Purification and structural characterization of lectin with antibacterial and anticancer properties from grubs of hide beetle, Dermestes frischii.

Lectins or haemagglutinins are diverse classes of non-immune proteins; they bind to carbohydrates and are abundant in nature. In the present study, a coleopteran lectin from grubs of hide beetle, Dermestes frischii called DFL, was purified by glutaraldehyde (fixative-agent) fixed hen erythrocytes and characterized further for its functional properties. The purified DFL was stable between pH range 5 to 9 and heat-stable up to 50 °C. It was insensitive to EDTA and did not require any divalent cations. DFL native molecular mass was approximately 69 kDa with three different polypeptide subunits of 33 (pI ~4.4), 22 (pI ~6) and 14 (pI ~4.4) kDa. Haemagglutinating activity of DFL was highly inhibited by N-acetyl-D-glucosamine. DFL partial peptide sequences obtained from peptide mass fingerprinting experiments matched with amino acid sequences of lectins from different organisms confirmed its nature. Biological properties of purified DFL namely antibacterial and bacterial agglutination experiments revealed that DFL have both the effects against laboratory cultures of Aeromonas hydrophila, Enterococcus faecalis, Escherichia coli and habitat bacterial isolates of Staphylococcus cohnii and Bacillus cereus. In addition, the DFL exhibited substantial anticancer properties against HeLa cells. These results concluded that purified DFL could serve as a potent therapeutic agent for various biomedical applications.

Isolation, characterization of galactose-specific lectin from Odoiporus longicollis and its antibacterial and anticancer activities.

Lectins are renowned hemagglutinins and multivalent proteins with a well known quality for sugar-binding specificity that participate significantly in invertebrate defense functions. Studies on biological activity of lectin from coleopteran insect are very scarce. In this study, lectin from the hemolymph in the grub of banana pest, Odoiporus longicollis was subjected to purification, biochemical and functional characterizations. The lectin was purified by PEG precipitation and ion-exchange chromatography using Q-Sepharose as a matrix. The purified lectin showed hemagglutination activity against rat erythrocytes, heat-labile, cation independent and insensitive to EDTA. Further, the carbohydrate affinity of this lectin was found with mannitol, adonitol, L-arabinose, L-rhamnose, D-galactose and sorbitol. The native form of purified lectin was calculated as 360 kDa by FPLC system. Denatured gel electrophoresis of the purified lectin consisted of five distinct polypeptides with molecular weights approximately 160, 60, 52, 40 and 38 kDa, respectively. The amino acid sequences obtained through peptide mass fingerprinting analysis exhibited homologies to the known conserved regions of galactose binding lectins. Further, the purified lectin exhibited bacterial inhibition with LPS from Serratia marcescens. In addition, isolated lectin also exerted bacterial agglutination, antibacterial and anti-proliferative activity against Mycobacterium smegmatis, Bacillus pumilus and Neuro 2a cell line, respectively.

Studies on isolation, characterization of fucoidan from brown algae Turbinaria decurrens and evaluation of it's in vivo and in vitro anti-inflammatory activities.

In the present study, the anti-nociception and anti-inflammatory activity of fucoidan isolated from T. decurrens on formalin induced paw-edema in mice model were investigated. The extracted fucoidan contain 54.86% of total sugar, 23.51% of sulfate and 3.4% of protein. The monosaccharide composition analysis revealed that fucoidan encompassed of fucose (59.3%), galactose (12.6%), mannose (9.6%), rhamnose (6.4%) and xylose (11.4%). Further, the structural characterization was done by UV-visible spectroscopy, X-ray diffraction, FT-IR and 1HNMR analysis. The fucoidan reduced the licking time thereby suggesting anti-nociceptive effect and decreased the size of paw swelling in the formalin induced inflammatory edema condition. The isolated fucoidan could significantly decreased the MDA and also increase the SOD, CAT, GPx, GST and GSH activity in paw edema tissue of formalin injected mice. Furthermore, fucoidan administration retained p65/NF-κB transcription factor in the cytosol thereby showing down regulation of the gene expression of pro-inflammatory mediators such as IL-1ß, COX-2 and MMP-9 in fucoidan treated mice. The anti-inflammatory effect of fucoidan was attributed to its capacity on modulating the levels of enzymatic antioxidants, master regulator NF-κB and pro-inflammatory cytokines. The fucoidan has reduced LPS induced cytotoxicity in IC-21 macrophage at a dose depended on manner.

