Antibiofilm activity of carotenoid crocetin against Staphylococcal strains.

Staphylococcus aureus and Staphylococcus epidermidis stand as notorious threats to human beings owing to the myriad of infections they cause. The bacteria readily form biofilms that help in withstanding the effects of antibiotics and the immune system. Intending to combat the biofilm formation and reduce the virulence of the pathogens, we investigated the effects of carotenoids, crocetin, and crocin, on four Staphylococcal strains. Crocetin was found to be the most effective as it diminished the biofilm formation of S. aureus ATCC 6538 significantly at 50 µg/mL without exhibiting bactericidal effect (MIC >800 µg/mL) and also inhibited the formation of biofilm by MSSA 25923 and S. epidermidis at a concentration as low as 2 µg/mL, and that by methicillin-resistant S. aureus MW2 at 100 µg/mL. It displayed minimal to no antibiofilm efficacy on the Gram-negative strains Escherichia coli O157:H7 and Pseudomonas aeruginosa as well as a fungal strain of Candida albicans. It could also curb the formation of fibrils, which partly contributes to the biofilm formation in S. epidermidis. Additionally, the ADME analysis of crocetin proclaims how relatively non-toxic the chemical is. Also, crocetin displayed synergistic antibiofilm characteristics in combination with tobramycin. The presence of a polyene chain with carboxylic acid groups at its ends is hypothesized to contribute to the strong antibiofilm characteristics of crocetin. These findings suggest that using apocarotenoids, particularly crocetin might help curb the biofilm formation by S. aureus and S. epidermidis.

Crocin ameliorates neuroinflammation and cognitive impairment in mice with Alzheimer's disease by activating PI3K/AKT pathway.

BACKGROUND: Crocin has a good prospect in the treatment of Alzheimer's disease (AD), but the mechanisms underlying its neuroprotective effects remain elusive. This study aimed to investigate the neuroprotective effects of Crocin and its underlying mechanisms in AD. METHODS: AD mice were set up by injecting Aß25-35 solution into the hippocampus. Then, the AD mice were injected intraperitoneally with 40 mg/kg/day of Crocin for 14 days. Following the completion of Crocin treatment, an open-field test, Y-maze test and Morris water maze test were conducted to evaluate the impact of Crocin on spatial learning and memory deficiency in mice. The effects of Crocin on hippocampal neuron injury, proinflammatory cytokine expressions (IL-1ß, IL-6, and TNF-α), and PI3K/AKT signaling-related protein expressions were measured using hematoxylin and eosin staining, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) experiments, respectively. RESULTS: Crocin attenuated Aß25-35-induced spatial learning and memory deficiency and hippocampal neuron injury. Furthermore, the Western blot and qRT-PCR results showed that Crocin effectively suppressed inflammation and activated the PI3K/AKT pathway in Aß25-35-induced mice. CONCLUSION: Crocin restrained neuroinflammation via the activation of the PI3K/AKT pathway, thereby ameliorating the cognitive dysfunction of AD mice.

The immunoregulatory property of mesenchymal stem cells in Crocin treatment by expression modulation of microRNA-155, microRNA-21, microRNA-23b, microRNA-126a, and their target inflammatory genes.

