Epigenetics and mitochondrial dysfunction insights into the impact of the progression of non-alcoholic fatty liver disease.

A metabolic problem occurs when regular functions of the body are disrupted due to an undesirable imbalance. Nonalcoholic fatty liver disease (NAFLD) is considered as one of the most common in this category. NAFLD is subclassified and progresses from lipid accumulation to cirrhosis before advancing to hepatocellular cancer. In spite of being a critical concern, the standard treatment is inadequate. Metformin, silymarin, and other nonspecific medications are used in the management of NAFLD. Aside from this available medicine, maintaining a healthy lifestyle has been emphasized as a means of combating this. Epigenetics, which has been attributed to NAFLD, is another essential feature of this disease that has emerged as a result of several sorts of research. The mechanisms by which DNA methylation, noncoding RNA, and histone modification promote NAFLD have been extensively researched. Another organelle, mitochondria, which play a pivotal role in biological processes, contributes to the global threat. Individuals with NAFLD have been documented to have a multitude of alterations and malfunctioning. Mitochondria are mainly concerned with the process of energy production and regulation of the signaling pathway on which the fate of a cell relies. Modulation of mitochondria leads to elevated lipid deposition in the liver. Further, changes in oxidation states result in an impaired balance between the antioxidant system and reactive oxygen species directly linked to mitochondria. Hence mitochondria have a definite role in potentiating NAFLD. In this regard, it is essential to consider the role of epigenetics as well as mitochondrial contribution while developing a medication or therapy with the desired accuracy.

Targeting molecular signal transduction pathways in hepatocellular carcinoma and its implications for cancer therapy.

Hepatocellular carcinoma is a substantial health concern. It is currently the third dominating cause of mortality associated with cancer worldwide. The development of hepatocellular carcinoma is an intricate process that encompasses the impairment of genetic, epigenetic, and signal transduction mechanisms contributing to an aberrant metabolic system, enabling tumorigenesis. Throughout the past decade, research has led to the revelation of molecular pathways implicated in the progression of this notorious disorder. The altered signal transduction pathways, such as the mitogen-activated protein kinase pathway, phosphoinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, WNT/ß-catenin pathway, hepatocyte growth factor/c-MET pathway, and just another kinase/signal transducers and activators of transcription signaling pathway is of much therapeutic significance, as targeting them may avail to revert, retard or avert hepatocarcinogenesis. The present review article sums up the contemporary knowledge of such signaling mechanisms, including their therapeutic targets and betokens that novel and efficacious therapies can be developed only by the keen understanding of their character in hepatocarcinogenesis. In additament, we address the role of consequential therapeutic agents and preclinical nondrug therapies known for combating hepatocarcinogenesis.

Elucidation of 7,8-dihydroxy flavone in complexing with the oxidative stress-inducing enzymes, its impact on radical quenching and DNA damage: an in silico and in vitro approach.

Oxidative stress (OS) has been attributed to the progression of various disorders, including cancer, diabetes, and cardiovascular diseases. Several antioxidant compounds and free radical quenchers have been shown to mitigate oxidative stress. However, large-scale randomized controlled trials of such compounds on chronic disease aversion have yielded paradoxical and disappointing results due to the constrained cognizance of their oxidative mechanisms and therapeutic targets. The current study sought to identify the potential therapeutic targets of 7,8-Dihydroxyflavone (7,8-DHF) by analyzing its interactions with the enzymes implicated in oxidative stress and also to explore its radicle quenching potential and prophylactic impact on the H2O2-induced DNA damage. Through the in silco approach, we investigated the antioxidant potential of 7,8-DHF by evaluating its interactions with the human oxidative stress-inducing enzymes such as myeloperoxidase (MPO), NADPH oxidase (NOX), nitric oxide synthase (NOS), and xanthine oxidase (XO) and a comparative analysis of those interactions with known antioxidants (Ascorbic acid, Melatonin, Tocopherol) used as controls. The best-scoring complex was adopted for the simulation analysis in investigating protein-ligand conformational dynamics. The in vitro radicle quenching potential was evaluated by performing a spectrum of antioxidant assays, and radical quenching was observed in a dose-dependent fashion with IC50 values of < 60 µM/mL. Further, we probed its anti-hemolytic potential and prophylactic impact in avian erythrocytes subjected to H2O2-induced hemolysis and DNA damage by implementing hemolysis and comet assays. The protective effect was more pronounced at higher concentrations of the drug.Communicated by Ramaswamy H. Sarma.

