Therapeutic potential of saffron in brain disorders: From bench to bedside.

Saffron is a spice derived from the flower of Crocus sativus L., which has been used for centuries as a coloring and flavoring agent, as well as a source of medicinal compounds. Saffron contains various bioactive constituents, such as crocin, crocetin, safranal, picrocrocin, and kaempferol, that have shown potential benefits for human health. Among them, crocin is the most abundant and characteristic constituent of saffron, responsible for its bright red color and antioxidant properties. One of the most promising applications of saffron and its constituents is in the prevention and treatment of neurological disorders, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, and other brain disorders. Saffron and its constituents have been reported to exert neuroprotective effects through various mechanisms, such as modulating neurotransmitters, enhancing neurogenesis, reducing neuroinflammation, regulating oxidative stress, activating the Nrf2 signaling pathway, and modulating epigenetic factors. Several clinical and preclinical studies have demonstrated the efficacy and safety of saffron and its constituents in improving cognitive function, mood, and other neurological outcomes. In this review, we summarize the current evidence on the therapeutic potential of saffron and its constituents in neurological disorders, from bench to bedside. We also discuss the challenges and future directions for the development of saffron-based therapies for brain health.

Antiulcer activity of Mauritia flexuosa L.f. (Arecaceae) pulp oil: An edible Amazonian species with functional properties.

Mauritia flexuosa, known as buriti in Brazil, is a widespread palm tree in Amazonia. It has many ethnobotanical uses, including food, oil, and medicine. The oil obtained from buriti's fruit pulp has high levels of monounsaturated fatty acids, carotenoids, and tocopherols, and is used in the food, cosmetic, and pharmaceutical industries for its antioxidant properties. Many biological activities have been reported for buriti oil, such as antioxidant, antimicrobial, chemopreventive, and immunomodulatory. Due to its high content of bioactive compounds, buriti oil is considered a functional ingredient with possible benefits in preventing oxidative stress and chronic diseases, particularly in the gastrointestinal tract. Peptic ulcer disease is a multifactorial disorder, involving lesions in the stomach and duodenum mucosa, which has a complex healing process. In this context, some nutrients and bioactive compounds help the maintenance of gastrointestinal mucosal integrity and function, such as carotenoids, tocopherols, and unsaturated fatty acids, which makes buriti oil an interesting candidate to be used in the prevention and management of gastrointestinal diseases. This study aimed to evaluate the gastroprotective and antiulcer effects of buriti oil and its possible mechanisms of action. Buriti oil reduced the ulcerative area and lipid peroxidation induced by ethanol. The gastroprotective activity of buriti oil partially depends on nitric oxide and sulfhydryl compounds. In acetic acid-induced gastric ulcers, buriti oil accelerated healing and stimulated the formation of new gastric glands. These results demonstrated the potential of buriti oil as a functional ingredient to promote health benefits in the gastrointestinal tract.

Does crocin create new hope for the treatment of oral problems? A focus on periodontitis.

According to the World Health Organization (WHO) reports, oral health has an indispensable role in the maintenance of human public health. However, oral problems, especially periodontitis, are known as bad players in this issue. Periodontitis, as the most prevalent oral disease, is a type of chronic illness mediated by bacterial pathogens and immune system reactions, which is linked with the destruction of tooth-protecting tissues, such as alveolar bone and periodontal ligament. Periodontitis has a high prevalence (over 40% in the United States) and can be associated with other systemic ailments, for instance, arthritis, osteoporosis, metabolic syndrome, cancer, respiratory diseases, chronic kidney disease, and Alzheimer's disease. The common treatments for periodontitis are classified into invasive (surgical) and noninvasive (antibiotic therapy, scaling, and root planning) methods; however, these therapies have not reflected enough effectiveness for related patients. New documents inform the beneficial effects of plant-based compounds in healing various disorders, like periodontitis. In conjunction with this subject, it has been revealed that crocin, as an active component of saffron, regulates the balance between osteoclasts and osteoblasts and has a stroking role in the accumulation of the most common collagen in teeth and bone (type 1 collagen). Besides, this carotenoid compound possesses anti-inflammatory and anti-oxidative effects, which can be associated with the therapeutic processes of crocin in this oral disease. Hence, this narrative review study was performed to reflect the reparative/regenerative aspects of crocin agonist periodontitis.

