The Therapeutic Potential of Harpagophytum procumbens and Turnera subulata and Advances in Nutraceutical Delivery Systems in Neurodegenerative Diseases.

This review article covers the therapeutic potential of the plants Harpagophytum procumbens and Turnera subulata in the treatment of neurodegenerative diseases. Despite the recognition of their beneficial properties, there is notable shortage of specific clinical and in vitro studies on these species regarding neurodegenerative diseases. Compounds such as harpagosides and vite-xin-2-O-rhamnoside, found in Harpagophytum procumbens and Turnera subulata, respectively, as well as other antioxidants and anti-inflammatory agents, are associated with mechanisms of action that involve reducing oxidative stress and modulating the inflammatory response, indicating their therapeutic potential in these pathologies. Additionally, the use of nutraceuticals derived from medicinal plants has emerged as a promising approach, offering natural therapeutic alternatives. However, the pressing need for studies focusing on the pharmacokinetics, safety, and pharmacological interactions of these extracts for the treatment of neurodegenerative diseases is emphasized. This review also evaluated advances in nutraceutical delivery systems, highlighting technological innovations that can optimize the precise delivery of these compounds to patients. Such findings highlight the gaps in the study of these plants for the treatment of neurodegenerative diseases and, at the same time, the potential for opening new perspectives in the treatment of neurodegenerative diseases, providing expectations for innovative solutions in this critical domain of medicine.

New Functional Foods with Cactus Components: Sustainable Perspectives and Future Trends.

The growing interest in a healthy lifestyle has contributed to disseminating perspectives on more sustainable natural resource management. This review describes promising aspects of using cacti in the food industry, addressing sustainable, nutritional, and functional aspects of the plant's production. Our study provides an overview of the potential of cacti for the food industry to encourage the sustainable cultivation of underutilized cactus species and their commercial exploitation. The commercial production of cacti has advantages over other agricultural practices by mitigating damage to ecosystems and encouraging migration to sustainable agriculture. The application of cactus ingredients in food development has been broad, whether in producing breads, jellies, gums, dyes, probiotics, and postbiotic and paraprobiotic foods. However, in the field of probiotic foods, future research should focus on technologies applied in processing and researching interactions between probiotics and raw materials to determine the functionality and bioactivity of products.

Paraprobiotics and Postbiotics-Current State of Scientific Research and Future Trends toward the Development of Functional Foods.

The potential of paraprobiotics and postbiotics to be used as beneficial agents for human health has caused an effort by the scientific community to gather information about the bioactivity of these compounds and production methods. Understanding the evolution of scientific research in this area of study is important to understand the future perspectives and the main bottlenecks of scientific and technological development involving these compounds. In this scenario, this review work used a bibliometric analysis tool intending to improve the scientific documentation, bringing information and communicating the results to the scientific community through the quantitative analysis of the current literature, available in one of the main databases, the Web of Science, also providing recent information on the evolution and future perspectives in the field of paraprobiotic and postbiotic development. The results of this study showed that the main studies discuss the bioactivity of these compounds. Concerning the development of functional foods, there is a need for extensive research on production methods and the interaction of these compounds with food. However, it concluded that much still needs to be studied to prove the claims of bioactivity, especially when used for the development of functional foods.

Production and Shelf-Life Study of Probiotic Caja (Spondias mombin L.) Pulp Using Bifidobacterium animalis ssp. Lactis B94.

The highly nutritional caja fruit (Spondias mombin L.) is an accessible source of vitamins and antioxidants that are indispensable for the human diet. The objective of the present work was to study the production of a probiotic caja pulp using Bifidobacterium animalis ssp. lactis B94. Firstly, a kinetic study was performed on the fermentation of the caja pulp with Bifidobacterium animalis ssp. lactis B94 to determine the optimum conditions of the process. Growth kinetics revealed that the ideal time for ending the fermentation would be at 22 h because it corresponds to the end of the exponential phase. Both the whole pulp and the probiotic pulp were characterized for pH, acidity, total soluble solids, water content, phenolic content, reducing carbohydrates, ascorbic acid, and total carotenoids. Physicochemical characterization revealed similar results between the whole and the probiotic pulp. The stability test demonstrated that the probiotic pulp is stable and preserved the probiotic attributes of the final product. In conclusion, our results reveal that caja pulp can be considered a favorable medium for the Bifidobacterium animalis ssp. lactis B94 growth and consequently can be explored biotechnologically for new food products.

