In Situ Reaction-Generated Aldehyde-Scavenging Polypeptides-Curcumin Conjugate Nanoassemblies for Combined Treatment of Spinal Cord Injury.

The microenvironment after traumatic spinal cord injury (SCI) involves complex pathological processes, including elevated oxidative stress, accumulated reactive aldehydes from lipid peroxidation, excessive immune cell infiltration, etc. Unfortunately, most of current neuroprotection therapies cannot cope with the intricate pathophysiology of SCI, leading to scant treatment efficacies. Here, we developed a facile in situ reaction-induced self-assembly method to prepare aldehyde-scavenging polypeptides (PAH)-curcumin conjugate nanoassemblies (named as PFCN) for combined neuroprotection in SCI. The prepared PFCN could release PAH and curcumin in response to oxidative and acidic SCI microenvironment. Subsequently, PFCN exhibited an effectively neuroprotective effect through scavenging toxic aldehydes as well as reactive nitrogen and oxygen species in neurons, modulating microglial M1/M2 polarization, and down-regulating the expression of inflammation-related cytokines to inhibit neuroinflammation. The intravenous administration of PFCN could significantly ameliorate the malignant microenvironment of injured spinal cord, protect the neurons, and promote the motor function recovery in the contusive SCI rat model.

Biocatalytic Production of Odor-Active Fatty Aldehydes from Fungal Lipids.

Odor-active fatty aldehydes are important compounds for the flavor and fragrance industry. By a coupled enzymatic reaction using an α-dioxygenase (α-DOX) and an aldehyde dehydrogenase (FALDH), scarcely available aldehydes from the biotransformation of margaroleic acid [17:1(9Z)] were characterized and have shown highly interesting odor profiles, including citrus-like, soapy, herbaceous, and savory notes. In particular, (Z)-8-hexadecenal and (Z)-7-pentadecenal exhibited notable meaty odor characteristics. Submerged cultivation of Mortierella hyalina revealed the accumulation of the above-mentioned, naturally uncommon fatty acid 17:1(9Z). Its production was significantly increased by the modulation of culture conditions, whereas the highest accumulation was observed after 4 days at 24 °C and l-isoleucine supplementation. The lipase-, α-DOX-, and FALDH-mediated biotransformation of M. hyalina lipid extract resulted in a complex aldehyde mixture with a high aldehyde yield of ∼50%. The odor qualities of the formed aldehydes were assessed by means of gas chromatography-olfactometry, and several of the obtained fatty aldehydes have been sensorially described for the first time. To assess the aldehyde mixture's potential as a flavor ingredient, a sensory evaluation was conducted. The obtained product exhibited intense citrus-like, green, and soapy odor impressions.

Oxidized Dietary Oil, High in Omega-3 and Omega-6 Polyunsaturated Fatty Acids, Induces Antioxidant Responses in a Human Intestinal HT29 Cell Line.

When oxidized, dietary oils generate products which have the potential to cause adverse effects on human health. The objective of the study was to investigate whether lipid oxidation products in an oxidized dietary oil can be taken up in intestinal cells, induce antioxidant stress responses and potentially be harmful. The in vitro cell model HT29 was exposed to camelina oil with different extents of oxidation, or only 4-hydroxy-2-hexenal (HHE) or 4-hydroxy-2-nonenal (HNE). The cellular content of HHE increased with an increasing extent of oxidation of the camelina oil added to the cell's growth media, whereas HNE did not show a similar trend. Deuterated HHE was taken up by the HT29 cells, with 140 µM HHE metabolized within 0.5-1 h. The low oxidation degree of the camelina oil increased the gene expression of antioxidant markers (GPX, ATF6, XBP1). The increase in the gene expression of SOD at medium oxidation levels of the oil might indicate different regulation mechanisms. Highly oxidized camelina oil and a low concentration of HHE, over time, induced SOD and catalase enzyme activity in HT29 cells. Oxidized camelina oil contains multiple oxidation products which can be responsible for the intracellular responses observed in HT29 cells, while HHE and HNE in combination with other oxidation products induce antioxidant defence responses.

Non-targeted metabolomic analysis of variation of volatile fractions of ginseng from different habitats by HS-SPME-GC-MS coupled with chemometrics.