Recent progress in practical applications of a potential carotenoid astaxanthin in aquaculture industry: a review.

Astaxanthin is the main natural C40 carotenoid used worldwide in the aquaculture industry. It normally occurs in red yeast Phaffia rhodozyma and green alga Haematococcus pluvialis and a variety of aquatic sea creatures, such as trout, salmon, and shrimp. Numerous biological functions reported its antioxidant and anti-inflammatory activities since astaxanthin possesses the highest oxygen radical absorbance capacity (ORAC) and is considered to be over 500 more times effective than vitamin E and other carotenoids such as lutein and lycopene. Thus, synthetic and natural sources of astaxanthin have a commanding influence on industry trends, causing a wave in the world nutraceutical market of the encapsulated product. In vitro and in vivo studies have associated astaxanthin's unique molecular features with various health benefits, including immunomodulatory, photoprotective, and antioxidant properties, providing its chemotherapeutic potential for improving stress tolerance, disease resistance, growth performance, survival, and improved egg quality in farmed fish and crustaceans without exhibiting any cytotoxic effects. Moreover, the most evident effect is the pigmentation merit, where astaxanthin is supplemented in formulated diets to ameliorate the variegation of aquatic species and eventually product quality. Hence, carotenoid astaxanthin could be used as a curative supplement for farmed fish, since it is regarded as an ecologically friendly functional feed additive in the aquaculture industry. In this review, the currently available scientific literature regarding the most significant benefits of astaxanthin is discussed, with a particular focus on potential mechanisms of action responsible for its biological activities.

Phytochemical analysis of carotenoid profile in Mentha piperita and Artemisia vulgaris: cytotoxicity in tumoral cells and evaluation of plasmid DNA cleavage.

Several medicinal plants have been administered to cancer patients attributed to their anticarcinogenic and chemoprotective properties, in addition to lower toxicity compared to traditional therapies. The aim was to investigate the antioxidant properties and carotenoid composition of aqueous extracts of Mentha piperita or Artemisia vulgaris which were previously found to exert beneficial effects on human health through diet. aqueous extracts exhibited potent antioxidant activity. A diversity of carotenoids was identified in these extracts using HPLC-PDA-MS/MS. Both extracts contained predominantly all-trans-lutein as the main component within this class. In order to investigate antioxidant properties, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) techniques were used. The (3-4,5 dimethylthiazol-2, 5 diphenyl tetrazolium bromide) (MTT) and Crystal Violet assays assessed cellular cytotoxicity. Assessments of presence of reactive species were carried out following exposure of oral squamous cell carcinoma cell line (SCC-4) to various aqueous extracts of M piperita or A vulgaris utilizing dichlorofluorescein diacetate (DCFH-DA) and nitric oxide (NO) assays. Exposure to these extracts induced severe cytotoxic effects, which led to investigation of the biochemical and molecular mechanisms underlying this observed effect. Data demonstrated that both solutions induced oxidative stress and DNA damage, especially at higher concentrations using agarose gel subjected to electrophoresis. It is known that exposure to excess amounts of antioxidants results in a prooxidant effect which is beneficial in cancer therapy. Further, the extracts were found to reduce viability of SCC-4 in culture, indicating that this antitumoral activity may be of therapeutic importance and requires further study.

Effects of carotenoid supplementation on colour, growth and physiological function of the endemic dwarf chameleon fish (Badis badis).

