The impact of magnesium biotinate and arginine silicate complexes on metabolic dysfunctions, antioxidant activity, inflammation, and neuromodulation in high-fat diet-fed rats.

Biotin and arginine play crucial roles in lipid metabolism and may offer promising interventions against obesity. This study examined the combined effect of magnesium biotinate (MgB) and inositol-stabilized arginine silicate complex (ASI) on obesity-related oxidative imbalance, inflammation, lipid metabolism and neuromodulation in rats on a high-fat diet (HFD). Forty rats were divided into five groups: (a) control: rats were fed a standard diet containing 12% of energy from fat; (b) HFD: rats were fed the HFD with 42% of energy from fat; (c) HFD + MgB: rats were fed the HFD and given 0.31 mg/kg body weight (BW) MgB, (d) HFD + ASI: rats were fed the HFD and were given 12.91 mg/kg BW ASI), and (e) HFD + MgB + ASI: rats were fed the HFD and given 0.31 mg/kg BW MgB and 12.91 mg/kg BW ASI). The combined administration of MgB and ASI reduced the levels of serum cholesterol, free fatty acid (FFA), and malondialdehyde (MDA), as well as liver inflammatory cytokines, sterol regulatory element-binding protein 1-c (SREBP-1c), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) proteins (P < 0.001) compared to HFD rats without supplementation. Moreover, this combination increased the activities of antioxidant enzymes (P < 0.05) and boosted the brain-derived neurotrophic factor (BDNF), serotonin, dopamine (P < 0.001), as well as liver insulin receptor substrate 1 (IRS-1) and peroxisome proliferator-activated receptor gamma (PPAR-γ) (P < 0.001). These findings suggest that combining MgB and ASI could deter liver fat accumulation and enhance lipid metabolism in HFD-fed rats by modulating various metabolic pathways and neuromodulators related to energy metabolism. This combination demonstrates potential in addressing obesity and its related metabolic dysfunctions.

Impact of a Novel Valerian Extract on Sleep Quality, Relaxation, and GABA/Serotonin Receptor Activity in a Murine Model.

Insomnia is a major global health issue, highlighting the need for treatments that are both effective and safe. Valerian extract, a traditional remedy for sleep problems, offers potential therapeutic options. This research examined the potential sleep-enhancing effects of VA (Valerian Pdr%2) in mice. The study evaluated sleep quality by comparing the impact of the VA extract against melatonin on brain activity, using electrocorticography (ECoG) to assess changes in brain waves. For this purpose, the study utilized two experimental models on BALB/c mice to explore the effects of caffeine-induced insomnia and pentobarbital-induced sleep. In the first model, 25 mice were assigned to five groups to test the effects of caffeine (caffeine, 7.5 mg/kg i.p) alone, caffeine with melatonin (2 mg/kg), or caffeine with different doses of valerian extract (100 or 300 mg/kg) given orally on brain activity, assessed via electrocorticography (ECoG) and further analyses on the receptor proteins and neurotransmitters. In the second model, a different set of 25 mice were divided into five groups to examine the impact of pentobarbital (42 mg/kg) alone, with melatonin, or with the valerian extract on sleep induction, observing the effects 45 min after administration. The study found that ECoG frequencies were lower in groups treated with melatonin and two doses of valerian extract (100 and 300 mg/kg), with 300 mg/kg showing the most significant effect in reducing frequencies compared to the caffeine control group, indicating enhanced sleep quality (p < 0.05). This was supported by increased levels of serotonin, melatonin, and dopamine and higher levels of certain brain receptors in the melatonin and valerian extract groups (p < 0.05). Modulatory efficacy for the apoptotic markers in the brain was also noted (p < 0.05). Additionally, melatonin and both doses of VA increased sleep duration and reduced sleep onset time compared to the pentobarbital control, which was particularly notable with high doses. In conclusion, the findings suggest that high doses (300 mg/kg) of valerian extract enhance both the quantity and quality of sleep through the GABAergic pathway and effectively increase sleep duration while reducing the time to fall asleep in a pentobarbital-induced sleep model in mice.

Beneficial effects of a novel polyherbal formulation on the skeletal muscle antioxidant status, inflammation, and muscle-signaling proteins in exercised rats.