Investigation of antioxidant and anticancer potential of fucoidan from Sargassum polycystum.

The present study was aimed to evaluate the antioxidant and anticancer potential of fucoidan isolated from Sargassum polycystum. The isolated fucoidan was successfully purified by DEAE cellulose-ion exchange chromatography and dialysis. Totally four active fractions (F1-F4) were collected and explored its chemical constitution by calorimetric assays. Among them, fraction 2 (F2) showed the higher yield percentage, fucose and sulphate content. Further, monosaccharide composition, structural and functional properties of the F2 was analyzed by HPLC, FTIR and NMR. F2 shows highest DPPH radical scavenging activity (55.94 ±â€¯0.69%), reducing power (0.33 absorbance rate), hydrogen peroxide scavenging activity (71.76 ±â€¯2.14%) and nitric oxide radical scavenging activity (51.81 ±â€¯1.04%) at 1000 µg/ml. The cell viability of MCF-7 and HCT-15 cell lines was proportionate to the concentration of F2 with an estimated IC50 was 20 and 50 µg/ml respectively. The fluorescence and confocal laser scanning microscopic analysis demonstrated the apoptotic morphological changes and cell mediated death in F2 treated cancer cells. Higher amount of LDH release was found in the F2 treated cancer cells than the control group. Thus, the present finding proved that the isolated F2 encompasses significant antioxidant and anticancer property.

A focus on resveratrol and ocular problems, especially cataract: From chemistry to medical uses and clinical relevance.

Low vision and blindness are important health problems that affect millions of people throughout the world. The most common and important pathologies are diabetic retinopathy, age-related macular degeneration, glaucoma as well as cataracts. The latter consists of an opacification of the lens of the eye which impedes the passage of light and represents one of the most important causes of vision loss. Among the risk factors for cataract development, there are life-style factors such as the use of tobacco, abuse of alcohol and unhealthy diet. In light of this, dietary components that possess anti-oxidant activity, such as polyphenols for instance, can be considered good candidates for human studies in the prevention and or treatment of such diseases. Among dietary components, the antioxidant capacity of certain polyphenols is well known, and these could be good candidates. In this review we focus our attention on the current scientific literature regarding to the effects of resveratrol on cataracts and other ocular diseases, along with its potential mechanism/s of action. A large number of preclinical studies support the involvement of resveratrol in clinical trials for the prevention and treatment of eye diseases induced by oxidative stress and inflammation, such as age-related cataract.

Zeaxanthin and ocular health, from bench to bedside.

Cataracts, glaucoma, and age-related macular degeneration are known as major ocular problems which cause blindness among the elderly population worldwide. Oxidative stress plays an important role in both the initiation and progression of ocular problems and with respect to this; dietary antioxidants can serve as a therapeutic strategy for the improvement of ocular health. Zeaxanthin is known as one of the most important and common xanthophyll carotenoids, possessing multiple therapeutic effects such as strong antioxidant and pro-oxidant behaviour as well as anti-inflammatory effects. A growing body of literature shows that zeaxanthin mitigates ocular problems and suppresses oxidative stress in the retinal tissues. This paper aims to critically review the available literature regarding the beneficial effects of zeaxanthin on ocular problems with emphasis on its chemistry, bioavailability, and sources.

Epigallocatechin gallate attenuates fibroblast proliferation and excessive collagen production by effectively intervening TGF-ß1 signalling.