The global ornamental fish trade is expanding in response to increased demand for indigenous fish on the global market, while exogenous carotenoids can improve colouration. The 60-day trial investigated the effect of carotenoid supplementation, via Artemia, on colouration, growth and immunophysiology of Badis badis (dwarf chameleon fish). Carotenoid was enriched at 40 ppm (T1), 80 ppm (T2) and 120 ppm (T3) and compared with controls, C1 (unenriched) and C2 (oil-enriched). Fish larvae (average weight 0.12 g) were fed enriched-unenriched Artemia in triplicates (5 × 3) in aquarium tanks (15 L). C1 and T2 had better skin colour (lightness and whiteness) in the posterolateral and caudal fins respectively. The value of redness (a*) in the anterolateral region was higher in T2 and T3 (p < 0.05). The anterolateral red index was higher (p < 0.05) in T2 and T3, whereas in the posterolateral and caudal fins, T1 and T2 were higher (p < 0.05). Compared to C1 and C2, the hue angle in carotenoid groups was found to be low (p < 0.05). No significant change in the growth performance was noticed (p > 0.05). Immune scores such as lysozyme and alkaline protease were highest in T3 (p < 0.05), whereas protease activity was highest in T2 (80 ppm). Stress biomarkers, viz., superoxide dismutase, catalase and malondialdehyde were low in groups fed enriched Artemia (p < 0.05). The integrated biomarker response means and star plot area were lower in the enriched groups (T1-T3), while T2 was the lowest. Overall findings reveal that dietary carotenoid improves the colouration and immune status, but fail to promote growth. Furthermore, 80 ppm enrichment dose improves the overall performance. The findings can help fish keepers improve fish colour and health status through carotenoid supplementation.

Enzyme-Based Biostimulants Influence Physiological and Biochemical Responses of Lactuca sativa L.

Biostimulants (BSs) are natural materials (i.e., organic or inorganic compounds, and/or microorganisms) having beneficial effects on plant growth and productivity, and able to improve resilience/tolerance to biotic and abiotic stresses. Therefore, they represent an innovative alternative to the phyto- and agrochemicals, being environmentally friendly and a valuable tool to cope with extreme climate conditions. The objective of this study was to investigate the effects of several biomolecules (i.e., Xylanase, ß-Glucosidase, Chitinase, and Tramesan), alone or in combinations, on lettuce plant growth and quality. With this aim, the influence of these biomolecules on biomass, pigment content, and antioxidant properties in treated plants were investigated. Our results showed that Xylanase and, to a lesser extent, ß-Glucosidase, have potentially biostimulant activity for lettuce cultivation, positively influencing carotenoids, total polyphenols, and ascorbic acid contents; similar effects were found with respect to antioxidative properties. Furthermore, the effect of the more promising molecules (Xylanase and ß-Glucosidase) was also evaluated in kiwifruit cultured cells to test their putative role as sustainable input for plant cell biofactories. The absence of phytotoxic effects of both molecules at low doses (0.1 and 0.01 µM), and the significantly enhanced cell biomass growth, indicates a positive impact on kiwifruit cells.

Simultaneous extraction of crocin and geniposide from gardenia fruits (Gardenia jasminoides Ellis) by probe-type ultrasound-assisted natural deep eutectic solvents and their inhibition effects on low density lipoprotein oxidation.

The simultaneous extraction of crocin and geniposide from gardenia fruits (Gardenia jasminoides Ellis) was performed by integrating natural deep eutectic solvents (NADES) and ultrasound-assisted extraction (UAE). Among the eight kinds of NADES screened, choline chloride-1,2-propylene glycol was the most suitable extractant. The probe-type ultrasound-assisted NADES extraction system (pr-UAE-NADES) demonstrated higher extraction efficiency compared with plate-type ultrasound-assisted NADES extraction system (pl-UAE-NADES). Orthogonal experimental design and a modified multi-index synthetic weighted scoring method were adopted to optimize pr-UAE-NADES extraction process. The optimal extraction conditions that had a maximum synthetic weighted score of 29.46 were determined to be 25 °C for extraction temperature, 600 W for ultrasonic power, 20 min for extraction time, and 25% (w/w) for water content in NADES, leading to the maximum yields (7.39 ± 0.20 mg/g and 57.99 ± 0.91 mg/g, respectively) of crocin and geniposide. Thirty-three compounds including iridoids, carotenoids, phenolic acids, flavonoids, and triterpenes in the NADES extract were identified by LC-Q-TOF-MS2 coupled with a feature-based molecular networking workflow. The kinetics evaluation of the conjugated dienes generation on Cu2+-induced low density lipoprotein (LDL) oxidation via the four-parameter logistic regression model showed that crocin increased the lag time of LDL oxidation in a concentration-dependent manner (15 µg/mL, 30 µg/mL, 45 µg/mL) by 12.66%, 35.44%, and 73.42%, respectively. The quantitative determination for fluorescence properties alteration of the apolipoprotein B-100 exhibited that crocin effectively inhibited the fluorescence quenching of tryptophan residues and the modification of lysine residues caused by reactive aldehydes and malondialdehydes. The pr-UAE-NADES showed significant efficiency toward the simultaneous extraction of crocin and geniposide from gardenia fruits. And this study demonstrates the potential utility of gardenia fruits in developing anti-atherogenic functional food.