Cultivated ginseng (CG), transplanted ginseng (TG) and mountain cultivated ginseng (MCG) classified by the habitat type all belong to Panax ginseng and were reported to have similar types of secondary metabolites. Nonetheless, owing to the distinctly diverse habitats in which these ginseng types grow, their pharmacological effects differ. In the present study, an emerging analytical approach involving headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was established to effectively distinguish among CG, TG and MCG. First, the volatile components were analysed and identified by using the NIST library combined with measured retention indices (Kovats', RI), and a total of 78 volatile components were finally characterized, which included terpenes, alcohols, esters, aldehydes and alkynols. Furthermore, multivariate statistical approaches, principal component analysis (PCA) and orthogonal partial least-squares discrimination analysis (OPLS-DA) were subsequently utilized to screen for compounds of significance. Under optimized HS-SPME-GC-MS conditions, 12, 16, and 16 differential markers were screened in the CG-TG, CG-MCG and TG-MCG groups, respectively. Our study suggested that HS-SPME-GC-MS analysis combined with metabolomic analytical methods and chemometric techniques can be applied as potent tools to identify chemical marker candidates to distinguish CG, TG and MCG.

Short-chain aldehydes increase aluminum retention and sensitivity by enhancing cell wall polysaccharide contents and pectin demethylation in wheat seedlings.

Upon environmental stimuli, aldehydes are generated downstream of reactive oxygen species and thereby contribute to severe cell damage. In this study, using two wheat genotypes differing in aluminum (Al) tolerance, we investigated the effects of lipid peroxidation-derived aldehydes on cell wall composition and subsequent Al-binding capacities. The spatial accumulation of Al along wheat roots was found to the generation of reactive aldehydes, which are highly localized to the apical regions of roots. Elimination of aldehydes by carnosine significantly reduced Al contents in root tips, with a concomitant alleviation of root growth inhibition. In contrast, root growth and Al accumulation were exacerbated by application of the short-chain aldehyde (E)-2-hexenal. We further confirmed that cell wall binding capacity, rather than malate efflux or pH alteration strategies, is associated with the aldehyde-induced accumulation of Al. Scavenging of lipid-derived aldehydes reduced Al accumulation in the pectin and hemicellulose 1 (HC1) fractions of root cell walls, whereas exposure to (E)-2-hexenal promoted a further accumulation of Al, particularly in the cell wall HC1 fraction of the Al-sensitive genotype. Different strategies were introduced by pectin and HC1 to accumulate Al in response to aldehydes in wheat roots. Accumulation in pectin is based on a reduction of methylation levels in response to elevated pectin methylesterase activity and gene expression, whereas that in HC1 is associated with an increase in polysaccharide contents. These findings indicate that aldehydes exacerbate Al phytotoxicity by enhancing Al retention in cell wall polysaccharides.

Aldehyde oxidases mediate plant toxicant susceptibility and fecundity in the red flour beetle, Tribolium castaneum.

Aldehyde oxidases (AOXs) are a group of metabolic enzymes that play critical roles in the degradation of xenobiotics and chemicals. However, the physiological function of this enzyme in insects remains poorly understood. In this study, three TcAOX genes (TcAOX1, TcAOX2, TcAOX3) were identified and characterized from Tribolium castaneum genome. Spatiotemporal expression profiling showed that TcAOX1 expression was most highly expressed at the early pupal stage and was predominantly expressed in the antennae of adults, indicating that TcAOX1 was involved in the degradation of chemical signals; TcAOX2 expression was most highly expressed at the late pupal stage and was mainly expressed in the fat body, epidermis of larvae and adults, respectively; and TcAOX3 expression was in all stages and was primarily expressed in the head of adults. Moreover, the transcripts of TcAOX2 and TcAOX3 were significantly induced after exposure to plant oil, and RNA interference (RNAi) targeting of each of them enhanced the susceptibility of beetles to this plant toxicant, suggesting that these two genes are associated with plant toxicant detoxification. Intriguingly, knockdown of the TcAOX1 led to reductions in female egg-laying but unchanged the hatchability and the development of genital organs, suggesting that this gene may mediate fecundity by effecting the inactivation of chemical signals in T. castaneum. Overall, these results shed new light on the function of AOX genes in insects, and could facilitate the development of research on pest control management.