Background/aim: Exhausting exercise can damage muscle tissue due to free radical interactions. It is hypothesized that the increase in free radicals following muscle injury, either due to oxidative damage to biomolecules or the activation of inflammatory cytokines, may lead to secondary muscle damage. This study investigated the effects of a novel joint health formula (JHF) containing bisdemethoxycurcumin-enriched curcumin, 3-O-Acetyl-11-keto-beta-boswellic acid-enriched Boswellia (AKBA), and Ashwagandha on exhaustion time, grip strength, antioxidant status, and muscle-signaling proteins in exhaustively exercised rats. Materials and methods: Twenty-eight rats were divided into four groups: Control (C), exercise (E), E + JHF 100 (100 mg/kg), and E + JHF 200 (200 mg/kg). Results: An increase in time to exhaustion and grip strength was recorded with JHF supplementation in a dose-dependent manner (p < 0.0001). In addition, serum and muscle lactate dehydrogenase, malondialdehyde, myoglobin, creatine kinase, and lactic acid concentrations were decreased in the groups supplemented with JHF, particularly at the high dose of JHF (200 mg/kg) (p < 0.0001 for all). JHF supplementation also increased antioxidant enzyme activities and suppressed the production of inflammatory cytokines compared to the exercise group (p < 0.0001). Moreover, JHF reduced the levels of PGC-1α, p-70S6K1, MAFbx, MuRF1, and p-mTOR proteins in muscle tissue compared to the exercise group (p < 0.05), being more effective at high doses. Conclusion: These findings show that JHF might reduce muscle damage by modulating antiinflammatory, antioxidant, and muscle mass regulatory pathways in exhausted training rats. At the same time, JHF improved exercise performance and grip strength.

Emergent approach to small bowel tumors: diagnosis and treatment.

BACKGROUND: This study presents the diagnosis and treatment of rare small bowel tumors through clinical cases. METHODS: Patients treated between 2000 and 2023 were included in the study. The clinical records of the patients were analyzed retrospectively. RESULTS: A total of 34 patients were included in the study. Of these patients, 26 (75.5%) were male and eight (23.5%) were female. The mean age of the patients was 62.1 years. The most common symptoms and signs were abdominal pain (76.4%), bloating (38.2%), and nausea and vomiting (17.6%). Diagnostic methods included computed tomography (CT) (82.3%), upper gastrointestinal double balloon enteroscopy (35.2%), and capsule endoscopy (5.8%). Diagnoses included adenocarcinoma in 13 cases, gastrointestinal stromal tumors (GISTs) in 12 cases, and neuroendocrine tumors (NETs) in two cases. CONCLUSION: Small bowel tumors frequently present with abdominal pain, bloating, and nausea and vomiting. CT and endoscopic procedures are the primary diagnostic tools. Small bowel cancers are often diagnosed late due to subtle clinical findings and the limitations of endoscopic imaging. Targeted screening strategies may be beneficial for certain at-risk and symptomatic patient groups. Early surgical intervention offers significant advantages for diagnosed patients.

A highly bioavailable curcumin formulation ameliorates inflammation cytokines and neurotrophic factors in mice with traumatic brain injury.

A novel curcumin formulation increases relative absorption by 46 times (CurcuWIN®) of the total curcuminoids over the unformulated standard curcumin form. However, the exact mechanisms by which curcumin demonstrates its neuroprotective effects are not fully understood. This study aimed to investigate the impact of a novel formulation of curcumin on the expression of brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), a main component of the glial scar and growth-associated protein-43 (GAP-43), a signaling molecule in traumatic brain injury (TBI). Mice (adult, male, C57BL/6j) were randomly divided into three groups as follows: TBI group (TBI-induced mice); TBI + CUR group (TBI mice were injected i.p. curcumin just after TBI); TBI+ CurcuWIN® group (TBI mice were injected i.p. CurcuWIN® just after TBI). Brain injury was induced using a cold injury model. Injured brain tissue was stained with Cresyl violet to evaluate infarct volume and brain swelling, analyzed, and measured using ImageJ by Bethesda (MD, USA). Western blot analysis was performed to determine the protein levels related to injury. While standard curcumin significantly reduced brain injury, CurcuWIN® showed an even greater reduction associated with reductions in glial activation, NF-κB, and the inflammatory cytokines IL-1ß and IL-6. Additionally, both standard curcumin and CurcuWIN® led to increased BDNF, GAP-43, ICAM-1, and Nrf2 expression. Notably, CurcuWIN® enhanced their expression more than standard curcumin. This data suggests that highly bioavailable curcumin formulation has a beneficial effect on the traumatic brain in mice.

