Inhibition of eukaryotic elongation factor-2 confers to tumor suppression by a herbal formulation Huanglian-Jiedu decoction in human hepatocellular carcinoma

ETHNOPHARMACOLOGICAL RELEVANCE: An oriental medicinal formulation, Huanglian Jiedu Decoction (HLJDD), has been well documented in few Traditional Chinese Medicine Classics 1300 years ago for treatment of heat and dampness-related diseases. Its effect is well accepted in Asian community, including China, Japan and Korea. Recent studies have postulated HLJDD as a regimen for cancer treatment, especially liver cancer, but the underlying mechanism is unknown. The aim of this study was to examine the suppressive effect of HLJDD on the growth of hepatocellular carcinoma (HCC) and its possible underlying mechanism. METHODS: Chemical composition of HLJDD was analyzed by high performance liquid chromatography. The tumor suppressive effect of HLJDD was determined on both HCC cells and xenograft model. Nascent protein synthesis was detected with Click-IT protein labeling technology; protein expression was determined by immunoblotting and imunnohistochemical analysis. RESULTS: Quality analysis revealed that HLJDD of different batches is consistent in both chemical composition and bioactivities. HLJDD inhibited HCC cell proliferation at its non-toxic doses, and suppressed growth and angiogenesis in xenografted murine model. HLJDD suppressed the synthesis of nascent protein via inactivation of eEF2 without deregulating the translation initiation factors. The major components in HLJDD, geniposide, berberine and baicalin, additively act on eEF2, and contributed to the responsible activity. HLJDD-activated eEF2 kinase (eEF2K) led to eEF2 inactivation, and activation of AMPK signaling may be responsible for the eEF2K induction. Blocked AMPK activity in HLJDD-treated HCC cells attenuated eEF2K activation as well as the inhibitory effect of the formula. In nutrient deprived HCC cells with inactivated eEF2, the inhibitory effect of HLJDD in tumor cell expansion was interfered. CONCLUSION: Our results indicate that HLJDD has potential in blocking HCC progression with involvement of eEF2 inhibition. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.postprin

Transcriptomics Analysis of Candida albicans

Candida albicans is the major invasive fungal pathogen of humans, causing diseases ranging from superficial mucosal infections to disseminated, systemic infections that are often life-threatening. Resistance of C. albicans to antifungal agents and limited antifungal agents has potentially serious implications for management of infections. As a famous multiherb prescription in China, Huanglian Jiedu Decoction (HLJJD, Orengedokuto in Japan) is efficient against Trichophyton mentagrophytes and C. albicans. But the antifungal mechanism of HLJDD remains unclear. In this study, by using RNA-seq technique, we performed a transcriptomics analysis of gene expression changes for C. albicans under the treatment of HLJDD. A total of 6057 predicted protein-encoding genes were identified. By gene expression analysis, we obtained a total of 735 differentially expressed genes (DEGs), including 700 upregulated genes and 35 downregulated genes. Genes encoding multidrug transporters such as ABC transporter and MFS transporter were identified to be significantly upregulated. Meanwhile, by pathway enrichment analysis, we identified 26 significant pathways, in which pathways of DNA replication and transporter activity were mainly involved. These results might provide insights for the inhibition mechanism of HLJDD against C. albicans

Treatment Effects of Ischemic Stroke by Berberine, Baicalin, and Jasminoidin from Huang-Lian-Jie-Du-Decoction (HLJDD) Explored by an Integrated Metabolomics Approach

Berberine, baicalin, and jasminoidin were major active ingredients of Huang-Lian-Jie-Du-Decoction (HLJDD), a famous prescription of traditional Chinese medicine (TCM), which has been used for the treatment of ischemic stroke. The aim of the present study was to classify their roles in the treatment effects of ischemic stroke. A rat model of middle cerebral artery occlusion (MCAO) was constructed to mimic ischemic stroke and treatment effects of berberine, baicalin, and jasminoidin, and HLJDD was assessed by neurologic deficit scoring, infarct volume, histopathology, immunohistochemistry, biochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. In addition, the 1H NMR metabolomics approach was used to assess the metabolic profiles, which combined with correlation network analysis successfully revealed metabolic disorders in ischemic stroke concerning the treatment of the three principal compounds from HLJDD for the first time. The combined results suggested that berberine, baicalin, and jasminoidin are responsible for the effectiveness of HLJDD on the treatment of ischemic stroke by amelioration of abnormal metabolism and regulation of oxidative stress, neuron autophagy, and inflammatory response. This integrated metabolomics approach showed its potential in understanding the function of complex formulae and clarifying the role of its components in the overall treatment effects

Natural Products Targeting on Oxidative Stress and Inflammation: Mechanisms, Therapies, and Safety Assessment

