Antioxidant and anticancer potentials of edible flowers: where do we stand?

Edible flowers are attracting special therapeutic attention and their administration is on the rise. Edible flowers play pivotal modulatory roles on oxidative stress and related interconnected apoptotic/inflammatory pathways toward the treatment of cancer. In this review, we highlighted the phytochemical content and therapeutic applications of edible flowers, as well as their modulatory potential on the oxidative stress pathways and apoptotic/inflammatory mediators, resulting in anticancer effects. Edible flowers are promising sources of phytochemicals (e.g., phenolic compounds, carotenoids, terpenoids) with several therapeutic effects. They possess anti-inflammatory, anti-diabetic, anti-microbial, anti-depressant, anxiolytic, anti-obesity, cardioprotective, and neuroprotective effects. Edible flowers potentially modulate oxidative stress by targeting erythroid nuclear transcription factor-2/extracellular signal-regulated kinase/mitogen-activated protein kinase (Nrf2/ERK/MAPK), reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA) and antioxidant response elements (AREs). As the interconnected pathways to oxidative stress, inflammatory mediators, including tumor necrosis factor (TNF)-α, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukins (ILs) as well as apoptotic pathways such as Bcl-2-associated X protein (Bax), Bcl-2, caspase and cytochrome C are critical targets of edible flowers in combating cancer. In this regard, edible flowers could play promising anticancer effects by targeting oxidative stress and downstream dysregulated pathways.

Hepatotoxic evaluation of toosendanin via biomarker quantification and pathway mapping of large-scale chemical proteomics.

Drug-induced liver injury (DILI) is a major side effect, sometimes can't be exactly evaluated by current approaches partly as the covalent modification of drug or its reactive metabolites (RMs) with proteins is a possible reason. In this study, we developed a rapid, sensitive, and specific analytical method to assess the hepatotoxicity induced by drug covalently modified proteins based on the quantification of the modified amino acids using toosendanin (TSN), a hepatotoxic chemical, as an example. TSN RM-protein adducts both in rat liver and blood showed good correlation with the severity of hepatotoxicity. Thus, TSN RM-protein adducts in serum can potentially serve as minimally invasive biomarkers of hepatotoxicity. Meanwhile, large-scale chemical proteomics analysis showed that at least 84 proteins were modified by TSN RMs in rat liver, and the bioinformatics analysis revealed that TSN might induce hepatotoxicity through multi-target protein-protein interaction especially involved in energy metabolism. These findings suggest that our approach may serve as a valuable tool to evaluate DILI and investigate the possible mechanism, especially for complex compounds.

Identification of Anti-Inflammatory and Anti-Proliferative Neolignanamides from Warburgia ugandensis Employing Multi-Target Affinity Ultrafiltration and LC-MS.

Previous reports have illustrated that the incidence and mortality of cancer are increasing year by year worldwide. In addition, the occurrence, development, recurrence and metastasis of cancer are closely related to inflammation, which is a kind of defensive response of human body to various stimuli. As an important medicinal plant in Africa, Warburgia ugandensis has been reported to have certain anti-inflammatory and anti-proliferative activities, but its specific components and mechanisms of action remain elusive. To tackle this challenge, affinity ultrafiltration with drug targets of interest coupled to high-performance liquid chromatography-mass spectrometry (AUF-HPLC-MS/MS) could be utilized to quickly screen out bioactive constituents as ligands against target enzymes from complex extracts of this plant. AUF-HPLC-MS/MS with four drug targets, i.e., cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), topoisomerase I (Top I) and topoisomerase II (Top II) were used to rapidly screen and characterize the anti-inflammatory and anti-proliferative natural ligands from W. ugandensis, and the resulting potential active compounds as ligands with specific binding affinity to COX-2, 5-LOX, Top I and Top II, were isolated with modern separation and purification techniques and identified with spectroscopic method like NMR, and then their antiinflammatory and anti-proliferative activities were tested to verify the screening results from AUF-HPLC-MS/MS. Compounds 1 and 2, which screened out and identified from W. ugandensis showed remarkable binding affinity to COX-2, 5-LOX, Top I and Top II with AUF-HPLC-MS/MS. In addition, 1 new compound (compound 3), together with 5 known compounds were also isolated and identified from W. ugandensis. The structure of compound 3 was elucidated by extensive 1D, 2D NMR data and UPLC-QTOF-MS/MS. Furthermore, compounds 1 and 2 were further proved to possess both anti-inflammatory and anti-proliferative activities which are in good agreement with the screening results using AUF-HPLC-MS/MS. This work showcased an efficient method for quickly screening out bioactive components with anti-inflammatory and anti-proliferative activity from complex medicinal plant extracts using AUF-HPLC-MS/MS with target enzymes of interest, and also demonstrated that neolignanamides (compounds 1 and 2) from W. ugandensis would be the active components responsible for its anti-inflammatory and anti-proliferative activity with the potential to treat cancer and inflammation.