Citrus depressa Hayata peel ameliorates nonalcoholic fatty liver and modulates the activity of hepatic drug-metabolizing enzymes and transporters in rats fed a high-fat diet.

Citrus depressa Hayata is a small, green citrus fruit native to Taiwan and Japan. Citrus peel contains polymethoxylated flavones, including nobiletin and tangeretin, and may exhibit strong antioxidant and anti-inflammatory activities. A preliminary study revealed that Citrus depressa Hayata peel (CDHP) ethanolic extract reduced fat accumulation and the concentration of reactive oxygen species in human HepG2 cells exposed to oleic acid. The effects of CDHP on the activity of hepatic drug-metabolizing enzymes and membrane transporters in high-fat (HF) diet-induced fatty liver were investigated. Male rats were fed a low-fat diet, a HF diet, and a HF diet containing 4% CDHP for 11 weeks. The low-fat and HF diet respectively contained 13.5% and 38.1% of daily total calories from dietary fat. CDHP supplementation reduced the HF diet-induced accumulation of triglycerides in the liver and lowered hepatic fatty acid synthase activity. Higher faecal excretions of cholesterol, triglycerides, and total bile acids were observed after CDHP treatment. CDHP lowered the HF diet-induced increase in the mRNA expressions of nuclear factor erythroid 2-related factor 2, aryl hydrocarbon receptor, pregnane X receptor, and peroxisome proliferator-activated receptor-α and the activities of cytochrome P-450 (CYP)1A1, 1A2, 2B, and 2E1. However, increased hepatic CYP3A activity was observed in rats fed the HF diet containing CDHP. A higher hepatic multidrug resistance-associated protein 2 level was observed after CDHP treatment. After CDHP administration (1 g per kg body weight) for 1 h, nobiletin was found in plasma and various tissues and was abundant in the liver. An in vitro study revealed that the activity of various CYP enzymes in liver microsomes was inhibited by CDHP ethanolic extract and nobiletin, with IC50 values ranging from 18.5 to 54.4 µg ml-1 and from 13.0 to 33.2 µM, respectively. The results of this study suggest that CDHP might reduce hepatic steatosis and alter drug-metabolizing enzymes and transporters in HF diet-induced nonalcoholic fatty liver diseases.

[Elucidation of Phenomena Involving Cyanobacteria in Freshwater Ecosystem by Chemically Ecological Approach].

Lakes Sagami and Tsukui are reservoirs constructed by connecting to the Sagami River. Because of eutrophication of the lakes, cyanobacteria have appeared every year. This review deals with phenomena related to occurrence of cyanobacteria that have been observed for 40 years since 1974 at the lakes. These 40 years of observations raised three interesting issues including the retention of cyanobacteria on their surfaces. These phenomena have been attributed to the usual factors, such as illuminance, nutrition and water temperature, but our research results suggested that they cannot be resolved without the introduction of another factor. We have attempted to elucidate various phenomena involving cyanobacteria in lake ecosystems by chemical ecological methods using volatile organic compounds (VOCs) produced by the cyanobacteria as indicators. One of the VOCs, ß-cyclocitral, was significantly involved in the above phenomena, which was considered to be produced by the carotenoid cleavage dioxygenase (CCD) of the cyanobacteria. ß-Cyclocitral was not produced in the two known CCDs, but two additional CCDs to Microcystis aeruginosa participated to produce the ß-cyclocitral. These CCDs did not directly produce ß-cyclocitral, but it was accumulated in cells as their precursors. The released ß-cyclocitral underwent a Baeyer-Villiger-like oxidation. It was speculated that Microcystis activated the CCD genes through density stress and produced ß-cyclocitral, which acted as an allelopathic substance. As a result, the number of cells of cyanobacteria decreased, and the resulting nitrogen and phosphorus were fed to the living cyanobacteria. It is postulated that this "quorum sensing" was functioning in the above-mentioned issues.

Simultaneous Determination of Multiple Reactive Carbonyl Species in High Fat Diet-Induced Metabolic Disordered Mice and the Inhibitory Effects of Rosemary on Carbonyl Stress.

