Brown-Algae Polysaccharides as Active Constituents against Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease is a metabolic disorder characterized by lipid overloading in hepatocytes that can progress pathogenically and even end in hepatocellular carcinoma. Nonalcoholic fatty liver disease pharmacological treatment is still limited by unwanted side effects, whereas the use of food components with therapeutic potential is advisable. The culinary use of marine algae is traditional for some populations and reviving worldwide, with promising health outcomes due to the large number of bioactive compounds found in seaweeds. The present review focuses on brown-algae polysaccharides, particularly fucoidan, alginate, and laminarin, and summarizes the experimental evidence of their potential effects against nonalcoholic fatty liver disease onset and progression. In vitro and in vivo studies demonstrate that brown-algae polysaccharides exert beneficial actions on satiety feeling, caloric intake, fat absorption, and modulation of the gut microbiota, which could account for indirect effects on energy and lipid homeostasis, thus diminishing the fat overload in the liver. Specific effects against nonalcoholic fatty liver disease pathogenesis and worsening are also described and sustained by the antioxidant, anti-inflammatory, and antisteatotic properties of brown-algae polysaccharides. Further studies are required to clarify the mechanism of action of brown-algae polysaccharides on liver cells, to determine the composition and bioavailability of brown-algae polysaccharides present in different algal sources and to probe the clinical availability of these compounds in the form of algal foods, food supplements, and regulated therapeutics.

Antitumor Activity of Ethanolic Extract from Thymbra Spicata L. aerial Parts: Effects on Cell Viability and Proliferation, Apoptosis Induction, STAT3, and NF-kB Signaling.

Thyme-like plants including Thymbra spicata L. are widely used as food and folk medicinal remedies in the Mediterranean area. This study aimed to explore the in vitro antitumor potential of polyphenol-enriched extracts from aerial parts of T. spicata. The ethanolic extract significantly inhibited proliferation of different human tumor cell lines, without significant effects on non-neoplastic cells. A deeper investigation of the molecular mechanism sustaining the in vitro antitumor activity of the extract was carried on the human breast cancer cells MCF-7 in comparison with the normal breast cells MCF-10A. The effects on MCF-7 cells were associated with the following: (i) production of reactive oxygen species (ROS) and release of nitric oxide; (ii) apoptosis induction; and (iii) reduction in STAT3 and NF-kB phosphorylation. The ethanolic extract from T. spicata leaves might represent a novel therapeutic tool in combination with conventional chemotherapy to reduce the adverse side effects and drug resistance.

Antioxidant and Antisteatotic Activities of Fucoidan Fractions from Marine and Terrestrial Sources.

Fucoidan is a fucose-rich sulfated polysaccharide typically found in the cell wall of marine algae but also recently isolated from terrestrial sources. Due to a variety of biological activities, including antioxidant properties, fucoidan exhibits an attractive therapeutic potential against a wide array of metabolic diseases associated with oxidative stress. We used FTIR, 1H NMR and 13C NMR spectroscopy to investigate the structural features of a fucoidan fraction extracted from the brown alga Cystoseira compressa (CYS). The antioxidant potential of CYS was measured by DPPH, ABTS and FRAP assays, which revealed a radical scavenging capacity that was confirmed in in vitro cellular models of hepatic and endothelial cells. The same antioxidant effects were observed for another fucoidan fraction previously identified in the terrestrial tree Eucalyptus globulus (EUC). Moreover, in hepatic cells, CYS and EUC exhibited a significant antisteatotic action, being able to reduce intracellular triglyceride content through the regulation of key genes of hepatic lipid metabolism. EUC exerted stronger antioxidant and antisteatotic effects as compared to CYS, suggesting that both marine and terrestrial sources should be considered for fucoidan extraction and therapeutic applications.

Antioxidant and Antisteatotic Activities of a New Fucoidan Extracted from Ferula hermonis Roots Harvested on Lebanese Mountains.

Fucoidan is a fucose-rich sulfated polysaccharide with attractive therapeutic potential due to a variety of biological activities, including antioxidant action. Fucoidan is typically found in the cell wall of marine brown algae, but extra-algal sources have also been discovered. In the present work, for the first time we extracted a water soluble fucoidan fraction from the roots of the terrestrial shrub Ferula hermonis. This fucoidan fraction was termed FUFe, and contained fucose, glucose, sulfate, smaller amounts of monosaccharides such as galactose and mannose, and a minor quantity of proteins. FUFe structural features were investigated by FTIR, 1H NMR and 13C NMR spectroscopy. The antioxidant property of FUFe was measured by DPPH, ABTS and FRAP assays, which revealed a high radical scavenging capacity that was confirmed in in vitro cellular models. In hepatic and endothelial cells, 50 µg/mL FUFe could reduce ROS production induced by intracellular lipid accumulation. Moreover, in hepatic cells FUFe exhibited a significant antisteatotic action, being able to reduce intracellular triglyceride content and to regulate the expression of key genes of hepatic lipid metabolism. Altogether, our results candidate FUFe as a possible bioactive compound against fatty liver disease and related vascular damage.

