The Combined Antioxidant Effects of N-Acetylcysteine, Vitamin D3, and Glutathione from the Intestinal-Neuronal In Vitro Model.

Chronic oxidative stress has been consistently linked to age-related diseases, conditions, and degenerative syndromes. Specifically, the brain is the organ that significantly contributes to declining quality of life in ageing. Since the body cannot completely counteract the detrimental effects of oxidative stress, nutraceuticals' antioxidant properties have received significant attention in recent years. This study assesses the potential health benefits of a novel combination of glutathione, vitamin D3, and N-acetylcysteine. To examine the combination's absorption and biodistribution and confirm that it has no harmful effects, the bioavailability of the mixture was first evaluated in a 3D model that mimicked the intestinal barrier. Further analyses on the blood-brain barrier was conducted to determine the antioxidant effects of the combination in the nervous system. The results show that the combination reaches the target and successfully crosses the blood-brain and intestinal barriers, demonstrating enhanced advantages on the neurological system, such as a reduction (about 10.5%) in inflammation and enhancement in cell myelination (about 20.4%) and brain tropism (about 18.1%) compared to the control. The results support the cooperative effect of N-acetylcysteine, vitamin D3, and glutathione to achieve multiple health benefits, outlining the possibility of an alternative nutraceutical approach.

Effects of Nutraceutical Compositions Containing Rhizoma Gastrodiae or Lipoic Acid in an In Vitro Induced Neuropathic Pain Model.

BACKGROUND: Peripheral neuropathy is caused by a malfunction in the axons and myelin sheaths of peripheral nerves and motor and sensory neurons. In this context, nonpharmacological treatments with antioxidant potential have attracted much attention due to the issues that some conventional pharmaceutical therapy can generate. Most of these treatments contain lipoic acid, but issues have emerged regarding its use. Considering this, the present study evaluated the beneficial effects of nutraceuticals based on Gastrodiae elata dry extract 10:1 or lipoic acid in combination with other substances (such as citicholine, B vitamins, and acetyl L-carnitine). METHOD: To assess the combination's absorption and biodistribution and exclude cytotoxicity, its bioavailability was first examined in a 3D intestinal barrier model that replicated oral ingestion. Subsequently, a 3D model of nerve tissue was constructed to investigate the impacts of the new combination on the significant pathways dysregulated in peripheral neuropathy. RESULTS: Our findings show that the novel combination outperformed in initial pain relief response and in recovering the mechanism of nerve healing following Schwann cell injury by successfully crossing the gut barrier and reaching the target site. CONCLUSION: This article describes a potential alternative nutraceutical approach supporting the effectiveness of combinations with Gastrodiae elata extract in decreasing neuropathy and regulating pain pathways.

Developing New Cyclodextrin-Based Nanosponges Complexes to Improve Vitamin D Absorption in an In Vitro Study.

Vitamin D plays an important role in numerous cellular functions due to the ability to bind the Vitamin D receptor (VDR), which is present in different tissues. Several human diseases depend on low vitamin D3 (human isoform) serum level, and supplementation is necessary. However, vitamin D3 has poor bioavailability, and several strategies are tested to increase its absorption. In this work, the complexation of vitamin D3 in Cyclodextrin-based nanosponge (CD-NS, in particular, ßNS-CDI 1:4) was carried out to study the possible enhancement of bioactivity. The ßNS-CDI 1:4 was synthesized by mechanochemistry, and the complex was confirmed using FTIR-ATR and TGA. TGA demonstrated higher thermostability of the complexed form. Subsequently, in vitro experiments were performed to evaluate the biological activity of Vitamin D3 complexed in the nanosponges on intestinal cells and assess its bioavailability without cytotoxic effect. The Vitamin D3 complexes enhance cellular activity at the intestinal level and improve its bioavailability. In conclusion, this study demonstrates for the first time the ability of CD-NS complexes to improve the chemical and biological function of Vitamin D3.

