Potential Implications of Rimonabant on Age-Related Oxidative Stress and Inflammation

Over the last decades, growing interest has turned to preventive and therapeutic approaches for achieving successful aging. Oxidative stress and inflammation are fundamental features of cardiovascular diseases; therefore, potential targets of them can improve cardiac outcomes. Our study aimed to examine the involvement of the endocannabinoid system, especially the CB1 receptor blockade, on inflammatory and oxidant/antioxidant processes. Twenty-month-old female and male Wistar rats were divided into rimonabant-treated and aging control (untreated) groups. Rimonabant, a selective CB1 receptor antagonist, was administered at the dose of 1 mg/kg/day intraperitoneally for 2 weeks. Cardiac amounts of ROS, the antioxidant glutathione and superoxide dismutase (SOD), and the activity and concentration of the heme oxygenase (HO) enzyme were detected. Among inflammatory parameters, nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and myeloperoxidase (MPO) enzyme activity were measured. Two weeks of low dose rimonabant treatment significantly reduced the cardiac ROS via boosting of the antioxidant defense mechanisms as regards the HO system, and the SOD and glutathione content. Consistently, the age-related inflammatory response was alleviated. Rimonabant-treated animals showed significantly decreased NF-κB, TNF-α, and MPO levels. Our findings prove the beneficial involvement of CB1 receptor blocker rimonabant on inflammatory and oxidative damages to the aging heart.

Effects of Isorhamnetin on Diabetes and Its Associated Complications: A Review of In Vitro and In Vivo Studies and a Post Hoc Transcriptome Analysis of Involved Molecular Pathways

Diabetes mellitus, especially type 2 (T2DM), is a major public health problem globally. DM is characterized by high levels of glycemia and insulinemia due to impaired insulin secretion and insulin sensitivity of the cells, known as insulin resistance. T2DM causes multiple and severe complications such as nephropathy, neuropathy, and retinopathy causing cell oxidative damages in different internal tissues, particularly the pancreas, heart, adipose tissue, liver, and kidneys. Plant extracts and their bioactive phytochemicals are gaining interest as new therapeutic and preventive alternatives for T2DM and its associated complications. In this regard, isorhamnetin, a plant flavonoid, has long been studied for its potential anti-diabetic effects. This review describes its impact on reducing diabetes-related disorders by decreasing glucose levels, ameliorating the oxidative status, alleviating inflammation, and modulating lipid metabolism and adipocyte differentiation by regulating involved signaling pathways reported in the in vitro and in vivo studies. Additionally, we include a post hoc whole-genome transcriptome analysis of biological activities of isorhamnetin using a stem cell-based tool.

Nitric Oxide as a Remedy against Oxidative Damages in Apple Seeds Undergoing Accelerated Ageing

Seed ageing is associated with a high concentration of reactive oxygen species (ROS). Apple (Malus domestica Borkh.) seeds belong to the orthodox type. Due to a deep dormancy, they may be stored in dry condition at 5 °C for a long time, without viability loss. In the laboratory, artificial ageing of apple seeds is performed by imbibition in wet sand at warm temperature (33 °C). The aim of the work was to study nitric oxide (NO) as a seed vigour preservation agent. Embryos isolated from apple seeds subjected to accelerated ageing for 7, 14, 21 or 40 days were fumigated with NO. Embryo quality was estimated by TTC and MDA tests. ROS level was confirmed by NBT staining. We analysed the alteration in transcript levels of CAT, SOD and POX. NO fumigation of embryos of seeds aged for 21 days stimulated germination and increased ROS level which correlated to the elevated expression of RBOH. The increased total antioxidant capacity after NO fumigation was accompanied by the increased transcript levels of genes encoding enzymatic antioxidants, that could protect against ROS overaccumulation. Moreover, post-aged NO application diminished the nitro-oxidative modification of RNA, proving NO action as a remedy in oxidative remodelling after seeds ageing.

