Nutraceuticals, Volume 3, Issue 2 (June 2023) – 9 articles

Vitamin D is an essential nutrient with important immunomodulatory properties. As a fat-soluble compound, Vitamin D (and its D₃ form) is immiscible with water, which presents challenges to absorption. In an in vitro setting, the current study characterizes novel micellar formulations of Vitamin D₃ designed to improve absorption. Techniques used to evaluate and compare the micellar formulations against a non-micellar formula include the following: cryo-SEM to determine morphology; laser diffraction to determine particle size and distribution; zeta potential to determine stability of the particles; solubility assays to determine solubility in water and gastrointestinal media; and Caco-2 cell monolayers to determine intestinal permeability. Results show advantageous features (particle size range in the low micrometres with an average zeta potential of −51.56 ± 2.76 mV), as well as significant improvements in intestinal permeability, in one optimized micellar formula (LipoMicel^®). When introduced to Caco-2 cells, LipoMicel’s permeability was significantly better than the control (p < 0.01; ANOVA). Findings of this study suggest that the novel micellar form of Vitamin D₃ (LipoMicel) has the potential to promote absorption of Vitamin D₃. Thus, it can serve as a promising candidate for follow-up in vivo studies in humans. Full article

Purpose: To evaluate the association of CYP1A2 and ADORA2A gene polymorphisms, paraxanthine concentrations, and habitual caffeine (CAF) intake with respect to muscular performance after acute CAF supplementation. Methods: A total of 27 resistance-trained males participating in the study ingested either 5 mg/kg of CAF or PL 45 min before a battery of exercise tests in a cross-over design. DNA was tested for the rs5751876 and rs762551 polymorphisms. Results: CAF improved performance in jumping average power, average velocity, max velocity, bench press in the first set, and peak power in the second set. For the CYP1A2 genotype, C allele carriers improved in jumping average velocity (CAF: 1.77 ± 0.14 m/s, PL: 1.71 ± 0.16 m/s, p < 0.001), and AA homozygotes improved set 1 bench press (CAF: 9.7 ± 1.7 reps, PL: 8.9 ± 1.8 reps, p = 0.046). For the ADORA2A genotype, CC (CAF: 1.70 ± 0.20 m/s, PL: 1.67 ± 0.19 m/s, p = 0.005) and CT (CAF: 1.79 ± 0.09 m/s, PL: 1.74 ± 0.11 m/s, p < 0.001) improved in jumping average velocity and CT also improved in bench press set 2 peak power (CAF: 363 ± 76 W, PL: 323 ± 59 W, p = 0.021). For CAF habituation, CAF improved jumping average power (p = 0.007) and jumping average velocity (p < 0.001) in high users but not in low users (p > 0.05). Conclusions: CAF may improve jumping and bench press performance, irrespective of genotypes, but the associations with the genotypes in CYP1A2 and ADORA2A genes, as well as habitual CAF intake, are not clear and require further investigation. Full article

Comorbidities associated with obesity, including diabetes and kidney diseases, greatly increase mortality rates and healthcare costs in obese patients. Studies in animal models and clinical trials have demonstrated that L-serine supplementation is a safe and effective therapeutic approach that ameliorates the consequences of obesity. However, little is known about the effects of L-Serine supplementation following high-fat diet (HFD) consumption and its role in the mRNA expression of markers of kidney injury. We provide a descriptive action by which L-serine administration ameliorated the consequences of HFD consumption in relation to weight loss, glucose homeostasis as well as renal mRNA expression of markers of kidney injury. Our results indicated that L-Serine supplementation in drinking water (1%, ad libitum for 12 weeks) in male C57BL/6J mice promoted a significant reduction in body weight, visceral adipose mass (epididymal and retroperitoneal fat pads) as well as blood glucose levels in mice consuming a HFD. In addition, the amino acid significantly reduced the mRNA expression of the Kidney Injury Marker 1 (KIM-1), P2Y purinoceptor 1 (P2RY1), as well as pro-inflammatory cytokines (IL-6 and TNFα). L-serine administration had no effect on mice consuming a standard chow diet. Collectively, our findings suggest that L-serine is an effective compound for long-term use in animal models and that it ameliorates the metabolic consequences of HFD consumption and reduces the elevated levels of renal pro-inflammatory cytokines occurring in obesity. Full article

Growing evidence indicates chronic low-grade systemic inflammation as a major pathophysiological mechanism of obesity. Systemic inflammation provokes an immune response in the brain through the activation of microglia that results in the development of neuroinflammation, cellular senescence, and occurrence of neurological dysfunction. In the efforts to identify an innovative intervention with potential efficacy on obesity and associated complications, our aim was to study the capability of the dietary supplement Dekosilhue^® (DKS), successfully used for improving the control of body weight, to attenuate microglia senescent phenotype. Microglia senescence was induced by intermittent stimulation of BV2 cells with LPS 500 ng/mL every 72 h for 4 h/day, over a period of 10 days. DKS (100 µg/mL) treatment reduced ß-galactosidase activity and expression, the formation of senescence-associated heterochromatin foci to control levels, and increased cell viability of senescent BV2 (2 folds of control). DSK reduced the expression of Nuclear Factor-kB (NF-kB) (20% lower than control), a key molecule involved in the acquisition of the senescence-associated secretory phenotype (SASP). DKS promoted a neuroprotective effect by increasing the cell viability of SH-SY5Y neuronal cells exposed to the senescent BV2 conditioned medium to values of non-senescent cells. In conclusion, DKS attenuated the senescent microglia phenotype, showing senotherapeutic activity that might be further investigated as adjunctive intervention for obesity and obesity-related neurological disturbances. Full article

