Bixa Orellana Seeds Research Articles

Bixa orellana (Bixaceae) seeds as a potential source of bioactive compounds for modulating postprandial hyperglycemia.

α-Amylase (α-AMY) and α-glucosidase (α-GLU) inhibitors are important for controlling postprandial hyperglycemia (PHG). Bixa orellana (annatto) reported inhibitory activity against these enzymes because of its bioactive compound content. However, an understanding of its inhibitory mechanisms and metabolic profile is necessary to establish its therapeutic potential. The present study aimed to elucidate the inhibitory mechanisms of B. orellana extract (BOE) on α-AMY and α-GLU, identify and quantify its bioactive compounds using metabolomics (untargeted and targeted) analyses, and evaluate their interactions through in silico approaches. BOE exhibited IC50 values of 37.75 and 47.06 mg mL-1 for α-AMY and α-GLU, respectively, indicating mixed and competitive inhibition types. Thirty-six putative compounds were identified by untargeted metabolomics, mainly fatty acids (dethiobiotin, occidentalol, palmitic acid, norbixin, among others). The most significant biosynthetic pathways included secondary metabolites (unclassified), unsaturated fatty acids, phenylpropanoids and flavonoid metabolism. Eighteen compounds were identified and quantified by the targeted analysis, such as l-phenylalanine, gallic acid, protocatechuic acid and naringenin. In silico studies highlighted xanthoangelol, norbixin, myricetin and 26-hydroxybrassinolide as key compounds with the highest binding affinities to enzyme active sites. BOE effectively inhibited α-AMY and α-GLU, with gallic acid, naringenin, xanthoangelol, norbixin and 26-hydroxybrassinolide identified as key bioactive contributors. These findings provide molecular evidence of the inhibitory mechanisms of BOE and support its potential for PHG management and diabetes control. © 2024 Society of Chemical Industry.

Effects of E-Cigs on Physiological Pathways and Proposed Therapeutic Intervention with Bixin.

Electronic cigarettes (e-cigs) have increased in popularity and usage over the last few decades. There is rising concern regarding the long-term effects of e-cigs on human health, considering their relatively recent introduction to the market. E-cigs are generally composed of a liquid containing nicotine and various chemicals, a battery, a vaporization chamber, and a coil that serves to heat the liquid upon inhalation of the mouthpiece. While e-cigs were initially introduced as a healthy alternative to cigarette smoking, recent research has demonstrated the cytotoxic effects of nicotinic e-cig devices on multiple cell types, including epithelial and endothelial cells, along with causing dysregulation of inflammatory pathways. This review will discuss the harmful effects of e-cigs on the human body, highlighting the physiological impact of e-cigs on pulmonary, cardiovascular, and cerebrovascular health. Moreover, this review will highlight the potential therapeutic effects of bixin, an apocarotenoid found in the seeds of Bixa orellana, also known as the achiote tree, due to its innate anti-inflammatory, antioxidant, and anti-cancer activities that have been demonstrated in recent research. Nanotechnology has surfaced in the past few decades as a powerful tool for medicinal practice. Specifically, nanoparticles serve as a potential method for treating various conditions and diseases. Bixin nanoparticles show promise as a viable method for treating e-cig-induced damage due to the innate properties of bixin and the advantages of using nanoparticles compared to conventional medicinal interventions.

Introduction of Bixa orellanaL. in Apsheron Conditions

The article, for the first time at the Institute of Dendrology of Azerbaijan NAS, presents information on the introduction, reproduction and bioecological characteristics of the species Bixa orellana L. in the conditions of Absheron. Seeds of Bixa orellana L. were obtained by exchange from the Central Botanical Garden of Padua, Italy. For the first time, the biological characteristics of Bixa orellana L. were studied in Absheron conditions, the morphological characteristics of its shoots, the growth dynamics of 1-2-year-old seedlings, the root system, and nutritional value. The plant is propagated by seeds and cuttings. Soil sowing (06.10.2021) was carried out in the first ten days of June. The first shoots were observed on 06.23.2021, mass shoots were observed on 06.30.2021. Germination was 80%, sprout survival rate was 60%. When propagating by cuttings, young shoots 8-10 cm high are selected and planted in fertile soil or wet sand. After 7-9 weeks they produce a lot of roots. After this, they can be moved to the field. In 1–2-year-old plant seedlings, the above-ground part (39-80 cm) develops better than the underground part (14-26.5 cm). The growth of Bixa orellana L. is divided into 2 periods; intensive height growth in the first period lasts from the second ten days of May to the end of June, the second - from the end of August to the third ten days of October. The annual growth was 20-25 cm. The growing season ranges from 280±5 days. This species is tolerant to the climatic conditions of Absheron.