Mesenchymal stem cells (MSCs) have high priority in clinical applications for treatment of immune disorders because of their immunomodulatory function. A lot of researches have currently been undertaken to enhance the stemness capacities of the cells and pick an excellent type of MSCs for clinical approaches. This study aims to assess the immunomodulatory related MicroRNAs (miRNAs) expression as well as their target genes in both adipose derived stem cells (Ad-SCs) and dental pulp derived stem cell (DP-SCs) in the presence or lack of Crocin (saffron plant's bioactive compound). For this purpose, first MSCs were extracted from adipose and dental pulp tissues, and then their mesenchymal nature was confirmed using flow cytometry and differentiation tests. Following the cell treatment with an optimal-non-toxic dose of Crocin (Obtained by MTT test), the expression of 4 selected immunomodulatory-related micro-RNAs (Mir-126, -21, -23, and-155) and their target genes (PI3K/ Akt 1 and 2/ NFKB and RELA) were assessed by RT-PCR. Our findings revealed that miRNA-23 and miRNA-126 were up-regulated in both types of cells treated with Crocin, while in the other side, miRNA-21 and miRNA-155 were down-regulated in DP-SCs and were up-regulated in Ad-SCs under treatment. Moreover, the real-time PCR results indicated that Crocin could significantly down regulate the expression of PI3K/ Akt1/ Akt2/ NFKB/ RELA genes in DP-SCs and PI3K/Akt2 genes in Ad-SCs and up regulate the expression of Akt1/ NFKB/ RELA genes in recent cells. Based on the analysis of the obtained data, the immunoregulatory effects of Crocin were higher in DP-SCs than in Ad-SCs. In conclusion, Crocin could control essential signaling pathways related to the inflammation by regulating the expression of related- miRNAs genes that play a key function in the immune regulation pathways in MSCs. Our findings can give an understanding of the mechanisms by which Crocin enhances the immunomodulatory feature of MSCs. According to the research findings, DP-SCs are probably a better immunomodulator in Crocin treatment than Ad-SCs and it may be helpful for MSCs selection in clinical applications for modulation or treatment of autoimmune disorders.

pH-Responsive Calcium Ions and Crocetin Releasing Hydrogel for Accelerating Skin Wound Healing.

The ideal and highly anticipated dressing for skin wounds should provide a moist environment, possess antibacterial properties, and ensure sustained drug release. In the present work, a hyaluronic acid-based hydrogel was formed by cross-linking crocetin and CaCO3@polyelectrolyte materials (CaCO3@PEM) microspheres with HA hydrogels via hydrogen bond and amido bonding (CaCO3@PEM@Cro@HA hydrogel, CPC@HA hydrogel). Moreover, the CPC@HA hydrogel had the capability of sustained, controlled release of calcium ions and crocetin via pH-sensitive and accelerated skin wound healing. The experiment results showed that the CPC@HA hydrogel exhibited porous network structures, stable physical properties, and had antibacterial properties and biocompatibility in vitro. In addition, the CPC@HA hydrogel covering on the skin wound could reduce inflammation and promote wound healing. The high expression of angiogenic cytokines (CD31) and epidermal terminal differentiation markers (Loricrin) of wound healing tissue suggested the CPC@HA hydrogel also had the function of promoting the remodeling of regenerated skin. Overall, CPC@HA hydrogel has promising potential for clinical applications in accelerating skin wound repair.

Shrimp Waste Upcycling: Unveiling the Potential of Polysaccharides, Proteins, Carotenoids, and Fatty Acids with Emphasis on Extraction Techniques and Bioactive Properties.

Shrimp processing generates substantial waste, which is rich in valuable components such as polysaccharides, proteins, carotenoids, and fatty acids. This review provides a comprehensive overview of the valorization of shrimp waste, mainly shrimp shells, focusing on extraction methods, bioactivities, and potential applications of these bioactive compounds. Various extraction techniques, including chemical extraction, microbial fermentation, enzyme-assisted extraction, microwave-assisted extraction, ultrasound-assisted extraction, and pressurized techniques are discussed, highlighting their efficacy in isolating polysaccharides, proteins, carotenoids, and fatty acids from shrimp waste. Additionally, the bioactivities associated with these compounds, such as antioxidant, antimicrobial, anti-inflammatory, and antitumor properties, among others, are elucidated, underscoring their potential in pharmaceutical, nutraceutical, and cosmeceutical applications. Furthermore, the review explores current and potential utilization avenues for these bioactive compounds, emphasizing the importance of sustainable resource management and circular economy principles in maximizing the value of shrimp waste. Overall, this review paper aims to provide insights into the multifaceted aspects of shrimp waste valorization, offering valuable information for researchers, industries, and policymakers interested in sustainable resource utilization and waste-management strategies.