Study of Fermentation Strategies by Lactobacillus gasseri for the Production of Probiotic Food Using Passion Fruit Juice Combined with Green Tea as Raw Material.

Foods fermented by Lactobacillus with probiotic properties convey health benefits to consumers, in addition to fulfilling the basic function of nourishing. This work aimed to evaluate the growth characteristics of L. gasseri in passion fruit juice and passion fruit added with green tea. Fermentation under evaluation of different pH (3.5-7.5), temperature (30-44 °C), and with the addition of green tea (7.5-15%), took place for 48 h. The results showed that a pH of 7.5 and temperature of 44 °C showed higher cell production, and it was also verified that the addition of 15% of green tea induced the growth of L. gasseri in passion fruit juice. The concentrations of probiotic cells observed were above 9 Log CFU.mL-1 and, therefore, they are promising products for consumption as a functional food and application in the food industry with potential health benefits.

Probiotics in Citrus Fruits Products: Health Benefits and Future Trends for the Production of Functional Foods-A Bibliometric Review.

The relationship between food and human health drives the search for knowledge of food components that are related to these benefits. The scientific community shows a growing interest in the knowledge of the interactions between components of citrus fruits and probiotics to develop ways to improve the quality of the food produced. In this bibliometric review, a study of scientific publications is carried out on the potential of probiotics in citrus fermentation, addressing the importance and future trends of plant-based products in the functional food group as an alternative to the dairy market. The review process of the articles initially took place with a bibliometric analysis and was followed by a literature review. The Scopus database was used in the search for articles, carried out in May 2021. The use of foods as carriers of probiotics is an alternative that has been growing and the surveys evaluated show the desire to diversify the probiotics available on the market. In addition, it was observed that citrus fruits have great potential for the development of functional foods due to their high acceptability and possibilities of development and application in various products.

Production of Probiotic Passion Fruit (Passiflora edulis Sims f. flavicarpa Deg.) Drink Using Lactobacillus reuteri and Microencapsulation via Spray Drying.

Probiotic foods offer many benefits to human health, causing increased interest in the development of new food products that exploit such benefits. However, traditional dairy foods are being replaced by other non-dairy foods to provide additional sources of benefits provided by bioactive molecules. Therefore, the objective of the present work was to study the production process of a probiotic fruit drink and then microencapsulate the probiotic pulp to stabilize the drink further. Passion fruit pulp (Passiflora edulis Sims f. flavicarpa Deg.) was fermented with Lactobacillus reuteri under different temperature conditions in combination with different pHs to find the best fermentation conditions. Different from dairy sources, the optimal conditions for the growth of Lactobacillus reuteri in the passion fruit pulp were found to be 30 °C at pH 3.18, where phenolic compounds could also be used as a secondary metabolic pathway. Spray-drying was performed using different conditions for microencapsulation. Process yields and Lactobacillus reuteri survival showed the dependency of droplet sizes, whereas phenolic compound retention was increased when higher amounts of gelatin were used. Therefore, the development of a new food product comprising a powdered fruit pulp rich in probiotic and phenolic compounds was possible.

Analysis of Arabidopsis thaliana Redox Gene Network Indicates Evolutionary Expansion of Class III Peroxidase in Plants.

Reactive oxygen species (ROS) are byproducts of aerobic metabolism and may cause oxidative damage to biomolecules. Plants have a complex redox system, involving enzymatic and non-enzymatic compounds. The evolutionary origin of enzymatic antioxidant defense in plants is yet unclear. Here, we describe the redox gene network for A. thaliana and investigate the evolutionary origin of this network. We gathered from public repositories 246 A. thaliana genes directly involved with ROS metabolism and proposed an A. thaliana redox gene network. Using orthology information of 238 Eukaryotes from STRINGdb, we inferred the evolutionary root of each gene to reconstruct the evolutionary history of A. thaliana antioxidant gene network. We found two interconnected clusters: one formed by SOD-related, Thiol-redox, peroxidases, and other oxido-reductase; and the other formed entirely by class III peroxidases. Each cluster emerged in different periods of evolution: the cluster formed by SOD-related, Thiol-redox, peroxidases, and other oxido-reductase emerged before opisthokonta-plant divergence; the cluster composed by class III peroxidases emerged after opisthokonta-plant divergence and therefore contained the most recent network components. According to our results, class III peroxidases are in expansion throughout plant evolution, with new orthologs emerging in each evaluated plant clade divergence.