Bixin, a New Atheroprotective Carotenoid Candidate, Prevents oxLDL-Induced Cytotoxicity and Mitochondrial Dysfunction in Macrophages: Involvement of the Nrf2 and NF-κB Pathways.

The accumulation of oxidized low-density lipoprotein (oxLDL) and its toxicity in the arterial wall have been implicated in atherosclerosis. This study aimed to investigate the mechanisms underlying the atheroprotective effect of bixin, a carotenoid obtained from the seeds of the tropical plant Bixa orellana, on Cu2+-induced LDL oxidation and oxLDL-mediated effects in J774A.1 macrophage cells. Bixin's effects were compared to those of lycopene, a carotenoid widely studied for its cardiovascular protective effects. LDL was isolated from human plasma, incubated with bixin or lycopene (positive control), and subjected to oxidation with CuSO4. Afterward, bixin or lycopene was incubated with J774A.1 macrophage cells and exposed to oxLDL. The levels of ROS, RNS, GSH, nitrite, mitochondrial function, and foam cell formation, as well as the expression of proteins related to the antioxidant and inflammatory status, were evaluated. The effect of bixin in inhibiting in vitro human-isolated LDL oxidation was more potent (5-6-fold) than that of lycopene. Bixin pretreatment reduced the atherogenic signaling triggered by oxLDL in the macrophages, namely the generation of reactive species, disturbance of nitric oxide homeostasis, mitochondrial dysfunction, and foam cell formation. The cytoprotective effects of bixin were accompanied by the upregulation of Nrf2 and the downregulation of the NF-kB pathways. Lycopene showed the same protective effect as bixin, except that it did not prevent mitochondrial dysfunction. The efficient performance of bixin makes it an ideal candidate for further trials as a new nutraceutical compound for the prevention of atherosclerosis.

From Extraction to Stabilization: Employing a 22 Experimental Design in Developing Nutraceutical-Grade Bixin from Bixa orellana L.

Bixin is the main carotenoid found in the outer portion of the seeds of Bixa orellana L., commercially known as annatto. This compound is industrially employed in pharmaceutical, cosmetic, and food formulations as a natural dye to replace chemical additives. This study aimed to extract bixin from annatto seeds and obtain encapsulated bixin in a powder form, using freeze-drying encapsulation and maltodextrin as encapsulating agent. Bixin was extracted from annatto seeds employing successive washing with organic solvents, specifically hexane and methanol (1:1 v/v), followed by ethyl acetate and dichloromethane for subsequent washes, to effectively remove impurities and enhance bixin purity, and subsequent purification by crystallization, reaching 1.5 ± 0.2% yield (or approximately 15 mg of bixin per gram of seeds). Bixin was analyzed spectrophotometrically in different organic solvents (ethanol, isopropyl alcohol, dimethylsulfoxide, chloroform, hexane), and the solvents chosen were chloroform (used to solubilize bixin during microencapsulation) and hexane (used for spectrophotometric determination of bixin). Bixin was encapsulated according to a 22 experimental design to investigate the influence of the concentration of maltodextrin (20 to 40%) and bixin-to-matrix ratio (1:20 to 1:40) on the encapsulation efficiency (EE%) and solubility of the encapsulated powder. Higher encapsulation efficiency was obtained at a maltodextrin concentration of 40% w/v and a bixin/maltodextrin ratio of 1:20, while higher solubility was observed at a maltodextrin concentration of 20% w/v for the same bixin/maltodextrin ratio. The encapsulation of this carotenoid by means of freeze-drying is thus recognized as an innovative and promising approach to improve its stability for further processing in pharmaceutical and food applications.

