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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.

Growing evidence emphasizes the role of inflammation and oxidative stress in the pathogenesis of Dry Eye Syndrome (DES). Concordantly, the importance of agents targeting the inflammatory cascade and oxidative stress in the treatment is also progressively increasing. Herein, the study has investigated the protective effects and underlying mechanism of allyl isothiocyanate (AITC) on the ocular surface in a benzalkonium chloride (BAC)-induced dry eye rat model.A total of twenty-one Wistar albino rats were used to form the following three groups: Control, BAC, BAC + AITC. DES was established by topical application of BAC (four times daily for two weeks) in two groups, of which one group was treated with AITC (10 mg/kg BW daily oral dosage) for four weeks. Rats were monitored by dry eye diagnostic tests during the study period, and eventually, corneal tissues were used to evaluate for histopathologic analyzes and inflammatory and oxidative status.A significant improvement was observed in various histopathologic and ophthalmologic findings, including tear volume, tear film integrity, ocular surface damage, ocular inflammatory signs, corneal thickness, and edema through AITC supplementation. AITC prominently balanced the inflammatory status and oxidative stress by lowering key proinflammatory mediators (NF-κB, TNF-α, IL-1β, IL-6, and IL-8) and increasing the activities of antioxidant enzymes (SOD, GSH-Px). Also, levels of protective tear proteins, including Muc1, Muc4, and Muc5 were recovered with AITC supplementation.AITC alleviates clinical and histopathologic signs related to DES. Antioxidative and anti-inflammatory properties of AITC play a significant role in the mechanism of action.

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 β-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 β-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.

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.

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.

Supplementary Table 1

Supplementary Table 1. Composition of the basal diet given to the study hens. Supplementary Table 2. Incidence of serous and mucinous adenocarcinoma in the study animals. Supplementary Table 3. RAS gene family mutation analysis. Supplementary Figure 1. Detection of curcumin in serum of the animals fed with curcumin by HPLC.

Genistein, the major isoflavone in soybean, has been reported to exert anticancer effects on various types of cancer including ovarian cancer; however, its chemopreventive effects and mechanisms of action in ovarian cancer have not been fully elucidated in spontaneously developing ovarian cancer models. In this study, we demonstrated the preventive effects and mechanisms of genistein in the laying hen model that develops spontaneous ovarian cancer at high incidence rates. Laying hens were randomized to three groups: control (3.01 mg/hen, n = 100), low (52.48 mg/hen n = 100), and high genistein supplementation (106.26 mg/hen/day; per group). At the end of 78 weeks, hens were euthanized and ovarian tumors were collected and analyzed. We observed that genistein supplementation significantly reduced the ovarian tumor incidence (P = 0.002), as well as the number and size of the tumors (P = 0.0001). Molecular analysis of the ovarian tumors revealed that genistein downregulated serum malondialdehyde, a marker for oxidative stress and the expression of NFκB and Bcl-2, whereas it upregulated Nrf2, HO-1, and Bax expression at protein level in ovarian tissues. Moreover, genistein intake decreased the activity of mTOR pathway as evidenced by reduced phosphorylation of mTOR, p70S6K1, and 4E-BP1. Taken together, our findings strongly support the potential of genistein in the chemoprevention of ovarian cancer and highlight the effects of the genistein on the molecular pathways involved in ovarian tumorigenesis.

We investigated the effect of daily dietary curcumin intake on the development and progression of spontaneous ovarian cancer in a galline (hen) model, as the chicken is the only nonhuman animal in which ovarian cancer spontaneously develops with a high prevalence. At the end of 12 months, ovarian cancer had spontaneously developed in 39% (35/90) of control hens not fed curcumin (n = 90). In comparison, it spontaneously developed in 27% (24/90) and 17% (15/90) of hens given curcumin at 25.8 (n = 90) and 53.0 mg/day (n = 90), respectively (P = 0.004). This represented significant dose-dependent reductions in overall ovarian cancer incidence in the 25.8 and 53.0 mg/day curcumin-fed groups (31% and 57%, respectively). Daily curcumin intake also reduced ovarian tumor sizes (P = 0.04) and number of tumors (P = 0.006). Evaluation of the molecular mechanisms underlying the chemopreventive and antitumor effects of curcumin revealed that NF-κB and STAT3 signaling pathways were significantly inhibited but that the nuclear factor erythroid 2/heme oxygenase 1 antioxidant pathway was induced by curcumin intake in a dose-dependent manner in ovarian tissues (P < 0.05). Sequencing of the Ras family genes (KRAS, NRAS, and HRAS) revealed less frequent KRAS and HRAS mutations in ovarian tumors in the curcumin-fed animals. In conclusion, our results demonstrated for the first time that daily curcumin intake leads to a significant and dose-dependent reduction in spontaneous ovarian cancer incidence and tumor growth, indicating a tremendous role for curcumin as a chemopreventive strategy for ovarian cancer. Cancer Prev Res; 11(1); 59–67. ©2017 AACR.