Polyphenol-enriched extracts of Sarcopoterium spinosum fruits for counteracting lipid accumulation and oxidative stress in an in vitro model of hepatic steatosis.

Sarcopoterium spinosum (L.) Spach is a Rosaceae shrub employed in the folk medicine in the Eastern Mediterranean basin. The previous few studies have focused on the S. spinosum roots, while the fruits have been poorly investigated. The present study aims to assess the biological properties of S. spinosum fruits collected in Lebanon and subjected to ethanolic, water or boiling water extraction. The extracts were compared for the phenol and flavonoid contents, and for the in vitro radical scavenging ability. The ethanolic extract (SEE) was selected and characterized by high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS) showing a phenolome rich in tannins (ellagitannins), flavonoids (quercetin derivatives), and triterpenes. The biological activity of SEE was tested on a cellular model of moderate steatosis consisting of lipid-loaded hepatic cells treated with increasing concentrations of SEE (1-25 µg/mL), or with corilagin or quercetin as comparison. In steatotic hepatocytes the SEE was able (i) to ameliorate the hepatosteatosis; (ii) to counteract the excess ROS and lipid peroxidation; (iii) to restore the impaired catalase activity. The results indicate that the ethanolic extract from S. spinosum fruits is endowed with relevant antisteatotic and antioxidant activities and might find application as nutraceutical product.

Protective effects of extracts from Ephedra foeminea Forssk fruits against oxidative injury in human endothelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Ephedra foeminea is a member of the Ephedraceae family which is widespread in the eastern Mediterranean area. In Lebanon, Ephedra is a popular remedy in traditional medicine to prevent and/or counteract many stress oxidative-related diseases like inflammation and bacterial infections. AIM OF THE STUDY: Oxidative stress leads to endothelial cell dysfunction, and is a major factor contributing to etiology of atherosclerosis and related diseases. This study aims to investigate the antioxidant and cytoprotective potential of extracts from E. foeminea fruits on human endothelial cells exposed to hydrogen peroxide (H2O2) to mimic in vitro vascular endothelium dysfunction. MATERIALS AND METHODS: Different extracts of E. foeminea fruits were prepared using pure ethanol (EE), methanol/water (EMW), pure hexane (Ehex) or ethyl acetate/water (Epoly) as extraction solvents. The phenolome profile of each extract was characterized using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS). Total phenolic and flavonoid content, and radical scavenging properties of the extracts were assessed spectrophotometrically. Then, the effects on human endothelial cells HECV were evaluated. RESULTS: Epoly extract showed the highest phenol and flavonoid content, and the highest radical scavenging capacity. On H2O2-insulted HECV cells Epoly was able: (i) to counteract the ROS/RNS production and lipid peroxidation; (ii) to rescue the ROS-dependent decrease in the mitochondrial membrane potential; (iii) to counteract the apoptosis induction; (iv) to restore endothelial cell viability and migration. CONCLUSIONS: The findings indicated that the polyphenol-enriched extract Epoly from E. foeminea fruits is endowed with in vitro anti-oxidant and anti-apoptotic effects and might be used as nutraceutical for treating ROS-related endothelium dysfunction and inflammation.

Antisteatotic and antioxidant activities of Thymbra spicata L. extracts in hepatic and endothelial cells as in vitro models of non-alcoholic fatty liver disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Thymbra spicata, a member of the Lamiaceae family, is native to eastern Mediterranean area. Leaves of this plant are rich in phenolic compounds and are a popular remedy of traditional medicine in Lebanon to prevent and/or counteract hyperlipidemia and hyperglycemia. AIM OF THE STUDY: To evaluate the antisteatotic and antioxidant activities of extracts from leaves of Thymbra spicata L. using in vitro models of non-alcoholic fatty liver disease (NAFLD), a leading cause of liver-related morbidity and mortality worldwide, for whom no effective treatments are still available. MATERIALS AND METHODS: Two different extracts from Thymbra spicata L. aerial parts were prepared using water (TW) or ethanol (TE) as solvent. Their chemical composition was characterized by gas and liquid chromatography coupled with mass spectrometry. Both extracts were tested on cultured hepatic and endothelial cells treated to mimic in vitro a multisistemic pathology such as NAFLD. We assayed the effects on lipid accumulation, free radical production, lipid peroxidation, cell migration. RESULTS: Both the total phenolic and the total flavonoid contents were higher in the ethanolic extract. Rosmarinic acid was the most abundant polyphenol in TW, while TE was richer in carvacrol. Our findings demonstrated that both extracts ameliorated lipid accumulation, oxidative stress and inflammation in the NAFLD cellular models. However, the aqueous extract was more effective to reduce hepatic steatosis, and the ethanolic extract had higheranti-oxidant potential and wound healing activity. CONCLUSIONS: T. spicata extracts could be promising bioactive products to develop natural therapeutic agents or dietary supplements to treat NAFLD and obesity-related metabolic disease. Our findings suggest that while the ethanolic extract might be used in preventing endothelium dysfunction, the aqueous extract would act better as lipid-lowering agent.