Effects of Whey Protein Combined with Amylopectin/Chromium on the Muscle Protein Synthesis and mTOR Phosphorylation in Exercised Rats.

This study aimed to examine the impact of varying doses of whey protein (WP) and amylopectin/chromium complex (ACr) supplementation on muscle protein synthesis (MPS), amino acid and insulin levels, and the rapamycin (mTOR) signaling pathways in exercised rats. A total of 72 rats were randomly divided into nine groups: (1) Exercise (Ex), (2) Ex + WPI to (5) Ex + WPIV with various oral doses of whey protein (0.465, 1.55, 2.33, and 3.1 g/kg) and (6) Ex + WPI + ACr to (9) Ex + WPIV + ACr with various doses of whey protein combined with 0.155 g/kg ACr. On the day of single-dose administration, the products were given by oral gavage after exercise. To measure the protein fractional synthesis rate (FSR), a bolus dose of deuterium-labeled phenylalanine was given, and its effects were evaluated 1 h after supplementation. Rats that received 3.1 g/kg of whey protein (WP) combined with ACr exhibited the most significant increase in muscle protein synthesis (MPS) compared to the Ex group (115.7%, p < 0.0001). In comparison to rats that received the same dose of WP alone, those given the combination of WP and ACr at the same dosage showed a 14.3% increase in MPS (p < 0.0001). Furthermore, the WP (3.1 g/kg) + ACr group exhibited the highest elevation in serum insulin levels when compared to the Ex group (111.9%, p < 0.0001). Among the different groups, the WP (2.33 g/kg) + ACr group demonstrated the greatest increase in mTOR levels (224.2%, p < 0.0001). Additionally, the combination of WP (2.33 g/kg) and ACr resulted in a 169.8% increase in 4E-BP1 levels (p < 0.0001), while S6K1 levels rose by 141.2% in the WP (2.33 g/kg) + ACr group (p < 0.0001). Overall, supplementation with various doses of WP combined with ACr increased MPS and enhanced the mTOR signaling pathway compared to WP alone and the Ex group.

Understanding Cr(III) Action on Mitochondrial ATP Synthase and AMPK Efficacy: Insights from Previous Studies-a Review.

Chromium supplementation has been notably recognized for its potential health benefits, especially in enhancing insulin sensitivity and managing glucose metabolism. However, recent studies have begun to shed light on additional mechanisms of action for chromium, expanding our understanding beyond its classical effects on the insulin-signaling pathway. The beta subunit of mitochondrial ATP synthase is considered a novel site for Cr(III) action, influencing physiological effects apart from insulin signaling. The physiological effects of chromium supplementation have been extensively studied, particularly in its role in anti-oxidative efficacy and glucose metabolism. However, recent advancements have prompted a re-evaluation of chromium's mechanisms of action beyond the insulin signaling pathway. The discovery of the beta subunit of mitochondrial ATP synthase as a potential target for chromium action is discussed, emphasizing its crucial role in cellular energy production and metabolic regulation. A meticulous analysis of relevant studies that were earlier carried out could shed light on the relationship between chromium supplementation and mitochondrial ATP synthase. This review categorizes studies based on their primary investigations, encompassing areas such as muscle protein synthesis, glucose and lipid metabolism, and antioxidant properties. Findings from these studies are scrutinized to distinguish patterns aligning with the new hypothesis. Central to this exploration is the presentation of studies highlighting the physiological effects of chromium that extend beyond the insulin signaling pathway. Evaluating the various independent mechanisms of action that chromium impacts cellular energy metabolism and overall metabolic balance has become more important. In conclusion, this review is a paradigm shift in understanding chromium supplementation, paving the way for future investigations that leverage the intricate interplay between chromium and mitochondrial ATP synthase.

Lutein/Zeaxanthin Isomers and Quercetagetin Combination Safeguards the Retina from Photo-Oxidative Damage by Modulating Neuroplasticity Markers and the Nrf2 Pathway.