Scope This study was carried out to investigate the efficacy of a new combination of root extracts of the Lepidium meyenii (maca) plant, known for its nutritional and energizing features as well as its antioxidant properties, on nutrient digestibility and nutrient transporters expression. Methods and results A total of 28 Sprague‐Dawley rats (8‐week‐old) were divided into four groups: (i) control, (ii) Lepidium m., (iii) high‐fat diet (HFD), and (iv) HFD+Lepidium m. Maca was given to the rats as a powdered combination of the plant roots with a daily dose of 40 mg per kg BW. Maca administration significantly increased the digestibility of dry matter (DM), organic matter (OM), crude protein (CP), and ether extract (EE), and some nutrient transporter (Pept1/2, Fatp1, Glut1/2, and Sglt1)‐expressions compared with non‐treated control and HFD groups in the jejunum and ileum tissues (p, Maca supplementation to the basal and HFD diets of the rats improved digestibility of DM, OM, CP, and EE along with the enhancement of Pept1/2, Fatp1, Glut1/2, and Sglt1 expressions in the jejunum and ileum of the rats.

© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.The present study aimed to investigate the effects of feeding zinc (Zn)-biofortified wheat on performance, digestibility, and concentrations of minerals in quails. Zinc biofortification of wheat has been realized in the field by ergonomically applying Zn to foliar two and three times, which increased grain Zn from 18 mg/kg (control) to 34 and 64 mg/kg. A total of 180 quails were divided into six groups, each containing 30 birds, and fed diets containing wheat grain with either 18, 34, or 64 mg/kg with or without zinc picolinate (ZnPic) supplementation. Bodyweight, feed intake, feed efficiency, and cold carcass weights were greater (P = 0.0001) when the quails were fed a diet containing the biofortified wheat-containing 64 mg Zn/kg. Nitrogen, ash, Ca, P, Zn, Cu, and Fe retentions were greater with the Zn-biofortified wheat-containing 64 mg Zn/kg (P ≤ 0.026). The nutrient excretions were low with feeding a diet containing biofortified wheat-containing 64 mg Zn/kg (P ≤ 0.023). Serum, liver, and heart Zn concentrations increased with feeding biofortified wheat-containing 64 mg Zn/kg (P ≤ 0.002). Thigh meat Fe concentrations increased with increasing Zn concentrations of the wheat samples used (P = 0.0001), whereas the liver Cu concentrations decreased with feeding the wheat-containing 64 mg Zn/kg (P = 0.004). The Zn-biofortified wheat-containing greater Zn concentrations, particularly 64 mg Zn/kg, is a good replacement for corn in the poultry diet as long as its availability and low cost for better performance, greater digestibility, and elevated tissue Zn and Fe concentrations.

Background/aim Sjögren’s syndrome (SS) is an autoimmune disease and its pathogenesis is still not completely clear. The wingless (Wnt)/β-catenin pathway has recently been shown to play an important role in inflammation. This study aims to determine the serum and saliva levels of Dickkopf (DKK)1 and sclerostin and to evaluate Wnt-1 and Wnt-3a expression in the salivary gland in patients with primary SS. Materials and methods This study included 30 patients diagnosed with SS, 30 patients diagnosed with systemic lupus erythematosus (SLE), and 29 healthy controls. Serum and saliva levels of DKK1 and sclerostin were measured and the expressions of Wnt1 and Wnt3a in the salivary gland were measured immunohistochemically. Results Serum DKK1 and sclerostin levels were lower in the SS and SLE groups compared to the control group (both p < 0.001). Saliva DKK1 levels were higher in the SS group compared to the control and SLE groups (p = 0.004 and p = 0.009, respectively). Wnt1 and Wnt3a expression were found in salivary gland tissue samples in 71.4% of primary SS patients and relatively frequent than control group. Conclusions Serum DKK1 and sclerostin levels in primary SS and SLE were decreased. Moreover, levels of Wnt1 and Wnt3a expression in the salivary gland were also elevated in primary SS. Therefore, it can be concluded that the Wnt/β-catenin pathway activities may be altered in case of glandular inflammation.

Background/aim This study was conducted to elucidate the effects of lutein/zeaxanthin isomers (L/Zi) on lipid metabolism, oxidative stress, NF-κB/Nrf2 pathways, and synaptic plasticity proteins in trained rats. Materials and methods Wistar rats were distributed into four groups: 1) control, 2) L/Zi: rats received L/Zi at the dose of 100 mg/kg by oral gavage, 3) exercise, 4) exercise+L/Zi: rats exercised and received L/Zi (100 mg/kg) by oral gavage. The duration of the study was eight weeks. Results Exercise combined with L/Zi reduced lipid peroxidation and improved antioxidant enzyme activities of muscle and cerebral cortex in rats (p < 0.001). In the Exercise + L/Zi group, muscle and cerebral cortex Nrf2 and HO-1 levels increased, while NF-κB levels decreased (p

Background/aim Numerous studies show that cancer risk is reduced by consumption of soy-based foods containing genistein, but its effects on the glycogen synthase kinase-3 pathway (GSK-3) in ovarian cancer is unknown. Therefore, we tested the properties of genistein on inflammatory biomarkers and GSK-3 signaling pathways in the ovaries of old laying hens with ovarian cancer. Materials and methods A total of 300 laying hens were distributed into three groups as follows: group 1, animals fed a standard diet (comprising 22.39 mg of genistein/kg of diet); groups 2 and 3, animals fed a standard diet reconstituted with supplementation of 400 mg or 800 mg of genistein/kg of diet, respectively. Results Genistein modulated the inflammatory biomarkers by decreasing serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL- 6), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) compared with control (p < 0.001). Moreover, it upregulated insulin receptor substrate-1 (p-IRS-1) and protein kinase B (p-AKT), but downregulated GSK-3α and β after treatment. It acts in a dose-dependent manner. Conclusion Genistein exhibited an anticancer effect by reducing proinflammatory biomarkers levels and inhibiting GSK-3 expression in the ovaries of old laying hens. It is a potential candidate in the chemoprevention and/or treatment of ovarian cancer.