Contribution of salidroside to the relieve of symptom and sign in the early acute stage of osteoarthritis in rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Rhodiola has been used to treat cough, hemoptysis, fever, pain, bruise and other symptoms which are related to injury and inflammation over a thousand years in traditional Tibetan medicine. Salidroside (p-hydroxyphenethyl-ß-D-glucoside) is one of the most potent bioactive ingredients of the genus Rhodiola. AIM OF STUDY: The present study aimed to explore whether salidroside could alleviate the clinical symptom and sign in the early acute stage of osteoarthritis (OA) in monosodium iodoacetate (MIA) rat model, and its underlying mechanisms. MATERIALS AND METHODS: Osteoarthritis (OA) was induced in rat knees by intra-articular injection of MIA; simultaneously salidroside was administered by intravenous injection. Pain behaviors were evaluated by knee-bend test, hind limb weight-bearing asymmetry and hind paw mechanical withdrawal threshold. The joint swelling was determined by the difference of knee joint diameter. Inflammatory exudates in synovial fluid were evaluated by leukocyte counting and protein content. Cytokines, chemokines, reactive oxygen species (ROS) and reactive nitrogen species (RNS) markers were determined by Enzyme-linked immunosorbent assay (ELISA) and colorimetric assay in synovial fluid. Pro-inflammatory gene expressions in synovial tissue were detected by quantitative real time RT-PCR (qRT-PCR). Nuclear factor kappa-B (NF-κB) DNA binding assay and western blot were used to determine NF-κB activation and ROS marker protein expression in synovial tissue. Glycosaminoglycan (GAG) content in the cartilage was measured by dimethylmethylene blue method. Hematoxylin and eosin (H&E), Safranin O-fast green and a modified Mankin grading system were used to evaluate the histology of articular cartilage. RESULTS: Salidroside could alleviate pain and joint swelling in the early acute stage of OA in rat model, reduced the number of leukocytes, total protein content, proinflammatory mediators and ROS/RNS markers in synovial fluid, down regulated the expression of proinflammatory genes in synovium, inhibited the activation of NF- κ B and oxidative stress response in synovium, promoted the synthesis of cartilage GAG, prevented the loss of proteoglycan and chondrocyte degeneration. CONCLUSIONS: Salidroside effectively alleviates acute symptom and sign of OA in rat model by its anti-inflammatory and antioxidant affects to inhibit synovial inflammation, which provides a new strategy to prevent the onset and progression of OA.

Efficacy and safety of vitamin C for atrial fibrillation after cardiac surgery: A meta-analysis with trial sequential analysis of randomized controlled trials.

