Immunomodulatory activity of brown algae Turbinaria ornata derived sulfated polysaccharide on LPS induced systemic inflammation.

BACKGROUND: Inflammation and oxidative stress are common pathologies in a wide range of chronic diseases. Polysaccharides are known to exhibit antioxidant and anti-inflammatory potential and are suggested to possess immunomodulatory potential. PURPOSE: Herein, the immunomodulatory activity of a sulfated polysaccharide (PS) separated from a brown marine algae Turbinaria ornata is studied in LPS instigated systemic inflammation in experimental rats. STUDY DESIGN AND METHODS: Male SD rats are pretreated with different doses of PS (2.5, 5, 10 mg/kg bw) for a week followed by inducing systemic inflammation using LPS (10 mg/kg i.p.). Blood withdrawn after 8 h of LPS injection is subjected to hematological analysis (WBC, HCT, and PLT). After 24 h of LPS induction, cardiac tissue was isolated and subjected to biochemical, molecular, and histopathological analysis. Effect of PS pre-treatment (2.5, 5, 10 mg/kg bw) was checked by assessing serum parameters (AST, CK-MB, and γGT), antioxidant markers (LPO, GSH, SOD, Grx) and inflammatory markers (IL1ß, IL6, IL10, NFκB), followed by analyzing the iNOS, PI3k and Akt to identify the probable mode of action. RESULTS: Elevated levels of AST, CK-MB, and γGT in serum were significantly reduced on PS pretreatment. LPS significantly raised the LPO and Grx levels in heart tissue whereas, PS pre-treatment significantly reduced LPO and Grx levels. GSH and SOD levels were reduced upon LPS induction and were brought to near normal by HD of PS. PS also reduced the mRNA levels of IL6, Trx, and increased IL10 levels in the heart tissue substantiating its anti-inflammatory and antioxidant potency. Further, IL1ß, NFκB, iNOS, and pPI3k/pAkt expressions were significantly modulated by PS in the cardiac tissue substantiating the immunomodulatory effect. A trend of improvement in the inflammatory pathology was also observed in the heart tissue compared to LPS control, as confirmed by histopathology analysis. CONCLUSION: Altogether, this study concludes the immunomodulatory potential of PS from the marine macroalgae Turbinaria ornata significantly and prevents LPS induced systemic inflammation in the cardiac tissue presumably influenced by the glucopyranose and fucopyranose subunits in the polysaccharide.

Macrotyloma uniflorum a plant food alleviates the metabolic syndrome through modulation of adipokines and PPARs.

A sedentary lifestyle combined with the intake of high-calorie diet has been the paramount cause of metabolic syndrome (MS) which is now a serious concern of public health worldwide as it involves the coexistence of hypertension, hyperlipidemia, glucose intolerance, and obesity. Hence, identifying a suitable strategy to overcome the worldwide menace of MS is imperative. Macrotyloma uniflorum a lesser known legume is highly nutritious and notable for its ethano-medicinal potential. Herein, the influence of M. uniflorum in high-fat dietinduced metabolic changes in a rodent model of metabolic syndrome was evaluated. Serum levels of glucose, total cholesterol, triglycerides, VLDL-c, and bodyweight were decreased, whereas HDL-c was increased in M. uniflorum-treated MS rats. The protein expression (AMPK-α, PPAR-α, and PPAR-γ) and gene expression (leptin, adiponectin, resistin, UCP2, NF-κB, and IL-6) results are impressive to highlight that M. uniflorum modulates the pathological conditions of MS and proves to be cardioprotective. Furthermore, the histopathological analysis confirmed the pathological changes and substantiates the influence of M. uniflorum to overcome MS. The HPLC and GC (MS) profiling reveals the presence of an array of polyphenols such as rutin (694.61 µg/g), catechin (500.12 µg/g), epicatechin (158.10 µg/g), gallic acid (17.98 µg/g), ferulic acid (10.911 µg/g), daidzein (6.51 µg/g), and PUFA, respectively, which probably exhibits the therapeutic effect on MS and associated complications by modulating lipid metabolism and adipogenesis. PRACTICAL APPLICATIONS: Metabolic disorders like CVD and diabetes are leading cause of mortality and morbidity worldwide. With emerging issues on adverse effects of modern drugs, the emphasis on "Food is Medicine and Medicine as Food" has taken dramatic dimensions in the healthcare sector. Therefore, nutraceuticals are in great demand in the developed world off late. Legumes, are potent elements in a balanced diet next to cereals. Exploring the medicinal properties of legumes could bring a revolution in public health and nutraceutical industries. This study scientifically validated the phytochemicals in M. uniflorum for its functional potential in the management of Metabolic Syndrome (MS). This study would help the nutraceutical industries to develop functional foods using M. uniflorum seeds to make porridges and soups or nutraceutical supplements with the bioflavonoids isolated from M. uniflorum for the management of metabolic disorders by mitigating hyperlipidemia, oxidative stress, and inflammation.