The objective of this study was to investigate the effects of a novel form of biotin (magnesium biotinate) on serum glucose, lipid profile, and hepatic lipid metabolism-related protein levels in rats. Forty-two rats were divided into six groups and fed a standard diet-based egg white powdered diet supplemented with either d-biotin at 0.01, 1, or 100 mg/kg BW or magnesium biotinate at 0.01, 1, or 100 mg/kg BW for 35 days. Neither form of biotin influenced (p > 0.05) serum glucose or insulin concentrations. Serum total cholesterol and triglyceride decreased with biotin from both sources (p < 0.05). Concentrations were lower with magnesium biotinate when comparing the 1 mg/kg dose (p < 0.05). Serum, liver, and brain biotin and liver cyclic guanosine monophosphate (cGMP) concentrations were greater when rats were treated with magnesium biotinate versus d-biotin, particularly when comparing the 1 and 100 mg/kg dose groups (p < 0.05). Both biotin forms decreased the liver SREBP-1c and FAS and increased AMPK-alpha 1, ACC-1, ACC-2, PCC, and MCC levels (p < 0.05). The magnitudes of responses were more emphasized with magnesium biotinate. Magnesium biotinate, compared with a commercial d-biotin, is more effective in reducing serum lipid concentrations and regulating protein levels of lipid metabolism-related biomarkers.

© 2022 The Author(s)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.

BackgroundWe 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.MethodsIn 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.FindingsNotably, 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 (P10-fold lower than its clinical maximum tolerated dose (MTD) – accelerates the healing of excision wounds as well burn injury in diabetic rats.

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-β, 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.

Magnesium (Mg) is an essential mineral required for many physiological processes, including ionic balances in ocular tissues. We compared the effects of different Mg-chelates (Mg oxide, MgO vs. Mg picolinate, MgPic) on retinal function in a high-fat diet (HFD) rats. Forty-two rats were divided into six groups and treated orally for 8 weeks as follows: Control, MgO, MgPic, HFD, HFD + MgO, and HFD + MgPic. Mg was administered at 500 mg of elemental Mg/kg of diet. HFD intake increased the levels of retinal MDA and NF-κB, INOS, ICAM, and VEGF but downregulated Nrf2. However, in rats supplemented with MgO and MgPic, the retinal MDA level was decreased, compared with the control and HFD rats. Activities of antioxidant enzymes (SOD, CAT, and GPx) were increased in HFD animals given Mg-chelates (p < 0.001), MgPic being the most effective. Mg supplementation significantly decreased the expression levels of NF-κB, INOS, ICAM, and VEGF in HFD rats while increasing the level of Nrf2 (p < 0.001). Mg supplementation significantly decreased the levels of NF-κB, INOS, ICAM, and VEGF and increased Nrf2 level in HFD rats (p < 0.001), with stronger effects seen from MgPic. Mg attenuated retinal oxidative stress and neuronal inflammation and could be considered as an effective treatment for ocular diseases.

This study investigated the effects of marine phytoplankton supplementation on 1) perceived recovery and ground reaction forces in humans following a non-functional overreaching resistance-training program and 2) myogenic molecular markers associated with muscle cell recovery in a rat model. In the human trial, a 5-week resistance-training program with intentional overreaching on weeks 2 and 5 was implemented. Results indicate that marine phytoplankton prompted positive changes in perceived recovery at post-testing and, while both marine phytoplankton and placebo conditions demonstrated decreased peak and mean rate of force development following the overreaching weeks, placebo remained decreased at post-testing while marine phytoplankton returned to baseline levels. In the rat model, rats were divided into four conditions: (i) control, (ii) exercise, (iii) exercise + marine phytoplankton 2.55 mg·d-1, or (iv) exercise+marine phytoplankton 5.1 mg·d-1. Rats in exercising conditions performed treadmill exercise 5 d·wk-1 for 6 weeks. Marine phytoplankton in exercising rats increased positive and decrease negative myogenic factors regulating satellite cell proliferation. Taken together, marine phytoplankton improved perceptual and functional indices of exercise recovery in an overreaching human model and, mechanistically, this could be driven through cell cycle regulation and a potential to improve protein turnover.

Background/aim Mango ginger (MG: curcuma amada) has antioxidant and antiinflammatory activities. The aim was to evaluate the antiarthritic potential efficacy of MG on collagen-induced arthritis. Materials and methods Twenty-one female Wistar-albino rats were divided into three groups. Arthritis was induced by intradermal injections of type II collagen and Freund’s adjuvant. MG extract was orally administered starting from the first collagen injection. TNF-α, IL-6, IL-17, obestatin, sclerostin, and DKK-1 serum levels were determined, and perisynovial inflammation and cartilage-bone destruction in the paws were histologically evaluated. Moreover, joint tissue TNF-α, IL-17, NF-κB, and COX-2 levels were analyzed. Results TNF-α, IL-17, IL-6, and DKK-1 serum levels were increased, and obestatin and sclerostin serum levels were decreased in the arthritis group compared to the control group. However, MG supplements decreased TNF-α, IL-17, IL-6, and DKK-1 serum levels and increased obestatin and sclerostin serum levels. Similarly, while collagen injection increased tissue TNF-α, IL-17, NF-κB, and COX-2 levels, MG decreased TNF-α, IL-17, and NF-κB levels. Moreover, MG ameliorated perisynovial inflammation and cartilage-bone destruction in the paws. Conclusion MG ameliorates arthritis via actions on inflammatory ways and wingless (Wnt) signaling pathway. These results suggest that MG may have a considerable potential efficacy for the treatment of rheumatoid arthritis.