Pulmonary fibrosis (PF) poses a huge burden to the patients and society due to lack of an effective treatment drug. Activation of fibrocyte, fibroblast and myofibroblasts are important steps in the development of PF. Targeting this common pathway with natural chemicals may lead to the development of new drug regimens for PF treatment. In this study, PF was induced in male Wistar rats by intratracheal administration of Bleomycin (BLM). Epigallocatechin gallate (EGCG) was administered to one of the groups of rats to test its efficacy against the development of PF. Bleomycin-induction resulted in significant elevation of matrix metalloproteinase (MMP)-2 and -9 expression, increased RNA and protein expression of transforming growth factor (TGF)-ß1, Smads and alpha-smooth muscle actin (α-SMA). EGCG treatment normalized the BLM induced aberrations in these rats. The protective role of EGCG was also validated in vitro using the WI-38 fibroblast cell line. TGF-ß1 incubated cells exhibited increased fibroblast proliferation and hydroxyproline levels with a concomitant decrease in the expression of MMPs 2 and 9. An increase in protein expression levels of p-Smad, α-SMA and type I collagen (COL1A) was also exhibited by fibroblasts upon TGF-ß1 incubation. Simultaneous treatment of EGCG to WI-38 cells significantly decreased these protein expressions alongside normalizing the MMPs expression. The study revealed that EGCG inhibited fibroblast activation and collagen accumulation by inhibiting TGF-ß1 signalling and thus can be considered as an effective drug against PF.

Cytoprotective and anti-inflammatory effects of kernel extract from Adenanthera pavonina on lipopolysaccharide-stimulated rat peritoneal macrophages.

OBJECTIVE: To investigate mechanism of anti-inflammatory activity of Adenanthera pavonina (A. pavonina) extracts. METHODS: Rat peritoneal macrophages were treated with different concentrations of lipopolysaccharide and H2O2 in the presence and absence of kernel extract from A. pavonina. Nitric oxide, Superoxide anion generation, cell viability and nuclear fragmentation were investigated. RESULTS: The pre-treatment of kernel extract from A. pavonina suppressed nitric oxide, superoxide anion, cell death, nuclear fragmentation in lipopolysaccharide and H2O2 stimulated or induced macrophages, respectively. CONCLUSIONS: These results suggest that A. pavonina extract suppresses the intra cellular peroxide production.

Berberine inhibits Smad and non-Smad signaling cascades and enhances autophagy against pulmonary fibrosis.

UNLABELLED: Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative lung disorder of unknown aetiology. Transforming growth factor-ß1 (TGF-ß1)-mediated Smad and non-Smad signaling cascades are considered as central players in accelerating pulmonary fibrosis. We earlier reported berberine's amelioration against TGF-ß1-mediated pro-fibrotic effects in bleomycin-induced pulmonary fibrosis. The present study aimed to determine the regulatory role of berberine on abrogated Smad 2/3 and FAK-dependent PI3K/Akt-mTOR signaling cascades in bleomycin-induced pulmonary fibrosis. Male Wistar rats were subjected to single intratracheal instillation of bleomycin (2.5 U/kg) on day 0, and berberine treatments were provided in either preventive or therapeutic modes, respectively. Berberine mitigated the elevated expression of fibrotic markers, α-smooth muscle actin (α-SMA), fibronectin, collagens I and III and reversed bleomycin-induced ultrastructural alterations in the lungs. Berberine inhibited the bleomycin-induced raise in p-Smad 2/3 and enhanced Smad 7 expression. Berberine blocked the activation of FAK and PI3K/Akt against bleomycin-induced dysregulation, with subsequent raise in PTEN expression. In addition, by inhibiting p-mTOR, berberine stimulated autophagy as evidenced by increase in Beclin-1, LC3-II levels with enhanced autophagosome formation. Cumulatively, through targeted inhibition of dysregulated Smad and FAK-dependent PI3K/Akt-mTOR signaling axis, berberine attenuated the fibrotic insults of bleomycin. KEY MESSAGE: Berberine inhibits Smad 2/3 activation and enhances Smad 7 in bleomycin-induced rat lungs. Bleomycin-induced activation of FAK is inhibited by berberine. Berberine inhibits bleomycin-induced activation of PI3K/Akt cascade. Berberine inhibits mTOR activation to enhance autophagy and suppresses fibrotic markers.