Inhibition of Cyclooxygenase Enzyme by Bioflavonoids in Horsegram Seeds Alleviates Pain and Inflammation.

BACKGROUND: Inflammation and pain, mainly induced by the prostaglandins synthesized by the cyclooxygenase enzymes, may cause distress. To overcome this unpleasant stress in a safer manner, numerous natural molecules are proven for modulating the COX enzymes. Epicatechin and daidzein are two bioactive natural compounds present in horsegram, a legume known for its medicinal properties. OBJECTIVE: The present study aims at evaluating the potential of horsegram, and some of its bioactive molecules, to be used as an anti-inflammatory and analgesic agent mediated by the inhibition of COX enzymes, which can be recommended as a substitute for chemically synthesized NSAIDs. METHODS: The present work involved the quantification of epicatechin and daidzein present in horsegram seeds. The COX enzyme inhibitory nature of epicatechin and daidzein was tested using in silico docking analysis with Autodock software and was further confirmed by in vitro COX inhibitory biochemical assays. Furthermore, the anti-inflammatory and analgesic activities of the horsegram seeds were evaluated in animal experiments. RESULTS: Horsegram seeds contain 158.1 microgram/g and 6.51 microgram/g of epicatechin and daidzein respectively. The docking studies reveal that both the bioactive molecules exhibit better binding efficiency with COX-2 protein as compared to COX-1. Hence, in vitro COX-2 inhibitory assay was performed for epicatechin, daidzein and compared with known analgesic agent diclofenac which revealed a pronounced dose dependent inhibitory activity. Furthermore, the analgesic and anti-inflammatory activity of horsegram in experimental animals exhibited a dose dependent effect which might be due to the presence of the bioactive compounds such as epicatechin and daidzein. CONCLUSION: The results suggest that epicatechin and daidzein present in horsegram are potent cyclooxygenase inhibitors and thus would be helpful in the management of inflammation and pain.

Antidiabetic effect of mangiferin in combination with oral hypoglycemic agents metformin and gliclazide.

BACKGROUND: Diabetes mellitus poses serious threat to the global population due to the alarming diabetic complications it leads to. The current therapeutic options available can be improved for better efficiency and maximum benefits. Combination therapy has been commonly used to improve the efficacy and to minimize the side effects of drugs in current clinical use. PURPOSE: The present study aims to assess the interaction between a natural molecule mangiferin with the commercially available oral hypoglycemic drugs metformin and gliclazide in diabetic rats. METHODS: In this study, the in vitro cytotoxicity and glucose uptake studies were performed in HepG2 cells. Based on experimental data, the combination index of the hypoglycemic drugs like metformin and gliclazide in combination with different doses of mangiferin was determined using COMPUSYN software. Further, in vivo studies were performed in HFD + STZ induced diabetic male Sprague Dawley rats. Serum parameters, enzyme markers, hepatic oxidative stress markers, gene and protein expression studies and histopathological analyses were performed in rat liver to identify the mode of action of the combination drug administration. RESULTS: The in vitro studies on HepG2 cells suggest a positive interaction of mangiferin with both metformin and gliclazide at specific concentrations as evidenced by glucose uptake. The hepatic enzymes, oxidative stress markers, carbohydrate metabolizing enzymes, gene (AMPK, Akt, ACC ß and Glut-2) and protein (PPARα, PPARγ) expression confirmed the results of the in vitro studies. Both the combinations of mangiferin with metformin and mangiferin with gliclazide exhibited potent antidiabetic effect. The combination of mangiferin with metformin was insulin dependent (Akt pathway) whereas the combination of mangiferin and gliclazide was insulin independent (AMPK pathway). CONCLUSION: The overall results suggest that combination of mangiferin with both metformin and gliclazide alleviates diabetic conditions potentially at specific doses and modulates the adverse effect of high dose of commonly used OHD's. This combination therapy can be translated for its clinical use as a diabetes management strategy.

