Hydroxytyrosol prevents dermal papilla cells inflammation under oxidative stress by inducing autophagy

Hydroxytyrosol (HT), a primary phenolic antioxidant in olive oil, can afford protection from oxidative stress (OS) in different cells, including skin cells. In particular, it regulates several inflammation‐associated processes as well as in improving the antioxidant defense system. However, there is no information about HT used in the treatment of hair loss. This work aimed at exploring the potential protective actions of HT against OS in rat dermal papilla cells. After treatment, the related expression of protein and messenger RNA were detected using morphological and molecular analyses. The results showed that HT significantly reduced intracellular reactive oxygen species level, apoptotic markers and inflammation induced by OS and enhanced cell survival by regulating autophagy. Furthermore, HT enhanced the secretion of hair growth factors in the anti‐inflammation process. These results suggest that HT has a significant protective ability against OS and encourage the use of this biological ingredient as a possible tool to prevent alopecia.     

羟基酪醇作为线粒体营养素的调控机制

地中海饮食,特别是橄榄油,赋予了地中海周边国家人民对于退行性疾病的强力抵抗,尤其是心血管疾病和肿瘤的发生率以及致死率相对更低。羟基酪醇是橄榄油中的多酚类化合物之一,在防治紫外辐射、糖尿病、老年性视网膜黄斑病变、心血管疾病以及肿瘤等方面都具有重要的生物学效应。将具体阐述羟基酪醇作为一种线粒体营养素（如通过调节线粒体的动态变化以及Nrf2介导的抗氧化酶的诱导等）如何促进其有益功能。     

Hydroxytyrosol glucuronides protect renal tubular epithelial cells against H(2)O(2) induced oxidative damage

Hydroxytyrosol (2-(3′,4′-dihydroxyphenyl)ethanol; HT), the most active ortho-diphenolic compound, present either in free or esterified form in extravirgin olive oil, is extensively metabolized in vivo mainly to O-methylated, O-sulfated and glucuronide metabolites. We investigated the capacity of three glucuronide metabolites of HT, 3′-O-β-d-glucuronide and 4′-O-β-d-glucuronide derivatives and 2-(3′,4′-dihydroxyphenyl)ethanol-1-O-β-d-glucuronide, in comparison with the parent compound, to inhibit H₂O₂ induced oxidative damage and cell death in LLC-PK1 cells, a porcine kidney epithelial cell line. H₂O₂ treatment exerted a toxic effect inducing cell death, interacting selectively within the pro-death extracellular-signal relate kinase (ERK 1/2) and the pro-survival Akt/PKB signaling pathways. It also produced direct oxidative damage initiating the membrane lipid peroxidation process. None of the tested glucuronides exhibited any protection against the loss in renal cell viability. They also failed to prevent the changes in the phosphorylation states of ERK and Akt, probably reflecting their inability to enter the cells, while HT was highly effective. Notably, pretreatment with glucuronides exerted a protective effect at the highest concentration tested against membrane oxidative damage, comparable to that of HT: the formation of malondialdehyde, fatty acid hydroperoxides and 7-ketocholesterol was significantly inhibited.     

Enzymatic hydrolysis of olive wastewater for hydroxytyrosol enrichment

Aspergillus niger broth culture on wheat bran was assessed for olive wastewater (OW) hydrolysis in order to release hydroxytyrosol (HT). The enzyme profiles of this culture broth gave essentially (IU/L): 3000 β-glucosidase and 100 esterase. Hydrolysis activity of A. niger enzyme preparation was evaluated by using three substrates: raw OW, phenolic fraction extracted from OW by ethyl acetate and its corresponding exhausted fraction. Large amounts of free simple phenolics were released from exhausted fraction and raw OW after enzymatic treatment. HPLC analyses show that HT was the main phenolic compound. One step of ethyl acetate extraction of hydrolysed OW allowed the recovery of 0.8 g of HT per litre of OW. The antioxidant activity of extracts from OW and exhausted fraction, measured by DPPH method, was drastically enhanced after hydrolysis treatment. This study demonstrates that hydrolysed OW is a potential source of bioactive phenolic compounds with promising applications in food and pharmaceutical industries.     

