Efficacy and Safety of a Fixed Combination of Glycyrrhizic Acid and Essential Phospholipids in Non-Alcoholic Fatty and Alcoholic Liver Disease: Results from Randomized Placebo-Controlled Trials

Background. Drug treatment of non-alcoholic fatty and alcoholic liver disease remains an urgent, unsolved problem. Due to the commonality of many pathogenetic mechanisms and predictors of progression, a universal approach to the search for a therapeutic agent can be considered. Aims pooled analysis of the results of two multicenter, randomized, double-blind, placebo-controlled studies of a fixed combination of glycyrrhizic acid and essential phospholipids in two dosage forms to study its efficacy and safety in non-alcoholic fatty and alcoholic liver disease, in the presence and absence of predictors of disease progression. Methods. The pooled analysis included 180 patients with non-alcoholic fatty liver disease (Gepard study) and 120 patients with alcoholic liver disease (Jaguar study). Patients of the main group received a fixed combination of 5.0 g intravenous jet 3 times a week for the first 2 weeks; then 2 capsules 3 times a day for the next 10 weeks. Patients in the control group received placebo according to the same scheme. The total duration of treatment was 12 weeks in the Gepard study (1 course of stepwise therapy) and 24 weeks in the Jaguar study (2 courses of stepwise therapy). A comparative analysis of the efficacy and safety of a fixed combination and a placebo was carried out, in the presence and absence of predictors of progression, separately for each nosology and in a mixed sample. Results. In patients with non-alcoholic fatty and alcoholic liver disease who received the fixed combination, in contrast to the placebo group, there was a statistically more significant decrease in the level of biochemical markers of inflammation alanine aminotransferase, aspartate aminotransferase, adiponectin, and the value of the AktiTest index. There was no negative trend in the NAFLD fibrosis score; more significant positive dynamics of FibroTest is shown. Predictors of disease progression hyperglycemia, hyperlipidemia, age did not have a negative impact on the results in the study group. The efficacy of the study drug was noted in patients with non-alcoholic fatty liver disease and normal body weight; data were obtained indicating its possible effectiveness with a high activity of the inflammatory process associated with alcoholic liver damage. The frequency of adverse events in the study and control groups was comparable. Conclusions. Based on a generalized analysis of the results of two studies, promising directions for the study and use of a fixed combination of glycyrrhizic acid and essential phospholipids were identified: non-alcoholic fatty liver disease without obesity, alcoholic steatohepatitis of high activity (as an adjuvant); steatohepatitis of non-alcoholic and alcoholic etiology, combined with hyperglycemia and hyperlipidemia.

Influence of coronavirus infection on the course of psoriasis

A new SARS-CoV-2-associated coronavirus infection pandemic began in late 2019. The present article is devoted to the analysis of the mechanisms of COVID-19 impact on the course of psoriasis and its consequences. According to the scientific literature, patients with psoriasis are somewhat more likely to be infected with coronavirus infection than the healthy population, but tolerate it in a milder form. At the same time, cases of psoriatic process exacerbation during the active phase of the disease and after COVID-19 have been described. The negative effect of infection on skin disease can be explained by the common genome of the two nosologies, the «cytokine storm» and the prescription of COVID-19 drugs. In addition, both COVID-19 and psoriasis can cause liver dysfunction related to the specific pathogenesis of the diseases as well as the prescribed therapy. The article describes our own experience of monitoring patients with exacerbation of psoriasis against the background of coronavirus infection with pathological changes in liver tests. Inclusion of a fixed combination of glycyrrhizic acid and essential phospholipids in the complex treatment allowed to stop the exacerbation of the psoriatic process more effectively, to reduce the activity of liver enzymes without worsening the clinical conditions associated with COVID-19. Thus, in particular, a clinically significant improvement of the skin condition was recorded. In patient B., alanine aminotransferase activity decreased to 44.4 U/L and aspartate aminotransferase activity to 18.2 U/L. In turn, in patient M. the activity of liver enzymes decreased to 37.8 U/L and 34.7 U/L, respectively. The prescription of this drug can be considered pathogenetically justified, given the effect of glycyrrhizic acid on the production of key cytokines involved in the inflammatory process in psoriasis, coronavirus infection and liver pathology. In addition, the hypothesis of the ability of glycyrrhizic acid to prevent the entry of SARS-CoV-2 into the cell by reducing the expression of angiotensin-converting enzyme 2 is of interest.