OBJECTIVES: Antioxidant supplement is an option in preventing postoperative atrial fibrillation (AF) after cardiac surgery. However, the benefits and adverse effects of vitamin C have not been well assessed. We aimed to systematically evaluate the efficacy and safety of vitamin C in preventing postoperative AF in adult patients after cardiac surgery. METHODS: PubMed, EMBASE, and the Cochrane library databases from inception to September 2016 were searched. Randomized controlled trials (RCTs) that evaluated the efficacy and safety of vitamin C in preventing postoperative AF in adult patients after cardiac surgery were identified. The primary outcome was the incidence of postoperative AF. Secondary outcomes included the length of intensive care unit (ICU) stay, length of hospital stay, and stroke events. RESULTS: Eight RCTs incorporating 1060 patients were included. Compared with placebo group, vitamin C treatment was associated with a substantial reduction in postoperative AF (OR, 0.47; 95% CI, 0.36-0.62; evidence rank: moderate), with no significant heterogeneity (I2 44%; P = 0.09). Trial sequential analysis showed that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit, establishing sufficient and conclusive evidence. In addition, vitamin C administration was not associated with any length of stay, including in the ICU (evidence rank: low) and hospital (evidence rank: low), respectively. CONCLUSIONS: Short-term treatment with vitamin C is safe, and may reduce the incidence of postoperative AF after cardiac surgery. Future studies as well as more high quality RCTs are still warranted to confirm the effects of different durations of vitamin C on cardiac surgery.

[Research advances in the role of vitamin D in autism spectrum disorders].

The etiology and pathogenic mechanism of autism spectrum disorders (ASD) are still unclear. The relationship between vitamin D and ASD has drawn attention in recent years due to common vitamin D deficiency in children with ASD. This article reviews the peripheral blood levels of vitamin D in children with ASD, the possible reasons for hypovitamin D and its possible roles in the etiology of ASD and the efficacy of vitamin D supplementation in ASD.

[The effect of ω-3 fatty acid supplementation in parenteral nutrition on the outcome of patients with sepsis: a systematic review and meta-analysis].

OBJECTIVE: To determine whether the supplementation of ω-3 polyunsaturated fatty acids in parenteral nutrition (PN) confers treatment benefits to outcomes of septic patients. METHODS: The databases of MEDLINE, EMBASE, Cochrane central register of controlled trials, the CNKI and the Wanfang biomedicine were searched to identify prospective randomized controlled trials (RCTs) which compared the ω-3 polyunsaturated fatty acids supplemented with the standard PN on outcomes of adult patients with sepsis from January 1996 to June 2013. The methodological quality of the included studies was evaluated, and the Cochrane Collaboration RevMan 5.0 was used for data analysis. RESULTS: A total of 12 studies enrolling 721 patients were included. Significant reduction in 28-day mortality [relative risk (RR) 0.77, 95% confidence interval (95%CI) 0.59 to 0.99, P=0.04], short intensive care unit [ICU, weighted mean difference (WMD)=-3.10, 95%CI -5.98 to -0.21, P=0.04] and hospital length of stay (WMD=-3.12, 95%CI -4.65 to -1.60, P<0.000 1) were observed in patients receiving ω-3 polyunsaturated fatty acids supplemented PN. There was no differences in days of mechanical ventilation between patients with or without adding ω-3 polyunsaturated fatty acids in PN (WMD=1.33, 95%CI -5.09 to 7.75, P=0.69). CONCLUSIONS: Meta-analysis results demonstrated that PN supplemented with ω-3 polyunsaturated fatty acids was beneficial in improving the outcomes of patients with sepsis. However, this conclusion must be interpreted with caution due to the low quality of the enrolled trials.

Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells.

Recently, salidroside (p-hydroxyphenethyl-beta-d-glucoside) has been identified as one of the most potent compounds isolated from plants of the Rhodiola genus used widely in traditional Chinese medicine, but pharmacokinetic data on the compound are unavailable. We were the first to report the cytotoxic effects of salidroside on cancer cell lines derived from different tissues, and we found that human breast cancer MDA-MB-231 cells (estrogen receptor negative) were sensitive to the inhibitory action of low-concentration salidroside. To further investigate the cytotoxic effects of salidroside on breast cancer cells and reveal possible ER-related differences in response to salidroside, we used MDA-MB-231 cells and MCF-7 cells (estrogen receptor-positive) as models to study possible molecular mechanisms; we evaluated the effects of salidroside on cell growth characteristics, such as proliferation, cell cycle duration, and apoptosis, and on the expression of apoptosis-related molecules. Our results demonstrated for the first time that salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells and may be a promising candidate for breast cancer treatment.