Phytochemical investigations and antiproliferative secondary metabolites from Thymus alternans growing in Slovakia.

CONTEXT: Thymus alternans Klokov (Lamiaceae) is a neglected species of the genus Thymus (Sect. Serpyllum) endemic to Carpathian area, where it is used as a flavouring agent and for medicinal purposes. OBJECTIVE: The aim of the work was to identify antiproliferative constituents from the flowering aerial parts of this plant. MATERIALS AND METHODS: Thymus alternans extracts were analyzed by HPLC-MSn and subjected to extensive chromatographic separations. The isolated compounds (phenolics and triterpenes) were structurally elucidated by MS and 1D and 2D NMR experiments. Essential oil (EO) composition was determined by GC-FID and GC-MS. Six purified triterpenes and EO were assayed for in vitro antiproliferative activity against a panel of human cancer cells, namely, breast (MDA-MB 231), colon (HCT-15 and HCT116), lung (U1810), pancreatic (BxPC3), melanoma (A375) and cervical carcinoma (A431) cells. RESULTS: The structures of the isolated compounds were achieved on the basis of H-NMR and MS experiments. Luteolin-4'-O-ß-d-glucopyranoside (P1), chrysoeriol-7-O-ß-d-glucopyranoside (P2), chrysoeriol-5-O-ß-d-glucopyranoside (P3), apigenin-7-O-ß-d-glucopyranoside (P4), rosmarinic acid (P5), rosmarinic acid-3'-O-ß-d-glucopyranoside (P6), caffeic acid-3-O-ß-d-glucopyranoside (P7), 3α-hydroxy-urs-12,15-diene (T1), α-amyrin (T2), ß-amyrin (T3), isoursenol (T4), epitaraxerol (T5), and oleanolic acid (T6). GC-MS analysis revealed that the EO of T. alternans was devoid of phenols and belonged to the nerolidol-chemotype, that is typical of the Sect. Serpyllum. The six purified triterpenes (T1-T6) were active with IC50 ranging from 0.5 to 5 µM being comparable or better than those of reference compounds betulinic acid and cisplatin. The EO exhibited significant effects on A375, MDA-MB 231 and HCT116 cell lines with IC50 in the range of 5-8 µg/mL. CONCLUSION: The reported results suggest that T. alternans can be considered as a good source of phytoconstituents with possible importance in the pharmaceutical field.

Managing a Mass CO Poisoning: Critical Issues and Solutions From the Field to the Hyperbaric Chamber.

Carbon monoxide acute intoxication is a common cause of accidental poisoning in industrialized countries and sometimes it produces a real mass casualty incident. The incident described here occurred in a church in the province of Verona, when a group of people was exposed to carbon monoxide due to a heating system malfunction. Fifty-seven people went to the Emergency Department. The mean carboxyhemoglobin (COHb) level was 10.1±5.7% (range: 3-25%). The clinicians, after medical examination, decided to move 37 patients to hyperbaric chambers for hyperbaric oxygen (HBO) therapy. This is the first case report that highlights and analyses the logistic difficulties of managing a mass carbon monoxide poisoning in different health care settings, with a high influx of patients in an Emergency Department and a complex liaison between emergency services. This article shows how it is possible to manage a complex situation with good outcome. (Disaster Med Public Health Preparedness. 2017;11:251-255).

Secondary Metabolites of Alchemilla persica Growing in Iran (East Azarbaijan).

Phytochemical investigations of Alchemilla persica Rothm. growing in Iran were performed taking into account both the volatile and polar constituents. The hydrodistilled essential oil was analysed by GC-MS that revealed the presence of alkanes (27.8%), diterpenoids (19.6%) and sesquiterpene hydrocarbons (17.1%) as the major constituents, while tannins and flavonol glycosides were identified as the most abundant constituents of the methanol extract by HPLC-MS. A. persica can be a valuable source of ellagitannins and polyphenols.