As potential endogenous biomarkers, reactive carbonyl species (RCS) have gained abundant attention for monitoring oxidative and carbonyl stress. However, there is no accurate method to evaluate multiple RCS in biological samples. In this study, a 2,4-dinitrophenylhydrazine (DNPH) derivatization-based LC-MS method was developed and validated to quantitate eight RCS: malondialdehyde (MDA), acrolein (ACR), 4-hydroxy-2-nonenal (4-HNE), 4-oxo-2-nonenal (4-ONE), methylglyoxal (MGO), glyoxal (GO), 3-deoxyglucosone (3-DG), and 2-keto-d-glucose (2-Keto). Subsequently, the method was applied to assess the RCS in low fat (LF), high fat (HF), and HF plus rosemary extract (RE) diet-fed mouse samples. The quantitative results on RCS levels indicated that the HF diet significantly increased the total RCS levels in mouse urine, plasma, and kidney with an average rate of 280.69%, 153.87%, and 61.30%, respectively. The RE administration significantly inhibited the elevated RCS levels induced by the HF diet, especially for MDA, 4-ONE, 4-HNE, and 2-Keto in mouse plasma, and ACR and 2-Keto in mouse kidney. This is the first study to simultaneously measure eight RCS in biological samples and demonstrate that RE was able to eliminate the accumulation of the HF diet-induced RCS.

Digestive n-6 Lipid Oxidation, a Key Trigger of Vascular Dysfunction and Atherosclerosis in the Western Diet: Protective Effects of Apple Polyphenols.

SCOPE: A main risk factor of atherosclerosis is a Western diet (WD) rich in n-6 polyunsaturated fatty acids (PUFAs) sensitive to oxidation. Their oxidation can be initiated by heme iron of red meat leading to the formation of 4-hydroxy-2-nonenal (4-HNE), a cytotoxic aldehyde. An increased 4-HNE production is implicated in endothelial dysfunction and atherosclerosis. By contrast, a diet rich in proanthocyanidins reduces oxidative stress and arterial diseases. This study evaluates the effects of a WD on vascular integrity in ApolipoproteinE (ApoE-/- ) mice and the protective capacity of apple extract and puree rich in antioxidant proanthocyanidins. METHODS AND RESULTS: ApoE-/- mice are fed during 12 weeks with a WD with or without n-6 PUFAs. Moreover, two WD + n-6 PUFAs groups are supplemented with apple puree or phenolic extract. An increase in digestive 4-HNE production associated with a rise in plasmatic 4-HNE and oxidized LDL concentrations is reported. Oxidizable n-6 PUFAs consumption is associated with a worsened endothelial dysfunction and atherosclerosis. Interestingly, supplementations with apple polyphenol extract or puree prevented these impairments while reducing oxidative stress. CONCLUSION: n-6 lipid oxidation during digestion may be a key factor of vascular impairments. Nevertheless, an antioxidant strategy can limit 4-HNE formation during digestion and thus durably protect vascular function.

Stabilization of Delphinidin in Complex with Sulfobutylether-ß-Cyclodextrin Allows for Antinociception in Inflammatory Pain.

Aims: Delphinidin (DEL) is a plant-derived antioxidant with clinical potential to treat inflammatory pain but suffers from poor solubility and low bioavailability. The aim of the study was to develop a well-tolerated cyclodextrin (CD)-DEL complex with enhanced bioavailability and to investigate the mechanisms behind its antinociceptive effects in a preclinical model of inflammatory pain. Results: CD-DEL was highly soluble and stable in aqueous solution, and was nontoxic. Systemic administration of CD-DEL reversed mechanical and heat hyperalgesia, while its local application into the complete Freund's adjuvant (CFA)-induced inflamed paw dose-dependently reduced mechanical hyperalgesia, paw volume, formation of the lipid peroxidation product 4-hydroxy-2-nonenal (4-HNE), and tissue migration of CD68+ macrophages. CD-DEL also directly prevented 4-HNE-induced mechanical hyperalgesia, cold allodynia, and an increase in the intracellular calcium concentration into transient receptor potential ankyrin 1 expressing cells. Both 4-HNE- and CFA-induced reactive oxygen species (ROS) levels were sensitive to CD-DEL, while its capacity to scavenge superoxide anion radicals (inhibitory concentration 50 [IC50]: 70 ± 5 µM) was higher than that observed for hydroxyl radicals (IC50: 600 ± 50 µM). Finally, CD-DEL upregulated heme oxygenase 1 that was prevented by HMOX-1 siRNA in vitro. Innovation:In vivo application of DEL to treat inflammatory pain is facilitated by complexation with CD. Apart from its antioxidant effects, the CD-DEL has a unique second antioxidative mechanism involving capturing of 4-HNE into the CD cavity followed by displacement and release of the ROS scavenger DEL. Conclusion: CD-DEL has antinociceptive, antioxidative, and anti-inflammatory effects making it a promising formulation for the local treatment of inflammatory pain.