Curcuma longa and Trigonella foenum graecum-enriched nutrient mixture from germinated Macrotyloma uniflorum and Vigna radiate ameliorate nonalcoholic fatty liver diseases in rats.

The prevalence of nonalcoholic fatty liver is increasing due to modern lifestyle. Germinated and dehulled Macrotyloma uniflorum and Vigna radiate were shown to have enhanced nutrients. Curcuma longa and Trigonella foenum graecum were proven hepatoprotective.The supplementation of the nutrient herbal mixture to the MCD diet-induced steatosis shows reduced hepatic fat accumulation and lipid profile, and liver injury markers in serum also reserved in normal. Increased serum albumin in the treatment group indicates that the liver function is enhanced than that of steatosis. The supplementation of the herbal mixture has preserved the hepatic antioxidant. Zymographic analysis of matrix metalloproteinase, western blot determination of α-SMA, and histological evolution (H&E, Sirius red) depicted reduced fibrosis and reveled management of hepatic stellate cells in quiescent form. The present study concludes that the herbal mixture has reduced hepatocyte fat accumulation in steatotic animals, and curtailed the oxidative stress, further it prevents the progression of steatohepatitis. PRACTICAL APPLICATIONS: Fatty liver diseases can be treated by modulating the diet composition such as consuming food rich in the nutrient herbal mixture. In this study, the nutrient mixture was made with dynamic food processing techniques such as germination, dehulling, and milling to augment the nutritional contents. Besides, Macrotyloma uniflorum, Vigna radiate, Curcuma longa, and Trigonella foenum graecum were used to improve the medicinal value and antioxidant. This formulation could target the various stages of NAFLD. This study revealed that the nutrient herbal mixture reduces the steatosis of the liver and curtailed the progression of steatohepatitis from hepatic steatosis. Since the edible foodstuff was used to make the nutrient mixture, it has excellent clinical application.

Nutrient mixture from germinated legumes: Enhanced medicinal value with herbs-attenuated liver cirrhosis.

Among various food processing strategies, germination and dehulling enhance the nutritional content of the food, and the addition of herbs to this could improve the medicinal value. The milled powders of germinated Macrotyloma uniflorum (horse gram) and Vigna radiata (green gram) were used to make the nutrient mixture. Further, Curcuma longa (turmeric) and Trigonella foenum graecum (fenugreek) were used to improve its medicinal value. The prepared nutrient mixture has high nutritional value, antioxidant potential, and reduced antinutrient factors. Supplementation of nutrient mixture reduced oxidative stress-mediated hepatocyte injury on the CCl4 -induced liver cirrhosis model. Further, histological examination (H&E and Sirius red), matrix metalloproteinase gelatin zymography, and Western blot revealed the management of hepatic stellate cells in an inactive stage thereby reduced cirrhosis. These findings conclude that the supplementation of nutrient mixture formulation protected and effectively prevented liver cirrhosis. PRACTICAL APPLICATIONS: This study has a good impact on nutritional therapy for liver diseases. Many of the chronic liver diseases are associated with severe malnutrition and hypoalbuminemia, which further worsens the condition. This study would emphasize the nutritional therapy to treat such imbalance and enriching the medicinal value of nutrition mixture with herbs could target different pathophysiological changes and provide better defense in liver disease patients. Since this nutrient mixture is from common edible natural resources, it could reach the pharmaceutical industry's attention to the highest production and marketing.