Biochemical Composition, Antioxidant Capacity and Protective Effects of Three Fermented Plants Beverages on Hepatotoxicity and Nephrotoxicity Induced by Carbon Tetrachloride in Mice.

Functional beverages play an essential role in our modern life and contribute to nutritional well-being. Current efforts to understand and develop functional beverages to promote health and wellness have been enhanced. The present study aimed to investigate the production of three fermented plants beverages (FPBs) from aromatic and medicinal plants and to evaluate the fermented product in terms of physio-biochemical composition, the aromatic compounds, antioxidant activity, and in vivo protective effects on hepatotoxicity and nephrotoxicity induced by carbon tetrachloride (CCl4). The results showed that the fermented beverage NurtBio B had the highest levels of polyphenols, flavonoids, and tannins; 242.3 ± 12.4 µg GAE/mL, 106.4 ± 7.3 µg RE/mL and 94.2 ± 5.1 µg CE/mL, respectively. The aromatic profiles of the fermented beverages showed thirty-one interesting volatile compounds detected by GC-MS headspace analyses such as benzaldehyde, Eucalyptol, Fenchone, 3-Octadecyne, Estragole, and Benzene propanoic acid 1-methylethyl ester. In addition, the fermentation process was significantly improved, indicating its great potential as a functional food with both strong antioxidant activity and good flavor. In vivo administration of CCl4 in mice induced hepatotoxicity and nephrotoxicity by a significant rise in the levels of serum liver and kidney biomarkers. The protective effects of the FPBs showed that they significantly restored the majority of these biological parameters to normal levels, along with increase antioxidant enzyme activities, as well as an improvement of histopathological changes, suggesting their protective effects.

The antioxidant 2,3-dichloro,5,8-dihydroxy,1,4-naphthoquinone inhibits acetyl-cholinesterase activity and amyloid ß42 aggregation: A dual target therapeutic candidate compound for the treatment of Alzheimer's disease.

Alzheimer's disease is characterized by amyloid ß aggregation and cholinergic neurodegeneration. In the present study, pure DDN (2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone) was examined, for the first time, for its dual potential as inhibitor of acetylcholinesterase (AChE) and Aß42 aggregation. Such investigation was encouraged by the in vitro high antioxidant potential of DDN. Indeed, it revealed interesting antioxidant activity with IC50 values of 9.8 and 4.3 µM for ABTS and reducing power, respectively. The ability of DDN to counteract Aß42 aggregation was evaluated by thioflavine-T assay. Strong inhibition of Aß42 aggregation of more than 90% at 25 µM was measured. Moreover, results showed that DDN inhibited AChE (IC50 = 14.5 µM). To better understand the interactions between DDN and AChE, molecular docking was performed. Obtained data predicted a high interaction characterized by hydrogen bonding at TYR337 as for galanthamine (positive control). Several residues involved in AChE hydrophobic interactions were similarly implicated in binding of this domain to DDN (ASP74, THR83, and TYR124). All these data would be useless if DDN could not pass the blood-brain barrier. So, DDN was loaded into alginate microspheres to enhance its stability and bioavailability. Thereafter, drug release profiles were assessed using immersion cell apparatus.

1,2,4-trihydroxynaphthalene-2-O-ß-D-glucopyranoside: A new powerful antioxidant and inhibitor of Aß42 aggregation isolated from the leaves of Lawsonia inermis.

Mounting evidence indicates free radicals as toxic species causing damage to human cells leading to the pathogenesis of many diseases such as neurodegenerative disease. Plant derived antioxidants are considered as promising strategy to prevent free radical toxicity. In this study, the crude extract (CE), 50%MeOH, Petroleum Ether (PE) and Ethyl acetate (EA) fractions of Lawsonia inermis leaves were investigated for their antioxidant activity and their ability to counteract amyloid-ß42 (Aß42) aggregation. Elution of the most bioactive fraction (EA) on silica gel column chromatography led to six sub-fractions. The most active sub-fraction (1) was further resolved on silica gel column chromatography. A new compound with powerful antioxidant and anti-Aß42 aggregation properties was purified and characterised by spectroscopic methods as 1,2,4-trihydroxynaphthalene-2-O-ß-D-glucopyranoside (THNG). This finding suggests that the antioxidant and anti-Aß42 aggregation activities of L. inermis leaves are strongly correlated to this compound.