Biosynthesis of silver nanoparticles using ethanolic petals extract of Rosa indica and characterization of its antibacterial, anticancer and anti-inflammatory activities.

The present study was aimed at biosynthesis of silver nanoparticles (AgNPs) using ethanolic extract of rose (Rosa indica) petals and testing their potential antibacterial activity using selective human pathogenic microbes, anticancer activity using human colon adenocarcinoma cancer cell line HCT 15 as well as anti-inflammatory activity using rat peritoneal macrophages in vitro. The biologically synthesized AgNPs were also characterized by UV-visible spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). The characterized AgNPs showed an effective antibacterial activity against Gram negative (Escherichia coli, Klebsiella pneumoniae) than Gram positive (Streptococcus mutans, Enterococcus faecalis) bacteria. MTT assay, analysis of nuclear morphology, mRNA expression of Bcl-2, Bax and protein expression of caspase 3 as well as 9, indicated potential anticancer activity. In addition, green synthesized AgNPs also attenuated cytotoxicity, nuclear morphology and free radical generation (O2(-) and NO) by rat peritoneal macrophages in vitro. The results of our study show the potential green synthesis of silver nanoparticles in mitigating their toxicity while retaining their antibacterial activities.

Apoptosis in liver cancer (HepG2) cells induced by functionalized gold nanoparticles.

An ethnopharmacological approach for biosynthesis of gold nanoparticles is being demonstrated using seed coat of Cajanus cajan. Medicinal value of capping molecule investigated for anticancer activity and results disclose its greater potential. The active principle of the seed coat [3-butoxy-2-hydroxypropyl 2-(2,4-dihydroxyphenyl) acetate] is elucidated. Rapid one-step synthesis yields highly stable, monodisperse (spherical) gold nanoparticles in the size ranging from 9 to 41 nm. Anticancer activity has been studied using liver cancer cells and cytotoxic mechanism has been evaluated using MTT, Annexin-V/PI Double-Staining Assay, Cell cycle, Comet assay and Flow cytometric analysis for apoptosis. The present investigation will open up a new possibility of functionalizing gold nanoparticles for apoptosis studies in liver cancer cells.

Inhibition of diabetic-cataract by vitamin K1 involves modulation of hyperglycemia-induced alterations to lens calcium homeostasis.

This study investigated the potential of vitamin K1 against streptozotocin-induced diabetic cataract in Wistar rats. A single, intraperitoneal injection of streptozotocin (STZ) (35 mg/kg) resulted in hyperglycemia, accumulation of sorbitol and formation of advanced glycation end product (AGE) in eye lens. Hyperglycemia in lens also resulted in superoxide anion and hydroxyl radical generation and less reduced glutathione suggesting oxidative stress in lens. Hyperglycemia also resulted in increase in lens Ca2+ and significant inhibition of lens Ca2+ ATPase activity. These changes were associated with cataract formation in diabetic animals. By contrast treatment of diabetic rats with vitamin K1 (5 mg/kg, sc, twice a week) resulted in animals with partially elevated blood glucose and with transparent lenses having normal levels of sorbitol, AGE, Ca2+ ATPase, Ca2+, and oxidative stress. Vitamin K 1 may function to protect against cataract formation in the STZ induced diabetic rat by affecting the homeostasis of blood glucose and minimizing subsequent oxidative and osmotic stress. Thus, these results show that Vitamin K1 inhibits diabetic-cataract by modulating lens Ca2+ homeostasis and its hypoglycemic effect through its direct action on the pancreas.

Hesperidin induces apoptosis and triggers autophagic markers through inhibition of Aurora-A mediated phosphoinositide-3-kinase/Akt/mammalian target of rapamycin and glycogen synthase kinase-3 beta signalling cascades in experimental colon carcinogenesis.