Docosahexaenoic Acid (DHA) Supplementation Alters Phospholipid Species and Lipid Peroxidation Products in Adult Mouse Brain, Heart, and Plasma.

The abundance of docosahexaenoic acid (DHA) in phospholipids in the brain and retina has generated interest to search for its role in mediating neurological functions. Besides the source of many oxylipins with pro-resolving properties, DHA also undergoes peroxidation, producing 4-hydroxyhexenal (4-HHE), although its function remains elusive. Despite wide dietary consumption, whether supplementation of DHA may alter the peroxidation products and their relationship to phospholipid species in brain and other body organs have not been explored sufficiently. In this study, adult mice were administered a control or DHA-enriched diet for 3 weeks, and phospholipid species and peroxidation products were examined in brain, heart, and plasma. Results demonstrated that this dietary regimen increased (n-3) and decreased (n-6) species to different extent in all major phospholipid classes (PC, dPE, PE-pl, PI and PS) examined. Besides changes in phospholipid species, DHA-enriched diet also showed substantial increases in 4-HHE in brain, heart, and plasma. Among different brain regions, the hippocampus responded to the DHA-enriched diet showing significant increase in 4-HHE. Considering the pro- and anti-inflammatory pathways mediated by the (n-6) and (n-3) polyunsaturated fatty acids, unveiling the ability for DHA-enriched diet to alter phospholipid species and lipid peroxidation products in the brain and in different body organs may be an important step forward towards understanding the mechanism(s) for this (n-3) fatty acid on health and diseases.

Salicylaldehyde derivatives from a marine-derived fungus Eurotium sp. SCSIO F452.

Two pairs of new salicylaldehyde derivative enantiomers, salicylaldehydiums A and B (1 and 2), along with five known analogues were isolated and identified from a marine-derived fungus Eurotium sp. SCSIO F452. Their structures and absolute configuration were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. All the new optical pure enantiomers [(+)-1, (-)-1, (+)-2, (-)-2] were evaluated for their cytotoxic and antioxidative activities. Compound (-)-1 exhibited weak cytotoxic activity.

Antioxidative effects of a novel dietary supplement Neumentix in a mouse stroke model.

BACKGROUND: During an acute stroke, reactive oxygen species are overproduced and the endogenous antioxidative defense systems are disrupted. Therefore, antioxidative therapy can be a promising scheme to reduce the severity of stroke. Neumentix is a novel antioxidative supplement produced from a patented mint line and contains a high content of rosmarinic acid (RA). Although Neumentix has proven diverse efficacy and safety in clinical trials, its effect on strokes is unclear. METHODS: Mice that were treated with Neumentix or vehicle for 14 days underwent transient middle cerebral artery occlusion (tMCAO) for 60 min. Mice were sacrificed 5 days after tMCAO. RESULTS: Neumentix preserved body weight after tMCAO, showed a high antioxidative effect in serum, and reduced infarction volume compared to the vehicle. The expression of 4-hydroxy-2-nonenal, Nε-(carboxymethyl) lysine, and 8-hydroxy-2'-deoxyguanosine was reduced in Neumentix-treated mice. CONCLUSION: The antioxidative effect of Neumentix was confirmed. This is the first report to demonstrate the antioxidative effect of Neumentix on strokes.

Capsaicinoid nonivamide improves nonalcoholic fatty liver disease in rats fed a high-fat diet.