Exposure to light-emitting diode (LED) light is a primary cause of retinal damage, resulting in vision loss. Several plant-derived substances, such as lutein and quercetagetin (QCG), show promise in supporting eye health. In this study, the impact of lutein/zeaxanthin (L/Z, Lutemax 2020) and QCG were evaluated individually and together in a rat model of LED-induced retinal damage. A total of 63 Wistar rats were allocated into nine groups (n = 7). For 28 days, the rats received L/Z (10 or 20 mg/kg BW), quercetin (QC, 20 mg/kg BW), QCG (10 or 20 mg/kg BW), or a mixture of different lutein and QCG dosages, after which they were exposed to LED light for 48 h. LED exposure led to a spike in serum malondialdehyde (MDA) and inflammatory cytokines, as well as an increase in retinal NF-κB, ICAM, GFAP, and MCP-1 levels (p < 0.0001 for all). It also reduced serum antioxidant enzyme activities and retinal Nrf2, HO-1, GAP43, NCAM, and outer nuclear layer (ONL) thickness (p < 0.0001 for all). However, administering L/Z and QCG, particularly a 1:1 combination of L/Z and QCG at 20 mg/kg, effectively reversed these changes. The treatment suppressed NF-κB, ICAM, GFAP, and MCP-1 while enhancing Nrf2, HO-1, GAP43, and NCAM and preventing ONL thickness reduction in LED-induced retinal damage rats. In conclusion, while LED light exposure caused retinal damage, treatment with L/Z, QC, and QCG, particularly a combined L/Z and QCG regimen, exhibited protective effects on the retina. This is possibly due to the modulation of neuroplasticity markers and nuclear transcription factors in the rats' retinal cells.

Nicotinamide Riboside and Phycocyanin Oligopeptides Affect Stress Susceptibility in Chronic Corticosterone-Exposed Rats.

Nicotinamide riboside (NR) is an NAD+ precursor capable of regulating mammalian cellular metabolism. Phycocyanin oligopeptide (PC), a phytonutrient found in blue-green algae, has antioxidant and anti-inflammatory properties. This study explored the effects of NR, PC, and their combination on the telomere length as well as inflammatory and antioxidant status of rats under chronic stress conditions (CS). Forty-nine rats were allocated into seven groups: control, chronic stress (CS), CS with NR (26.44 mg/kg), a low dose of 2.64 mg/kg of PC (PC-LD), or a high dose of 26.44 mg/kg PC (PC-HD), NR + PC-LD, and NR + PC-HF. The rats were given daily corticosterone injections (40 mg/kg) to induce stress conditions, or NR and PC were orally administered for 21 days. NR and PC supplementation, particularly NR plus PC, increased the serum antioxidant enzyme activities, hepatic nicotinamide adenine (NAD+) content, and telomere length (p < 0.001 for all) compared to the CS group. The levels of serum malondialdehyde (MDA), liver interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), IL-1ß, and IL-8 were reduced under the CS condition (p < 0.001). In addition, CS decreased the levels of hepatic telomere-related proteins and sirtuins (SIRT1 and 3), whereas administration of NR and PC or their combination to CS-exposed rats increased the levels of telomere-related proteins (e.g., POT1b, TRF1 and TRF2), SIRT3 and NAMPT (p < 0.05). In conclusion, NR and PC, especially their combination, can alleviate metabolic abnormalities by enhancing hepatic cytokines, SIRT3, NAMPT, and NAD+ levels in CS-exposed rats. More research is needed to further elucidate the potential health effects of the combination of NR and PC in humans.

Mango ginger (Curcuma amada Roxb.) may alleviate the effect of high-fat diet/streptozotocin-induced diabetes by activation of the GSK-3ß/Fyn/Nrf2 pathway.

Mango ginger (MG) exhibits antioxidant, anti-inflammatory, and antihyperglycemic effects; however, the exact mechanism of action of MG extract in relation to its antidiabetic properties remains unclear. To investigate the potential antidiabetic effect of MG extract, we used a high-fat diet (HFD)/low-dose streptozotocin (STZ)-induced type 2 diabetic rat model. A total of 28 male Wistar rats were randomly divided into four groups: (i) Control, (ii) MG (50 mg/kg/day of MG extract), (iii) HFD + STZ (40 mg/kg i.p.), and (iv) HFD + STZ + MG. Following a 12-week administration of MG extract, significant reductions were observed in serum glucose, insulin, free fatty acid, cholesterol, and triglyceride levels in diabetic rats (p < .0001 for all). MG extract supplementation led to an increase in the total antioxidant capacity of the serum and a decrease in malondialdehyde (MDA) levels in both the serum and liver (p < .0001). Furthermore, hepatocellular fat accumulation was partially attenuated in the HFD + STZ + MG group. Notably, MG extract inhibited glycogen synthase kinase-3ß (GSK-3ß) in the liver (p < .01) and downregulated Fyn expression, resulting in elevated nuclear factor erythroid 2-related factor 2 (Nrf2) activity in the HFD + STZ + MG group compared to the HFD + STZ group (p < .05). The increased activity of Nrf2 in the HFD + STZ + MG group likely promoted the upregulation of heme oxygenase 1 (HO-1) in the liver (p < .0001). In conclusion, MG extract may exert antidiabetic effects by augmenting the antioxidant defense system through the regulation of GSK-3ß/Fyn/Nrf2 in a rat model of type 2 diabetes.