The objective of this study was to shed light on the effect of a novel Lepidium peruvianum (Maca) blend on anti-fatigue capacities in exercised rats. Twenty-eight male albino rats were allocated into four groups (n = 7) at random: (i) Control (vehicle), (ii) Maca: (40 mg/kg/BW), (iii) WL-FST: weight-loaded forced swimming test group, and (iv) WL-FST + Maca group. Maca supplementation increased swimming time to exhaustion (p .01), while decreased serum lactate and liver glycogen concentrations. Maca addition resulted in lower levels of serum, liver, and muscle MDA (p .05). Muscle GPx activity increased in both Maca groups (p .001). Moreover, NF-κB levels were less in the WL-FST + Maca compared to the WL-FST group (p .001). Nrf1, Nrf2, PGC-1α, SIRT1, and TFAM levels were augmented in the WL-FST + Maca compared to the WL-FST (p .05). Consequently, our Maca blend increased endurance capacity and prevented exercise-induced oxidative stress and lactic acid buildup. PRACTICAL APPLICATIONS: The brassica species Lepidium peruvianum (maca) has been consumed in Peru for centuries to enhance mood, libido, and energy. Although the positive effects of this plant on energy metabolism are accredited, the underlying molecular mechanisms of these effects have not been sufficiently elucidated. The current study's findings suggest that this innovative, exclusive maca powder blend can boost endurance while preventing oxidative stress and lactic acid buildup during acute exercise. The mechanism of this efficacy is thought to be caused by maca's regulatory properties on energy metabolism signaling receptors and strong antioxidant scavenging effects on the free radicals that are produced by prolonged exhaustive exercise periods.

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-1β, 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.

BackgroundThe identification of effective strategies capable of reducing the case mortality rate of high-risk COVID-19 is an urgent and unmet medical need. 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.govIdentifier:NCT03680105) (Uckun et al., Front. Pharmacol. 11, 594321. 10.3389/fphar.2020.594321). Here we report data from a pilot clinical study (RPI-015) which examined the safety, tolerability, and feasibility of using RJX in combination with clinical standard of care (SOC) in hospitalized COVID-19 patients with pneumonia (ClinicalTrials.govIdentifier:NCT04708340). In addition to our early clinical proof of concept (POC) data, we also present non-clinical POC from a mouse model of CRS and ARDS that informed the design of the reported clinical study.Methods13 patients, who were hospitalized with COVID-19 pneumonia and abnormally elevated serum inflammatory biomarkers markers ≥3 months prior to the identification of the first confirmed U.S case of the Omicron variant, were treated with IV RJX (daily x 7 days) plus SOC. Non-clinical POC study examined the ability of RJX plus dexamethasone (DEX) to improve the survival outcome in the lipopolysaccharide (LPS)-Galactosamine (GalN) mouse model of fatal cytokine release syndrome (CRS), sepsis and acute respiratory distress syndrome (ARDS).FindingsIn the Phase 1 clinical study, none of the 13 patients developed a treatment-related DLT, SAE, or Grade 3-5 AEs. Nine (9) of the 12 evaluable patients, including 3 patients with hypoxemic respiratory failure, showed rapid clinical recovery. In the non-clinical POC study in LPS-GalN challenged mice, the combination of RJX plus DEX was more effective than RJX alone or DEX alone, reversed the CRS as well as inflammatory tissue damage in the lungs and liver, and improved the survival outcome. Taken together, these findings provide the early clinical and non-clinical POC for the development of RJX as an adjunct to the SOC in the multi-modality management of high-risk COVID-19.

L-Theanine is commonly used to improve sleep quality through inhibitory neurotransmitters. On the other hand, Mg

Rheumatoid arthritis (RA) is a disabling inflammatory disorder. Ginger is used for food and medicine to treat arthralgia, sprains, and muscle aches. Anti-inflammatory effects of ginger have been observed. The aim of our study was to detect the effects of ginger on experimentally induced inflammatory arthritis.Female Wistar albino rats (n = 21) were randomly separated into three groups (control, arthritis, and arthritis + ginger). Arthritis was generated by an appropriate method using type 2 collagen and Freund's adjuvant (collagen-induced arthritis model). The ginger group was treated starting at the first collagen injection with ginger root extract for 32 days by oral gavage (50 mg/kg/daily). Interleukin (IL)-6, IL-17, tumor necrosis factor-α (TNF-α), sclerostin, dickkopf-related protein-1 (DKK-1), and obestatin serum levels were studied by enzyme-linked immunosorbent assay method. Tissue TNF-α, IL-17, cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB) levels were detected using the Western blot method.Mean arthritis score and serum levels of TNF-α, IL-6, and IL-17 were significantly decreased in ginger group than in the arthritis group. Increased sclerostin serum level and decreased DKK-1 serum levels were detected in ginger group compared with arthritis group. The decreases of IL-17, TNF-α, COX-2, and NF-κB tissue levels were statistically significant in the ginger group compared with arthritis group. Histopathological evaluation of the ginger group showed a decrease in the inflammation score compared to arthritis group.It can be concluded that ginger has protective properties in the development of inflammatory arthritis. The antiarthritic acts of ginger are related to NF-κB activity and Wnt pathway. Thus, it may be suggested that ginger is a candidate to research in human RA treatment.

