bixin and Disease-Models--Animal

Topics: Animals; Antioxidants; Bixaceae; Carotenoids; Disease Models, Animal; DNA Repair; Humans; Keratinocytes; Mice; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Plant Extracts; PPAR alpha; PPAR gamma; Skin; Skin Neoplasms; Sunlight; Toll-Like Receptor 4; Ultraviolet Rays

Accumulating evidence has implicated the potential of natural compounds in treatment of asthma. Bixin is a natural food coloring isolated from the seeds of Bixa Orellana, which possesses anti-tumor, anti-inflammatory and antioxidative properties. Nevertheless, its therapeutic effect in asthma has not been elucidated. Our present study demonstrated that administration of Bixin suppressed allergic airway inflammation and reversed glucocorticoids resistance, as well as alleviated airway remodeling and airway hyperresponsiveness (AHR) in asthmatic mice. In vitro studies showed that Bixin treatment could inhibit the development of epithelial-mesenchymal transition (EMT) mediated by transforming growth factor beta (TGF-β) signaling. Importantly, Bixin antagonized activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway both in vitro and in vivo. Above all, our findings reveal that Bixin functions as a potent antagonist of PI3K/Akt signaling to protect against allergic asthma, highlighting a novel strategy for asthma treatment based on natural products.

Topics: Allergens; Animals; Anti-Asthmatic Agents; Asthma; Bixaceae; Carotenoids; Disease Models, Animal; Female; Humans; Mice; Mice, Inbred BALB C; Oncogene Protein v-akt; Ovalbumin; Phosphatidylinositol 3-Kinases; Respiratory Hypersensitivity; Signal Transduction; Transforming Growth Factor beta

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Carbon Tetrachloride; Carotenoids; Disease Models, Animal; Fibrosis; Inflammation Mediators; Kidney; Kidney Diseases; Male; Mice, Inbred ICR; Myeloid Differentiation Factor 88; NF-E2-Related Factor 2; Oxidative Stress; PPAR gamma; Signal Transduction; Smad3 Protein; Toll-Like Receptor 4; Transforming Growth Factor beta1

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.

Topics: Animals; Antioxidants; Anxiety; Carotenoids; Depression; Diabetes Mellitus, Experimental; Disease Models, Animal; Glutathione; Glycated Hemoglobin; Hippocampus; Hyperalgesia; Hyperglycemia; Lipid Peroxidation; Male; Neuralgia; Oxidative Stress; Rats; Rats, Wistar; Sciatic Nerve; Streptozocin

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Bixaceae; Carotenoids; Carrageenan; Disease Models, Animal; Edema; Inflammation; Male; Mice; Pain Measurement; Rats; Rats, Wistar

Associations between obesity, diabetes type II, and steatosis have long been recognized. However, a pharmacotherapy that acts in a multifactorial manner controlling the interactions between these conditions is not available. A variety of natural plants, functional fatty acids, and other natural dietary compounds have been used in various anti-obesity products. We investigated the effects of oral administration of an antioxidant carotenoid pigment Bixin and Bixin: β-Cyclodextrin in an obese murine model. C57BL/6 male mice (4-5 weeks) received standard diet (2.18 kcal per 1 g) (CT) and high-fat diet (4.38 kcal per 1 g) (CT/OB, BIX and BIX/βCD) (n = 10 per group). After 16 weeks, the BIX and BIX/βCD were treated by gavage (100 μL day-1) for six weeks, with water (CT and CT/OB groups) and (50 mg kg-1 day-1), Bixin (BIX group) or Bix: β-CD (BIX/βCD). Body weight, Lee's Index, adiposity, CHT, TG, CHT/HDL-c, glucose levels (metabolic markers) and, liver markers (AST and ALT) were determined. All metabolic and liver parameters exhibited down-regulation after oral administration of BIX and BIX/βCD. Particularly relevant was Lee's Index and adiposity in BIX- and BIX/βCD-treated groups (339.18 g/cm -BIX and 327.58 g/cm -BIX/βCD vs. 360.68 g/cm -CT/OB animals), this finds associated with the insulin sensitivity test, showed a clear association between reduction of adipose tissue and decrease of peripherical insulin resistant. In conclusion, our study suggested that the oral administration of the Bixin and Bix: β-CD inclusion compound improved the metabolic parameters evaluate in obese mice, being more palatable and hepatoprotective.

Topics: 3T3-L1 Cells; Adipocytes; Adiposity; Animals; beta-Cyclodextrins; Biomarkers; Blood Glucose; Carotenoids; Diet, High-Fat; Disease Models, Animal; Dose-Response Relationship, Drug; Fatty Liver; Glucose Metabolism Disorders; Hypoglycemic Agents; Hypolipidemic Agents; Lipids; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Time Factors

Mechanical ventilation (MV) is a therapeutic intervention widely used in the clinic to assist patients that have difficulty breathing due to lung edema, trauma, or general anesthesia. However, MV causes ventilator-induced lung injury (VILI), a condition characterized by increased permeability of the alveolar-capillary barrier that results in edema, hemorrhage, and neutrophil infiltration, leading to exacerbated lung inflammation and oxidative stress. This study explored the feasibility of using bixin, a canonical NRF2 inducer identified during the current study, to ameliorate lung damage in a murine VILI model. In vitro, bixin was found to activate the NRF2 signaling pathway through blockage of ubiquitylation and degradation of NRF2 in a KEAP1-C151 dependent manner; intraperitoneal (IP) injection of bixin led to pulmonary upregulation of the NRF2 response in vivo. Remarkably, IP administration of bixin restored normal lung morphology and attenuated inflammatory response and oxidative DNA damage following MV. This observed beneficial effect of bixin derived from induction of the NRF2 cytoprotective response since it was only observed in Nrf2(+/+) but not in Nrf2(-/-) mice. This is the first study providing proof-of-concept that NRF2 activators can be developed into pharmacological agents for clinical use to prevent patients from lung injury during MV treatment.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Carotenoids; Disease Models, Animal; DNA Damage; Dose-Response Relationship, Drug; Female; Kelch-Like ECH-Associated Protein 1; Lung; Mice; Mice, Knockout; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Phosphorylation; Protective Agents; Signal Transduction; Ubiquitination; Ventilator-Induced Lung Injury