Evaluation of Antidiabetic and Antioxidant Potential of Methanolic Extract of Bixa orellana Seeds

Diabetes is considered a serious health problem in Bangladesh and worldwide. The disease is infesting all over the mother earth possessing the most damage associated with physical, mental and financial situation of the population. In this context, it’s truly essential to find an effective, safe yet economically suitable alternative medicine compared to commercially available noxious chemical drugs. Objective: This study aims to find the potential of an alternative natural extract produced from Bixa orellana seeds which is safer and more affordable comparable to the commercially available synthetic agents to reduce Hyperglycemia. It also makes effort to find the seed extracts’ ability to reduce oxidation in comparison to a standard drug, Ascorbic acid. Methodology: This is a Pharmacological study using animal model utilising rat as subjects. The rats were induced as diabetic by injecting alloxan intraperitonially and as treatment Bixa Orellana seed extracts were given to them at 500mg/kg and 1000mg/kg doses and compared with the hypogycemic effect of standard anti-diabetic drug, Metformin Hydrochloride at the dose of 100mg/kg. For analyzing the anti-oxidant activity, the DPPH free radical scavenging assay method has been used, where the IC50 values of both the Bixa Orellana seed extract and the reference drug, Ascorbic acid was collated. Results: It was found that the seed extracts used at 500 mg/kg and 1000 mg/kg evidently reduced the blood glucose level as opposed to the diabetic control group, more importantly with the rats treated with standard, Metformin Hydrochloride. Therefore, the study revealed that the seed extract can be effectively used to treat diabetic patients without any side effects. This experimentation, also by assessing the IC50 values, disclosed that the Bixa Orellana seed extract has moderate to substantial anti-oxidant potential in contrary to the reference drug.

Overcoming dormancy in seeds of Bixa orellana L.

Annatto seeds, Bixa orellana L., have dormancy mechanisms that make their germination difficult, requiring testing of different methods to enable their reproduction. Thus, the objective was to evaluate the emergence of Bixa orellana seeds submitted to solutions and periods of imbibition to overcome dormancy. The experimental design was completely randomized, with a 4×2 factorial arrangement. The evaluated seeds were from the red Piave cultivar, with a solution of distilled water and gibberellic acid (GA3) at a concentration of 125 mg L-1 in the imbibition periods of 0, 4, 10, and 24 hours. Emergence test, shoot height, stem diameter, root length, shoot, and root dry matter, and Dickson's quality index was evaluated. The solutions did not interfere with the development of the plants in the periods. It was concluded that annatto seeds in a GA3 solution for a period of 24 hours are efficient for overcoming dormancy.

The Status and Trends of Food Fraud in Tamale, Ghana

Despite its seriousness, food fraud has not received the necessary attention in Ghana’s discourse on food safety. Food fraud is generally considered as the intentional misrepresentation of the contents or identity of food for economic gain. The study was aimed at assessing the food fraud awareness level of participants as well as the foods most likely to be implicated in food fraud cases in Tamale, Ghana. Data was collected from 385 participants, including food business operators and consumers, via a simple random sampling technique using a structured questionnaire. Most participants (54%) were not aware of food fraud and its related activities before the study. Beverages and juices, fruits and vegetables, spices, oils, meat and fish, baked foods, honey, milk, and semi-processed local foods such as groundnut paste, "Dawadawa," “Kulikuli zim,” and “Agushi powder” were all revealed to be implicated in food fraud by respondents. Adulteration was the most common food fraud action, but tampering, substitution, and mislabeling were also identified as ongoing in the study area. “Moora” (Bixa orellana seeds) was revealed as the key adulterant used in most foods. Food fraud, which is a threat to consumer health and well-being, is active in the region and is predicted to increase without strict regulation and increased sensitization about its dangers. The fight against food fraud should be refocused on making food defense systems like vulnerability analysis and critical control points (VACCP) a key aspect of food safety systems to tackle food fraud.

Intramuscular compatibility of an injectable anti-inflammatory nanodispersion from a standardized Bixa orellana oil (Chronic®): a toxicological study in Wistar rats.