Abnormalities in the homeostasis mechanisms involved in cell survival and apoptosis are contributing factors for colon carcinogenesis. Interventions of these mechanisms by pharmacologically safer agents gain predominance in colon cancer prevention. We previously reported the chemopreventive efficacy of hesperidin against colon carcinogenesis. In the present study, we aimed at investigating the potential of hesperidin over the abrogated Aurora-A coupled pro-survival phosphoinositide-3-kinase (PI3K)/Akt signalling cascades. Further, the role of hesperidin over apoptosis and mammalian target of rapamycin (mTOR) mediated autophagic responses were studied. Azoxymethane (AOM) induced mouse model of colon carcinogenesis was involved in this study. Hesperidin treatment was provided either in initiation/post-initiation mode respectively. Hesperidin significantly altered AOM mediated anti-apoptotic scenario by modulating Bax/Bcl-2 ratio together with enhanced cytochrome-c release and caspase-3, 9 activations. In addition, hesperidin enhanced p53-p21 axis with concomitant decrease in cell cycle regulator. Hesperidin treatment caused significant up-regulation of tumour suppressor phosphatase and tensin homologue (PTEN) with a reduction in the expression of AOM mediated p-PI3K and p-Akt. Additionally, hesperidin administration exhibited inhibition against p-mTOR expression which in turn led to stimulation of autophagic markers Beclin-1 and LC3-II. Aurora-A an upstream regulator of PI3K/Akt pathway was significantly inhibited by hesperidin. Furthermore, hesperidin administration restored glycogen synthase kinase-3 beta (GSK-3ß) activity which in turn prevented the accumulation of oncoproteins ß-catenin, c-jun and c-myc. Taken together, hesperidin supplementation initiated apoptosis via targeted inhibition of constitutively activated Aurora-A mediated PI3K/Akt/GSK-3ß and mTOR pathways coupled with autophagic stimulation against AOM induced colon carcinogenesis.

Fisetin modulates mitochondrial enzymes and apoptotic signals in benzo(a)pyrene-induced lung cancer.

The present study was aimed to delineate in vivo mechanisms of orally administered fisetin with special reference to mitochondrial dysfunction in lung tissues employing benzo(a)pyrene (B(a)P) as the model lung carcinogen. The recent revival of interest in the study of mitochondria has been stimulated by the evidence that genetic and/or metabolic alterations in this organelle lead to a variety of human diseases including cancer. These alterations could be either causative or contributing factors. Hence, the activities of mitochondrial-specific enzymes of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and tumor marker, carcinogenic embryonic antigen were analyzed in control and experimental groups of mice. The induction of apoptotic and anti-apoptotic proteins such as Bcl-2/Bax, cytochrome c, caspase-9 and caspase-3 was confirmed by the immunohistochemistry and Western blot analyses. Furthermore, transmission electron microscopy study of lung sections of B(a)P-induced mice showed the presence of phaemorphic cells with dense granules and increased mitochondria. All the aberrations were alleviated when the mice were treated with fisetin (25 mg/kg body weight). The results proved fisetin to be a very successful drug in combating the mitochondrial dysfunction in an experimental model of lung carcinogenesis induced by B(a)P.

Ameliorative effect of ferulic acid against renal injuries mediated by nuclear factor-kappaB during glycerol-induced nephrotoxicity in Wistar rats.

The pathogenesis of glycerol-induced myoglobinuric acute renal failure involves ischemia, vascular congestion and reactive oxygen metabolites. In this study, we have investigated for the first time, the role of ferulic acid in attenuating glycerol-induced nephrotoxicity. Male Wistar rats were injected intramuscularly with 8 mL/kg body weight of 50% glycerol, glycerol + ferulic acid at the dose of 5, 10, 15, 20 and 25 mg/kg body weight. After 24 h, the rats were sacrificed and the kidneys were removed for histological and immunohistochemical studies. Furthermore, determinations of lipid peroxidation (LPO) as well as antioxidant enzymes were also analyzed; blood, urine samples were collected in order to quantify renal function and nitric oxide generation, respectively. Glycerol-induced rats showed a significant increase in the level of urinary markers assessed in serum as well as kidney and these were reversed upon ferulic acid treatment. A significant increase in urine nitric oxide, serum as well as kidney LPO, decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione were observed in glycerol-induced rats. Immunohistochemical study in glycerol-induced rats demonstrated an increase in the level of nuclear factor-kappaB (NF-κB). All these effects induced by glycerol were reduced upon treatment with ferulic acid in a dose-dependent manner. To conclude, ferulic acid enhances antioxidants and decreases NF-κB, thereby protecting the cells against stress induced by glycerol.