The Effect of Residual Gastric Volume on Body Mass Index, Excess Weight Loss Rate and Metabolic Response after Sleeve Gastrectomy.

BACKGROUND/AIM: To investigate the metabolic response and body mass index reduction according to the remaining stomach volume between 6-12 months after the operation in patients who underwent sleeve gastrectomy surgery for obesity and to determine the relationship between the remaining stomach volume and metabolic improvement. Materials and Methods: Patients underwent sleeve gastrectomy in a single center by the same team and with the same standardized method. Residual gastric volumes were calculated from three-dimensional computed tomography images obtained 6-12 months postoperatively. BMI, excess weight loss (EWL), total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL), triglyceride, hemoglobin A1c (HbA1c), total protein, albumin values were recorded preoperatively and at the time of residual volume measurement. Results: There were 49 subjects with a mean SD preoperative BMI of 47.26+-6.21 kg/m2 and mean age 37.51+-10.88 years. Mean residual volume was 155.36+-56.71 cc. Residual volume was associated with postoperative mean BMI (28.44+-3.23 kg/m2; p 0.001) and postperative mean EWL%(29.27+-7.66; p=0.001). Residual gastric volume was also negative correlated with postoperative mean HbA1c (p=0.004). HbA1c (p=0.828), LDL (p=0.661), HDL (p=0.848), triglycerides (p=0.641), VLDL (p=0.794), total protein relation (p=0.539) and albumin (p=0.824) were analyzed before and after surgery and were not correlated with residual gastric volume. CONCLUSION: The smaller the residual gastric volume after laparoscopic sleeve gastrectomy, the higher the %EWL and the greater the decrease in HbA1c. This study show that laparoscopic sleeve gastrectomy is an effective surgical procedure in patients with Type 2 diabetes mellitus.

Garlic Exosomes Promote Hair Growth Through the Wnt/ß-catenin Pathway and Growth Factors.

Background Exosomes are membrane-derived nanovesicles produced by cells and play an important role in intercellular communication. Objectives This study aimed to investigate the effects of garlic exosome (GE) on hair growth. Methods Forty-two Sprague-Dawley/Wistar albino rats were randomly divided into six groups: non-shaved control, shaved control, topical control, GE 2 mg, GE 4 mg, and topical GE. At the end of the experiment, the number of hair follicles, follicle diameter, and subcutaneous tissue thicknesses were measured histopathologically. The Wnt-1, ß-catenin, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), and collagen I levels were measured by the Western Blot method. Results The anagen follicle counts of the GE 2 mg, 4 mg, and topical GE groups were 66.57±15.49, 105.71±25.06, and 55.29±6.72, and were significantly higher than the control groups (p<0.01, p<0.001 and p<0.05, respectively). The follicle diameter of the GE 4 mg group was higher than the others (p<0.05). The Wnt-1, PDGF, VEGF, TGF-ß1, and collagen I levels of all GE groups, and the ß-catenin levels of the GE 4 mg and topical GE groups were significantly higher than the control groups (p<0.05). Conclusion GE induces hair growth in rats via the Wnt-1, ß-catenin, VEGF, PDGF, and TGF-ß1 signaling pathways.

