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.

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.

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 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.

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.

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.

Evaluation of the potential of Rejuveinix plus dexamethasone against sepsis.

Aim: Our main objectives were to compare the effects of Rejuveinix (RJX), dexamethasone (DEX) and their combination on the severity of sepsis and survival outcome in an animal model of fatal sepsis. Methods: We used the LPS plus D-galactosamine mouse model of sepsis to compare the anti-inflammatory activities of RJX, dexamethasone and a combination of RJX plus DEX. Additionally, we examined the clinical feasibility and tolerability of combining RJX with DEX in COVID-19 patients in a clinical phase I study. Data were analyzed using standard methods. Results & conclusion: RJX exhibited potent anti-inflammatory activity in the murine sepsis model. The combination of RJX plus DEX was more effective than either agent alone, decreased the inflammatory cytokine responses and associated organ damage, and improved the survival outcome in mice. In the phase I clinical study, RJX plus DEX was well tolerated by COVID-19 patients.

RJX Improves Wound Healing in Diabetic Rats.

Background: We recently reported the clinical safety profile of RJX, a well-defined intravenous GMP-grade pharmaceutical formulation of anti-oxidant and anti-inflammatory vitamins as active ingredients, in a Phase 1 study in healthy volunteers (ClinicalTrials.gov Identifier: NCT03680105) (Uckun et al., Front. Pharmacol. 11, 594321. 10.3389/fphar.2020.594321). The primary objective of the present study was to examine the effects of GMP-grade RJX on wound and burn injury healing in diabetic rats. Methods: In the present study, a rat model of T2DM was used that employs HFD in combination with a single injection of STZ intraperitoneally (i.p) at a moderate dose level (45 mg/kg). Anesthetized diabetic rats underwent full-thickness skin excision on the back or were subjected to burn injury via a heated brass probe and then started on treatments with normal saline (NS = vehicle) or RJX administered via intraperitoneal injections for three weeks. Findings: Notably, diabetic rats treated with the 1.25 mL/kg or 2.5 mL/kg RJX (DM+RJX groups) rapidly healed their wounds as fast as non-diabetic control rats. Inflammatory cell infiltration in the dermis along with fibrin and cell debris on the epithelial layer persisted for up to 14 days in the DM+NS group but not in RJX-treated groups. The histopathological score of wound healing on days 7 and 14 was better in diabetic rats treated with RJX than diabetic rats treated with NS and comparable to the scores for non-diabetic healthy rats consistent with an accelerated healing process. The residual wound area of RJX-treated rats was significantly smaller than that of NS-treated diabetic rats at each evaluation time point (P<0.001). The accelerating effect of RJX on diabetic wound healing was dose-dependent. We obtained similar results in the burn injury model. Our results demonstrate that RJX - at a dose level >10-fold lower than its clinical maximum tolerated dose (MTD) - accelerates the healing of excision wounds as well burn injury in diabetic rats.

Sodium pentaborate pentahydrate promotes hair growth through the Wnt/ß-catenin pathway and growth factors.

BACKGROUND: Boron (B) is an element involved in many physiological processes in humans and accelerates wound healing and increases angiogenesis. This study aimed to evaluate the possible effects of sodium pentaborate pentahydrate (NaB) on hair growth and reveal its effects on Wnt-1, ß-catenin, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor-ß1 (TGF-ß1) signaling pathways, which are important molecular mechanisms involved in hair growth. METHODS: Thirty-five Sprague-Dawley/Wistar albino rats were randomly divided into five groups: non-shaved control, shaved control, NaB 1 mg (shaved + NaB 1 mg elemental B/kg CA), NaB 2 mg (shaved + NaB 2 mg elemental B/kg CA), and NaB 4 mg (shaved + NaB 4 mg elemental B/kg CA). Hair density was measured using the trichoscopy method. Dorsal skin samples were examined histopathologically at the end of the 42nd day, and follicle count, follicle diameter, and subcutaneous tissue thickness were recorded. Wnt-1, ß-catenin, PDGF, VEGF, TGF-ß1, and collagen I levels were analyzed with the Western blot method. RESULTS: In trichoscopy measurements, hair density increased in the NaB 4 mg group (90.9%). In histopathological examination, anagen follicles were observed to increase in the NaB 1 mg and 2 mg groups (p < 0.05). Follicle diameter increased in all NaB groups (p < 0.05). The Wnt-1, ß-catenin, PDGF, VEGF, TGF-ß1, and collagen I level increased in the NaB 1 mg and 2 mg groups (p < 0.05), but they were similar in the NaB 4 mg group compared to the control groups (p > 0.05). CONCLUSION: NaB 1 and 2 mg B/kg supplementation induces the anagen phase in rats via Wnt-1, ß-catenin, VEGF, PDGF, and TGF-ß1 signaling pathways. NaB 4 mg B/kg suppresses these pathways and adversely affects hair growth.

Protective effect of a novel polyherbal formulation on experimentally induced osteoarthritis in a rat model.