Berberine attenuates bleomycin induced pulmonary toxicity and fibrosis via suppressing NF-κB dependant TGF-ß activation: a biphasic experimental study.

Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating and fatal lung disorder with high mortality rate. Unfortunately, to date the treatment for IPF remains unsatisfying and in severe cases lung transplantations are performed as a therapeutic measure. Thus, it becomes great interest to find novel agents to treat IPF. Berberine, a plant alkaloid known for its broad pharmacological activities remains a remedy against multiple diseases. This study was hypothesized to investigate the antifibrotic potential of berberine against bleomycin-induced lung injury and fibrosis, a tentative animal model. Male wistar rats were subjected to single intratracheal instillation of 2.5 U/kg of bleomycin on day 0. Berberine treatments were either provided in preventive or therapeutic mode respectively. Berberine administration significantly ameliorated the bleomycin mediated histological alterations and reduced the inflammatory cell infiltrate in BALF. Berberine significantly blocked collagen accumulations with parallel reduction in the hydroxyproline level. The immunological sign of bleomycin stimulated mast cell deposition and histamine release were considerably reduced by berberine. Berberine enhanced the antioxidant status, through upregulating the redox sensing transcription factor nuclear factor E2-related factor 2 (Nrf2). Berberine inhibited the bleomycin mediated activation of inflammatory mediator nuclear factor kappa B (NF-κB) and suppressed its downstream target inducible nitric oxide synthase (iNOS). Strikingly, berberine exhibited target attenuation of tumor necrosis factor alpha (TNF-α) and key pro-fibrotic mediator, transforming growth factor beta 1 (TGF-ß1). Taken together, this study reveals the beneficial effects of berberine against bleomycin mediated fibrotic challenge through activating Nrf2 and suppressing NF-κB dependent inflammatory and TGF-ß1 mediated fibrotic events.

Hesperidin alleviates oxidative stress and downregulates the expressions of proliferative and inflammatory markers in azoxymethane-induced experimental colon carcinogenesis in mice.

OBJECTIVE: Colon cancer is a common malignant neoplasm causing huge morbidity and mortality worldwide. Current therapeutic interventions are unsatisfying, which necessitates novel chemopreventive strategies. The present study was intended to elucidate the chemopreventive efficacy of hesperidin against azoxymethane (AOM)-induced mouse colon carcinogenesis. MATERIALS AND METHODS: Swiss albino mice were subjected to intraperitoneal injections of AOM once a week for 3 consecutive weeks. Hesperidin treatments were provided in the initiation or post-initiation phases. The number and multiplicity of aberrant crypt foci (ACF), tumor incidence and antioxidant status were determined. Histopathological analyses, proliferating cell nuclear antigen (PCNA) index and modulations in the expression of inflammatory markers such as nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were studied. RESULTS: Hesperidin treatments significantly inhibited the number and multiplicities of AOM-induced ACF and tumor incidence. Hesperidin reduced oxidative stress parameters and enhanced antioxidant status. A marked decrease in the PCNA index was evident on hesperidin administration. Hesperidin treatments caused a prominent downregulation of NF-κB and its target molecules iNOS and COX-2, thereby combating inflammation. CONCLUSION: This study proves the chemopreventive efficacy of hesperidin against the deleterious traits of colon carcinogenesis including accelerated proliferation, inflammation and persistent oxidative stress.

Ameliorative effects of curcumin against renal injuries mediated by inducible nitric oxide synthase and nuclear factor kappa B during gentamicin-induced toxicity in Wistar rats.