Demyelination is generally observed in different neurodegenerative disorders, including Multiple sclerosis (MS). It is known that high-dose biotin supplementation stabilizes MS progression. To reduce the effective dose of biotin, here we synthesized a new and superior form of biotin, which is a complex of magnesium ionically bound to biotin (MgB) and compared its dose-dependent effect with biotin alone after lysolecithin (LPC)-induced demyelination in rats. Myelination was studied with luxol fast blue staining and revealed that the most significant remyelination occurred in the MgB groups. We observed dose-dependent improved spatial memory in both biotin and MgB combined animals. Furthermore, we detected decreased inflammatory proteins in both treatment groups, which were more prominent in high-dose MgB treated animals, associated with improved NF-κB, OP, and MMP-9 proteins. We further analyzed biotin-related proteins and observed that both biotin and particularly MgB reverses the LPC-induced reduction of these proteins. Furthermore, we have observed that biotin but particularly MgB improves neuronal transmission proteins, Synapsin-1, PSD-93, and PSD 95. Moreover, increased BDNF, GAP-43, and ICAM were detected in both treatment groups, especially significant in high-dose MgB treated animals. Increased GFAP, which indicates reactive gliosis, was observed in LPC treated animals, which were reversed particularly by high-dose MgB treatment. The present data reveal the dose-dependent beneficial effect of biotin on demyelination processes. However, a combination of biotin with Mg resulted in a more potent effect than biotin alone. The robust impact of MgB encourages proof-of-concept studies with MgB in human MS patients.

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.

Curcumin positively affects performance during exercise and subsequent recovery. However, curcumin has limited bioavailability unless consumed in larger doses. In the current study, we examined the impact of a new formulation of curcumin, Next-Generation Ultrasol Curcumin (NGUC), which is relatively more bioavailable than natural curcumin on exhaustion time, grip strength, muscle damage parameters, and serum and muscle proteins. A total of 28 rats were randomly grouped as control (C, non-supplemented), exercise (E, non-supplemented), E+NGUC100 (supplemented with 100 mg/kg BW NGUC), and E+NGUC200 (supplemented with 200 mg/kg NGUC). Grip strength and exhaustion time were increased with NGUC supplementation (p &lt, 0.0001). Creatine kinase (CK), lactate dehydrogenase (LDH), lactic acid (LA), myoglobin, malondialdehyde (MDA) concentrations were reduced in serum, and muscle tissue in NGUC supplemented groups (p &lt, 0.05). In contrast, NGUC supplementation elevated the antioxidant enzyme levels compared to the non-supplemented exercise group (p &lt, 0.01). Additionally, inflammatory cytokines were inhibited with NGUC administration (p &lt, 0.05). NGUC decreased PGC-1α, p-4E-BP1, p-mTOR, MAFbx, and MuRF1 proteins in muscle tissue (p &lt, 0.05). These results indicate that NGUC boosts exercise performance while reducing muscle damage by targeting antioxidant, anti-inflammatory, and muscle mass regulatory pathways.

Environmental light pollution due to artificial light may increase the rate and severity of retinal diseases, and plant-based nutritional interventions with antioxidant properties have the potential to reverse this phenomenon. We aimed to investigate the potential effects of allyl isothiocyanate (AITC) against white light-emitting diode (LED)-induced retinal degeneration (RD) in the rats.Twenty-eight male rats were allocated as: (i) Control, (ii) LED, (iii) LED + AITC (10 mg/kg BW), (iv) LED + AITC (20 mg/kg BW). Rats were administered with AITC for 28 days, followed by two days of intense environmental LED light (750AITC lowered the serum and retina malondialdehyde (MDA) levels while significantly (In conclusion, four weeks of AITC administration to the rats showed specific protective effects against two days of intense LED light-induced retinal damage; through antiinflammatory, antioxidant, anti-apoptotic, and modulating mitochondrial metabolic pathways.

Magnesium (Mg) deficiency may affect bone metabolism by increasing osteoclasts, decreasing osteoblasts, promoting inflammation/oxidative stress, and result in subsequent bone loss. The objective of the present study was to identify the molecular mechanism underlying the bone protective effect of different forms of Mg (inorganic magnesium oxide (MgO) versus organic magnesium picolinate (MgPic) compound) in rats fed with a high-fat diet (HFD). Forty-two Wistar albino male rats were divided into six group (n = 7): (i) control, (ii) MgO, (iii) MgPic, (iv) HFD, (v) HFD + MgO, and (vi) HFD + MgPic. Bone mineral density (BMD) increased in the Mg supplemented groups, especially MgPic, as compared with the HFD group (p &lt, 0.001). As compared with the HFD + MgO group, the HFD + MgPic group had higher bone P (p &lt, 0.05) and Mg levels (p &lt, 0.001). In addition, as compared to MgO, MgPic improved bone formation by increasing the levels of osteogenetic proteins (COL1A1 (p &lt, 0.001), BMP2 (p &lt, 0.001), Runx2 (p &lt, 0.001), OPG (p &lt, 0.05), and OCN (p &lt, 0.001), IGF-1 (p &lt, 0.001)), while prevented bone resorption by reducing the levels of RANK and RANKL (p &lt, 0.001). In conclusion, the present data showed that the MgPic could increase osteogenic protein levels in bone more effectively than MgO, prevent bone loss, and contribute to bone formation in HFD rats.