The Relationship Between Laboratory Findings and Mortality in COVID-19 Patients Requiring Intensive Care.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shows a wide clinical manifestation from asymptomatic infection to life-threatening respiratory failure. This study aimed to determine the relationship between the survival and demographic data, comorbidity status, and laboratory parameters of coronavirus disease 2019 (COVID-19) patients requiring intensive care. MATERIAL AND METHODS: We retrospectively analyzed 236 patients requiring intensive care whose diagnosis was confirmed by the SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test. The patients were divided into two groups in terms of survival. Demographic data; procalcitonin and C-reactive protein (CRP) levels; leukocyte, lymphocyte, and neutrophil counts in hemogram and neutrophil-to-lymphocyte ratio (NLR) levels; and lower respiratory and blood cultures were examined, and the relationships between these parameters and survival were evaluated with hypothesis testing. RESULTS:  In the study, 156 (66.1%) males and 80 (33.9%) females, a total of 236 patients, were included. Sixty-seven (28.3%) surviving patients were determined as Group 1, and 169 (71.7%) deceased patients were determined as Group 2. A statistically significant difference was found between the groups in terms of mean age (p<0.001) and gender distribution (p=0.011). In laboratory parameters, a significant difference was observed between the groups in lymphocyte count (p=0.001), NLR (p<0.001), and procalcitonin levels (p<0.001). Although leukocyte (p=0.075), neutrophil (p=0.031), and CRP (p=0.112) levels were higher in Group 2, there was no statistical difference. Mortality was found to be higher in patients with comorbidity (p=0.012) or co-infection (p=0.002). CONCLUSION: High levels of neutrophil count, NLR, and procalcitonin; low lymphocyte count; the presence of comorbidity; and secondary bacterial infection were found to be associated with mortality in COVID-19 patients in the intensive care unit.

The effect of different boron compounds on nutrient digestibility, intestinal nutrient transporters, and liver lipid metabolism.

BACKGROUND: Gastrointestinal health is essential for maintaining a healthy lifestyle. Improving nutrient absorption and energy metabolism are the critical targets for intestinal health. This study aimed to determine the effects of different boron (B) derivatives on nutrient digestibility, intestinal nutrient transporters, and lipid metabolism in rats. METHODS: Twenty-one rats were allocated to three groups (n = 7) as follows: (i) Control, (ii) Sodium pentaborate pentahydrate (SPP), and (iii) boric acid (BA). The rats were fed a chow diet (AIN-93M) and supplemented with 8 mg/kg elemental B from SPP (45.2 mg/kg BW) and BA (42.7 mg/kg BW) via oral gavage every other day for 12 weeks. The nutrient digestibility of rats in each group was measured using the indigestible indicator (chromium oxide, Cr2 O3, 0.20%). At the end of the experiment, animals were decapitated by cervical dislocation and jejunum, and liver samples were taken from each animal. The nutrient transporters and lipid-regulated transcription factors were determined by RT-PCR. RESULTS: The nutrient digestibility (except for ash) was increased by SPP and BA supplementation (p < 0.05). SPP and BA-supplemented rats had higher jejunal glucose transporter 1 (GLUT1), GLUT2, GLUT5, sodium-dependent glucose transporter 1 (SGLT1), fatty acid transport protein-1 (FATP1), and FATP4 mRNA expression levels compared to nonsupplemented rats (p < 0.0001). BA-supplemented rats had remarkably higher peroxisome proliferator-activated receptor gamma (PPARγ) levels than nonsupplemented rats (p < 0.0001). In contrast, sterol regulatory element-binding protein 1c (SREBP-1c), liver X receptor alpha (LxR-α), and fatty acid synthase (FAS) levels decreased by SPP supplementation compared to other groups (p < 0.05). DISCUSSION: SPP and BA administration enhanced nutrient digestibility, intestinal nutrient transporters, and liver lipid metabolism in rats.

Cannabinoid compounds in combination with curcumin and piperine display an anti-tumorigenic effect against colon cancer cells.

Currently, use of cannabinoids is limited to improve adverse effects of chemotherapy and their palliative administration during treatment is curiously concomitant with improved prognosis and regressed progression in patients with different tumor types. Although, non-psychoactive cannabidiol (CBD) and cannabigerol (CBG) display antineoplastic effects by repressing tumor growth and angiogenesis both in cell line and animal models, their use as chemotherapeutic agents is awaiting further investigation. Both clinical and epidemiological evidence supported by experimental findings suggest that micronutrients such as curcumin and piperine may present a safer strategy in preventing tumorigenesis and its recurrence. Recent studies demonstrated that piperine potentiates curcumin's inhibitory effect on tumor progression via enhancing its delivery and therapeutic activity. In this study, we investigated a plausible therapeutic synergism of a triple combination of CBD/CBG, curcumin, and piperine in the colon adenocarcinoma using HCT116 and HT29 cell lines. Potential synergistic effects of various combinations including these compounds were tested by measuring cancer cell proliferation and apoptosis. Our findings revealed that different genetic backgrounds of HCT116 and HT29 cell lines resulted in divergent responses to the combination treatments. Triple treatment showed synergism in terms of exhibiting anti-tumorigenic effects by activating the Hippo YAP signaling pathway in the HCT116 cell line.