The ability of supercritical CO2 carrot and pumpkin extracts to counteract inflammation and oxidative stress in RAW 264.7 macrophages stimulated with LPS or MDA-MB-231 cell-conditioned media.

Supercritical fluid extraction with CO2 (SFE) is an alternative technology to conventional solvent extraction (CSE), to obtain food-grade bioactives from plants. Here, SFE and CSE extracts from carrot and pumpkin matrices, impregnated with hempseed or flaxseed oil as co-solvents, were characterized by HPLC and GC-MS, and their ability to counteract the inflammatory and oxidative phenomena underlying the onset of several pathologies was assessed in vitro. All extracts showed dose-dependent anti-inflammatory potential and demonstrated an ability to interfere with the pro-inflammatory effects of breast cancer cell-conditioned media, and to inhibit reactive oxygen species (ROS) accumulation and nitrite production (NP) in lipopolysaccharide-stimulated macrophages. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is involved in these response mechanisms, as highlighted by the increased mRNA levels of its target genes revealed by quantitative real-time PCR analyses. NP and ROS concentrations negatively correlated with α-tocopherol and most carotenoids, but positively with the total tocopherol/total carotenoid ratio, suggesting an idiosyncratic effect of these bioactives on cell responses and emphasizing the need to focus on extract constituents' interactions.

A Narrative Review: The Effect and Importance of Carotenoids on Aging and Aging-Related Diseases.

Aging is generally defined as a time-dependent functional decline that affects most living organisms. The positive increase in life expectancy has brought along aging-related diseases. Oxidative stress caused by the imbalance between pro-oxidants and antioxidants can be given as one of the causes of aging. At the same time, the increase in oxidative stress and reactive oxygen species (ROS) is main reason for the increase in aging-related diseases such as cardiovascular, neurodegenerative, liver, skin, and eye diseases and diabetes. Carotenoids, a natural compound, can be used to change the course of aging and aging-related diseases, thanks to their highly effective oxygen-quenching and ROS-scavenging properties. Therefore, in this narrative review, conducted using the PubMed, ScienceDirect, and Google Scholar databases and complying with the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines, the effects of carotenoids on aging and aging-related diseases were analyzed. Carotenoids are fat-soluble, highly unsaturated pigments that occur naturally in plants, fungi, algae, and photosynthetic bacteria. A large number of works have been conducted on carotenoids in relation to aging and aging-related diseases. Animal and human studies have found that carotenoids can significantly reduce obesity and fatty liver, lower blood sugar, and improve liver fibrosis in cirrhosis, as well as reduce the risk of cardiovascular disease and erythema formation, while also lowering glycated hemoglobin and fasting plasma glucose levels. Carotenoid supplementation may be effective in preventing and delaying aging and aging-related diseases, preventing and treating eye fatigue and dry eye disease, and improving macular function. These pigments can be used to stop, delay, or treat aging-related diseases due to their powerful antioxidant, restorative, anti-proliferative, anti-inflammatory, and anti-aging properties. As an increasingly aging population emerges globally, this review could provide an important prospective contribution to public health.

Effect of Extraction Methods on the Antioxidant Potential and Cytotoxicity of the Combined Ethanolic Extracts of Daucus carota L., Beta vulgaris L., Phyllanthus emblica L. and Lycopersicon esculentum against Gastric Adenocarcinoma Cells.