Bixa orellana L. is a plant popularly known as "ucurum", "annatto", and "achiote". It is native to South America, and its seeds are an abundant source of geranylgeraniol and tocotrienols. Nanoencapsulation is a valuable technique that can decrease the drug needed to achieve an effect, decreasing potential toxicity, side effectsand potentiate the anti-inflammatory effect. This study aimed to evaluate the acute toxicity of an intramuscular application of a nanodispersion containing a standardized extract from the seeds of Bixa orellana (NBO) in Wistar rats. The chemical evaluation showed δ-tocotrienol at 0.725 ± 0.062mg/mL (72.6 ± 0.9%). The stability study showed the nanoparticles had an average size from 53.15 ± 0.64 to 59.9 ± 3.63nm, with a polydispersity index ranging from 0.574 ± 0.032 to 0.574 ± 0.32, Zeta potential from 18.26 ± 0.59 to 19.66 ± 1.45mV. After testing the intramuscular application of NBO with doses from 1 to 5mg/kg in animals, it was observed that the acute treatment did not elicit any toxic effects within this range. The dose of 10mg/kg, although not affecting hematological and biochemical parameters (CPK, LDH, myoglobin, AST, ALT, TC, TG, glucose levels, creatinine, and urea), could induce some muscle tissue changes, including leukocyte infiltration, morphological chances, and potentially necrosis. In conclusion, the results showed that the treatments devoided toxicity between 1 and 5mg/kg.

Biosynthesis of Bixa orellana seed extract mediated silver nanoparticles with moderate antioxidant, antibacterial and antiproliferative activity

Biosynthesis of metallic silver nanoparticles (AgNPs) has gained much interest and offers an attractive alternate to physical and chemical approaches. In recent year several safe, easy, cost-effective, reproducible, and environmentally friendly synthesis approaches for silver nanoparticles have been developed. In this research work, a simple, cheap, and unexplored method was applied on green synthesis of AgNPs using secondary metabolites extracted from Bixa orellana seeds. The seeds are rich of flavonoids and phenolic compounds which presumably responsible for the fast reduction and stabilization of silver ion into silver nanoparticles. The biosynthesis process is very likely to be able to reduce silver ions under simple physiological conditions. The surface plasmon resonance (SPR) that was appeared at 420 nm in UV–vis spectrum, had confirmed the formation of AgNPs. Moreover, the functional groups in secondary metabolite that act as reducing, capping and stabilizing agents for silver nanoparticles, are identified by Fourier transform infrared (FTIR) spectra. An X-ray diffraction analysis generated four peaks for Bixa orellana seed extract mediated AgNPs positioned at 2θ angles of 38.1°, 44.2°, 64.6°, and 77.5° corresponding to crystal planes (111), (200), (220), and (311). Field emission scanning electron microscope (FESEM) and transmission electron microscopy (TEM) images confirmed the formation of nanosized silver particles. The z-average of the synthesized particles measured by dynamic light scattering (DLS) was found to be 92.9 nm. AgNPs synthesized exhibited remarkable antioxidant activity, antibacterial and antiproliferative activity against human breast (MCF-7) cell line. On the basis of our results, we conclude that biologically synthesized AgNPs exhibited favorable characteristics and have the potential to be used in biomedical fields.

Dynamics of annatto pigment synthesis and accumulation in seeds of Bixa orellana L. revealed by integrated chemical, anatomical, and RNA-Seq analyses.

Bixin is a commercially valuable apocarotenoid pigment found in the seed aril of Bixa orellana. The dynamics and regulation of its biosynthesis and accumulation during seed development remain largely unknown. Here, we combined chemical, anatomical, and transcriptomic data to provide stage-specific resolution of the cellular and molecular events occurring during B. orellana seed development. Seeds at five developmental stages (S1-S5) were used for analysis of bixin content and seed anatomy, and three of them (S1, S3, and S4) were selected for Illumina HiSeq sequencing. Bixin accumulated in large quantities in seeds compared with other tissues analyzed, particularly during the S2 stage, peaking at the S4 stage, and then decreasing slightly in the S5 stage. Anatomical analysis revealed that bixin accumulated in the large central vacuole of specialized cells, which were scattered throughout the developing mesotesta at the S2 stage, but enlarged progressively at later stages, until they occupied most of the parenchyma in the aril. A total of 13 million reads were generated and assembled into 73,381 protein-encoding contigs, from which 312 were identified as containing 1-deoxy-D-xylulose-5-phosphate/2-C-methyl-D-erythritol-4-phosphate (DOXP/MEP), carotenoid, and bixin pathways genes. Differential transcriptome expression analysis of these genes revealed that 50 of them were sequentially and differentially expressed through the seed developmental stages analyzed, including seven carotenoid cleavage dioxygenases, eight aldehyde dehydrogenases, and 22 methyltransferases. Taken together, these results show that bixin synthesis and accumulation in seeds of B. orellana are a developmentally regulated process involving the coordinated expression of DOXP/MEP, carotenoid, and bixin biosynthesis genes.