Evaluation of pea/rice and amylopectin/chromium as an alternative protein source to improve muscle protein synthesis in rats.

BACKGROUND: A preclinical study reported that the combination of an amylopectin/chromium complex (ACr) of branched-chain amino acids (BCAA) significantly enhanced muscle protein synthesis (MPS). This study was conducted to determine the effects of the addition of ACr complex to a pea/rice (PR) protein on MPS, insulin, muslin levels, and the mTOR pathway in exercised rats. METHODS: Twenty-four rats were divided into three groups: (i) exercise (Ex); (ii) Ex + PR 1:1 blend (0.465 g/kg BW); (iii) Ex + PR + ACr (0.155 g/kg BW). On the day of single-dose administration, after the animals were exercised at 26/m/min for 2 h, the supplement was given by oral gavage. The rats were injected with a bolus dose (250 mg/kg BW, 25 g/L) of deuterium-labeled phenylalanine to determine the protein fractional synthesis rate (FSR) one h after consuming the study product. RESULTS: The combination of PR and ACr enhanced MPS by 42.55% compared to the Ex group, while Ex + PR alone increased MPS by 30.2% over the Ex group (p < 0.0001) in exercised rats. Ex + PR plus ACr significantly enhanced phosphorylation of mTOR and S6K1 (p < 0.0001), and 4E-BP1 (p < 0.001) compared to the Ex (p < 0.0001). PR to ACr also significantly increased insulin and musclin levels (p < 0.0001) in exercised rats. Additionally, compared to Ex + PR alone, Ex + PR + ACr enhanced mTOR (p < 0.0001) and S6K1 (p < 0.0001) levels. CONCLUSION: These data suggested that PR + ACr may provide an alternative to animal proteins for remodeling and repairing muscle by stimulating MPS and mTOR signaling pathways in post-exercised rats. More preclinical and clinical human studies on combining pea/rice and amylopectin/chromium complex are required.

The effect of oral administration of undenatured type II collagen on monosodium iodoacetate-induced osteoarthritis in young and old rats.

We investigated whether different doses of undenatured type II collagen (undenatured collagen, UC-II) help improve monosodium iodoacetate (MIA)-induced (osteoarthritis) OA in young and old rats. A total of 70 rats were divided into five groups: (1) control; (2) MIA (a single intra-articular injection of MIA); (3)-(5) MIA+ Undenatured Collagen with various oral doses (0.66, 1.33, and 2 mg/kg). The results showed that all doses of undenatured collagen in both age groups reduced knee diameter, while the two higher doses (1.33 mg/kg and 2 mg/kg) reduced the Mankin score and increased most gait measurements as early as day 14 compared to the MIA rats. However, the 2 mg/kg dose showed the best efficacy in improving Mankin score and gait measurements by 28 days post-OA induction. In young but not old rats, all doses of undenatured collagen reduced the Kellgren-Lawrence score compared to the MIA group. Undenatured collagen reduced the levels of most inflammatory and cartilage breakdown markers in serum and knee joint cartilage in both age groups. In conclusion, this data suggests that while all doses of undenatured collagen supplementation may ameliorate MIA-induced OA symptoms, the higher doses showed faster improvement in gait measurements and were more efficacious for overall joint health in rats.

The effects of melatonin against atherosclerosis-induced endothelial dysfunction and inflammation in hypercholesterolemic rats.

The aim of this study was to investigate the effects of melatonin on the serum asymmetric dimethylarginine (ADMA) levels and the expressions of vaspin, visfatin, dimethylarginine dimethylaminohydrolase (DDAH), and signal transducer and activator of transcription-3 (STAT-3) for evaluation of endothelial function and inflammation in the hypercholesterolemic rats. Rats were divided into 5 groups: (1) control, (2) hypercholesterolaemia, (3) melatonin administrated concurrently with cholesterol diet, (4) melatonin administrated only last 2 weeks and fed with cholesterol diet, (5) atorvastatin administered only last 2 weeks fed with cholesterol diet. Although an increase was observed in the expressions of visfatin and STAT-3 and the serum ADMA levels, the vaspin and DDAH protein expressions were found to decrease with hypercholesterolemic diets. Melatonin was determined to restore all the parameters to the normal levels. In conclusion, melatonin may have protective and therapeutic effects on hypercholesterolaemia by regulating vaspin, STAT-3, DDAH, and ADMA signalling pathways and create similar effects with atorvastatin.