Frequent consumption of fruits and vegetables in the daily diet may alleviate the risk of developing chronic diseases. Daucus carota L. (carrot), Beta vulgaris L. (beetroot) Phyllanthus emblica L. (amla), and Lycopersicon esculentum M (tomatoes) are traditionally consumed functional foods that contain a high concentration of antioxidants, ascorbic acid, polyphenols, and numerous phytochemicals. This study assessed how three distinct preparation methods affect the phenolic, flavonoid, carotenoid, and ascorbic acid contents, antioxidant level, and cytotoxicity of the combined fruit extract. The fruit samples were taken in the ratio of carrot (6): beetroot (2): tomato (1.5): amla (0.5) and processed into a lyophilized slurry (LS) extract, lyophilized juice (LJ) extract, and hot-air oven-dried (HAO) extract samples. The sample extracts were assessed for their phytoconstituent concentrations and antioxidant and cytotoxic potential. The total phenolic content in LS, LJ, and HAO extracts was 171.20 ± 0.02, 120.73 ± 0.02, and 72.05 ± 0.01 mg gallic acid equivalent/100 g, respectively and the total flavonoid content was 23.635 ± 0.003, 20.754 ± 0.005, and 18.635 ± 0.005 mg quercetin equivalent/100 g, respectively. Similarly, total ascorbic acid content, carotenoids, and antioxidant potential were higher in the LS and LJ extracts than in HAO. Overall, the LS extract had a substantially higher concentration of phytochemicals and antioxidants, as well as higher cytotoxic potential, compared to the LJ and HAO extracts. The LS extract was tested in the MKN-45 human gastric cancer cell line to demonstrate its effective antioxidant potential and cytotoxicity. Hence, lyophilization (freezing) based techniques are more effective than heat-based techniques in preserving the phytoconstituents and their antioxidant and cytotoxic potential.

Preparative separation of iridoid glucosides and crocins from Gardeniae Fructus using sequential macroporous resin column chromatography and evaluation of their anti-inflammatory and antioxidant activities.

Iridoid glycosides (geniposide (GP), genipin-1-gentiobioside (GB), etc.) and crocins (crocin Ⅰ (CR1), crocin Ⅱ(CR2), etc.) are two main bioactive components in Gardeniae Fructus (GF), which is a famous traditional Chinese medicine. Iridoid glycosides exhibit many activities and are used to manufacture gardenia blue pigment for the food industry. Crocins are rare natural water-soluble carotenoids that are often used as food colorants. A sequential macroporous resin column chromatography technology composed of HC-500B and HC-900B resins was developed to selectively separate iridoid glucosides and crocins from GF. The adsorption of GP on HC-900B resin was an exothermic process. The adsorption of CR1 on HC-500B resin was an endothermic process. The two kinds of components were completely separated by a sequential resin column. GB and GP were mainly found in product 1 (P1) with purities of 11.38% and 46.83%, respectively, while CR1 and CR2 were mainly found in product 2 (P2) with purities of 12.32% and 1.40%, respectively. The recovery yields of all the compounds were more than 80%. The above results showed that sequential resin column chromatography technology achieved high selectivity and recovery yields. GF extract, P1 and P2 could significantly inhibit the secretion of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 cells, indicating that iridoid glycosides and crocins provide a greater contribution to the anti-inflammatory activity of GF. At the same time, compared to the GF extract and P1, P2 exhibited stronger scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, indicating that crocins may provide a significant contribution to the antioxidant activity of GF.

Revisiting carotenoids as dietary antioxidants for human health and disease prevention.

Humans are unique indiscriminate carotenoid accumulators, so the human body accumulates a wide range of dietary carotenoids of different types and to varying concentrations. Carotenoids were once recognized as physiological antioxidants because of their ability to quench singlet molecular oxygen (1O2). In the 1990s, large-scale intervention studies failed to demonstrate that supplementary ß-carotene intake reduces the incidence of lung cancer, although its antioxidant activity was supposed to contribute to the prevention of oxidative stress-induced carcinogenesis. Nevertheless, the antioxidant activity of carotenoids has attracted renewed attention as the pathophysiological role of 1O2 has emerged, and as the ability of dietary carotenoids to induce antioxidant enzymes has been revealed. This review focuses on six major carotenoids from fruit and vegetables and revisits their physiological functions as biological antioxidants from the standpoint of health promotion and disease prevention. ß-Carotene 9',10'-oxygenase-derived oxidative metabolites trigger increases in the activities of antioxidant enzymes. Lutein and zeaxanthin selectively accumulate in human macular cells to protect against light-induced macular impairment by acting as antioxidants. Lycopene accumulates exclusively and to high concentrations in the testis, where its antioxidant activity may help to eliminate oxidative damage. Dietary carotenoids appear to exert their antioxidant activity in photo-irradiated skin after their persistent deposition in the skin. An acceptable level of dietary carotenoids for disease prevention should be established because they can have deleterious effects as prooxidants if they accumulate to excess levels. Finally, it is expected that the reason why humans are indiscriminate carotenoid accumulators will be understood soon.