Development and characterization of blends formulated with banana peel and banana pulp for the production of blends powders rich in antioxidant properties.

The food product industry is increasingly looking for foods with nutritional properties that can provide health benefits. Additionally, a challenge for the food industry is the use of all raw materials. For these reasons, banana peel that is a raw material from Banana (Musa spp.) fruit emerges as potential for new food product development. Here, we developed powder blends using a lyophilization process for the preparation of flour to potential use in cookies, bread, and pasta products. Three formulations were designed; the main difference in the formulations was the use of banana peel concentration. Our results showed that blends produced with banana peel presented physical-chemical properties considered suitable for use in food industry. Moreover, the evaluated morphological parameters reveal the properties of the powders. The blends formulated with banana peel have more antioxidant properties, showing that the banana peel may be an attractive option to generate powders with high antioxidant properties.

Antioxidant and Anti-Inflammatory Properties of Anacardium occidentale Leaf Extract.

In tropical America, principally in Northeastern Brazil, the leaf extract of Anacardium occidentale is traditionally used for treatment of different diseases. However, chemical and biological properties and activities of Anacardium occidentale are poorly investigated and known. Here, we evaluated the antioxidant and anti-inflammatory activities "in vitro" of leaf extract from Anacardium occidentale. Our results show that leaf extract exhibits antioxidant activity when used to treat RAW 264.7 macrophage cells. Antioxidant effects were observed by decrease in oxidative damage in macrophage cells treated with 0.5 µg/mL and 5 µg/mL of leaf extract. Moreover, leaf extract reversed oxidative damage and inflammatory parameters induced in LPS-stimulated RAW 264.7 macrophage cells. Leaf extract at 0.5 µg/mL and 5 µg/mL was able to inhibit release of TNF-α and IL-1ß in LPS-stimulated cells. Taken together, our results indicate antioxidant and anti-inflammatory effects of leaf extract from Anacardium occidentale and reveal the positive effects that intake of these products can mediate in biological system.

Targeted inhibition of RAGE in substantia nigra of rats blocks 6-OHDA-induced dopaminergic denervation.

The receptor for advanced glycation endproducts (RAGE) is a pattern-recognition receptor associated with inflammation in most cell types. RAGE up-regulates the expression of proinflammatory mediators and its own expression via activation of NF-kB. Recent works have proposed a role for RAGE in Parkinson's disease (PD). In this study, we used the multimodal blocker of RAGE FPS-ZM1, which has become available recently, to selectively inhibit RAGE in the substantia nigra (SN) of rats intracranially injected with 6-hydroxydopamine (6-OHDA). FPS-ZM1 (40 µg per rat), injected concomitantly with 6-OHDA (10 µg per rat) into the SN, inhibited the increase in RAGE, activation of ERK1/2, Src and nuclear translocation of NF-kB p65 subunit in the SN. RAGE inhibition blocked glial fibrillary acidic protein and Iba-1 upregulation as well as associated astrocyte and microglia activation. Circulating cytokines in serum and CSF were also decreased by FPS-ZM1 injection. The loss of tyrosine hydroxylase and NeuN-positive neurons was significantly inhibited by RAGE blocking. Finally, FPS-ZM1 attenuated locomotory and exploratory deficits induced by 6-OHDA. Our results demonstrate that RAGE is an essential component in the neuroinflammation and dopaminergic denervation induced by 6-OHDA in the SN. Selective inhibition of RAGE may offer perspectives for therapeutic approaches.

Extracellular superoxide dismutase is necessary to maintain renal blood flow during sepsis development.