Osteoarthritis (OA) is a musculoskeletal disorder mainly found in elderly individuals. Modern treatment of OA, like nonsteroidal anti-inflammatory drugs, corticosteroids, hyaluronic acid injections, etc., is linked to long-term side effects. We evaluated the anti-osteoarthritic properties of a novel joint health formula (JHF) containing Bisdemethoxycurcumin enriched curcumin, 3-O-Acetyl-11-keto-beta-Boswellic acid-enriched Boswellia, and Ashwagandha in monosodium iodoacetate (MIA)-induced knee OA in rats. Twenty-eight female rats were distributed into four groups: Control, OA, OA + JHF (100 mg/kg), and OA + JHF (200 mg/kg). JHF decreased the right joint diameters but increased the paw area and stride length compared to the OA group with no treatment. JHF significantly reduced the arthritic conditions after four weeks of supplementation (p < 0.05). JHF significantly decreased TNF-α, IL-1ß, IL-10, COMP, and CRP in the serum of osteoarthritic rats (p < 0.0001). We observed reduced lipid peroxidation but increased SOD, GSH-Px, and CAT activities in response to JHF treatment in OA animals. JHF down-regulated MMP-3, COX-2, and LOX-5 and improved the histological structure of the knee joint of osteoarthritic rats. JHF demonstrated a protective effect against osteoarthritis, possibly due to anti-inflammatory and antioxidant activity in experimentally induced osteoarthritis in rats, and could be an effective option in the management of OA.

A Novel Theanine Complex, Mg-L-Theanine Improves Sleep Quality via Regulating Brain Electrochemical Activity.

L-Theanine is commonly used to improve sleep quality through inhibitory neurotransmitters. On the other hand, Mg2+, a natural NMDA antagonist and GABA agonist, has a critical role in sleep regulation. Using the caffeine-induced brain electrical activity model, here we investigated the potency of L-theanine and two novel Mg-L-theanine compounds with different magnesium concentrations on electrocorticography (ECoG) patterns, GABAergic and serotonergic receptor expressions, dopamine, serotonin, and melatonin levels. Furthermore, we evaluated the sleep latency and duration in the pentobarbital induced sleep model. We herein showed that L-theanine, particularly its various complexes with magnesium increases the expression of GABAergic, serotonergic, and glutamatergic receptors, which were associated with decreased ECoG frequency, increased amplitude, and enhanced delta wave powers. Besides increased dopamine, serotonin, and melatonin; decreased MDA and increased antioxidant enzyme levels were also observed particularly with Mg-complexes. Protein expression analyses also showed that Mg-L-theanine complexes decrease inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) levels significantly. In accordance with these results, Mg complexes improved the sleep latency and duration even after caffeine administration. As a result, our data indicate that Mg-L-theanine compounds potentiate the effect of L-theanine on sleep by boosting slow-brain waves, regulating brain electrical activity, and increasing neurotransmitter and GABA receptor levels.

Effects of magnesium picolinate, zinc picolinate, and selenomethionine co-supplementation on reproductive hormones, and glucose and lipid metabolism-related protein expressions in male rats fed a high-fat diet.

This study aimed to examine the impacts of the magnesium picolinate (MgPic), zinc picolinate (ZnPic), and selenomethionine (SeMet) alone or as a combination on blood metabolites, oxidative enzymes, reproductive hormones, and glucose and lipid metabolism-related protein expressions in Wistar rats fed a high-fed diet (HFD). The rats were fed either a control, HFD, or HFD supplemented with a single (MgPic, ZnPic, SeMet) or two or three organic mineral combinations. Body weights, visceral fat, serum glucose, insulin, total cholesterol, triglycerides, leptin, malondialdehyde (MDA) concentrations as well as liver sterol regulatory element-binding protein-1c (SREBP-1c), liver X receptor alpha (LXRα), ATP citrate lyase (ACLY), fatty acid synthase (FAS), and nuclear factor kappa B (NF-κB) levels increased, while serum testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and insulin-like growth factor (IGF-1) concentrations along with liver nuclear factor erythroid 2-related factor 2 (Nrf2) levels declined in HFD rats (P < 0.05). Supplementing each organic mineral, but particularly the combination of HFD + MgPic + ZnPic + SeMet reversed the responses with various degrees. None of the organic elements alone or as a combination of two exerted a prominent effect on parameters measured. Although not additive or synergistic, the combination of all organic minerals added to HFD (HFD + MgPic + ZnPic + SeMet) provided the greatest responses.

Effect of boron element on photoaging in rats.

BACKGROUND: The present study further assessed the effects of oral and topical applications of boron, which is known to have antiinflammatory and wound healing effects, on photoaging. METHODS: A total of 49 eight-week-old female Wistar albino rats randomly divided into seven groups (control, shaved control, shaved+UVB, topical dermabor 2% (D2), and %5 (D5), systemic sodium perborate tetrahydrate (SPT) 2% (SPT2) and 4% (SPT4). To induce an experimental photoaging, the rats were exposed to UVB at an emission spectrum of 290-320 nm. Biochemical, molecular, skin, histological, and collagen content analyzes were made at the end of the study. RESULTS: Increased skin inflammatory parameters (COX-2, IL-8, NF-KB, IL-6, and TNF-α) levels in UVB-exposed groups were inhibited in all treatment groups. The tissue level of hydroxyproline and elastase was found to decrease in all UVB-exposed group. The level of hydroxyproline was significantly higher in the D2 and D5 groups than in the SPT2 and SPT4 groups. The level of elastase was significantly lower in the D2 and D5 groups than in the SPT2 and SPT4 groups. CONCLUSIONS: In future, boron may be developed as a functionally protective treatment against photoaging caused by UVB, and may be included in sun protection systems.