Fucoxanthin, a marine derived carotenoid, attenuates surgery-induced cognitive impairments via activating Akt and ERK pathways in aged mice.

BACKGROUND: Fucoxanthin is the most abundant marine carotenoid derived from brown seaweeds, possesses antioxidant, anti-inflammatory, and neuroprotective properties, and might be benefit for the treatment of neurological disorders. Post-operative cognitive dysfunction (POCD) is a neurological symptom with learning and memory impairments, mainly affecting the elderly after surgery. However, there is no effective treatments for this symptom. PURPOSES: In this study, we evaluated the neuroprotective effects of fucoxanthin against POCD in aged mice after surgery. STUDY DESIGN AND METHODS: The animal model of POCD was established in 12 - 14 month aged mice with a laparotomy. Curcumin was used as a positive control. The beneficial effects of fucoxanthin on POCD was analyzed by behavioral tests. Pro-inflammatory cytokines were measured by Enzyme-linked Immunosorbent Assay (ELISA). And the expressions of key proteins in the Akt and ERK signaling pathways were analyzed by Western blotting analysis. The morphology of microglial cells and astrocytes was explored by immunohistochemical staining. The activity of antioxidant superoxide dismutase (SOD) and catalase (CAT) were measured by anti-oxidative enzyme activity assays. RESULTS: Fucoxanthin at 100 - 200 mg/kg significantly attenuated cognitive dysfunction, with a similar potency as curcumin, in aged mice after surgery. In addition, fucoxanthin and curcumin significantly increased the expression of pAkt, prevented the activation of microglial cells and astrocytes, and inhibited the secretion of pro-inflammatory interleukin-1ß (IL - 1ß) and tumor necrosis factor-α (TNF-α). Furthermore, fucoxanthin and curcumin elevated the ERK pathway and potently increased the activity of antioxidant enzymes. Most importantly, U0126, an inhibitor of the ERK pathway, and wortmannin, an inhibitor of the Akt pathway, significantly abolished the cognitive-enhancing effects, as well as the inhibition of neuroinflammation and the reduction of oxidative stress, induced by fucoxanthin in aged mice after surgery. CONCLUSION: Fucoxanthin might be developed as a functional food or drug for the treatment of POCD by inhibiting neuroinflammation and enhancing antioxidant capacity via the activation of the Akt and ERK signaling pathways.

Phytoconstituents, antioxidant and antiglycation activity of Chrysophyllum cainito L., Hancornia speciosa Gomes and Plinia glomerata Berg. fruits.

The present study verified the presence of phytoconstituents and evaluated antioxidant (DPPH, FRAP, NO and TBARS tests) and antiglycation (REM test) activities of unconventional wild edible fruits Chrysophyllum cainito, Hancornia speciosa and Plinia glomerata. It was verified the presence of phenolic compounds for all fruits and flavonoids were observed only for C. cainito, which presented in its peel the highest total phenols (90.34 µg GAE mg-1) and flavonoids (30.4 µg RE mg-1) content. Sugar concentration was significant for all fruits, where H. speciosa showed the highest reducing sugar content (576.12 mg g-1) and C. cainito pulp showed the highest total sugar content (858.67 mg g-1). All fruits presented vitamin C and carotenoids, highlighting P. glomerata with the best results for ascorbic acid (2260.94 mg 100 g-1) and carotenoids (59.62 µg g-1). Extracts presented antioxidant activity, highlighting C. cainito peel that presented 65.64% (DPPH), 231.34 µM TE L-1 (FRAP), 49.34% (NO) and 22.56% (TBARS), while in antiglycation evaluation, P. glomerata showed evident activity. Therefore, it was possible to determine different phytoconstituents, and antioxidant and antiglycation activities of the fruits. These data provide subsidies for application of these fruits in new studies, to increase knowledge and preservation of these species.