Bacterioruberin: Biosynthesis, Antioxidant Activity, and Therapeutic Applications in Cancer and Immune Pathologies.

Halophilic archaea, also termed haloarchaea, are a group of moderate and extreme halophilic microorganisms that constitute the major microbial populations in hypersaline environments. In these ecosystems, mainly aquatic, haloarchaea are constantly exposed to ionic and oxidative stress due to saturated salt concentrations and high incidences of UV radiation (mainly in summer). To survive under these harsh conditions, haloarchaea have developed molecular adaptations including hyperpigmentation. Regarding pigmentation, haloarchaeal species mainly synthesise the rare C50 carotenoid called bacterioruberin (BR) and its derivatives, monoanhydrobacterioruberin and bisanhydrobacterioruberin. Due to their colours and extraordinary antioxidant properties, BR and its derivatives have been the aim of research in several research groups all over the world during the last decade. This review aims to summarise the most relevant characteristics of BR and its derivatives as well as describe their reported antitumoral, immunomodulatory, and antioxidant biological activities. Based on their biological activities, these carotenoids can be considered promising natural biomolecules that could be used as tools to design new strategies and/or pharmaceutical formulas to fight against cancer, promote immunomodulation, or preserve skin health, among other potential uses.

Crocin (bioactive compound of Crocus sativus L.) potently restores REM sleep deprivation-induced manic- and obsessive-compulsive-like behaviors in female rats.

Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors including hyperlocomotion. On the other hand, crocin (one of the main compounds of Crocus sativus L. or Saffron) may be beneficial in the improvement of mental and cognitive dysfunctions. Also, crocin can restore the deleterious effects of SD on mental and cognitive processes. In this study, we investigated the effect of REM SD on female rats' behaviors including depression- and anxiety-like behaviors, locomotion, pain perception, and obsessive-compulsive-like behavior, and also, the potential effect of crocin on REM SD effects. We used female rats because evidence on the role of REM SD in modulating psychological and behavioral functions of female (but not male) rats is limited. REM SD was induced for 14 days (6h/day), and crocin (25, 50, and 75 mg/kg) was injected intraperitoneally. Open field test, forced swim test, hot plate test, and marble burying test were used to assess rats' behaviors. The results showed REM SD-induced manic-like behavior (hyperlocomotion). Also, REM SD rats showed decreased anxiety- and depression-like behavior, pain subthreshold (the duration it takes for the rat to feel pain), and showed obsessive compulsive-like behavior. However, crocin at all doses partially or fully reversed REM SD-induced behavioral changes. In conclusion, our results suggested the possible comorbidity of OCD and REM SD-induced manic-like behavior in female rats or the potential role of REM SD in the etiology of OCD, although more studies are needed. In contrast, crocin can be a possible therapeutic choice for decreasing manic-like behaviors.

Preventive effects of crocin, a natural compound from saffron, against nicotine­induced oxidative stress and neurobehavioral disturbances.

Nicotine is a psychostimulant that induces neurochemical and behavioral changes upon chronic administration, leading to neurodegenerative conditions associated with smoking. As of now, no preventive or therapeutic strategies are known to counteract nicotine­induced neurodegeneration. In this study, we explore the neuroprotective effects of crocin, a bioactive agent commonly found in saffron - a spice derived from the flower of Crocus sativus - using a rat model. The dose­dependent effects of crocin were evaluated in nicotine­induced neurodegeneration and compared with a control group. Neurobehavioral changes, assessed through the elevated plus maze, the open field test, the forced swim test, and the Morris water maze, as well as oxidative stress in the hippocampus, were evaluated. Interestingly, nicotine administration resulted in depression, anxiety, and abnormal motor and cognitive functions, while crocin treatment protected the rat brain from these abnormalities. The beneficial effects of crocin were associated with reduced oxidative stress biomarkers such as malondialdehyde, along with increases in superoxide dismutase, glutathione peroxidase, and glutathione reductase activities. These results demonstrate that crocin can mitigate nicotine­induced neurodegeneration by reducing oxidative stress, potentially offering a protective measure against neurodegenerative effects in smokers.