Comparative study of natural dye-sensitized solar cells using inedible extracts from kumkum, kamala and malabar spinach fruits

In this work, natural dyes were extracted from inedible plant sources, especially seeds of Bixa orellana (kumkum), pericarp of Mallotus phillipensis (kamala) fruits and ripe fruits of Basella alba (malabar spinach) and a detailed comparative study on the efficiency of such extracts or natural compounds as dye sensitizers for solar cell performed. The major constituents or pigments in these extracts are bixin in Bixa orellana, rottlerin in Mallotus phillipensis and betalain/betacyanin in Basella alba fruits. The efficiency of the best performing devices was 0.67% for kumkum, 0.55% for kamala and 0.32% for malabar spinach extracts. Theoretical calculations were also performed to compare the results and it showed congruity with the experimental observations. The thermodynamic parameters such as the electron injection efficiency and the regeneration efficiency were calculated using density function theory (DFT) for the three natural dyes and it was observed that kumkum dye to be the most efficient and malabar spinach to be the least efficient among the three natural dye sensitizers as the same trend with the experimental results. These bio-compatible and inedible extracts are easily available and inexpensive for their use as sensitizers as an alternative to the toxic and expensive synthetic sensitizers.

Pigment and oil content estimation in seeds of Bixa orellana L.

Bixa orellana L. is an economic tree native to the Neotropics. It is perennial in nature growing up to a height ranging from 2 to 8 m. Bixa orellana L. shows phenotypic variation in flower color, pod color, pod shape, height as well as girth. The tree gives a natural colorant called ‘Annatto’ that is second most demanded dye in the world. Selection of trees based on high pigment content becomes a must for this economic tree. Identification of phenotypic character for selection of trees with desirable pigment content was the aim of the study. It was found that cordate pods with green pericarp and maroon bristles gave the highest bixin content, although norbixin content was found to be similar in all pod shapes, cordate pods with maroon pericarp and bristles were advantageous. For selection for oil content conical pods with maroon pericarp and bristles were the most appropriate amongst all.

A Synergism of Eco-Friendly Dyeing of Cotton Fabric and Therapeutic Benefits of Bixa Orellana Seed

Background and objectives: The present research is aimed to study the eco-friendly nature and therapeutic application of the natural dye from the seed extract of Bixa orellana for maximizing the benefits of cotton fabric. Materials and methods: A natural dye was extracted from Bixa orellana seeds by hot water and ethanolic extraction method. This dye was examined for its ability with pre-mordanting and post-mordanting of cotton fabrics with ferrous sulphate, hydrated double sulphate and tamarind seed powder in order to improve the aesthetics and natural color shades on cotton fabrics. Furthermore, the dyed cotton fabric was used to analyze the antibacterial efficacy of cotton fabric against bacterial culture such as Bacillus cereus, Escherichia coli, Proteus mirabilis, Salmonella typhi and Klebsiella pneumoniae. Results: Our results suggest that pre- mordanting of cotton fabric with ferrous sulphate, alum and tamarind seed shows good dye fixation rate and stronger color than post-mordanting. Dyeing of cotton fabric with the ethanol extract of Bixa orellana seeds gave excellent and beautiful shades than the ones extracted with hot water. Furthermore, cotton fabric dyed with ethanol extracted was found significantly active against human pathogens compared to cloth dyed with hot water extract. The results evidenced that cotton knitted fabrics showed an increase in dye uptake with natural mordant and strength with a considerable reduction in antimicrobial activity. Conclusion: This research adumbrated developing a greener technology to cabalistic use of Bixa orellana seed extract applied on cotton cloths for coloring and in future find commercial use as a functional finishing agent (for newborns, clothing for burns, injured soldiers and hospitals) for health protection with semi-durable therapeutic properties.