Nonalcoholic fatty liver disease (NAFLD) is a chronic disease that causes morbidity associated with metabolic syndrome. NAFLD is a worldwide problem and represents a major cause of liver injury, which can lead to liver cell death. We investigated the effects of nonivamide (pelargonic acid vanillylamide, PAVA; 1 mg/kg) and rosuvastatin (RSV; 10 mg/kg) on hepatic steatosis induced by a high-fat diet (HFD). Male Sprague-Dawley rats were fed a HFD for 16 weeks then received PAVA or RSV for 4 additional weeks. We examined the metabolic parameters, function, fat content, histological alterations, reactive oxygen species production, and apoptotic cell death of the liver, in addition to the expression of the following important molecules: transient receptor potential cation channel subfamily V member 1 (TRPV1) phosphorylation of sterol regulatory element binding protein (pSREBP-1c/SREBP-1c), total and membrane glucose transporter 2 (GLUT2), 4-hydroxynonenal (4-HNE), and cleaved caspase-3. HFD-induced hepatic steatosis was associated with significantly increased morphological disorganization, injury markers, oxidative stress, lipid peroxidation, and apoptosis. However, metabolic dysfunction and hepatic injury were reduced by RSV and PAVA treatment. PAVA regulated lipid deposition, improved insulin resistance, and decreased oxidative stress and apoptotic cell death. Therefore, PAVA represents a promising therapeutic approach for treating metabolic disorders in patients with NAFLD.

Can Medicinal Plants and Bioactive Compounds Combat Lipid Peroxidation Product 4-HNE-Induced Deleterious Effects?

The toxic reactive aldehyde 4-hydroxynonenal (4-HNE) belongs to the advanced lipid peroxidation end products. Accumulation of 4-HNE and formation of 4-HNE adducts induced by redox imbalance participate in several cytotoxic processes, which contribute to the pathogenesis and progression of oxidative stress-related human disorders. Medicinal plants and bioactive natural compounds are suggested to be attractive sources of potential agents to mitigate oxidative stress, but little is known about the therapeutic potentials especially on combating 4-HNE-induced deleterious effects. Of note, some investigations clarify the attenuation of medicinal plants and bioactive compounds on 4-HNE-induced disturbances, but strong evidence is needed that these plants and compounds serve as potent agents in the prevention and treatment of disorders driven by 4-HNE. Therefore, this review highlights the pharmacological basis of these medicinal plants and bioactive compounds to combat 4-HNE-induced deleterious effects in oxidative stress-related disorders, such as neurotoxicity and neurological disorder, eye damage, cardiovascular injury, liver injury, and energy metabolism disorder. In addition, this review briefly discusses with special attention to the strategies for developing potential therapies by future applications of these medicinal plants and bioactive compounds, which will help biological and pharmacological scientists to explore the new vistas of medicinal plants in combating 4-HNE-induced deleterious effects.

Harpagophytum procumbens Extract Ameliorates Allodynia and Modulates Oxidative and Antioxidant Stress Pathways in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) is a deliberating disorder with impairments in locomotor deficits and incapacitating sensory abnormalities. Harpagophytum procumbens (Hp) is a botanical widely used for treating inflammation and pain related to various inflammatory and musculoskeletal conditions. Using a modified rodent contusion model of SCI, we explored the effects of this botanical on locomotor function and responses to mechanical stimuli, and examined possible neurochemical changes associated with SCI-induced allodynia. Following spinal cord contusion at T10 level, Hp (300 mg/kg, p.o.) or vehicle (water) was administered daily starting 24 h post-surgery, and behavioral measurements made every-other day until sacrifice (Day 21). Hp treatment markedly ameliorated the contusion-induced decrease in locomotor function and increased sensitivity to mechanical stimuli. Determination of Iba1 expression in spinal cord tissues indicated microglial infiltration starting 3 days post-injury. SCI results in increased levels of 4-hydroxynonenal, an oxidative stress product and proalgesic, which was diminished at 7 days by treatment with Hp. SCI also enhanced antioxidant heme oxygenase-1 (HO-1) expression. Concurrent studies of cultured murine BV-2 microglial cells revealed that Hp suppressed oxidative/nitrosative stress and inflammatory responses, including production of nitric oxide and reactive oxygen species, phosphorylation of cytosolic phospholipases A2, and upregulation of the antioxidative stress pathway involving the nuclear factor erythroid 2-related factor 2 and HO-1. These results support the use of Hp for management of allodynia by providing resilience against the neuroinflammation and pain associated with SCI and other neuropathological conditions.

Toxic essential oils, part VI: Acute oral toxicity of lemon balm (Melissa officinalis L.) essential oil in BALB/c mice.