BACKGROUND: Extracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasing superoxide levels and preventing peroxynitrite generation, which is important in maintaining renal blood flow and in preventing acute kidney injury. However, the profile of ECSOD expression after sepsis is not fully understood. Therefore, we intended to evaluate the content and gene expression of superoxide dismutase (SOD) isoforms in the renal artery and their relation to renal blood flow. METHODS: Sepsis was induced in Wistar rats by caecal ligation and perforation. Several times after sepsis induction, renal blood flow (12, 24 and 48 h); the renal arterial content of SOD isoforms, nitrotyrosine, endothelial and inducible nitric oxide synthase (e-NOS and i-NOS), and phosphorylated vasodilator-stimulated phosphoprotein (pVASP); and SOD activity (3, 6 and 12 h) were measured. The influence of a SOD inhibitor was also evaluated. RESULTS: An increase in ECSOD content was associated with decreased 3-nitrotyrosine levels. These events were associated with an increase in pVASP content and maintenance of renal blood flow. Moreover, previous treatment with a SOD inhibitor increased nitrotyrosine content and reduced renal blood flow. CONCLUSIONS: ECSOD appears to have a major role in decreasing peroxynitrite formation in the renal artery during the early stages of sepsis development, and its application can be important in renal blood flow control and maintenance during septic insult.

Regulation of lung oxidative damage by endogenous superoxide dismutase in sepsis.

BACKGROUND: The purpose of this research is to study the relationship between superoxide dismutase (SOD) and lung redox state in an animal model of sepsis. METHODS: Sepsis was induced in rats by the cecal ligation and perforation model (CLP). After 3, 6, and 12 h, CLP protein content and expression of SOD1, SOD2, and SOD3 were evaluated, and SOD activity was assessed. Oxidative damage was determined by quantifying nitrotyrosine content. Lung localization of SOD3 was performed by immunohistochemistry. The protective effect of a SOD mimetic on oxidative damage, inflammation, and lung permeability was assessed 12 and 24 h after sepsis induction. RESULTS: Lung levels of SOD1 decreased 3 and 12 h after sepsis, but SOD2 and SOD3 increased, as well as SOD activity. These alterations were not associated with changes in sod gene expression. Nitrotyrosine levels increased 3 and 12 h after sepsis. The administration of a SOD mimetic decreased nitrotyrosine and proinflammatory cytokine levels and improved lung permeability. CONCLUSIONS: SOD2 and SOD3 increased after sepsis induction, but this was insufficient to protect the lung. Treatments based on SOD mimetics could have a role in lung injury associated with sepsis.

Schistosoma mansoni infection causes oxidative stress and alters receptor for advanced glycation endproduct (RAGE) and tau levels in multiple organs in mice.

Schistosomiasis is a parasitic disease caused by trematode worms from the Schistosoma genus and is characterized by high rates of morbidity. The main organs affected in this pathology, such as liver, kidneys and spleen, are shifted to a pro-oxidant state in the course of the infection. Here, we compared oxidative stress parameters of liver, kidney and spleen with other organs affected by schistosomiasis - heart, brain cortex and lungs. The results demonstrated that mice infected with Schistosoma mansoni had altered non-enzymatic antioxidant status in lungs and brain, increased carbonyl levels in lungs, and a moderate level of oxidative stress in heart. A severe redox imbalance in liver and kidneys and decreased non-enzymatic antioxidant capacity in spleen were also observed. Superoxide dismutase and catalase activities were differently modulated in liver, kidney and heart, and we found that differences in Superoxide dismutase 2 and catalase protein content may be responsible for these differences. Lungs had decreased receptor for advanced glycation endproduct expression and the brain cortex presented altered tau expression and phosphorylation levels, suggesting important molecular changes in these tissues, as homeostasis of these proteins is widely associated with the normal function of their respective organs. We believe that these results demonstrate for the first time that changes in the redox profile and expression of tissue-specific proteins of organs such as heart, lungs and brain are observed in early stages of S. mansoni infection.

Retinol induces morphological alterations and proliferative focus formation through free radical-mediated activation of multiple signaling pathways.

