Green tea extract for treatment of cancers: A systematic review protocol.

BACKGROUND: Previous clinical studies suggested that green tea extract (GTE) may benefit patients with a variety of cancers. However, its efficacy is still inconclusive. Thus, the objective of this study will systematically collate the clinical studies testing its efficacy and safety for cancers. METHODS: We will perform a systematic review of clinical studies assessing the efficacy of GTE in variety of cancers. We will search Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDILINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), and Chinese Biomedical Literature Database (CBM) using a comprehensive strategy. We will also screen the reference lists of relevant studies to identify any additional studies for potential inclusion. All databases will be searched up to February 1, 2019. All eligible case-control studies and randomized controlled trials will be included in this study. Two independent authors will review all searched literature. Upon inclusion of trials, we will extract data by using a predefined standardized form. The risk of bias assessment will be evaluated by using Cochrane risk of bias tool. We will use RevMan 5.3 software to pool the data and carry out meta-analysis. RESULTS: The primary outcome includes overall response rate. The secondary outcomes comprise of overall survival, progression-free survival, the disease control rate, and any adverse events. CONCLUSIONS: The results of this study will contribute to the understanding of the efficacy of GTE in the setting of cancers and promote future research of GTE in patients with cancers. DISSEMINATION AND ETHICS: The results of this systematic review are expected to be published through peer-reviewed journals. This study does not need ethic approval, because it does not utilize individual patient data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019125111.

Mangiferin Accelerates Glycolysis and Enhances Mitochondrial Bioenergetics.

One of the main causes of hyperglycemia is inefficient or impaired glucose utilization by skeletal muscle, which can be exacerbated by chronic high caloric intake. Previously, we identified a natural compound, mangiferin (MGF) that improved glucose utilization in high fat diet (HFD)-induced insulin resistant mice. To further identify the molecular mechanisms of MGF action on glucose metabolism, we conducted targeted metabolomics and transcriptomics studies of glycolyic and mitochondrial bioenergetics pathways in skeletal muscle. These data revealed that MGF increased glycolytic metabolites that were further augmented as glycolysis proceeded from the early to the late steps. Consistent with an MGF-stimulation of glycolytic flux there was a concomitant increase in the expression of enzymes catalyzing glycolysis. MGF also increased important metabolites in the tricarboxylic acid (TCA) cycle, such as α-ketoglutarate and fumarate. Interestingly however, there was a reduction in succinate, a metabolite that also feeds into the electron transport chain to produce energy. MGF increased succinate clearance by enhancing the expression and activity of succinate dehydrogenase, leading to increased ATP production. At the transcriptional level, MGF induced mRNAs of mitochondrial genes and their transcriptional factors. Together, these data suggest that MGF upregulates mitochondrial oxidative capacity that likely drives the acceleration of glycolysis flux.

Effect of docosahexaenoic acid on traumatic brain injury in rats.

The present study aimed to investigate the protective effects of docosahexaenoic acid (DHA) on traumatic brain injury (TBI) in rats. A model of TBI was induced by lateral fluid percussion injury in adult rats and rats were randomly divided into the TBI-model group, TBI-low DHA group and TBI-high DHA group, while other healthy rats were assigned to the sham-operated group. Motor recovery was tested with beam-walking trials at 2, 7 and 15 days post-TBI. Cognitive recovery was tested with Morris water maze trials at 15 days post-TBI. The expression levels of caspase-3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were measured by western blotting. DHA protected against motor deficits induced by TBI in beam walking tests. All TBI-model groups had longer escape latency and swimming distances than the sham groups. Compared with the TBI-low DHA group, the TBI-high DHA group demonstrated shorter escape latency and swimming distances. DHA inhibited the expression of caspase-3 and the inhibition effect was more obvious at a high dosage. Furthermore, DHA dose-dependently rescued neurons by upregulating the Bcl-2:Bax ratio. DHA supplementation was a viable strategy to mitigate injury from TBI.

Myrciaria cauliflora extract improves diabetic nephropathy via suppression of oxidative stress and inflammation in streptozotocin-nicotinamide mice.