Substantial evidence suggests that overproduction of reactive oxygen species (ROS) and its associated oxidative stress and inflammatory responses play a crucial role in the pathogenesis of various human chronic diseases including diabetes, cardiovascular diseases, obesity, neurodegenerative diseases, and cancer. Enhanced ROS production can cause oxidative damage to the cellular macromolecules including lipids, proteins, and DNA. In addition, oxidative stress activates nuclear factor kappa B (NF-?B), nuclear factor-erythroid 2-related factor 2 (Nrf2), and antioxidant-responsive elements (ARE) to regulate anti-inflammatory and antioxidative genes involved in inflammatory responses and cellular defense mechanisms. Recent studies have showed that certain natural compounds and/or their derived small molecules have the ability to protect cells from oxidative stress and ameliorate various oxidative stress-related diseases. However, a large number of natural products are underutilized and unexploited because their bioactivities are unknown and the molecular mechanisms involved are yet to be identified. Understanding the mechanisms of actions of natural products would shed further light into the application of these compounds in the prevention and treatment of oxidative stress-related diseases in humans. This special issue includes two invited reviews and twelve original research articles that are focused on the antioxidative/anti-inflammatory effects of various natural compounds and their safety in vitro and in vivo. Further, these studies identified the cellular and molecular mechanisms underlying the bioactivities of these natural compounds

1H NMR-Based Metabolomics Reveals Refined-Huang-Lian-Jie-Du-Decoction (BBG) as a Potential Ischemic Stroke Treatment Drug With Efficacy and a Favorable Therapeutic Window

Huang-Lian-Jie-Du-Decoction (HLJDD) is a traditional Chinese medicine (TCM) used to treat ischemic stroke. However, the complexity of its chemical composition makes quality control difficult. Berberine, baicalin, and geniposide are the three main ingredients in HLJDD. Here, a formula of BBG comprised of berberine, baicalin, and geniposide, known as Refined-Huang-Lian-Jie-Du-Decoction, was investigated for its efficacy, therapeutic window, and mechanisms of action. BBG was assessed on two major types of ischemic stroke, cerebral ischemia-reperfusion (I/R) injury, and continuous ischemia injury, respectively. BBG showed efficacy comparable to HLJDD in the treatment of cerebral I/R injury within 5 h after injury initiation but did poorly in treating continuous ischemia injury. BBG exhibited neuroprotective effects on cerebral I/R injury by regaining the balance in energy metabolism, oxidative stress, amino acid metabolism, inflammation, and nucleic acid metabolism. These results suggested that BBG could be a good alternative to HLJDD, with high efficacy and a long therapeutic window, which shows great potential for drug development to treat stroke

Research progress on antidepressant effects and mechanisms of berberine

Depression, a global health problem with growing prevalence, brings serious impacts on the daily life of patients. However, the antidepressants currently used in clinical are not perfectly effective, which greatly reduces the compliance of patients. Berberine is a natural quaternary alkaloid which has been shown to have a variety of pharmacological effects, such as hypoglycemic, lipid-regulation, anti-cancer, antibacterial, anti-oxidation, anti-inflammatory, and antidepressant. This review summarizes the evidence of pharmacological applications of berberine in treating depression and elucidates the mechanisms of berberine regulating neurotransmitter levels, promoting the regeneration of hippocampal neurons, improving hypothalamic-pituitary-adrenal axis dysfunction, anti-oxidative stress, and suppressing inflammatory status in order to provide a reference for further research and clinical application of berberine

Application of Herbal Traditional Chinese Medicine in the Treatment of Acute Kidney Injury

Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid loss of renal function, which may further develop into chronic kidney damage (CKD) or even end-stage renal disease (ESRD). AKI is a global health problem associated with high morbidity and costly treatments, and there is no specific or effective strategy to treat AKI. In recent years, Traditional Chinese Medicine (TCM) has attracted more attention, with lines of evidence showing that application of TCM improved AKI, and the mechanisms of action for some TCMs have been well illustrated. However, reviews summarizing the progress in this field are still lacking. In this paper, we reviewed TCM preparations and TCM monomers in the treatment of AKI over the last 10 years, describing their renal protective effects and mechanisms of action, including alleviating inflammation, programmed cell death, necrosis, and reactive oxygen species. By focusing on the mechanisms of TCMs to improve renal function, we provide effective complementary evidence to promote the development of TCMs to treat AKI. Moreover, we also summarized TCMs with nephrotoxicity, which provides a more comprehensive understanding of TCMs in the treatment of AKI. This review may provide a theoretical basis for the clinical application of TCMs in the future

The potential of the gut microbiome for identifying Alzheimer’s disease diagnostic biomarkers and future therapies

Being isolated from the peripheral system by the blood–brain barrier, the brain has long been considered a completely impervious tissue. However, recent findings show that the gut microbiome (GM) influences gastrointestinal and brain disorders such as Alzheimer’s disease (AD). Despite several hypotheses, such as neuroinflammation, tau hyperphosphorylation, amyloid plaques, neurofibrillary tangles, and oxidative stress, being proposed to explain the origin and progression of AD, the pathogenesis remains incompletely understood. Epigenetic, molecular, and pathological studies suggest that GM influences AD development and have endeavored to find predictive, sensitive, non-invasive, and accurate biomarkers for early disease diagnosis and monitoring of progression. Given the growing interest in the involvement of GM in AD, current research endeavors to identify prospective gut biomarkers for both preclinical and clinical diagnoses, as well as targeted therapy techniques. Here, we discuss the most recent findings on gut changes in AD, microbiome-based biomarkers, prospective clinical diagnostic uses, and targeted therapy approaches. Furthermore, we addressed herbal components, which could provide a new venue for AD diagnostic and therapy research