Network pharmacology-based strategic prediction and target identification of apocarotenoids and carotenoids from standardized Kashmir saffron (Crocus sativus L.) extract against polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a hormonal disorder that affects women of reproductive age, characterized by a range of symptoms, including irregular menstrual cycles, excess male hormones (androgens), metabolic abnormalities such as hyperinsulinemia, hyperlipidemia, and metabolic disturbances like glucose imbalance. Botanical supplements are perceived first and safe choice over available regimens to regulate PCOS. There are several reports available stating that apocarotenoids, carotenoids, and whole extracts of Crocus sativus were identified to have a potential role in the management of women health. This study aimed to propose a network pharmacology-based method to determine the potential therapeutic pathways of phytoconstituents (apocarotenoids and carotenoids) of UHPLC-PDA standardized stigma-based Crocus sativus extract (CSE) for the management of PCOS. Furthermore, to validate the potential targets and signaling pathways, these apocarotenoids, and carotenoids were screened for molecular docking and in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions. The information regarding PCOS-related genes was retrieved from the PCOS knowledge database (PCOSKB), resulting in an established network between putative targets of PCOS and Crocus sativus extract phytochemicals to prevail the mechanism of action. Based on the screening conditions, 4 prominent targets namely, serine/threonine kinase 1 (AKT1), signal transducer and activator of transcription (STAT3), mitogen-activated protein kinase 3 (MAPK3), and mitogen-activated protein kinase 1 (MAPK1), were identified through network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that MAP kinase and serine-threonine pathways were found prominent targets in PCOS. Further, a molecular docking study shows that crocetin, picrocrocin, and safranal had the best binding affinity for the identified targets. In silico ADMET results revealed that carotenoids and apocarotenoids were found to have the maximum bioavailability and were able to cross the blood-brain barrier without any toxic effects. The combined results revealed that the apocarotenoids and carotenoids of Crocus sativus extract could act on various targets to regulate multiple pathways related to PCOS.

Saffron carotenoids reversed the UCMS-induced depression and anxiety in rats: Behavioral and biochemical parameters, and hippocampal BDNF/ERK/CREB and NR2B signaling markers.

BACKGROUND: Depression is a debilitating condition that affects the mind and the individual's body. The improving effects of saffron on depression and anxiety have long been discussed, with limited information about the molecular mechanism of action. HYPOTHESIS/PURPOSE: Investigating the effect of saffron carotenoids, Crocin and Crocetin, on depression and anxiety in rats by emphasizing some signaling pathways involved. STUDY DESIGN: Depression and anxiety were induced in rats via unpredictable chronic mild stress (UCMS). Then different rat groups were treated with Crocin, Crocetin, Fluoxetine, and vehicle. Behavioral tests were done before and after treatment. METHODS: The serum Serotonin and Corticosterone and the expression of some hippocampal signaling proteins were studied. Furthermore, bioinformatics tools were used to predict the interactions of Crocin/ Crocetin with the Serotonin transporter and NMDA receptor subunit NR2B. Then, the patch-clamp was used to study the interaction of Crocetin with the NMDA receptor. RESULTS: Various behavioral tests confirmed the induction of depression and the improvement of depression by these natural carotenoids. In addition, Crocin/ Crocetin significantly increased the decreased serum Serotonin and reduced the increased serum Corticosterone in the depressed groups. They also increased or caused a trend of increase in the CREB, ERK, BAD, BDNF, p11, and 5-HT1B expression in the hippocampus of the depressed groups. In addition, there were an increase or a trend in p-CREB/CREB, p-ERK1/2 /ERK1/2, and p-BAD/BAD ratios in the Crocin/ Crocetin treated depressed groups. However, the NR2B and FOXO3a expression showed a trend of decrease in depressed groups after treatment. The bioinformatics data indicated that Crocin/ Crocetin could bind to the Serotonin transporter (SLC6A4) and NR2B subunit of the NMDA receptor. Both carotenoids bind to the same site as Fluoxetine in the SLC6A4. However, they bound to different sites on the NR2B. So, Crocetin binds to NR2B at the same site as Ifenprodil. But Crocin bound to another site. The whole cell patch-clamp recording on the normal rat hippocampus revealed a significant decrease in the NMDA peak amplitude after Crocetin treatment, indicating its inhibitory effect on this receptor. CONCLUSION: The antidepressant activities of Crocin/ Crocetin are possibly due to their effects on Serotonin and Corticosterone serum concentrations, NR2B expression, and the downstream signaling pathways. Furthermore, these natural carotenoids, like Fluoxetine, induced an increasing tendency in p11 and 5HT1B in depressed rats.