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, β-catenin, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor-β1 (TGF-β1) signaling pathways, which are important molecular mechanisms involved in hair growth.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, β-catenin, PDGF, VEGF, TGF-βIn 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, β-catenin, PDGF, VEGF, TGF-βNaB 1 and 2 mg B/kg supplementation induces the anagen phase in rats via Wnt-1, β-catenin, VEGF, PDGF, and TGF-β1 signaling pathways. NaB 4 mg B/kg suppresses these pathways and adversely affects hair growth.

WOS: 000471268100003 The clinical use of cisplatin, which is a first-line anticancer agent, is highly restricted due to its adverse effects on kidneys that lead to nephrotoxicity. Therefore, some potential reno-protective substances have been used in combination with cisplatin to cope with nephrotoxicity. Due to its high antitumor activity and oxygen-carrying capacity, we investigated the molecular effects of squalene against cisplatin-induced oxidative stress and kidney damage in mice. Single dose of cisplatin (7 mg/kg) was given to male Balb/c mice. Squalene (100 mg/kg/day) was administered orogastrically to mice for 10 days. Following sacrification, molecular alterations were investigated as analysis of the levels of oxidative stress index (OSI), inflammatory cytokines and cell survival-related proteins in addition to histopathological examinations in mice kidney tissue. The level OSI and Interferon-gamma (IFN-gamma) decreased in the cisplatin and squalene cotreated mice compared to cisplatin-treated mice. Squalene treatment also increased the activation of protein kinase B (AKT). Furthermore, cisplatin-induced inactivation of mammalian target of rapamycin (mTOR) and histopathological damages were reversed by squalene. It may be suggested that squalene ameliorated the cisplatin-induced histopathological damages in the kidney through activation of AKT/mTOR signaling pathway by regulating the balance of the redox system due to its antioxidative effect.

Genistein, the major isoflavone in soybean, has been reported to exert anticancer effects on various types of cancer including ovarian cancer; however, its chemopreventive effects and mechanisms of action in ovarian cancer have not been fully elucidated in spontaneously developing ovarian cancer models. In this study, we demonstrated the preventive effects and mechanisms of genistein in the laying hen model that develops spontaneous ovarian cancer at high incidence rates. Laying hens were randomized to three groups: control (3.01 mg/hen, n = 100), low (52.48 mg/hen n = 100), and high genistein supplementation (106.26 mg/hen/day; per group). At the end of 78 weeks, hens were euthanized and ovarian tumors were collected and analyzed. We observed that genistein supplementation significantly reduced the ovarian tumor incidence (P = 0.002), as well as the number and size of the tumors (P = 0.0001). Molecular analysis of the ovarian tumors revealed that genistein downregulated serum malondialdehyde, a marker for oxidative stress and the expression of NFκB and Bcl-2, whereas it upregulated Nrf2, HO-1, and Bax expression at protein level in ovarian tissues. Moreover, genistein intake decreased the activity of mTOR pathway as evidenced by reduced phosphorylation of mTOR, p70S6K1, and 4E-BP1. Taken together, our findings strongly support the potential of genistein in the chemoprevention of ovarian cancer and highlight the effects of the genistein on the molecular pathways involved in ovarian tumorigenesis.

The purpose of this study was to test the effects of arginine-silicate-inositol complex (ASI), compared to a combination of the individual ingredients (A+S+I) of the ASI, on inflammatory markers and joint health in a collagen-induced arthritis (CIA) rat model. A total of 28 Wistar rats were divided into four groups: (i) Control; (ii) Arthritic group, rats subjected to CIA induction by injection of bovine collagen type II (A); (iii) Arthritic group treated with equivalent doses of the separate components of the ASI complex (arginine hydrochloride, silicon, and inositol) (A+S+I); (iv) Arthritic group treated with the ASI complex. The ASI complex treatment showed improved inflammation scores and markers over the arthritic control and the A+S+I group. ASI group had also greater levels of serum and joint-tissue arginine and silicon than the A+S+I group. Joint tissue IL-6, NF-κB, COX-2, TNF-α, p38 MAPK, WISP-1, and β-Catenin levels were lower in the ASI group compared to the other groups (P 0.05 for all). In conclusion, these results demonstrate that the ASI complex may be effective in reducing markers of inflammation associated with joint health and that the ASI complex is more effective than a combination of the individual ingredients.

