trans-sodium-crocetinate and Obesity

Saffron (Crocus sativus L.) has been introduced as a potential promising natural antioxidant with anti-obesity properties. In Persian Medicine, saffron has been used to control appetite and obesity.. The present study aims to investigate the effect of saffron and its bioactive compounds on adipocyte differentiation in human adipose-derived stem cells (ADSCs).. Flow-Cytometric analysis was performed to quantify the cell surface markers. The extracts cytotoxicity on hASCs was measured using alamarBlue® assay whereas their activities against adipocyte differentiation were studied using Oil Red O staining. The level of Peroxisome proliferator-activated receptor-γ (PPARγ), Fatty Acid Synthetase (FAS), and Glyceraldehyde-3-phosphate dehydrogenase (GAPHD) which are key proteins in cell differentiation was investigated by western blot analysis.. Flow-cytometry revealed the mesenchymal stem cells markers, CD44 and CD90, on ADSCs surface. The saffron, crocin, and crocetin significantly inhibited adipocyte differentiation while saffron up to 20 μg/mL and crocin, crocetin and safranal up to 20 μM did not exhibit cytotoxicity. The western blotting analysis revealed a remarkable reduction in the level of PPARγ, GAPDH, and FAS proteins by 10 and 20 μM of crocin and 2.5 and 5 μM of crocetin.. It seems that saffron, crocin, and crocetin could efficiently inhibit the differentiation of hASCs with benefits for the treatment and prevention of obesity.

Topics: Adipocytes; Carotenoids; Cell Differentiation; Crocus; Cyclohexenes; Humans; Mesenchymal Stem Cells; Obesity; Plant Extracts; PPAR gamma; Terpenes; Vitamin A

In diabetes mellitus type 2 (DM2), developed obesity is referred to as diabesity. Implementation of a healthy diet, such as the Mediterranean, prevents diabesity. Saffron is frequently used in this diet because of its bioactive components, such as crocetin (CCT), exhibit healthful properties. It is well known that obesity, defined as an excessive accumulation of fat, leads to cardiometabolic pathology through adiposopathy or hypertrophic growth of adipose tissue (AT).This is related to an impaired adipogenic process or death of adipocytes by obesogenic signals. We aimed to evaluate the effect of the pathogenic microenvironment and CCT, activating differentiation of healthy preadipocytes (PA). For this, we used human cryopreserved PA from visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) depots obtained from healthy and obese-DM2 donors. We studied the effect of a metabolically detrimental (diabesogenic) environment, generated by obese-DM2 adipocytes from VAT (VdDM) or SAT (SdDM), on the viability and accumulation of intracellular fat of adipocytes differentiated from healthy PA, in the presence or absence of CCT (1 or 10 μM). Intracellular fat was quantified by Oil Red O staining. Cytotoxicity was measured using the MTT assay. Our results showed that diabesogenic conditions induce cytotoxicity and provide a proadipogenic environment only for visceral PA. CCT at 10 μM acted as an antiadipogenic and cytoprotective compound.

Topics: Adipocytes; Adipogenesis; Adipokines; Adipose Tissue; Animals; Carotenoids; Cell Differentiation; Cell Line; Diabetes Mellitus; Humans; Intra-Abdominal Fat; Male; Obesity; Rats; Subcutaneous Fat; Vitamin A

Trans-sodium crocetinate (TSC) is a novel synthetic carotenoid compound that improves diffusion of small molecules, including oxygen, in solutions. TSC provides neuroprotection in healthy rats and rabbits. This study seeks to determine whether TSC is neuroprotective in obese mice. Sixteen-week-old CD-1 male mice that had been fed a high-fat diet for 10 weeks were subjected to a 90-min middle cerebral arterial occlusion (MCAO). They received TSC by two boluses through a tail vein 10 min after the onset of MCAO and reperfusion, respectively, with doses of 0.14, 0.28, and 0.7 mg/kg or by a bolus-infusion-bolus strategy with a dose of 0.14 mg/kg during MCAO. The neurological outcome was evaluated 72 hr after MCAO. Brain tissues were harvested 24 hr after MCAO to measure nitrotyrosine-containing proteins, 4-hydroxy-2-nonenal, matrix metalloproteinase (MMP)-2 and -9 activity and expression, and inflammatory cytokines. TSC given in the two-bolus strategy did not improve the neurological outcome. The bolus-infusion-bolus strategy significantly reduced brain edema, infarct volume, and hemorrhagic transformation and improved neurological functions. TSC reduced nitrotyrosine-containing proteins, MMP-9 activity and expression, and inflammatory cytokines in ischemic brain tissues. Our results indicate that TSC delivered by the bolus-infusion-bolus strategy provides neuroprotection in obese mice. This protection may occur through reduction of oxidative stress, MMP-9 activity, or inflammatory cytokines in the ischemic brain tissues.

Topics: Aldehydes; Analysis of Variance; Animals; Brain; Brain Ischemia; Carotenoids; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Matrix Metalloproteinases; Mice; Nervous System Diseases; Neuroprotective Agents; Obesity; Oxidative Stress; Reperfusion; Tyrosine; Vitamin A