The Potential of Natural Carotenoids-Containing Sericin of the Domestic Silkworm Bombyx mori.

Sericin derived from the white cocoon of Bombyx mori has been attracting more attention for its utilization in food, cosmetics, and biomedicine. The potential health benefits of natural carotenoids for humans have also been well-established. Some rare strains of Bombyx mori (B. mori) produce yellow-red cocoons, which endow a potential of natural carotenoid-containing sericin. We hypothesized that natural carotenoid-containing sericin from yellow-red cocoons would exhibit better properties compared with white cocoon sericin. To investigate the physicochemical attributes of natural carotenoid-containing sericin, we bred two silkworm strains from one common ancestor, namely XS7 and XS8, which exhibited different cocoon colors as a result of the inconsistent distribution of lutein and ß-carotene. Compared with white cocoon sericin, the interaction between carotenoids and sericin molecules in carotenoid-containing sericin resulted in a unique fluorescence emission at 530, 564 nm. The incorporation of carotenoids enhanced the antibacterial effect, anti-cancer ability, cytocompatibility, and antioxidant of sericin, suggesting potential wide-ranging applications of natural carotenoid-containing sericin as a biomass material. We also found differences in fluorescence characteristics, antimicrobial effects, anti-cancer ability, and antioxidants between XS7 and XS8 sericin. Our work for the first time suggested a better application potential of natural carotenoid-containing sericin as a biomass material than frequently used white cocoon sericin.

Crocin enhances the sensitivity to paclitaxel in human breast cancer cells by reducing BIRC5 expression.

Paclitaxel (PTX) is one of the first-line chemotherapeutic agents for treating breast cancer. However, PTX resistance remains a major hurdle in breast cancer therapy. Crocin, the main chemical constituent of saffron, shows anti-cancer activity against various types of cancer. However, the effect of crocin on the resistance of PTX in breast cancer is still unknown. CCK-8 and TUNEL assays were employed to detect cell viability and apoptosis, respectively. The targets of crocin were predicted using HERB database and the targets associated with breast cancer were acquired using GEPIA database. The Venn diagram was utilized to identify the common targets between crocin and breast cancer. Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) expression was detected by qRT-PCR and western blot analysis. The correlation between BIRC5 expression and survival was analyzed by Kaplan-Meier plotter and PrognoScan databases. Our data suggested that crocin aggravated PTX-induced decrease of viability and increase of apoptosis in MCF-7 and MCF-7/PTX cells. BIRC5 was identified as the target of crocin against breast cancer. Crocin inhibited BIRC5 expression in MCF-7 and MCF-7/PTX cells. BIRC5 is overexpressed in breast cancer tissues, as well as PTX-sensitive and PTX-resistant breast cancer cells. BIRC5 expression is related to the poor survival of patients with breast cancer. Depletion of BIRC5 strengthened PTX-induced viability reduction and promotion of apoptosis in MCF-7 and MCF-7/PTX cells. Moreover, BIRC5 overexpression reversed the inhibitory effect of crocin on PTX resistance in breast cancer cells. In conclusion, crocin enhanced the sensitivity of PTX in breast cancer cells partially through inhibiting BIRC5 expression.

Dual Role of Stratum Corneum Carotenes/Lycopene Against the Development of Chemotherapy-induced PPE in Patients With Cancer.