This study evaluated the effects of amylopectin (A) and chromium (Cr) forms alone or in combination on energy storage, muscle fatigue-related biochemical markers, and expression of peroxisome proliferator-activated receptors (PPAR-γ) and glucose transporter-2 and -4 (GLUT-2 and GLUT-4) in rats during exhaustive exercise. Thirty-five male Wistar rats were divided into 5 groups (n = 7) as follows: 1) exhaustive exercise (E); 2) E+A; 3) E+A+chromium picolinate (CrPic); 4) E+A+chromium histidinate (CrHis), and 5) E+A+CrPic+CrHis. Rats received 0.0316 g of amylopectin and 11.06 µg of elemental Cr kg$^{-1}$ body weight given as CrPic and CrHis per day. The mean duration of exercise differed (55 ± 1.15 vs. 76 ± 1.91) between groups (P < 0.05). Blood glucose level was significantly reduced in the E+A+CrPic+CrHis group compared to the E group. The E+A+CrPic+CrHis group was superior in terms of increasing muscle and liver glycogen contents and blood insulin concentration and of decreasing serum lactate concentration (P < 0.05 for all). However, A and Cr did not alter GLUT-2, GLUT-4, and PPAR-γ expressions. In conclusion, A in combination with supplemental Cr enhanced energy-yielding nutrient conservation and reduced muscle fatigue in exercised rats. They can also help prevent racehorse performance and disability problems.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and reshaped medical oncology practice over the past decade. However, despite unprecedented and durable clinical responses, most patients eventually fail to respond to ICI therapy due to primary or acquired resistance. There is a great need for complementary alternative medicine, such as botanicals and nutritional supplements, because of their capability to modulate a myriad of molecular mechanisms to prevent immunotherapy resistance and reduce its adverse effects. Mounting evidence suggests that phytochemicals, biologically active compounds derived from plants, can favorably regulate key signaling pathways involved in tumor development and progression. In addition, phytochemicals have been found to exert anticancer effects by altering the expression of checkpoint inhibitors of the immune response. The immunomodulatory activity of phytochemicals in the tumor microenvironment has recently received immense interest. Based on these immunomodulatory activities, phytochemicals could be candidates for combination with ICIs in future clinical studies. The current review focuses on the available evidence for combining phytochemicals with a discussion on the promising opportunities to enhance the efficacy of immune checkpoint inhibitors and potential challenges resulting from these combinations.

Background and Objective Because of the stomach-burning sensation it induces, capsaicin has been used at relatively low doses as a nutritional supplement, which has limited its bioavailability. The objective of this study was to investigate the serum bioavailability of capsaicin supplementation with or without a lipid multi-particulate (LMP) formulation. Methods Thirty-five rats were divided into five groups and administered capsaicin at either 0.2 or 1 mg/kg with or without the LMP formulation. Capsaicin bioavailability was assessed based on the area under the concentation-time curve (AUC), the time to peak concentration (T-max), and the peak serum concentration (C-max). Results For each formulation, the capsaicin C-max was reached at 90 min and decreased thereafter. Serum capsaicin concentrations were greater in rats administered the higher dose of capsaicin (1 mg/kg) in the LMP formulation at all measurement times (P

The purpose of this study was to observe the effects of a novel combination of inositol-stabilized arginine silicate complex (ASI) and magnesium biotinate (MgB) on the prevention of skin damage after UVB exposure in rats. Forty-nine Sprague-Dawley rats were randomized into one of the following groups: (1) NC, normal control, (2) SC, shaved control, (3) UVB (exposed to UVB radiation), (4) ASI+MgB-L (Low Dose), (5) ASI+MgB-H (High Dose), (6) ASI+MgB-L+MgB cream, (7) ASI+MgB-H+MgB cream. The results showed that ASI+MgB treatment alleviated the macroscopic and histopathological damages in the skin of rats caused by UVB exposure. Skin elasticity evaluation showed a similar trend. ASI+MgB increased serum Mg, Fe, Zn, Cu, Si, biotin, and arginine concentrations and skin hydroxyproline and biotinidase levels while decreasing skin elastase activity (p < 0.05) and malondialdehyde (MDA) concentration (p < 0.001). Moreover, ASI+MgB treatment increased skin levels of biotin-dependent carboxylases (ACC1, ACC2, PC, PCC, MCC) and decreased mammalian target of rapamycin (mTOR) pathways and matrix metalloproteinase protein levels by the regulation of the activator protein 1 (AP-1), and mitogen activated protein kinases (MAPKs) signaling pathways. In addition, ASI+MgB caused lower levels of inflammatory factors, including TNF-α, NFκB, IL-6, IL-8, and COX-2 in the skin samples (p < 0.05). The levels of Bax and caspase-3 were increased, while anti-apoptotic protein Bcl-2 was decreased by UVB exposure, which was reversed by ASI+MgB treatment. These results show that treatment with ASI and MgB protects against skin damage by improving skin appearance, elasticity, inflammation, apoptosis, and overall health.

The current work aimed to examine the properties of oral supplementation of niacinamide and undenatured type II collagen (UCII) on the inflammation and joint pain behavior of rats with osteoarthritis (OA). Forty-nine Wistar rats were allocated into seven groups; control (no MIA), MIA as a non-supplemental group with monosodium iodoacetate (MIA)-induced knee osteoarthritis, MIA + undenatured type II collagen (UCII) at 4 mg/kg BW, MIA + Niacinamide at 40 mg/kg BW (NA40), MIA + Niacinamide at 200 mg/kg BW (NA200), MIA + UCII + NA40 and MIA + UCII + NA200. Serum IL‐1β, IL‐6, TNF-α, COMP, and CRP increased in rats with OA and decreased in UCII and NA groups (p p p

Osteoarthritis (OA) is a chronic and debilitating disease of the knee joint. OA of the knee is initiated by physical damage and accumulated oxidative stress, followed by an exaggerated inflammation leading to cartilage damage. Currently, no effective and safe therapeutic option capable of restoring articular cartilage tissue and joint architecture is available. We here report a novel and highly bioavailable formulation of curcumin, labeled as Next Generation Ultrasol Curcumin (NGUC), which was 64.7 times more bioavailable than natural 95% curcumin extract as demonstrated in rat bioavailability studies. We further investigated the protective effect of NGUC against monosodium iodoacetate (MIA)‐induced knee OA in rats. Analysis of X-ray and histopathological images revealed that NGUC supplementation restored joint architecture and reduced swelling of joints induced by MIA. NGUC treatment caused a significant reduction in the levels of inflammatory mediators such as TNF-α, IL-1β, IL-6, COMP, and CRP, and expressions of MMP-3, 5-LOX, COX-2, and NFκB in synovial tissue of rats with MIA-induced OA. NGUC also decreased serum MDA level and increased the levels of antioxidant enzymes SOD, CAT, and GPX. Thus, our results indicate that a novel formulation of curcumin with enhanced bioavailability effectively ameliorates the pathophysiology of OA.