Naringenin Decreases α-Synuclein Expression and Neuroinflammation in MPTP-Induced Parkinson's Disease Model in Mice.

The present study was designed to ascertain the role of naringenin (NGN), a citrus fruit flavanone, against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced α-synuclein (SYN) pathology and neuroinflammation in a mouse model. NGN was administered to C57BL/6J mice once a day for 5 consecutive days prior to the MPTP intoxication. On day 5, 40-50 min after the NGN or vehicle administration, MPTP was injected in two divided doses (2× 40 mg/kg, i.p. at 16 h apart). The animals were observed for motor functions 48 h after the first MPTP injection. The animals were then euthanized, the brains collected to analyze SYN pathology, cytokines, and oxidative stress levels in the substantia nigra region. The NGN significantly downregulated SYN and upregulated dopamine transporter (DAT) and tyrosine hydroxylase (TH) protein expressions. It also downregulated tumor necrosis factor-α (TNFα) and interleukin 1ß (IL1ß) mRNA expressions and improved superoxide dismutase levels. It also reduced glutathione levels when compared to vehicle-treated PD animals. The upregulation of TH corroborates to an increase in dopamine, DOPAC, and homovanillic acid turnover and motor functions with NGN treatment. To summarize, NGN, a dietary flavone, has the potential to counteract MPTP-induced dopaminergic degeneration by regulating SYN pathology, neuroinflammation, and oxidative stress. This warrants the investigation of NGN's potential effects in a genetic model of PD.

Thraatchathi Chooranam, protects cardiomyocytes against oxidative stress.

Thraatchathi Chooranam (TC), is a polyphenol-rich Indian traditional medicine. Present study was undertaken to investigate the effects of TC against H2O2 induced oxidative stress and apoptotic damage in H9C2 cardiomyocytes. Cell viability assay indicated relative safety (IC50= 488.10±12.04 mg/ml) of TC. Pretreatment of cells with TC upregulated anti-apoptotic Bcl2, and anti-oxidants TRX1 and TRXR and downregulated Bax and HIF-α and inflammatory genes iNOS and TNF-α. Together, these findings show that TC has both anti-oxidant and anti-apoptotic properties. Further studies may be considered to identify the bioactive principle(s) and precise mechanisms of action of TC.

Simultaneous blockade of NMDA receptors and PARP-1 activity synergistically alleviate immunoexcitotoxicity and bioenergetics in 3-nitropropionic acid intoxicated mice: Evidences from memantine and 3-aminobenzamide interventions.

Interlink between excitotoxicity and cellular bioenergetics depletion is implicated as one of the central deteriorative pathways in many neurodegenerative diseases including Huntington's disease (HD). Chronic administration of 3-nitropropionic acid (3-NP) depletes ATP and NAD+; and increases TNFα, IL-6 and glutamate content resulting in "immunoexcitotoxicity". Present study was designed to determine whether the combination of memantine (MN) and 3-aminobenzamide (3-AB), PARP inhibitor, can ameliorate immunoexcitotoxicity and improve bioenergetics in a better manner than individual administration against 3-NP intoxication in mice. Animals were divided into eight groups (n =20/group) and allocated to different treatment protocols. 3-NP (10mg/kg, i.p.) was administered once in 4 days interval for a period of 28 days (total dose: 70mg/kg; in seven divided doses). Striatal succinate dehydrogenase (SDH), ATP and NAD levels (as bioenergetic markers); glutamate, microglial marker (IBA-1), astroglial marker (GFAP), cytokines (TNF-α and IL-6), and neurotrophin (BDNF) as immunoexcitotoxicity components were measured. Combination treatment (MN +3-AB) decreased brain glutamate, down-regulated IBA-1, up-regulated GFAP and BDNF expressions in 3-NP intoxicated mice. Further, combination (COM) treatment restored ATP/NAD and SDH activity, and also improved motor performance; and thus conferred a synergetic neuroprotection than individual treatments. To conclude, simultaneous blockade of NMDAr and suppression of PARP activity is necessary to ameliorate immunoexcitotoxicity and improve bioenergetics in 3-NP induced neurodegeneration. Treatment with MN+3-AB can be an efficient regimen in the symptomatic management of HD, at least partly.