AIM: Toxicity of retinol (vitamin A) has been previously associated with apoptosis and/or cell malignant transformation. Thus, we investigated the pathways involved in the induction of proliferation, deformation and proliferative focus formation by retinol in cultured Sertoli cells of rats. METHODS: Sertoli cells were isolated from immature rats and cultured. The cells were subjected to a 24-h treatment with different concentrations of retinol. Parameters of oxidative stress and cytotoxicity were analyzed. The effects of the p38 inhibitor SB203580 (10 µmol/L), the JNK inhibitor SP600125 (10 µmol/L), the Akt inhibitor LY294002 (10 µmol/L), the ERK inhibitor U0126 (10 µmol/L) the pan-PKC inhibitor Gö6983 (10 µmol/L) and the PKA inhibitor H89 (1 µmol/L) on morphological and proliferative/transformation-associated modifications were studied. RESULTS: Retinol (7 and 14 µmol/L) significantly increases the reactive species production in Sertoli cells. Inhibition of p38, JNK, ERK1/2, Akt, and PKA suppressed retinol-induced [(3)H]dT incorporation into the cells, while PKC inhibition had no effect. ERK1/2 and p38 inhibition also blocked retinol-induced proliferative focus formation in the cells, while Akt and JNK inhibition partially decreased focus formation. ERK1/2 and p38 inhibition hindered transformation-associated deformation in retinol-treated cells, while other treatments had no effect. CONCLUSION: Our results suggest that activation of multiple kinases is responsible for morphological and proliferative changes associated to malignancy development in Sertoli cells by retinol at the concentrations higher than physiological level.

The effects of vitamin A supplementation for 3 months on adult rat nigrostriatal axis: increased monoamine oxidase enzyme activity, mitochondrial redox dysfunction, increased ß-amyloid(1-40) peptide and TNF-α contents, and susceptibility of mitochondria to an in vitro H2O2 challenge.

Even though vitamin A has been viewed as an antioxidant molecule, recent findings demonstrate that such vitamin elicits pro-oxidant effects in vivo. Moreover, vitamin A supplements utilization may increase mortality rates among healthy subjects. However, the mechanism by which vitamin A elicits such effects remains to be better analyzed. In this regard, we investigated here the consequences of vitamin A supplementation at 500, 1000, or 2500 IU/kg day(-1) for 3 months on adult rat substantia nigra and striatum total and mitochondrial redox state (both oxidative and nitrosative stress markers), electron transfer chain activity, monoamine oxidase (MAO) enzyme activity, endoplasmic reticulum stress marker (BiP), α- and ß-synucleins, ß-amyloid peptide (1-40), dopamine D2 receptor (D2R), receptor for advanced glycation end products (RAGE), caspase-3 and caspase-8 enzyme activity and tumor necrosis factor-α (TNF-α) levels. Also, nigrostriatal mitochondria were isolated and challenged with 50 µM H2O2 in vitro after vitamin A supplementation and complexes I-III, II-III, and IV enzyme activity was recorded. We observed both total and mitochondrial oxidative and nitrosative stress, increased MAO enzyme activity, and increased levels of α-synuclein, ß-amyloid peptide, RAGE, and TNF-α, but decreased D2R in both rat brain areas. Furthermore, vitamin A supplementation induced a decrease in nigral, but not striatal, ß-synuclein levels in this work. Moreover, mitochondria isolated from both substantia nigra and striatum of vitamin A-treated rats were more sensitive to H2O2 than control mitochondria as assessed through the in vitro assay. Overall, these data may be useful to explain how vitamin A elicits neurotoxic effects chronically.

Redox characterization of usnic acid and its cytotoxic effect on human neuron-like cells (SH-SY5Y).

Usnic acid (UA) is the most common and abundant lichenic secondary metabolite with potential therapeutic application. Anti-inflammatory and antitumour properties have already been reported and UA-enriched extracts are widely used to treat several diseases in the folk medicine. First, we performed in silico evaluation of UA interactions with genes/proteins and important compounds for cellular redox balance and NO pathway. Then, we assessed UA redox properties against different reactive species (RS) generated in vitro, and evaluated its action on SH-SY5Y neuronal like cells upon hydrogen peroxide (H(2)O(2)), since no in vitro neurotoxicological data has been reported so far. Total reactive antioxidant potential index (TRAP) showed a significant antioxidant capacity of UA at the highest tested concentration; UA was also effective against hydroxyl radicals and reduced the formation of nitric oxide. In vitro, lipoperoxidation was enhanced by UA and changed the cellular viability at highest concentration of 20µg/mL for 1 and 4h, as well as 2 and 20µg/mL for 24h of treatment, according to MTT reduction assay. Moreover, UA did not display protective effects against H(2)O(2)-induced cell death in any case. Evaluation of intracellular RS production by the DCFH-based assay indicated that UA was able to induce changes in basal RS production at concentration of 20µg/mL for 1h and from 2ng/mL to 20µg/mL for 4 and 24h. In conclusion, UA could display variable redox-active properties, according to different system conditions and/or cellular environment. Moreover, our results suggest that potential neurotoxicological effects of UA should be further studied by additional approaches; for instance, in vivo and clinical studies.

