Seven isoflavonoids, including a new glycoside, (6aR,11aR)-medicarpin-3-O-gentiobioside (6), were isolated from the roots of Maackia amurensis using repeated column chromatography on a Toyopearl HW-50F sorbent and identified by HPLC-PDA-MS, 1 H NMR, 13 C, 1 H-1 H COSY, HSQC NMR and HMBC NMR analyses as daidzin (1), genistein-7-O-gentiobioside (2), pseudobaptigenin-7-O-gentiobioside (3), formononetin-7-O-gentiobioside (4), (6aR,11aR)maackiain-3-O-gentiobioside (5), and 5-O-methylgenistein-7-O-gentiobioside (7). In the model of oxidative stress induced by formalin injection, the isolated isoflavone and pterocarpan glucosides 1-7 were shown to reduce the formation of malondialdehyde (MDA) and other thiobarbituric acid reactive substances (TBARS), as well as glutathione peroxidase (GPO) activity in rats.
Review discusses the mechanisms of antioxidant and anti-inflammatory actions of flavonoids. In discussing the antioxidant effect detail the mechanisms of scavenging of reactive oxygen species, the chelation of transition metals, the activation of antioxidant enzymes. In consideration of anti-inflammatory action emphasis on the effects of flavonoids on the activity of the transcription factors and pathways involved in the formation of the inflammatory response. (For citation: Zverev YaF. Flavonoids through the eyes of a pharmacologist. Antioxidant and anti-inflammatory activities. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(4):5-13. doi: 10.17816/RCF1545-13).
The review focused on pharmacokinetics of the six major subclasses of flavonoids: their distribution, consumption and metabolism. Particular attention is paid to the problem of the bioavailability of these plant polyphenolic compounds, the differences of the effects obtained in experiments in vitro and in vivo. Discusses the dependence of the efficiency of flavonoids by the characteristics of the processes of metabolism in humans. Emphasizes the role of the epithelium of small intestine and microbiota of the colon in ensuring biological activity of flavonoids. (For citation: Zverev YaF. Flavonoids through the eyes of a pharmacologist. Features and problems of pharmacokinetics. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(2):4-11. doi: 10.17816/RCF1524-11).
The literature review is devoted to the study of the mechanisms of the cardioprotective action of a new class of glucose-lowering drugs glyflozins, which inhibit the joint transport of sodium and glucose in the proximal renal tubules. The large-scale clinical trials carried out in recent years have demonstrated the beneficial effect of these compounds not only on glycemic control, but also on the progression of heart failure in patients with diabetes mellitus. Analysis of literature data shows that the effect under consideration is due to both the positive systemic cardiovascular and direct cardiotropic action of the drugs. The first part of the review examines the systemic effect of drugs, including their diuretic, natriuretic and antihypertensive effects, increased hematocrit, vascular effects that influence arterial stiffness, smooth muscle tone, and endothelial dysfunction. The metabolic effects of type 2 sodium and glucose co-transport inhibitors are discussed separately, including an increase in lipolysis, the role of glucagon and activation of ketogenesis, and their contribution to the development of a probable cardioprotective effect.
The literature review is devoted to the study of the mechanisms of the cardioprotective action of a new class of glucose-lowering drugs glyflozins, which inhibit the joint transport of sodium and glucose in the proximal renal tubules. Favorable changes in ion transport in cardiomyocytes with the use of these drugs are considered. The inhibition of the activity of the sodium-hydrogen exchanger (NHE) was found, followed by a decrease in the activity of Na+/ Ca2+ exchange on the mitochondrial membranes of the cardiomyocytes, which leads to a decrease in the concentration of Ca2+ in the cytoplasm with a simultaneous increase in mitochondria. This initiates a number of intracellular signaling cascades that contribute to the optimization of mitochondrial homeostasis. The use of glyflozins, apparently, provides a balance between the fusion and fission of mitochondria, which determines the bioenergetic adaptation of the cell to the state of intracellular metabolism, weakens the development of the inflammatory response, fibrosis and oxidative stress in the myocardium, which are activated under conditions of diabetes mellitus. The point of view is discussed, according to which the mechanism of anti-inflammatory action of glyflozins is associated with inhibition of the activity of the NLRP3 inflammasome, which contributes to the progression of myocardial dysfunction and subsequent chronic heart failure. The results of clinical trials and experimental data on the beneficial effect of glyflozins in the development of various phenotypes of heart failure with reduced and preserved ejection fraction are analyzed. The assumption is substantiated about the prospects for wider use of these hypoglycemic drugs in heart failure, which is not limited to diabetes mellitus. The assumptions made require further experimental and clinical studies.
Introduction. Idiopathic hypercalciuria (IH) is one of the most common metabolic disorders in children and is one of the leading causes of calcium urolithiasis and osteoporosis. The strategic goal of treatment for IH is to reduce urinary calcium excretion. Materials and methods. The study included 93 IH children aged from 3 to 14 years with identified IH. At the first stage, IH children have been prescribed low sodium and high potassium diet with increased fluid intake for three months without additional drug therapy. For children with persistent IH at the second stage, the diet was supplemented daily with 1000-1500 mg of fish oil for children for 3 months. At the third stage of treatment, persistent IH patients were prescribed hydrochlorothiazide at a dose of 1 mg/kg for 3 months. After each stage of treatment, we analyzed IH’s manifestations in dynamics and monitored urinary calcium excretion by calcium/creatinine ratio (CCR). Results. Evaluation of clinical and laboratory manifestations of IH after the first stage of treatment showed the effectiveness of the diet in 59.1% of patients. Among 38 patients included in the second stage of therapy, the normalization of urinary calcium excretion was noted in 52.6% of cases. The third stage of therapy was performed in 18 patients (19% of the initial group of IH children patients). The normalization of CCR was achieved in 16 (88.9%) children. Conclusion. For the correction of IH in children, a step-by-step approach should be recommended, starting with recommendations on the drinking regimen and nutrition, then prescribing fish oil preparations and resorting to thiazide diuretics in the lack of an effect from the first stages of treatment.
The review presents the screening of the therapeutic effects of the Russia drug “Histochrome”, active substance of which is quinoid pigment marine - echinochrome A (2,3,5,6,8-pentahydroxy-7-ethyl-1,4-naphthoquinone). Assessing the pharmacological aspects of the drug authors have focused on cellular and molecular mechanisms of action of histochrome. The parallel between echinochrome A pharmacodynamics and its biological effects proves promising directions for expansion of the clinical application of the preparation “Histochrome”. (For citation: Talalaeva OS, Zverev YaF, Bryukhanov VM. The cellular and molecular mechanisms providing therapeutic efficiency of gistokhrom. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(4):58-68. doi: 10.17816/RCF15458-68).
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