Palmar-plantar erythrodysaesthesia (PPE) is a common side effect of chemotherapy treatment in patients with cancer. The exact pathophysiologic mechanisms of the development of PPE remain unclear. Here, we report two important physiological functions of carotenoids without hydroxyl groups (α-carotene, ß-carotene, γ-carotene, ξ-carotene, lycopene, phytoene, phytofluene and their isomers) in the stratum corneum (SC) of glabrous skin: The powerful antioxidant protection of the integrity of the SC components against the destructive action of free radicals and maintaining the skin barrier function by the creation of an orthorhombic organization of intercellular lipids within lamellae using carotenoids as a skeleton. The dual protective role of carotenoids without hydroxyl groups is important for both healthy skin and, in the authors' opinion, for the skin of chemotherapy-treated patients against the development of PPE, as the chemotherapy-induced reduction of the carotenoid concentration in the stratum corneum considerably weakens the skin resistance to cytotoxic and other adverse reactions.

NMR Study of Water-Soluble Carotenoid Crocin: Formation of Mixed Micelles, Interaction with Lipid Membrane and Antioxidant Activity.

Crocin is a unique water-soluble carotenoid found in crocus and gardenia flowers. Crocin has been shown to have a variety of pharmacological activities, such as antioxidant, anti-cancer, memory improvement, antidepressant, anti-ischemia, blood pressure lowering and aphrodisiac, gene protection and detoxification activities. Due to their amphiphilicity, crocin molecules form concentration-dependent self-associates (micelles) in a water solution. In the present study, using various NMR techniques (T2 relaxation and selective gradient NOESY), we have demonstrated that crocin forms mixed micelles with water-soluble drug delivery system glycyrrhizin and linoleic acid molecules. Note, that the spin-spin T2 relaxation time and NOESY spectroscopy are very sensitive to intermolecular interactions and molecular diffusion mobility. The second purpose of this work was the elucidation of the interaction of crocin with a model lipid membrane using NMR techniques and a molecular dynamics simulation and its effects on lipid oxidation. It was shown that the crocin molecule is located near the surface of the lipid bilayer and effectively protects lipids from oxidation by peroxyl radicals. The role of glycyrrhizin and vitamin C in metal-induced lipid oxidation was also elucidated. The results of this study may be useful for expanding the field of application of crocin in medicine and in the food industry.

Bioactive Compounds from Pigmented Corn (Zea mays L.) and Their Effect on Health.

Pigmented corn is a gramineae food of great biological, cultural and nutritional importance for many Latin American countries, with more than 250 breeds on the American continent. It confers a large number of health benefits due to its diverse and abundant bioactive compounds. In this narrative review we decided to organize the information on the nutrients, bioactive compounds and phytochemicals present in pigmented corn, as well as their effects on human health. Phenolic compounds and anthocyanins are some of the most studied and representative compounds in these grasses, with a wide range of health properties, mainly the reduction of pro-oxidant molecules. Carotenoids are a group of molecules belonging to the terpenic compounds, present in a large number of pigmented corn breeds, mainly the yellow ones, whose biological activity incorporates a wide spectrum. Bioactive peptides can be found in abundance in corn, having very diverse biological effects that include analgesic, opioid and antihypertensive activities. Other compounds with biological activity found in pigmented corn are resistant starches, some fatty acids, phytosterols, policosanols, phospholipids, ferulic acid and phlobaphenes, as well as a great variety of vitamins, elements and fibers. This review aims to disseminate and integrate the existing knowledge on compounds with biological activity in pigmented corn in order to promote their research, interest and use by scientists, nutrition professionals, physicians, industries and the general population.

Crocetin protects mouse brain from apoptosis in traumatic brain injury model through activation of autophagy.

BACKGROUND: Autophagy is recognized as a promising therapeutic target for traumatic brain injury (TBI). Crocetin is an aglycone of crocin naturally occurring in saffron and has been found to alleviate brain injury diseases. However, whether crocetin affects autophagy after TBI remains unknown. Therefore, we explore crocetin roles in autophagy after TBI. METHODS: We used a weight-dropped model to induce TBI in C57BL/6J mice. Neurological severity scoring (NSS) and grip tests were used to evaluate the neurological level of injury. Brain edema, neuronal apoptosis, neuroinflammation and autophagy were detected by measurements of brain water content, TUNEL staining, ELISA kits and western blotting. RESULTS: Crocetin ameliorated neurological dysfunctions and brain edema after TBI. Crocetin reduced neuronal apoptosis and neuroinflammation and enhanced autophagy after TBI. CONCLUSION: Crocetin alleviates TBI by inhibiting neuronal apoptosis and neuroinflammation and activating autophagy.