Myrciaria cauliflora is a functional food rich in anthocyanins, possessing antioxidative and anti-inflammatory properties. Our previous results demonstrated M. cauliflora extract (MCE) had beneficial effects in diabetic nephropathy (DN) and via the inhibition of Ras/PI3K/Akt and kidney fibrosis-related proteins. The purpose of this study was to assess the benefit of MCE in diabetes associated with kidney inflammation and glycemic regulation in streptozotocin-nicotinamide (STZ/NA)-induced diabetic mice. Compared with the untreated diabetic group, MCE significantly improved blood glucose and serum biochemical characteristic levels. Exposure to MCE increased antioxidative enzyme activity and diminished reactive oxygen synthesis. Mice receiving MCE supplementation had reduced intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), colony stimulating factor 1 (CSF-1), interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor α (TNF-α) levels compared to the untreated diabetic mice. Inflammatory and fibrotic related proteins such as collagen IV, fibronectin, Janus kinase (JAK), phosphorylated signal transducer and activator of transcription 3 (STAT3), protein kinase C beta (PKC-ß), and nuclear factor kappa B (NF-κB) were also inhibited by MCE treatment in STZ/NA mice. These results suggest that MCE may be used as a hypoglycemic agent and antioxidant in Type 2 diabetic mice.

Sulforaphane inhibits TNF-α-induced adhesion molecule expression through the Rho A/ROCK/NF-κB signaling pathway.

Endothelial dysfunction is an early indicator of cardiovascular diseases. Increased stimulation of tumor necrosis factor-α (TNF-α) triggers the inflammatory mediator secretion of endothelial cells, leading to atherosclerotic risk. In this study, we investigated whether sulforaphane (SFN) affected the expression of intracellular adhesion molecule-1 (ICAM-1) in TNF-α-induced ECV 304 endothelial cells. Our data showed that SFN attenuated TNF-α-induced expression of ICAM-1 in ECV 304 cells. Pretreatment of ECV 304 cells with SFN inhibited dose-dependently the secretion of proinflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and IL-8. SFN inhibited TNF-α-induced nuclear factor-κB (NF-κB) DNA binding activity. Furthermore, SFN decreased TNF-α-mediated phosphorylation of IκB kinase (IKK) and IκBα, Rho A, ROCK, ERK1/2, and plasminogen activator inhibitor-1 (PAI-1) levels. Collectively, SFN inhibited the NF-κB DNA binding activity and downregulated the TNF-α-mediated induction of ICAM-1 in endothelial cells by inhibiting the Rho A/ROCK/NF-κB signaling pathway, suggesting the beneficial effects of SFN on suppression of inflammation within the atherosclerotic lesion.

A polyphenol extract of Hibiscus sabdariffa L. ameliorates acetaminophen-induced hepatic steatosis by attenuating the mitochondrial dysfunction in vivo and in vitro.

Oxidative stress is the major contributor to acetaminophen (AAP)-caused liver damage. It promotes mitochondrial oxidative stress and collapses the mitochondrial membrane potential to cause cell death. We have previously shown that a polyphenol extract of Hibiscus sabdariffa L. (HPE) potentiated the antioxidative effect. We further examined in this study the possible mechanism of HPE against AAP-caused liver damage. BABL/c mice were orally fed with HPE (100, 200 or 300 mg/kg) for two weeks prior to an i.p. injection of 1000 mg/kg of AAP. The mice were decapitated 6 h after the AAP injection to collect the blood and liver for further determination. The results show that pretreating with HPE increased the level of glutathione (GSH), decreased the level of lipid peroxidation, and increased catalase activity in the liver. A histopathological evaluation shows that HPE could decrease AAP-induced liver sterosis accompanied by a decreased expression of AIF, Bax, Bid, and p-JNK in the liver. An in vitro assay revealed that HPE could reduce AAP-induced death of BABL/c normal liver cells (BNLs), reverse the lost mitochondrial potency and improve the antioxidative status, similarly to the results of the in vivo assay. We show in this study that HPE possessed the ability to protect the liver from AAP-caused injury. The protective mechanism might be regulated by decreasing oxidative stress and attenuating the mitochondrial dysfunction.