Chemical composition, antimicrobial and antioxidant activities data of three plants from Tunisia region: Erodium glaucophyllum, Erodium hirtum and Erodium guttatum.

In the present work, phytochemical contents (total phenolic content, total flavonoids, and condensed tannins), antioxidant potentials, and antimicrobial activities of three plants in the Mediterranean genus Erodium (Erodium glaucophyllum, Erodium hirtum, and Erodium guttatum) from the Tunisia region were analyzed. The results showed that E. glaucophyllum contained high levels of polyphenols, flavonoids, and tannins. Therefore, E. glaucophyllum possesses high antioxidant activities (2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power scavenging activities), and high inhibition of linoleic acid oxidation. All three plants exhibited high antimicrobial activities. This study highlights tree plants' importance as dietary sources for natural antioxidants can be used in traditional medicine and the pharmaceutical industry.

Inhibition of protein misfolding and aggregation by natural phenolic compounds.

Protein misfolding and aggregation into fibrillar deposits is a common feature of a large group of degenerative diseases affecting the central nervous system or peripheral organs, termed protein misfolding disorders (PMDs). Despite their established toxic nature, clinical trials aiming to reduce misfolded aggregates have been unsuccessful in treating or curing PMDs. An interesting possibility for disease intervention is the regular intake of natural food or herbal extracts, which contain active molecules that inhibit aggregation or induce the disassembly of misfolded aggregates. Among natural compounds, phenolic molecules are of particular interest, since most have dual activity as amyloid aggregation inhibitors and antioxidants. In this article, we review many phenolic natural compounds which have been reported in diverse model systems to have the potential to delay or prevent the development of various PMDs, including Alzheimer's and Parkinson's diseases, prion diseases, amyotrophic lateral sclerosis, systemic amyloidosis, and type 2 diabetes. The lower toxicity of natural compounds compared to synthetic chemical molecules suggest that they could serve as a good starting point to discover protein misfolding inhibitors that might be useful for the treatment of various incurable diseases.

A new purified Lawsoniaside remodels amyloid-ß42 fibrillation into a less toxic and non-amyloidogenic pathway.

Mounting evidence indicates soluble Aß42 oligomers as the most toxic species causing neuronal death which leads to the onset and progression of Alzheimer disease (AD). Recently, it has been found that neurotoxic Aß42 oligomers grow from monomeric species or arise following secondary nucleation by preformed mature fibrils. Thus, the use of natural compounds such as polyphenols to hinder the growth or to remodel Aß42 fibrils is one of the most promising strategies for AD treatment. In our previous study, we showed that 1, 2, 4-trihydroxynaphthalene-2-O-ß-d-glucopyranoside (THNG) inhibits Aß42 aggregation during the early steps of the aggregation process, inhibits its conformational change to a ß-sheet-rich structure, decreases its polymerization, inhibits its fibrillogenisis and reduces oxidative stress and aggregate cytotoxicity. Here, we used different spectroscopic and cell culture methods to check the effect of THNG on fibrils disaggregation. We showed that THNG binds to mature Aß42 fibrils, rearrange their secondary structure, and remodels them into non-amyloid, less toxic, species by inhibiting their interaction with the plasma membrane. Our findings reveal that THNG is a good agent to remodel amyloid fibrils and could be used as a starting molecular scaffold to design new anti-AD drugs.

1,2,4-trihydroxynaphthalene-2-O-ß-D-glucopyranoside delays amyloid-ß42 aggregation and reduces amyloid cytotoxicity.

Presently, misfolding and aggregation of amyloid-ß42 (Aß42 ) are considered early events in Alzheimer's disease (AD) pathogenesis. The use of natural products to inhibit the aggregation process and to protect cells from cytotoxicity of early aggregate grown at the onset of the aggregation path is one of the promising strategies against AD. Recently, we have purified a new powerful antioxidant and inhibitor of Aß42 aggregation from the leaves of Lawsonia inermis. The new compound was identified as a new Lawsoniaside; 1,2,4-trihydroxynaphthalene-2-O-ß-D-glucopyranoside (THNG). Herein, we show that THNG interferes with Aß42 aggregation, inhibits its conformational change to a ß-sheet-rich structure, decreases its polymerization into large fibrillar species, reduces oxidative stress, and aggregate cytotoxicity. These results indicate that THNG has great potential as a neuroprotective and therapeutic agent against AD. © 2018 BioFactors, 44(3):272-280, 2018.