Protective effect of crocin on peroxidation-induced oxidative stress and apoptosis in IPEC-J2 cells.

The antioxidant properties of crocin are attracting interest, yet the underlying mechanisms by which crocin mitigates oxidative stress-induced intestinal damage have not been determined. This study aimed to elucidate the effects of crocin on oxidative stress, apoptosis, and intestinal epithelial injury in intestinal epithelial cells (IPEC-J2). Using an H2O2-induced oxidative stress model in IPEC-J2 cells, crocin was added to assess its effects. Cell viability and apoptosis were evaluated using methyl thiazolyl tetrazolium assays and flow cytometry. Additionally, oxidative stress markers, such as superoxide dismutase (SOD), catalase (CAT), reactive oxygen species (ROS), and malondialdehyde (MDA), were quantified. We investigated, in which cell oxidation and apoptosis were measured at the gene and protein levels and employed transcriptome analysis to probe the mechanism of action and validate relevant pathways. The results showed that crocin ameliorates H2O2-induced oxidative stress by reducing ROS and MDA levels and by countering the reductions in CAT, total antioxidant capacity, and SOD. Crocin also attenuates the upregulation of key targets in the Nrf2 pathway. Furthermore, it effectively mitigated IPEC-J2 cell apoptosis caused by oxidative stress, as evidenced by changes in cell cycle factor expression, apoptosis rate, mitochondrial membrane potential, and apoptosis pathway activity. In addition, crocin preserves the integrity of the intestinal barrier by protecting tight junction proteins against oxidative stress. Transcriptome sequencing analysis suggested that the mitochondrial pathway may be a crucial mechanism through which crocin exerts its protective effects. In summary, crocin decreases oxidative stress molecule formation, inhibits Nrf2 pathway activity, prevents apoptosis-induced damage, enhances oxidative stress resistance in IPEC-J2 cells, and maintains redox balance in the pig intestine.

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.

Rats' testicular toxicity induced by bisphenol A is lessened by crocin via an antiapoptotic mechanism and bumped P-glycoprotein expression.

Bisphenol A (BPA) engenders testicular toxicity via hydroxyl free radical genesis in rat striatum and depletion of the endogenous antioxidants in the epididymal sperms. The multi-drug resistance efflux carrier; P-glycoprotein (P-gp) expel the BPA from the testis and is responsible for the testicular protection through the deactivation of numerous xenobiotics. In our study, we investigated whether the BPA-induced testicular toxicity could be circumvented through administration of an antioxidant; crocin (Cr). Implication of P-gp expression was also investigated. Rats administered BPA (10 mg/kg b.w. orally for 14 days), dropped the body weight, testes/body weight ratio, total protein content, testosterone, follicle stimulating hormone, luteinizing hormone, and sperm motility & count, total antioxidant status, glutathione content and antioxidant enzymes (superoxide dismutase and catalase), concomitant with the elevation of the percentage abnormal sperm morphology, as well as testicular lipid peroxides and nitrite/nitrate levels. Histopathological examination showed spermatogenesis disorders after the BPA rats exposure. The immunohistochemical study showed up-regulation of the P-gp as evident by increasing immunoreactivity in interstitial cells, with positive localization in some spermatogonia cells. The BPA-treated rats showed positive immunoreactivity against caspase-3. The co-intake of Cr (200 mg/kg b.w./day, i.p. 14 days) along with the BPA, significantly ameliorated all the mentioned parameters, boosted histopathological image, fell the caspase-3 up-regulation, and perched the P-gp expression. We showed that, Cr promotes P-gp as an approach to nurture the testicles against the BPA toxicity. In conclusion; Cr lessens the oxidative stress conditions to safeguard rats from the BPA-induced testicular toxicity and sex hormones abnormalities, reducing apoptosis and up-regulating P-gp.