Eccentric exercise induces muscle damage and inflammation, resulting in a state of reduced physical activity with muscle dysfunction and a feeling of tiredness after exercise. Creatine is known to act as an energy buffer, but it has also been suggested to exert inhibitory effects on muscle damage and peripheral inflammation. The purpose of this study was to test the hypothesis that creatine supplementation alleviates fatigue after eccentric exercise and to explore the mechanism of this effect. C57BL/6J mice were fed an AIN-93G-formulated control diet or a creatine-containing diet for 6 days and were then subjected to downhill running, a model of eccentric exercise, to assess the effects on the total creatine concentrations in skeletal muscle and brain tissue, spontaneous activity, the urine concentration of titin N-fragment, and inflammatory gene expression. The results showed that creatine supplementation significantly increased the total creatine concentrations in skeletal muscle and brain tissue. Furthermore, spontaneous activity significantly decreased after downhill running and creatine supplementation maintained a significantly higher level of spontaneous activity. In addition, creatine supplementation significantly suppressed the downhill-running-induced increase in the mRNA expression of genes encoding ICAM-1, E-selectin, CD18, and BKB1R in the soleus muscle and IL-1β in the hypothalamus. On the other hand, creatine supplementation did not clearly influence the urine concentration of titin N-fragment. These results indicate that creatine supplementation may alleviate fatigue after eccentric exercise by partially suppressing inflammation in slow-twitch skeletal muscle and brain tissue. Full article

Amber, a plant resin, exhibits an anti-stress effect and is used in traditional medicine. Recently, it has been speculated that amber may possess an anti-depressive effect. However, there is no evidence to support this efficacy. Thus, this study investigated the anti-depressive and oxidative-stress-ameliorating effects of amber extract in mice subjected to restraint stress. Mice were treated with amber extract (25 and 50 mg/kg, p.o.) and bupropion (10 mg/kg, p.o.) as positive control. Mice were then subjected to a tail suspension test, and their immobility time, body weight before and after stress, levels of stress-related hormones and neurotransmitters, and oxidative stress parameters were assessed. Amber supplementation did not affect the body weight of mice in any of the groups. Amber extract (25 and 50 mg/kg) demonstrated an anti-depressive effect by significantly decreasing the immobility time and adrenocorticotropin-hormone and corticosterone-hormone levels. Moreover, amber extract at a dose of 25 mg/kg increased the levels of dopamine and serotonin. Additionally, superoxide dismutase, catalase, and glutathione levels increased, whereas the malondialdehyde content decreased with amber supplementation. These findings confirm that amber may possess an anti-depressive effect and hence can be a useful alternative therapy for preventing and managing depression. Full article

The purpose of this study was to investigate the loading properties of the non-psychoactive cannabidiol (CBD) in a new nanostructured lipid carrier (NLC), evaluating its bioaccessibility in gastric and intestinal simulated physiological media. CBD has a low water solubility, as well as high instability in simulated physiological conditions and in the acidic media, which results in a very low bioavailability—less than 6%. NLCs containing CBD (10 mg/mL), Compritol 888 ATO, Lauroglycol 90, Labrafil 2125, Tween 20, and Poloxamer 188 were formulated. This resulted in them being suitable for oral administration because the size was less than 200 nm, polydispersity index 0.152, and ζ-potential −39.21 ± 1.89 mV. Recovery and encapsulation efficiency were 100% and 93%, respectively. After two hours of incubation in simulated gastric fluid (SGF), NLCs remained unchanged, protecting CBD from acidic medium. Indeed, CBD is also reported to be not stable in media with pH = 7.4 at 37 °C, but our studies evidenced that in the presence of the intestinal fluid, the NLC was digested and formed an emulsion, which can protect and preserve the CBD chemical structure, as confirmed by the 100% recovery found after six hours. Accordingly, CBD-loaded NLCs are a promising oral formulation that optimize bioaccessibility in the small intestine. Full article

Inspired by the potential functional activity of polyphenol compounds contained in raspberry (Rubus idaeus), we previously explored the effects of the cultivation environment and maturity on the polyphenolic profiles of raspberry leaves and fruits. Herein, building on our previous studies, we used high-performance liquid chromatography and liquid chromatography–mass spectrometry to profile the polyphenol compounds contained in five parts of raspberry flowers (receptacles, sepals, pistils, stamens, and petals), revealing the presence of (+)-catechin, (−)-epicatechin, procyanidin B4, procyanidin C3, sanguiin H-6, and lambertianin C in all flower parts. Petals also contained (−)-epicatechin-3,5-di-O-gallate, kaempferol-7-O-glucoside, and naringenin-7-O-glucoside as well as other flavan-3-ol derivatives efficiently scavenging free radicals and inhibiting the growth of cancer (HeLa S3) cells. Thus, raspberry flower petals were concluded to be a good source of characteristic and highly functional flavan-3-ol derivatives. Full article