Despite being renowned for its volatiles, the data on the toxicity of the essential oil of lemon balm (Melissa officinalis L., Lamiaceae) is rather limited compared to its solvent/water-soluble extractibles. In this study, the aerial parts essential oil of M. officinalis, with over 130 constituents identified herein, 26 of which detected for the first time, was investigated for acute oral toxicity in BALB/c mice. The oil, composed of predominantly monoterpene aldehydes, citronellal (21.2-21.8%), neral (17.8-18.4%), and geranial (22.9-23.5%), which were assayed in parallel with the oil in some tests, induced significant changes in animal behavior, as well as altered biochemical parameters reflecting liver and kidney functions. Different pathological changes in the stomach, duodenum, liver, and kidneys were detected when the oil was administered in doses higher than 1 g kg-1. A depletion in the liver/kidney antioxidant capacities and an increased rate of lipid peroxidation was noted for animals treated with lemon balm oil. The calculated value of the oral LD50 in BALB/c mice (2.57 g kg-1) infers that the essential oil is only moderately toxic.

ω-3 fish oil fat emulsion preconditioning mitigates myocardial oxidative damage in rats through aldehydes stress.

ω-3 fish oil fat emulsions contain a considerable quantity of unsaturated carbon-carbon double bonds, which undergo lipid peroxidation to yield low-dose aldehydes. These aldehydes may stimulate the production of antioxidant enzymes, thereby mitigating myocardial oxidative damage. This study aims to (1) verify the cardioprotective effect of ω-3 fish oil fat emulsion in vivo and in vitro, and (2) determine whether aldehyde stress is a protective mechanism. For modeling purposes, we pretreated rats with 2 ml/kg of a 10% ω-3 fish oil fat emulsion for 5 days in order to generate a sufficient aldehyde stress response to trigger the production of antioxidant enzymes, and we obtained similar response with H9C2 cells that were pretreated with a 0.5% ω-3 fish oil fat emulsion for 24 h. ω-3 fish oil fat emulsion pretreatment in vivo reduced the myocardial infarct size, decreased the incidence of arrhythmias, and promoted the recovery of cardiac function after myocardial ischemia/reperfusion injury. Once the expression of nuclear factor E2-related factor 2 (Nrf2) was silenced in H9C2 cells, aldehydes no longer produced enough antioxidant enzymes to reverse the oxidative damage caused by tert-butyl hydroperoxide (TBHP). Our results demonstrated that ω-3 fish oil fat emulsion enhanced the inhibition of oxidation and production of free radicals, and alleviated myocardial oxidative injury via activation of the Nrf2 signaling pathway.

Lipid protection by polyphenol-rich apple matrices is modulated by pH and pepsin in in vitro gastric digestion.

Lipid oxidation takes place in the gastric tract after the ingestion of a Western diet rich in ω-6 polyunsaturated fatty acids (PUFA) and red meat (heme iron). The incorporation of oxidation products such as 4-hydroxy-2-nonenal (4-HNE) into low-density lipoproteins is further correlated to endothelial dysfunction. Gastric postprandial stress could thus be reduced by antioxidant phytomicronutrients. The aim of this study was to investigate dietary lipid oxidation and its inhibition by apple polyphenols under different matrix forms (fresh fruit, puree, extract) under in vitro gastric digestion conditions. A deep insight was given into the two factors pH and pepsin governing the metmyoglobin-initiated lipid oxidation of sunflower oil-in-water emulsions simulating the physical state of dietary lipids. Our results first showed that pepsin accelerated lipid oxidation at pH 5 through the formation of a micro-metmyoglobin form likely displaying a higher accessibility to lipids. Spectroscopic studies further highlighted the formation of a reversible unfolded metmyoglobin form at pH 3 which was shown to be more pro-oxidant in the absence of pepsin. At nutritional levels, the three apple matrices inhibited less efficiently the accumulation of lipid-derived conjugated dienes and 4-HNE at pH 5 when pepsin was present whereas at pH 3 the opposite was true. High initial bioaccessibilities of monomeric phenolic compounds were evidenced for both puree (57-74%) and the phenolic extract (79-96%) compared to fresh apple (1-14%) supporting their greater antioxidant capacity. By contrast, the bioaccessibility of dimer B2 was low for all matrices suggesting non-covalent binding to apple pectins.