Protection of Aronia melanocarpa Fruit Extract from Sodium-Iodate-Induced Damages in Rat Retina

Age-related macular degeneration (AMD) is one of the major causes of blindness in elderly populations. However, the dry form of AMD has lack of effective treatments. The fruits of Aronia melanocarpa are rich in anthocyanins. In this study, the protective effects of aronia fruit extract on rat retina were investigated using a NaIO3-induced dry AMD model. Full-field electroretinograms (ERGs) showed that b-wave amplitudes were significantly decreased and the retina structures were disordered in the model. The extract treatment alleviated the injuries. The b-wave amplitudes increased 61.5% in Scotopic 0.01ERG, 122.0% in Photopic 3.0ERG, and 106.8% in Photopic 3.0 flicker; the retina structure disorder was improved with the thickness of outer nuclear layer increasing by 44.1%; and the malonaldehyde level was significantly reduced in extract-treated rat retinas compared to the model. The proteomics analysis showed the expressions of five crystallin proteins, α-crystallin A chain, β-crystallin B2, β-crystallin A3, α-crystallin B chain, and γ-crystallin S, which protect retina ganglion cells, were increased by 7.38-, 7.74-, 15.30-, 4.86-, and 9.14-fold, respectively, in the extract treatment compared to the control, which was also confirmed by immunoblotting. The results suggest that aronia fruit extract, probably due to its anthocyanins, could protect the rat retina by alleviating oxidative damages and by upregulating the crystallin proteins to protect its nerve system.

Folic Acid Protects Melanocytes from Oxidative Stress via Activation of Nrf2 and Inhibition of HMGB1

Vitiligo is a cutaneous depigmentation disease due to loss of epidermal melanocytes. Accumulating evidence has indicated that oxidative stress plays a vital role in vitiligo via directly destructing melanocytes and triggering inflammatory response that ultimately undermines melanocytes. Folic acid (FA), an oxidized form of folate with high bioavailability, exhibits potent antioxidant properties and shows therapeutic potential in multiple oxidative stress-related diseases. However, whether FA safeguards melanocytes from oxidative damages remains unknown. In this study, we first found that FA relieved melanocytes from H2O2-induced abnormal growth and apoptosis. Furthermore, FA enhanced the activity of antioxidative enzymes and remarkably reduced intracellular ROS levels in melanocytes. Subsequently, FA effectively activated nuclear factor E2-related factor 2 (Nrf2) pathway, and Nrf2 knockdown blocked the protective effects of FA on H2O2-treated melanocytes. Additionally, FA inhibited the production of proinflammatory HMGB1 in melanocytes under oxidative stress. Taken together, our findings support the protective effects of FA on human melanocytes against oxidative injury via the activation of Nrf2 and the inhibition of HMGB1, thus indicating FA as a potential therapeutic agent for the treatment of vitiligo.

Edible Mushrooms: A Comprehensive Review on Bioactive Compounds with Health Benefits and Processing Aspects

Mushrooms are well-known functional foods due to the presence of a huge quantity of nutraceutical components. These are well recognized for their nutritional importance such as high protein, low fat, and low energy contents. These are rich in minerals such as iron, phosphorus, as well as in vitamins like riboflavin, thiamine, ergosterol, niacin, and ascorbic acid. They also contain bioactive constituents like secondary metabolites (terpenoids, acids, alkaloids, sesquiterpenes, polyphenolic compounds, lactones, sterols, nucleotide analogues, vitamins, and metal chelating agents) and polysaccharides chiefly β-glucans and glycoproteins. Due to the occurrence of biologically active substances, mushrooms can serve as hepatoprotective, immune-potentiating, anti-cancer, anti-viral, and hypocholesterolemic agents. They have great potential to prevent cardiovascular diseases due to their low fat and high fiber contents, as well as being foremost sources of natural antioxidants useful in reducing oxidative damages. However, mushrooms remained underutilized, despite their wide nutritional and bioactive potential. Novel green techniques are being explored for the extraction of bioactive components from edible mushrooms. The current review is intended to deliberate the nutraceutical potential of mushrooms, therapeutic properties, bioactive compounds, health benefits, and processing aspects of edible mushrooms for maintenance, and promotion of a healthy lifestyle.