A new multifunctional hydroxytyrosol-clofibrate with hypolipidemic,antioxidant, and hepatoprotective effects

Oxidative stress has been regarded as the leading mechanism of the hepatotoxicity of clofibrate (CF). To achieve multifunctional novel hypolipidemic agents with hypolipidemia, antioxidant, and ameliorating liver injury, clofibric acid derivative hydroxytyrosol-clofibrate (CF-HT) was synthesized by molecular hybridization. CF-HT exhibited significant hypolipidemia, reducing serum triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 30%, 33%, and 29% in hyperlipidemic mice induced by Triton WR 1339. CF-HT also shown hepatoprotective effect, a significant decrease in hepatic indices toxicity was observed, i.e. aspartate and lactate transaminases (AST and ALT) activities, alkalines phosphatases (ALP), and total bilirubin (TBIL) levels. The liver weight and liver coefficient were also ameliorated. Serum superoxide dismutase (SOD) was significantly elevated, and serum catalase (CAT) and malondialdehyde (MDA) content were remarkably restored. The hepatic glutathione (GSH) content was obviously increased and hepatic oxidized glutathione (GSSG) content was reduced dramatically by CF-HT, as compared to the CF treated mice (p?<?0.05). Moreover, the histopathological damage that hepatocyte hyperplasia and hypertrophy was also significantly ameliorated by treatment with CF-HT. Therefore, the results indicated that CF-HT exerted more potent hypolipidemic activity and definite hepatoprotective effect which may mainly be associated with its antioxidative property in mice.     

羟基酪醇抗肿瘤机制研究进展

羟基酪醇是一种存在于橄榄中的多酚类化合物,具有良好的生物学效应.大量文献表明,羟基酪醇可以诱导多种肿瘤增殖抑制以及凋亡发生.作为一种含酚羟基化合物,羟基酪醇容易发生自氧化,加速其在体外的降解,同时生成过氧化氢.本文综述了羟基酪醇在肿瘤防治领域的研究进展及相应的机制研究,重点就羟基酪醇的自氧化在肿瘤治疗预防中所起的作用进行探讨.     

Possible involvement of oxidative stress in potassium bromate-induced genotoxicity in human HepG2 cells

Potassium bromate (KBrO₃, PB) is a by-product of ozone used as disinfectant in drinking water. And PB is also a widely used food additive. However, there is little known about its adverse effects, in particular those related to its genotoxicity in humans. The aim of this study was to investigate the genotoxic effects of PB and the underlying mechanisms, using human hepatoma cell line, HepG2. Exposure of the cells to PB caused a significant increase of DNA migration in single cell gel electrophoresis (SCGE) assay and micronuclei (MN) frequencies in micronucleus test (MNT) at all tested concentrations (1.56–12.5 mM and 0.12–1 mM), which suggested that PB-mediated DNA strand breaks and chromosome damage. To indicate the role of antioxidant in those effects, DNA migration was monitored by pre-treatment with hydroxytyrosol (HT) as an antioxidant in SCGE assay. It was found that DNA migration with pre-treatment of HT was dramatically decreased. To elucidate the genotoxicity mechanisms, the study monitored the levels of reactive oxygen species (ROS), glutathione (GSH) and 8-hydroxydeoxyguanosine (8-OHdG). PB was shown to induce ROS production (12.5 mM), GSH depletion (1.56–12.5 mM) and 8-OHdG formation (6.25–12.5 mM) in HepG2 cells. Moreover, lysosomal membrane stability and mitochondrial membrane potential were further studied for the mechanisms of PB-induced genotoxicity. A significant increase was found in the range of 6.25–12.5 mM in lysosomal membrane stability assay. However, under these PB concentrations, we were not able to detect the changes of mitochondrial membrane potential. These results suggest that PB exerts oxidative stress and genotoxic effects in HepG2 cells, possibly through the mechanisms of lysosomal damage, an earlier event preceding the oxidative DNA damage.     

Bioconversion of tyrosol into hydroxytyrosol and 3,4-dihydroxyphenylacetic acid under hypersaline conditions by the new Halomonas sp. strain HTB24

This paper reports the characterization of a Halomonas sp. strain (named HTB24) isolated from olive-mill wastewater and capable of transforming tyrosol into hydroxytyrosol (HT) and 3,4-dihydroxyphenylacetic acid (DHPA) in hypersaline conditions. This is the first time that a halophile has been shown to perform such reactions. The potent natural antioxidant HT was obtained through a C3 hydroxylation on the ring cycle, whereas DHPA was synthesized via the 4-hydroxyphenylacetic acid (HPA) pathway, which has been well described from other bacterial sources. HT was produced first, and then DHPA was detected in the medium accompanied by traces of HPA. HPA involved another pathway resulting from the activity of an aryl-dehydrogenase, which is suggested to be responsible for both tyrosol and hydroxytyrosol oxidation. Maximal HT content (2.30 mM) and maximal DHPA (5.15+/-0.42 mM) were obtained from a culture inoculated in the presence of 20 mM tyrosol and 0.5 g L(-1) yeast extract. Following this, DHPA was quickly degraded into 5-carboxymethyl-2-hydroxymuconic semialdehyde by a 2,3-dioxygenase, finally resulting in succinate and pyruvate. Phylogenetic analysis of the 16S rRNA gene revealed that this isolate was a member of the genus Halomonas. Strain HTB24, with a G+C content of 55.3 mol%, is closely related to Halomonas neptunia DSM 15720(T), 'Halomonas alkaliantarctica' DSM 15686(T) and Halomonas boliviensis DSM 15516(T).