The ameliorative role of curcumin in attenuating gentamicin-induced nephrotoxicity has been reported earlier however, the mechanism of action remains unclear. Gentamicin was injected intraperitoneally (100 mg/kg body weight) once daily for 6 days. Curcumin was administered orally (200 mg/kg body weight) once daily for 7, 15 and 30 days. Gentamicin-induced rats showed significant increase in the levels of kidney markers and the activities of urinary marker enzymes, which was reversed upon curcumin treatment. A significant increase in kidney lipid peroxidation (LPO) and decrease in activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) were observed in gentamicin-induced rats. Immunohistochemical, Western blot and RT-PCR studies in gentamicin-induced rats also demonstrated an increase in the levels of inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB). All these effects induced by gentamicin were reduced upon treatment with curcumin in a time dependent manner. To conclude, curcumin enhances antioxidants, and decreases iNOS and NF-κB, thereby protecting the cells against oxidative stress induced by gentamicin.

1, 2 di-substituted idopyranose from Vitex negundo L. protects against streptozotocin-induced diabetes by inhibiting nuclear factor-kappa B and inducible nitric oxide synthase expression.

The aim of this study is to investigate the mechanism of an action of compound isolated from Vitex negundo in streptozotocin-induced diabetic mice. Light microscopic examination of liver, kidney and pancreatic sections of streptozotocin-induced diabetic mice showed changes like coarsening of acinar cells of endoplasmic reticulum, destruction of ß-cells, and alteration in their secretory function were observed in the pancreas. Changes like dilation of vein, unusual concentric arrangement of hepatocytes, and liver fibrosis were observed in the liver. Thickening of tubules and expansion of glomerulus were observed in kidneys. All these altered parameters were reversed close to normal condition upon treatment using idopyranose. The results show the antidiabetic potential of idopyranose. Interestingly, liver, kidney, and pancreatic sections of diabetic mice fed with the isolated 1, 2 di-substituted idopyranose showed regeneration of hepatocytes, nephrocytes, as well as ß-cells and acinar region appeared normal with increased numbers of ß-cells. To understand the probable mechanism of action of 1, 2 di-substituted idopyranose, we analyzed proinflammatory inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) expression by immunohistochemistry and the results showed an increased iNOS and NF-κB levels in streptozotocin-induced diabetic liver, kidney and pancreas. Such high iNOS and NF-κB levels were inhibited in 1, 2 di-substituted idopyranose treated mice. The results suggest that 1, 2 di-substituted idopyranose helps in the protection of hepatocytes, nephrocytes and pancreatic ß-cells probably by its action against NF-κB and iNOS mediated inflammation in streptozotocin-induced diabetes.

Curcumin prevents free radical-mediated cataractogenesis through modulations in lens calcium.

The generation of free radicals has been implicated in the causation of cataract, and compounds that can scavenge free radicals ameliorate the disease process. This study investigated the possible free radical scavenging potential of curcumin at a dose of 75 mg/kg body wt on selenium-induced cataract in rat pups. Intraperitoneal injection of sodium selenite (15 micromol/kg body wt) into 8- to 10-day-old rat pups led to severe oxidative stress in the eye lens as evidenced by increased nitric oxide, superoxide anion, and hydroxyl radical generation and inducible nitric oxide synthase expression that probably led to cataract formation. Selenium exposure also caused an increase in total calcium in the eye lens and significantly inhibited the activity of Ca(2+) ATPase but not Na(+)/K(+) ATPase or Mg(2+) ATPase. On the other hand, pretreatment with curcumin, but not simultaneous or posttreatment, led to a decrease in oxidative stress and also rescued the selenium-mediated increase in lens Ca(2+) and inhibition of Ca(2+) ATPase activity in the eye lens. The results of this study demonstrate that an increase in free radical generation triggered by selenium could cause inactivation of lens Ca(2+) ATPase leading to Ca(2+) accumulation. This enhanced Ca(2+) can cause activation of calpain-mediated proteolysis in the lens, resulting in lens opacification. Curcumin in this study was able to prevent selenium-induced oxidative stress leading to activation of Ca(2+) ATPase and inhibition of lens opacification. Thus, curcumin has the potential to function as an anticataractogenic agent, possibly by preventing free radical-mediated accumulation of Ca(2+) in the eye lens.