Effects of a Combination of Arginine Silicate Inositol Complex and a Novel Form of Biotin on Hair and Nail Growth in a Rodent Model.

The purpose of this study was to examine the effects of a combination of inositol-stabilized arginine silicate complex (ASI) and magnesium biotinate (MgB) on hair and nail growth in an animal model. Twenty-eight female Sprague-Dawley rats (8 weeks old) were randomized into one of the following groups: (i) group (control), shaved; (ii) group (ASI), shaved + ASI (4.14 mg/rat/day); (iii) group (ASI + MgB I), shaved + ASI (4.14 mg/rat/day) + MgB (48.7 µg/rat/day); and (iv) group (ASI + MgB II), shaved + ASI (4.14 mg/rat/day) + MgB (325 µg/rat/day). On day 42, compared with the control group, while hair density (p < 0.05, p < 0.01, and p < 0.0001, respectively) and anagen ratio (p < 0.01, p < 0.01, and p < 0.001) increased in the ASI, ASI + MgB I, and ASI + MgB II groups, telogen ratio decreased (p < 0.01, p < 0.01, and p < 0.001, respectively). In the molecular analysis, VEGF, HGF, and KGF-2 increased in the ASI (p < 0.01, p < 0.01, and p < 0.05, respectively), ASI + MgB I (p < 0.0001 for all), and ASI + MgB II (p < 0.0001 for all) groups when compared to the control group. FGF-2 (p < 0.01) and IGF-1 (p < 0.001) were found to be increased in the ASI + MgB I and ASI + MgB II groups. SIRT-1 and ß-catenin increased in the ASI (p < 0.05 and p < 0.01), ASI + MgB I (p < 0.001 for both), and ASI + MgB II (p < 0.0001 for both) groups. Wnt-1 increased in the ASI + MgB I (p < 0.001) and ASI + MgB II (p < 0.0001) groups. In conclusion, the combination of ASI and MgB could promote hair growth by regulating IGF-1, FGF, KGF, HGF, VEGF, SIRT-1, Wnt, and ß-catenin signal pathways. It was also established that ASI did not affect nail growth, whereas the MgB combination was effective using a higher dose of biotin.

Combination of Phycocyanin, Zinc, and Selenium Improves Survival Rate and Inflammation in the Lipopolysaccharide-Galactosamine Mouse Model.

Sepsis is related to systemic inflammation and oxidative stress, the primary causes of death in intensive care units. Severe functional abnormalities in numerous organs can arise due to sepsis, with acute lung damage being the most common and significant morbidity. Spirulina, blue-green algae with high protein, vitamins, phycocyanin, and antioxidant content, shows anti-inflammatory properties by decreasing the release of cytokines. In addition, zinc (Zn) and selenium (Se) act as an antioxidant by inhibiting the oxidation of macromolecules, as well as the inhibition of the inflammatory response. The current study aimed to examine the combined properties of Zn, Se, and phycocyanin oligopeptides (ZnSePO) against lipopolysaccharide-D-galactosamine (LPS-GalN)-induced septic lung injury through survival rate, inflammatory, and histopathological changes in Balb/c mice. A total of 30 mice were allocated into three groups: normal control, LPS-GalN (100 ng of LPS plus 8 mg of D-galactosamine), LPS-GalN + ZnSePO (ZnPic, 52.5 µg/mL; SeMet, 0.02 µg/mL; and phycocyanin oligopeptide (PO), 2.00 mg/mL; at 1 h before the injection of LPS-GalN). Lung tissue from mice revealed noticeable inflammatory reactions and typical interstitial fibrosis after the LPS-GalN challenge. LPS-GalN-induced increased mortality rate and levels of IL-1, IL-6, IL-10, TGF-ß, TNF-α, and NF-κB in lung tissue. Moreover, treatment of septic mice LPS-GalN + ZnSePO reduced mortality rates and inflammatory responses. ZnSePO considerably influenced tissue cytokine levels, contributing to its capacity to minimize acute lung injury (ALI) and pulmonary inflammation and prevent pulmonary edema formation in LPS-GalN-injected mice. In conclusion, ZnSePO treatment enhanced the survival rate of endotoxemia mice via improving inflammation and oxidative stress, indicating a possible therapeutic effect for patients with septic infections.