Previous studies revealed that oxidative stress and inflammation are the main contributors to secondary injury after traumatic brain injury (TBI). In an earlier study, we reported that lutein/zeaxanthin isomers (L/Zi) exert antioxidative and anti-inflammatory effects by activating the nuclear factor-kappa B (NF-kappa B) and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. However, its precise role and underlying mechanisms were largely unknown after TBI. This study was conducted to investigate the potential mechanism of L/Zi isomers in a TBI model induced by a cold injury model in mice. To investigate the effects of L/Zi, male C57BL/6j mice-induced brain injury using the cold trauma model was allocated into two groups (n = 7): (i) TBI + vehicle group and (ii) TBI + L/Zi group (20 mg/kg BW). Brain samples were collected 24 h later for analyses. L/Zi given immediately after the injury decreased infarct volume and blood-brain barrier (BBB) permeability; L/Zi treatment also significantly reduced proinflammatory cytokines, including interleukin1 beta (IL-1 beta), interleukin 6 (IL-6), and NF-kappa B levels and increased growth-associated protein 43 (GAP-43), neural cell adhesion molecule (NCAM), brain-derived neurotrophic factor (BDNF), and Nrf2 levels compared with vehicle control. These data suggest that L/Zi improves mitochondrial function in TBI models, possibly decreasing inflammation and activating the Nrf2 pathway. OmniActive Health Technologies, NJ, USA ; Turkish Academy of Sciences

Osteoarthritis (OA) is an age-related joint disease that includes gradual disruption of the articular cartilage and the resulting pain. The present study was designed to test the effects of undenatured type II collagen (UC-II®) on joint inflammation in the monoiodoacetate (MIA) OA model. We also investigated possible mechanisms underlying these effects. Female Wistar rats were divided into three groups: (i) Control; (ii) MIA-induced rats treated with vehicle; (iii) MIA-induced rats treated with UC-II (4 mg/kg BW). OA was induced in rats by intra-articular injection of MIA (1 mg) after seven days of UC-II treatment. UC-II reduced MIA-induced Kellgren-Lawrence scoring (53.3%, P < 0.05). The serum levels of inflammatory cytokines [IL-1β (7.8%), IL-6 (18.0%), TNF-α (25.9%), COMP (16.4%), CRP (32.4%)] were reduced in UC-II supplemented group (P < 0.0001). In the articular cartilage, UC-II inhibited the production of PGE2 (19.6%) and the expression of IL-1β, IL-6, TNF-a, COX-2, MCP-1, NF-κB, MMP-3, RANKL (P < 0.001). The COL-1 and OPG levels were increased, and MDA decreased in UC-II supplemented rats (P < 0.001). UC-II could be useful to alleviate joint inflammation and pain in OA joints by reducing the expression of inflammatory mediators.

The current study aimed to investigate the effect of exercise combined with undenatured type II collagen (UCII) administration on endurance capacity, lipid metabolism, inflammation, and antioxidant status in rats. Twenty-one male Wistar albino rats were divided into three groups as follows: (1) Sedentary control, (2) Exercise (E), (3) Exercise + UCII (4 mg/kg BW/day, E + UCII). The findings showed that the exhaustive running time in the UCII group was significantly prolonged compared to that of the non-supplemented group (p &lt, 0.001). When compared to the control group, total serum cholesterol (TC, p &lt, 0.05) and triglyceride (TG, p &lt, 0.05) levels decreased, while creatinine kinase (CK) levels increased in the E group (p &lt, 0.001). Serum creatinine kinase levels were reduced in the E + UCII group compared to the E group (p &lt, 0.01). Serum lactate, myoglobin (p &lt, 0.01), and osteocalcin levels (p &lt, 0.01) increased significantly in exercised rats compared to sedentary control rats, while serum lactate (p &lt, 0.01) and myoglobin (p &lt, 0.0001) levels decreased in the E + UCII group compared to control. Additionally, UCII supplementation caused significant increases in antioxidant enzyme activities [SOD (p &lt, 0.01) and GSH-Px (p &lt, 0.05)] and decreases in malondialdehyde (MDA) and tumor necrosis factor (TNF-α) levels (p &lt, 0.001). Muscle lipogenic protein (SREBP-1c, ACLY, LXR, and FAS) levels were lower in the E + UCII group than in other groups. In addition, UCII supplementation decreased muscle MAFbx, MuRF-1, myostatin and increased MyoD levels in exercised rats. Moreover, the E + UCII group had lower muscle inflammatory markers [TNF-α (p &lt, 0.0001) and IL-1β (p &lt, 0.01)] than the control group. These results suggest exercise combined with UCII (4 mg/kg BW/day) modulates lipid, muscle, and antioxidant status in rats.