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Kaempferia parviflora (KP), a health-promoting herb, has been traditionally used for treating a variety of diseases. Pharmacological studies have claimed the various benefits from KP and its main effective methoxyflavones, including cellular metabolism-regulating activity, anticancer activity, vascular relaxation and cardioprotective activity, sexual enhancing activity, neuroprotective activity, antiallergic, anti-inflammatory, and antioxidative activity, antiosteoarthritis activity, antimicroorganism activity, and transdermal permeable activity. These might be associated with increased mitochondrial functions and activated cGMP-NO signaling pathway. However, the underlying molecular mechanisms of KP and its methoxyflavones are still under investigation. The clinical applications of KP and its methoxyflavones may be limited due to their low bioavailability. But promising strategies are on the way. This review will comprehensively discuss the biological activities of KP and its methoxyflavones. [ABSTRACT FROM AUTHOR]

Ionising radiation (IR) is a known carcinogen and poses a significant risk to the haematopoietic system for the development of leukaemia in part by induction of genomic instability. Induction of chronic oxidative stress has been assumed to play an important role in mediating the effect of IR on the haematopoietic system. However, there was no direct evidence to support this hypothesis prior to our studies. In our recent studies, we showed that exposure of mice to total body irradiation (TBI) induces persistent oxidative stress selectively in haematopoietic stem cells (HSCs) at least in part via up-regulation of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 4. Now, we found that post-TBI treatment with diphenylene iodonium (DPI), a pan NOX inhibitor, not only significantly reduces TBI-induced increases in reactive oxygen species (ROS) production, oxidative DNA damage and DNA double-strand breaks in HSCs but also dramatically decreases the number of cells with unstable chromosomal aberrations in the clonal progeny of irradiated HSCs. The effects of DPI are comparable to Mn (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin, a superoxide dismutase mimetic and a potent antioxidant. These findings demonstrate that increased production of ROS by NOX in HSCs mediates the induction of haematopoietic genomic instability by IR and that NOX may represent a novel molecular target to inhibit TBI-induced genomic instability. [ABSTRACT FROM PUBLISHER]

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common disease worldwide in an era of rapid economic growth. NAFLD is a multifactorial disease, involving multiple genetic, metabolic, and environmental factors, and is closely associated with metabolic syndrome, obesity, and cardiovascular disease. NAFLD can be classified into nonalcoholic fatty liver disease (NAFL) and nonalcoholic steatohepatitis (NASH), which can both progress to cirrhosis and even hepatocellular carcinoma (HCC). Due to the enormous burden of NAFLD and its complications, no FDA-approved drugs for the treatment of NAFLD are on the market, and therapeutic targets and drug therapies are being actively investigated. In view of the various pathological mechanisms of NAFLD, numbers of preclinical studies and clinical trials have made rapid progress. This review mainly summarizes the most recently characterized mechanisms and therapeutic targets in each mechanism of NAFLD, focusing on the mechanism and application potential. [ABSTRACT FROM AUTHOR]

Metabolic cardiomyopathy is an emerging cause of heart failure in patients with obesity, insulin resistance, and diabetes. It is characterized by impaired myocardial metabolic flexibility, intramyocardial triglyceride accumulation, and lipotoxic damage in association with structural and functional alterations of the heart, unrelated to hypertension, coronary artery disease, and other cardiovascular diseases. Oxidative stress plays an important role in the development and progression of metabolic cardiomyopathy. Mitochondria are the most significant sources of reactive oxygen species (ROS) in cardiomyocytes. Disturbances in myocardial substrate metabolism induce mitochondrial adaptation and dysfunction, manifested as a mismatch between mitochondrial fatty acid oxidation and the electron transport chain (ETC) activity, which facilitates ROS production within the ETC components. In addition, non-ETC sources of mitochondrial ROS, such as β-oxidation of fatty acids, may also produce a considerable quantity of ROS in metabolic cardiomyopathy. Augmented ROS production in cardiomyocytes can induce a variety of effects, including the programming of myocardial energy substrate metabolism, modulation of metabolic inflammation, redox modification of ion channels and transporters, and cardiomyocyte apoptosis, ultimately leading to the structural and functional alterations of the heart. Based on the above mechanistic views, the present review summarizes the current understanding of the mechanisms underlying metabolic cardiomyopathy, focusing on the role of oxidative stress. [ABSTRACT FROM AUTHOR]

Aims While a wealth of data has uncovered distinct microRNA (miR) expression alterations in hypertrophic and ischaemic/reperfused (I/R) hearts, little is known about miR regulation and response to ischaemic preconditioning (IPC). Methods and results We analysed miRs in murine hearts preconditioned with six cycles of 4 min ischaemia via coronary artery occlusion, followed by 4 min reperfusion in vivo. Both miRs within the miR-144/451 cluster were the most elevated among a cohort of 21 dysregulated miRs in preconditioned hearts, compared with shams. To investigate the significance of this finding, we examined IPC-mediated cardioprotection within a miR-144/451-knockout (KO) mouse model. Wild-type (WT) hearts exposed to IPC followed by I/R (30 min/24 h) showed a smaller infarction size compared with mice treated with I/R alone. In contrast, IPC failed to protect miR-144/451-KO hearts against infarct caused by I/R treatment. Thus, the miR-144/451 cluster is required for IPC-elicited cardioprotection. Rac-1, a key component of NADPH oxidase, was mostly up-regulated in KO hearts among three bona fide targets (Rac-1, 14-3-3ζ, and CUGBP2) for both miR-144 and miR-451. Accordingly, reactive oxygen species (ROS) levels were markedly increased in KO hearts upon IPC, compared with IPC-WT hearts. Pre-treatment of KO hearts with a Rac-1 inhibitor NSC23766 (20 mg/kg, ip) reduced IPC-triggered ROS levels and restored IPC-elicited cardioprotection. Using antagomiRs, we showed that miR-451 was largely responsible for IPC-mediated cardioprotection. Conclusion Loss of the miR-144/451 cluster limits IPC cardioprotection by up-regulating Rac-1-mediated oxidative stress signalling. [ABSTRACT FROM PUBLISHER]