Efficacy of Carotenoid-Loaded Gelatin Nanoparticles in Reducing Plasma Cytokines and Adipocyte Hypertrophy in Wistar Rats.

The present study investigated the effect of gelatin-based nanoparticles (EPG) loaded with a carotenoid-rich crude extract (CE) on systemic and adipose tissue inflammatory response in a model with inflammation induced by a high glycemic index and high glycemic load diet (HGLI). Nanoparticles synthesized were characterized by different physical and chemical methods. The in vivo investigation evaluated Wistar rats (n = 20, 11 days, adult male with 21 weeks) subdivided into untreated (HGLI diet), conventional treatment (nutritionally adequate diet), treatment 1 (HGLI + crude extract (12.5 mg/kg)), and treatment 2 (HGLI + EPG (50 mg/kg)) groups. Dietary intake, caloric intake and efficiency, weight, inflammatory cytokines tissue concentration, visceral adipose tissue (VAT) weight, histopathological analysis, and antioxidant activity in plasma and VAT were investigated. EPG showed the same physical and chemical characteristics as previous batches (95.2 nm, smooth surface, and chemical interactions between materials). The EPG-treated group was the only group promoting negative ∆dietary intake, ∆caloric efficiency, and ∆weight. In addition, it presented a significant reduction (p < 0.05) in IL-6 and leptin levels and a greater presence of multilocular adipocytes. The results suggest that EPG can act as a nutraceutical in adjuvant therapy for treating inflammatory diseases associated with adipose tissue accumulation.

Lycopene ­ the impact of supplementation on the skin aging process / Likopen ­ wplyw suplementacji na proces starzenia sie skóry.

The skin aging process is affected by multiple different factors (including sun exposure, smoking, poor diet) and reactive oxygen species (ROS). Under their influence, the skin becomes weaker, mainly elastin and collagen fibers are damaged. The amount of lipids is also reduced, leading to the death of the skin cells. The presence of free radicals also blocks the natural ability of the epidermis to regenerate. Each of these factors determines the acceleration of the signs of aging. To some extent, our body is able to deal with the free radicals by producing antioxidants. Regular supplementation is also a beneficial solution. Lycopene is a red pigment naturally found in tomatoes and is a known antioxidant. Among the carotenoids, it is the strongest singlet oxygen quencher and scavenger of peroxygen radicals, making it an important defense mechanism in the human body. The aim of this paper is to present the biological properties of lycopene in relation to its beneficial effect on the aging process of the skin.

Carotenoids for lung cancer chemoprevention and chemotherapy: Promises and controversies.

BACKGROUND: Lung cancer is one of the leading causes of malignancy in the world. Several therapeutical and chemopreventive approaches have been practised to mitigate the disease. The use of phytopigments including carotenoids is a well-known approach. However, some of the prominent clinical trials interrogated the efficacy of carotenoids in lung cancer prevention. METHODS: A elaborate literature survey have been performed investigating in vitro, in vivo, and clinical studies reported on the administration of carotenoids for chemoprevention and chemotherapy. RESULTS: Tobacco consumption, genetic factors, dietary patterns, occupational carcinogens, lung diseases, infection, and sex disparities are some of the prominent factors leading to lung cancer. Significant evidence has been found underlining the efficiency of carotenoids in alleviating cancer. In vitro studies have proven that carotenoids act through PI3K/ AKT/mTOR, ERK-MAPK pathways and induce apoptosis through PPAR, IFNs, RAR, which are p53 intermediators in lung cancer signaling. Animal models and cell lines studies showed promising results, while the outcomes of clinical trials are contradictory and require further verification. CONCLUSION: The carotenoids exert chemotherapeutic and chemopreventive effects on lung tumors which has been evidenced in numerous investigations. However, further analyses are necessary to the answer the uncertainties raised by several clinical trials.