ISOLATION, EXTRACTION, ANTIOXIDANT ACTIVITY AND STANDARDIZATION OF NATURAL DYES FROM BIXA ORELLANA L. SEEDS AND THE LEAVES OF LAWSONIA INERMIS L.

The antioxidant potential of different fractions of ethanol extracts of seeds of Bixa orellana L. (Bixaceae) and ethanolic extracts of leaves of Lawsonia inermis L. were investigated via 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity using ascorbic acid (Vitamin C) as a standard reference. The free radical scavenging activity of annatto extract ranged from 14.40% to 77.95% in Bixa orellana and 16.50% to 71.8 % in Lawsonia inermis relative to ascorbic acid (15% to 86%) at respective concentration between 10µm/ml and 50µm/ml. phytochemical analysis shows the presence of secondary metabolites such as alkaloids, saponin, tannin, terpenoids and phenolic groups. Hence, both the samples have potential source of new natural antioxidant. Another aim of this study is that the people to get the natural dyes instead of synthetic dye. Natural dyes are not only eco-friendly but also protect human skin. These two samples have both dyeing property and medicinal properties.

Bixin Prevents Colorectal Cancer Development through AMPK-Activated Endoplasmic Reticulum Stress.

Chemicals isolated from natural products have been broadly applied in the treatment of colorectal cancer (CRC). Bixin, an apocarotenoid from the seeds of Bixa orellana, exerts multiple pharmacological properties, including neuroprotective, anti-inflammatory, cardioprotective, and antitumor effects; yet, the therapeutic effects of Bixin on CRC are still unknown. Here, we described that Bixin treatment significantly inhibited the proliferation and motility of two CRC cell lines (CaCO2 and SW480) in vitro and in vivo. In addition, Bixin administration has sensitized CRC cells to TNF-related apoptosis-inducing ligand- (TRAIL-) induced cell apoptosis. Moreover, we showed that Bixin treatment initiated the activation of PERK/eIF-2α signal in CaCO2 and SW480 cells, leading to endoplasmic reticulum stress-associated apoptosis. Pharmacological inhibition of AMP-activated protein kinase (AMPK) abrogated the Bixin-induced activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF-2α) pathway, as well as reversed the inhibitory effects of Bixin on CRC development. In conclusion, this study indicated that Bixin treatment inhibits the progression of CRC through activating the AMPK/PERK/eIF-2α pathway, providing a novel potential strategy for clinical prevention of CRC.

Molecular interaction of natural dye based on Zea Mays and Bixa Orellana to nanocrystalline TiO2 into dye sensitized solar cells.

This work studies the interaction between natural dyes obtained from Peruvian Zea mays and Bixa orellana seeds and nanostructured titanium dioxide in order to evaluate their function as sensitizers into solar cell devices. The effective attachment of dyes to the TiO2 layer is corroborated by the comparison of UV-Visible absorption and FT-IR spectra of the extracted dye solutions and sensitized TiO2 electrodes. The principal compounds from the seed extraction of Zea mays and Bixa orellana are cyanidin-3-glucoside (C3G) and bixin, respectively, which were analyzed in an isolated dye/cluster TiO2 system by molecular dynamic simulation. The results showed that the chemisorption is carried out through a consecutive deprotonation process and Ti-O bond formation by the monodentate OH and COOH anchoring groups, for C3G and bixin, respectively. Finally, we tested the effect of the dye – TiO2 interaction on the charge transfer by the comparison of the current-voltage (I-V) curves and incident photon-to-current conversion efficiency (IPCE) of the cells. We found that dye agglomeration in films with Bixa orellana and the high charge recombination of films with Zea mays are critical points to be solved. For this reason, we propose the pretreatment of the TiO2 film before sensitization with Bixa orellana and analyze the effects of pH in Zea Mays solution, in order to obtain better device efficiencies.