Redox properties and cytoprotective actions of atranorin, a lichen secondary metabolite.

Atranorin (ATR) is a lichenic secondary metabolite with potential uses in pharmacology. Antinociceptive and antiinflammatory actions have been reported, and the use of atranorin-enriched lichen extracts in folk medicine is widespread. Nonetheless, very few data on ATR biological actions are available. Here, we evaluated free radical scavenging activities and antioxidant potential of ATR using various in vitro assays for scavenging activity against hydroxyl radicals, hydrogen peroxide, superoxide radicals, and nitric oxide. The total reactive antioxidant potential (TRAP) and total antioxidant reactivity (TAR) indexes and in vitro lipoperoxidation were also evaluated. Besides, we determined the cytoprotective effect of ATR on H(2)O(2)-challenged SH-SY5Y cells by the MTT assay. ATR exerts differential effects towards reactive species production, enhancing hydrogen peroxide and nitric oxide production and acting as a superoxide scavenger; no activity toward hydroxyl radical production/scavenging was observed. Besides, TRAP/TAR analysis indicated that atranorin acts as a general antioxidant, although it demonstrated to enhance peroxyl radical-induced lipoperoxidation in vitro. ATR was not cytotoxic, and also protected SH-SY5Y cells against H(2)O(2)-induced cell viability impairment. Our results suggest that ATR has a relevant redox-active action, acting as a pro-oxidant or antioxidant agent depending on the radical. Also, it will exert cytoprotective effects on cells under oxidative stress induced by H(2)O(2).

Vitamin A supplementation to pregnant and breastfeeding female rats induces oxidative stress in the neonatal lung.

Vitamin A is an essential micronutrient that regulates many biological processes through modulation of retinoic acid receptor-responsive genes. Vitamin A acts as a systemic antioxidant, participating in the modulation of diverse redox mechanisms involved in physiological and pathological processes. Different studies, however, observed that vitamin A and other retinoids may induce pro-oxidant/deleterious actions under certain conditions, leading to impairment of brain and lung function. Here, we studied the effect of vitamin A treatment at oral doses of 100 IU/kg, 200 IU/kg, and 300 IU/kg to female rats (Rattus norvegicus) during pregnancy and lactation on oxidative parameters of lungs from the offspring vitamin A supplementation induced increases in lipoperoxidation, protein carbonyl, activities of the antioxidant enzymes superoxide dismutase and catalase (200 IU/kg, and 300 IU/kg), and decreased sulphydryl protein (500 IU/kg) content in the neonatal lung.

Vascular redox imbalance in rats submitted to chronic exercise.

Exercise training has been used for treatment/prevention of many cardiovascular diseases, but the mechanisms need to be clarified. Thus, our aim was to compare oxidative stress parameters between rats submitted to a swimming training and sedentary rats (control). Twelve male rats were divided into two groups: control and exercise training. The exercise training had daily 1 h swimming sessions for 8 weeks and a load (5% of its body mass) was placed in rat's tail. Thereafter the animals were killed, aorta and heart were surgically removed and blood was collected. Body mass gain, thiobarbituric acid reactive species (TBARS), carbonyl content, total reactive antioxidant potential (TRAP), total antioxidant reactivity (TAR), superoxide dismutase (SOD) activity and catalase (CAT) activity were evaluated. The trained rats showed a lower body mass gain and no modifications on heart. An increased SOD activity was observed on aorta after the training, but no changes were seen for CAT activity, which led to an increased SOD/CAT ratio. The arterial TBARS was also increased for trained rats. The decrease in TRAP in exercise training was the single modification on plasma. Our findings suggest that the increased SOD activity could play a role in vascular adaptations to exercise training.