Rewiring phospholipid biosynthesis reveals robustness in membrane homeostasis and uncovers lipid regulatory players.

Intracellular transport of lipids by Lipid Transport Proteins (LTPs) is thought to work alongside vesicular transport to shuttle lipids from their place of synthesis to their destinations. Whereas many LTPs have been identified, it is largely unknown which routes and which LTPs a given lipid utilizes to navigate the multiple membranes of eukaryotic cells. The major and essential phospholipids, phosphatidylethanolamine (PE) and phosphatidylcholine (PC) can be produced by multiple pathways and, in the case of PE, also at multiple locations. Here, we present an approach in which we simplify and rewire yeast phospholipid synthesis by redirecting PE and PC synthesis reactions to distinct subcellular locations using chimeric enzymes fused to specific organelle targeting motifs. In rewired conditions, viability is expected to depend on homeostatic adaptation to the ensuing lipostatic perturbations and on efficient interorganelle lipid transport. We therefore performed genetic screens to identify factors involved in both of these processes. Among the candidates identified, we find genes linked to transcriptional regulation of lipid homeostasis, lipid metabolism and transport. In particular, we identify a requirement for Csf1 -an uncharacterized protein harboring a Chorein-N lipid transport domain- for survival under certain rewired conditions as well as lipidomic adaptation to cold, implicating Csf1 in interorganelle lipid transport and homeostatic adaptation.

Pathogenetic rationale for correction of endothelial dysfunction with quercetin in the complex treatment of non-alcoholic steatohepatitis and diabetic kidney disease in patients with type 2 diabetes mellitus

Objective — to determine effects of therapeutical complex, including metformin, rosuvastatin, essential phospholipids and quercetin, on the state of blood lipid spectrum, endothelial function, fibrinolysis system and platelet hemostasis, which are factors in the progression of nonalcoholic steatohepatitis (NASH) and diabetic kidney disease (DKD). Materials and methods. The investigation was performed in the dynamics of treatment of 60 NASH patients with type 2 diabetes mellitus (DM 2) and DKD of stage I — III. Depending on the prescribed treatment patients were randomized into 2 groups. The comparison group 1 (28 subjects) was administered hypocaloric diet with account of dietary restrictions #9, received essential phospholipids 300 mg 2 caps. 3 times a day) during 30 days for the NASH treatment, and antidiabetic and lipid‑lowering therapy with metformin hydrochloride 1000 mg per day, rosuvastatin (5 mg 1 time per day) for 1 month. Group 2 consisted of 32 patients and in addition to the similar 30 days of dietary recommendations, essential phospholipids, hypoglycemic and hypolipidemic therapy, received quercetin and povidone 500 mg intravenously in 100 ml of isotonic sodium 10 mg for 10 days. The mean age of patients was 53.8 ± 3.52 years. The comparison group consisted of 30 healthy age‑matching subjects. Results. Parameters of endothelial dysfunction, fibrinolysis and platelet hemostasis were determined to check the degree of endothelial‑protective effects of Quercetin against the background of the recommended protocol therapy. As a result of treatment, baseline significantly reduced NO levels (in 1.7 times) in patients of group 1 increased insignificantly (p > 0.05), and significantly raised in 1.5 times (p < 0.05) in group 2. This can be explained by effects of Quercetin as an endothelial protector, as well as by metformin effects, which reduces degree of insulin resistance and promotes body weight reduction, as well as reduction of hyperlipidemia level and probability of deposition of subendothelial proatherogenic fractions. Conclusions. Combined therapy of NASH with DM 2 and diabetic kidney disease with the use of essential phospholipids, statins and metformin with addition of Quercetin was more effective than traditional therapy: it significantly reduced the markers of NASH exacerbation, optimized blood lipid spectrum, restored endothelial functional state, eliminated the phenomena of hypercoagulable syndrome without the additional administration of antiplatelet agents.