Back Cover: A Unified Approach for the Total Synthesis of cyclo‐Archaeol, iso‐Caldarchaeol, Caldarchaeol, and Mycoketide (Angew. Chem. Int. Ed. 32/2021)

Archaeal lipids have been prepared by iridium-catalysed asymmetric hydrogenation, as reported by Adriaan J. Minnaard et al. in their Research Article on page 17497. Geranylgeraniol, extracted from Bixa orellana seeds, flows in the carafe with the iridium catalyst. The carafe symbolises Iris, the Greek goddess of the rainbow, after which iridium has been named. The final products are poured from it. Mycoketide, produced by M. tuberculosis, is depicted with a picture of the bacterium. The membrane-spanning lipids are represented by glucosylated caldarchaic acid, the grand prismatic spring in Yellowstone, and a picture of the prepared giant unilamellar vesicles.

Bixin attenuates mechanical allodynia, anxious and depressive-like behaviors associated with experimental diabetes counteracting oxidative stress and glycated hemoglobin

Neuropathic pain, depression, and anxiety are common comorbidities in diabetic patients, whose pathophysiology involves hyperglycemia-induced increased oxidative stress. Bixin (BIX), an apocarotenoid extracted from the seeds of Bixa orellana, has been used in traditional medicine to treat diabetes and has been recognized by its antioxidant profile. We aimed to investigate the effect of the BIX over the mechanical allodynia, depressive, and anxious-like behaviors associated with experimental diabetes, along with its involved mechanisms. Streptozotocin-induced diabetic rats were treated for 17 days (starting 14 days after diabetes induction) with the corresponding vehicle, BIX (10, 30 or 90 mg/kg; p.o), or INS (6 IU; s.c.). Mechanical allodynia, depressive, and anxious-like behavior were assessed by electronic Von Frey, forced swimming, and elevated plus-maze tests, respectively. Locomotor activity was assessed by the open field test. Blood glycated hemoglobin (HbA1) and the levels of lipid peroxidation (LPO) and reduced glutathione (GSH) were evaluated on the hippocampus, pre-frontal cortex, lumbar spinal cord, and sciatic nerve. Diabetic animals developed mechanical allodynia, depressive and anxious-like behavior, increased plasma HbA1, increased LPO, and decreased GSH levels in tissues analyzed. Repeated BIX-treatment (at all tested doses) significantly attenuated mechanical allodynia, the depressive (30 and 90 mg/kg) and, anxious-like behaviors (all doses) in diabetic rats, without changing the locomotor performance. BIX (at all tested doses) restored the oxidative parameters in tissues analyzed and reduced the plasma HbA1. Thereby, bixin may represent an alternative for the treatment of comorbidities associated with diabetes, counteracting oxidative stress and plasma HbA1.

Bixin Attenuates Experimental Autoimmune Encephalomyelitis by Suppressing TXNIP/NLRP3 Inflammasome Activity and Activating NRF2 Signaling.

Multiple sclerosis (MS), an autoimmune and degenerative disease, is characterized by demyelination and chronic neuroinflammation. Bixin is a carotenoid isolated from the seeds of Bixa orellana that exhibits various potent pharmacological activities, including antioxidant, anti-inflammatory, and anti-tumor properties. However, the effects of bixin on MS have not yet been examined. To evaluate the effects and underlying molecular mechanisms of bixin on MS, experimental autoimmune encephalomyelitis (EAE) was established in C57BL/6 mice, which were treated via intragastric administration of bixin solutions. To evaluate the molecular mechanisms of bixin, quantitative reverse-transcription PCR, western blot, immunohistochemistry, flow cytometry, and enzyme-linked immunosorbent assay analyses were performed. We found that bixin significantly improved the symptoms and pathology in EAE mice, reduced the release of inflammatory cytokines TNF-α, IL-6, IL-8, IL-17, and IFN-γ, and increased the expression of the anti-inflammatory cytokine IL-10. And bixin reduced the proportion of Th1 and Th17 cells in the spleen and CNS, and suppressed microglia aggregation, and TXNIP/NLRP3 inflammasome activity by scavenging excessive reactive oxygen species (ROS) in EAE mice. Furthermore, bixin inhibited inflammation and oxidative stress via activating nuclear factor erythroid 2-related factor 2 (NRF2), and its downstream genes in EAE mice, meanwhile, these effects were suppressed upon treatment with an NRF2 inhibitor, ML385. Bixin prevented neuroinflammation and demyelination in EAE mice primarily by scavenging ROS through activation of the NRF2 signaling pathway. Taken together, our results indicate that bixin is a promising therapeutic candidate for treatment of MS.