isolated from hexane- and EtOAc-soluble fractions of the stem bark of Magnolia officinalis, together with eight known compounds ( 4- 11). The structures of compounds 1- 3 were determined on the basis of spectroscopic and physicochemical data analysis. Compounds 1- 11 were tested in vitro for their cytotoxic activity against the K562, HeLa, and A549 cancer cell lines. Among the compounds tested, compound 1 showed the most potent cytotoxic activity against these cancer cell lines, with IC50 values of 3.9, 1.5, and 3.7 microg/mL, respectively.