Mitochondrial Respiration in Drosophila Ovaries after a Full Cycle of Oogenesis under Simulated Microgravity

Studies of the function of the female reproductive system in zero gravity are urgent for the future exploration of deep space. Female reproductive cells, oocytes, are rich in mitochondria, which allow oocytes to produce embryos. The rate of cellular respiration was determined to assess the functional state of the mitochondrial apparatus in Drosophila melanogaster ovaries in which the full cycle of oogenesis took place under simulated microgravity. Since cellular respiration depends on the state of the cytoskeleton, the contents of the main cytoskeletal proteins were determined by Western blotting. To modulate the structure of the cytoskeleton, essential phospholipids were administered per os at a dosage of 500 mg/kg in medium. The results of this study show that after a full cycle of oogenesis under simulated microgravity, the rate of cellular respiration in the fruit fly ovaries increases, apparently due to complex II of the respiratory chain. At the same time, we did not find any changes in the area of oocytes or in the content of proteins in the respiratory chain. However, changes were found in the relative contents of proteins of the actin cytoskeleton. There were no changes of essential phospholipids and no increase in the rate of cellular respiration of the ovaries after exposure to simulated microgravity. However, in the control, the administration of essential phospholipids led to a decrease in the efficiency of oxygen consumption in the flies’ ovaries due to complexes IV–V.

Effects of S-adenosyl methionine and essential phospholipids on serum biochemical parameters in simulated acute liver disease in late pregnancy

AIM: Liver diseases, developing in late pregnancy, remains a very important problem in obstetrics. In present study, the aim was to evaluate the effectiveness of monotherapy by essential phospholipids and by S-adenosyl methionine for simulated acute liver pathology during pregnancy using the biochemical parameters of blood serum. STUDY DESIGN AND METHODS: Acute liver injury was simulated in rats from 15th to 18th day of pregnancy using tyloxapol (300 mg / kg daily). As drugs for monotherapy, Essentiale (Sanofi-Aventis, France) and Heptral (Abbott srl, Italy) were used separately and were administered to rats daily from the 16th to the 18th day of pregnancy (50 mg / kg and 35 mg / kg, respectively). On the 19th day of pregnancy, blood serum biochemical parameters were analyzed. RESULTS: In the model, the concentrations of triglycerides and cholesterol were sharply increased, which can be caused not only by the inhibitory effect of tyloxapol on the lipoprotein lipase of the lumen of blood vessels, but also by damage to liver cells with the accumulation of lipids in them. The activities of aminotransferases (ALT, AST), glutamate dehydrogenase and lactate dehydrogenase were statistically significantly increased. In healthy pregnant rats, the activity of alkaline phosphatase (ALP) decreased from 15th to 19th day of gestation, but under the treatment by tyloxapol in some cases the increase of ALP activity was observed. After using essential phospholipids in the model of acute liver injury, normal values of ALT and ALP activities were observed, and a significant decrease in triglycerides was revealed, which did not reach the normal values. After using S-adenosyl methionine in this model, the significant changes in blood serum parameters were not observed. By themselves, the drugs change several biochemical parameters in the serum of healthy pregnant rats. Heptral increases urea levels and Essentiale appears to increase AST activity. CONCLUSION: The use of essential phospholipids or S-adenosyl methionine as monotherapy in a model of acute liver damage in late pregnancy has demonstrated their low efficiency. It is possible that the combined use of drugs is necessary to increase the effectiveness. The use of S-adenosyl methionine should be carried out under the control of the urea level and glutamate dehydrogenase activity in serum. While using essential phospholipids, it is advisable to control the AST activity.

Steatohepatitis in Children with Obesity

The article discusses the issues of steatohepatitis development, diagnosis, and management in children. Steatohepatitis is one of the forms of non-alcoholic fatty liver disease diagnosed in 12–26% of children with obesity. The major pathogenetic factors are the following: oxidative stress, genetic predisposition, microbiota disorders, vitamin D deficiency. The information on the diagnostic algorithm is presented in accordance with the guidelines of the European and North American Societies of Pediatric Gastroenterologists, Hepatologists and Nutritionists. The characteristics of instrumental methods of steatohepatitis diagnostics (biopsy, ultrasound, magnetic resonance and computed tomography, elastography, biochemical tests) are given, as well as indications for their use in children are determined. The data on steatohepatitis management (including diet and physical activity) is presented. The use of hepatoprotective agents (ursodeoxycholic acid, essential phospholipids) and biologically active substances in children is discussed.