Nutrigenetic Interactions Might Modulate the Antioxidant and Anti-Inflammatory Status in Mastiha-Supplemented Patients With NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ≥ 30 kg/m2) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI > 35kg/m2) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene (LSS) associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene (MPC1) and the sphingolipid transporter-1 gene (SPNS1) associated with hemoglobin levels, the transforming growth factor-beta-induced gene (TGFBI) and the micro-RNA 129-1 (MIR129-1) associated with IL-6 and the granzyme B gene (GZMB) associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873, www.clinicaltrials.gov) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03135873.

Phytochemical characterization and effects on cell proliferation of Pinus nigra Arn. bark.

Pinus nigra Arn. bark extracts from Mokra gora (MG) and Tara mountains were analyzed with regard to their polyphenolic profile and antioxidative and antiproliferative activity. The ethanol extract from MG showed the highest phenolic, flavonoid, tannin, and proanthocyanidin content when compared with the acetone and methanol extracts from both sites. The same extract exhibited the highest ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) and ferric reducing antioxidant power (FRAP) radical scavenging ability and total antioxidant activity (TAA). On the basis of high-performance liquid chromatography analysis, catechin, caffeic, syringic, p-coumaric, and ferulic acids were predominantly present in the MG extracts. The ethanol extract from MG was rich in syringic acid, epicatechin and its derivatives, and ferulic acid and its derivatives. The bark extracts also exerted a high cytotoxic bioactivity against all evaluated cell lines (HeLa, MCF7, HT-29, and MRC-5). The antiproliferative activity of P. nigra bark is probably related to the ferulic acid content and its synergistic activity to caffeic acid and taxifolin. The antioxidative role of the presented phenols was confirmed through the obtained significant linear correlation between the total phenolic content and DPPH (r = .934) as well as the FRAP% of the extracts (r = .948). Also, the TAA significantly depended on the proanthocyanidins (r = .902) and tannin contents (r = .914). The composition of the presented compounds could be related to promising antioxidant and antiproliferative efficacy of MG bark.

Olive oil antioxidants and non-alcoholic fatty liver disease.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is estimated to affect 25% of adult people worldwide. Nowadays, there is no definite treatment for NAFLD. International guidelines define an approach based on lifestyle changes, included a health alimentary regimen. The Mediterranean diet (MD) represents the gold standard in preventive medicine, probably due to the harmonic combination of many elements with antioxidant and anti-inflammatory properties. Its prescription is also recommended in patients with NAFLD. Olive oil, as part of MD, is associated with benefits on human health especially regarding the cardiovascular system, obesity, diabetes and related metabolic disorders. Areas covered: An overview of the beneficial effects of olive oil in the prevention and treatment of NAFLD is given. Expert opinion: A large body of evidence emphasizes that olive oil, used as primary source of fat in MD, may play a crucial role in the health benefits of NAFLD patients. However, there are still scarce clinical data that evaluate the direct effect of olive oil in human with NAFLD.

May Patients with Alcohol Liver Disease Benefit from Herbal Medicines?

Alcoholism is currently listed as the third leading cause of death. Chronic alcohol consumption brings serious medical complications like gastrointestinal, cardiovascular, musculoskeletal, respiratory system disorders. Liver can be seriously damage by alcohol misuse. Alcoholic Liver Disease (ALD) is the first important warning sign of alcohol abuse. Since effective therapies for ALD are still limited, natural products in the treatment of ALD become very important. In this regard, there have been done very few clinical trials with poor results. Silymarin, glycyrrhizin, garlic show some promising results in ALD patients while the in vivo and in vitro studies with green tee, quercetin and curcumin indicate positive effect on patients with ALD.

Phytotherapy and NAFLD--from goals and challenges to clinical practice.

Non-alcoholic fatty liver disease (NAFLD) is a global problem and one of the most common liver diseases in the world. Various pharmacological and non-pharmacological therapies seem to be non-effective and the patients are often advised not to expect a positive outcome. Hence, even in the modern Western society many patients reach for traditional herbal products. Silymarin, a lipophilic extract derived from milk thistle (Silybum marianum) has been used in liver and bile disorders for centuries. Strong antifibrotic, antioxidant, antiviral and anti-inflammatory activities of silymarin joined with its metabolic effect proven in vitro make it ideal as a drug candidate in the therapy of NAFLD. Several recent randomized clinical studies have demonstrated that silymarin versus placebo significantly contributes to amelioration of the liver condition affected by NAFLD since it reduces steatosis severity, liver ballooning and fibrosis, followed by lowered aminotransferase levels in both short and long lasting therapies. Silymarin is also as efficient as an insulin sensitizer in the NAFLD therapy, but with less adverse effects. Phase III clinical trials have confirmed silymarin to be currently the best medication for the NAFLD patients, but the problems associated with its standardization, formulation and dosage are yet to be solved. However, green tea (Camellia sinensis) and licorice (Glycyrrhiza glabra) root extracts have also been studied in the clinical trials in the therapy of NAFLD patients. Some other herbal products, which have been tested on animals and have the potential to be used in clinical trials, are briefly summarized in this paper.