Effects of carotenoids on mitochondrial dysfunction.

Oxidative stress, an imbalance between pro-oxidant and antioxidant status, favouring the pro-oxidant state is a result of increased production of reactive oxygen species (ROS) or inadequate antioxidant protection. ROS are produced through several mechanisms in cells including during mitochondrial oxidative phosphorylation. Increased mitochondrial-derived ROS are associated with mitochondrial dysfunction, an early event in age-related diseases such as Alzheimer's diseases (ADs) and in metabolic disorders including diabetes. AD post-mortem investigations of affected brain regions have shown the accumulation of oxidative damage to macromolecules, and oxidative stress has been considered an important contributor to disease pathology. An increase in oxidative stress, which leads to increased levels of superoxide, hydrogen peroxide and other ROS in a potentially vicious cycle is both causative and a consequence of mitochondrial dysfunction. Mitochondrial dysfunction may be ameliorated by molecules with antioxidant capacities that accumulate in mitochondria such as carotenoids. However, the role of carotenoids in mitigating mitochondrial dysfunction is not fully understood. A better understanding of the role of antioxidants in mitochondrial function is a promising lead towards the development of novel and effective treatment strategies for age-related diseases. This review evaluates and summarises some of the latest developments and insights into the effects of carotenoids on mitochondrial dysfunction with a focus on the antioxidant properties of carotenoids. The mitochondria-protective role of carotenoids may be key in therapeutic strategies and targeting the mitochondria ROS is emerging in drug development for age-related diseases.

Natural Compounds in Non-Melanoma Skin Cancer: Prevention and Treatment.

The elevated occurrence of non-melanoma skin cancer (NMSC) and the adverse effects associated with available treatments adversely impact the quality of life in multiple dimensions. In connection with this, there is a necessity for alternative approaches characterized by increased tolerance and lower side effects. Natural compounds could be employed due to their safety profile and effectiveness for inflammatory and neoplastic skin diseases. These anti-cancer drugs are often derived from natural sources such as marine, zoonotic, and botanical origins. Natural compounds should exhibit anti-carcinogenic actions through various pathways, influencing apoptosis potentiation, cell proliferation inhibition, and metastasis suppression. This review provides an overview of natural compounds used in cancer chemotherapies, chemoprevention, and promotion of skin regeneration, including polyphenolic compounds, flavonoids, vitamins, alkaloids, terpenoids, isothiocyanates, cannabinoids, carotenoids, and ceramides.

Skin Protection by Carotenoid Pigments.

Sunlight, despite its benefits, can pose a threat to the skin, which is a natural protective barrier. Phototoxicity caused by overexposure, especially to ultraviolet radiation (UVR), results in burns, accelerates photoaging, and causes skin cancer formation. Natural substances of plant origin, i.e., polyphenols, flavonoids, and photosynthetic pigments, can protect the skin against the effects of radiation, acting not only as photoprotectors like natural filters but as antioxidant and anti-inflammatory remedies, alleviating the effects of photodamage to the skin. Plant-based formulations are gaining popularity as an attractive alternative to synthetic filters. Over the past 20 years, a large number of studies have been published to assess the photoprotective effects of natural plant products, primarily through their antioxidant, antimutagenic, and anti-immunosuppressive activities. This review selects the most important data on skin photodamage and photoprotective efficacy of selected plant carotenoid representatives from in vivo studies on animal models and humans, as well as in vitro experiments performed on fibroblast and keratinocyte cell lines. Recent research on carotenoids associated with lipid nanoparticles, nanoemulsions, liposomes, and micelles is reviewed. The focus was on collecting those nanomaterials that serve to improve the bioavailability and stability of carotenoids as natural antioxidants with photoprotective activity.