Gum odina prebiotic induced gut modulation for the treatment of colon cancer on Swiss albino mice: By using capecitabine loaded biopolymeric microsphere.

A complex illness with a current global hazard, colon cancer has many different manifestations. The efficacy of colon cancer therapy can be affected by the bacteria in the digestive tract. It is hypothesised that novel prebiotics like Gum Odina is emerging as preventative therapy to fight chronic gut illnesses by gut microbiota modulatory therapy when compared to traditional intervention. The first-line chemotherapy drug for colon cancer, capecitabine, lacks a carrier that can extend its half-life. Here, we use the prebiotic gum odina - sodium alginate conjugate to create a capecitabine loaded biopolymeric microspheres, which were previously established as excellent tools for colon cancer therapy. The accelerated stability study exhibited that the alteration in physicochemical properties was found to be negligible. When administered orally to mice with colon cancer, capecitabine raises intra-tumoral capecitabine concentration and slows drug elimination in the blood. Optimized formulation improves anti-tumor immunity over free capecitabine and decrease the tumor volume from 8 ±â€¯6.59 mm3 to 5.21 ±â€¯2.79 mm3. This prebiotics based microsphere combine's gut microbiota manipulation with chemotherapy to offer a potentially effective colon cancer treatment.

Immobilization of α-amylase in calcium alginate-gum odina (CA-GO) beads: An easily recoverable and reusable support.

A natural polysacharide, gum odina was collected from Odina wodier tree and purified. Purified gum odina was used with sodium alginate for immobilization of α-amylase. Calcium alginate-gum odina (CA-GO) beads were prepared by ionotropic gelation method to find the improvement of immobilization efficiency and reusability of α-amylase over calcium alginate (CA) beads. XRD, SEM, FTIR, beads diameter, enzyme leaching from beads, moisture content, total soluble matter and swelling study have been carried out to understand the physical morphology and mechanism of immobilization of enzyme in beads matrix. It has been observed that if the polymer ratio changes (keeping enzyme conc. & calcium Chloride conc. constant) then the size and shape of the beads will vary and at a particular range of polymer ratio, the optimal beads forms. At a certain conc.(4%w/v of SA and 1%w/v GO), the immobilization efficiency of CA-GO and CA beads were 92.71 ± 0.85 % (w/w) and 89.19 ± 0.35 %(w/w) respectively. After 8th time use, the CA-GO beads remain (~4 fold) more active than that of CA beads. The FTIR confirms that GO does not interfere with α-Amylase and alginate. Here, it can be concluded that CA-GO beads show better efficiency in respect to immobilization, reusability than CA beads only.

Correction: Anti-Inflammatory Activity of Odina wodier Roxb, an Indian Folk Remedy, through Inhibition of Toll-Like Receptor 4 Signaling Pathway.

[This corrects the article DOI: 10.1371/journal.pone.0104939.].

Antimicrobial loaded gum odina - gelatin based biomimetic spongy scaffold for accelerated wound healing with complete cutaneous texture.

The main objective of this study was to assess the therapeutic activity of gum odina and gelatin based biomimetic scaffold which was previously established as an excellent wound dressing material. In the accelerated stability study, the changes in physicochemical properties were found to be negligible. The cytotoxicity studies were carried out in-vitro and the results showed that upto 90% of the cells remained viable in presence of the scaffold, confirming its biocompatibility. Moreover, results depicted the superior ability of the scaffold to promote cutaneous healing by increasing the rate of wound contraction (about 98%), granulation formation, collagen deposition and formation of an intact epidermis within 18 days. A satisfactory amount of hydroxyproline (240.2 ± 6.67 µg/100 mg tissue) in scaffold treated groups at 21 days ensured the significant deposition of collagen to re-epithelialization. Further it can be hypothesized that the controlled levels of antioxidant enzymes (SOD, CAT) to diminish the oxidative stress in the wounded sites were due to the innate antioxidant properties of both blank and drug loaded scaffold. These results strongly indicated that the prepared scaffolds have strong potential for biomedical applications and it may serve as promising candidate for the next generation of wound treatment systems.

Nutritional analysis and molecular characterization of hybrid mushrooms developed through intergeneric protoplast fusion between Pleurotus sajor-caju and Calocybe indica with the purpose to achieve improved strains.

Two edible mushrooms Calocybe indica and Pleurotus sajor-caju were chosen as parent strains in this study to approach the concept of hybridization through the protoplast fusion technique. Protoplast fusion in presence of polyethylene glycol (PEG) was conducted between the parent strains and by further double selection screening method, six somatic hybrid lines were developed. Those fruit bodies of the hybrid lines showed phenotypic resemblance with Pleurotus sajor-caju when grown on paddy straw under favorable conditions. The hybridity of the newly developed somatic hybrid strains was established by barrage reaction, morphological traits, fruitbody parameter and, inter single sequence repeat (ISSR) profiling. One-way analysis of variance (ANOVA) was used for the analysis of phenotypic data of hybrid lines and parents. Five ISSR primers were used to generate 51 amplified DNA fragments ranged between 250 and 3000 bp in size in six hybrids and two parents with 90.19% polymorphism. Some of the hybrids contain some non-parental bands which indicate that recombination might happen in the hybrid genome hence confirming the hybridity of newly developed strains. The dendrogram was created using the Average Linkage (Between Groups) method based on ISSR profiling and genetic distance between parent-hybrids and hybrid-hybrid was analyzed by Jaccard's proximity matrix. A definite improvement in nutritional properties and biological activity was observed in the study. Due to ease in their cultivation, it can play a significant role in the rural economic development.

Characterization of an arabinogalactan isolated from gum exudate of Odina wodier Roxb.: Rheology, AFM, Raman and CD spectroscopy.

Purified gum odina (PGO) from Odina wodier Roxb. was characterized by rheology, AFM, Raman and CD spectroscopy, in vitro antioxidant activity against hydroxyl radical and superoxide radical, and total antioxidant capacity. The PGO dispersions exhibited pseudoplastic behaviour. The viscosity of dispersion increased with increasing PGO concentration, but decreased with increasing temperature and added salt concentration. The loss modulus was higher than storage modulus indicating prevalently viscous characteristics. AFM analysis showed irregular spherical lumps due to inter- and intramolecular interactions. The Raman spectrum of PGO was similar to that of gum arabic. Circular dichroism revealed partial adoption of polyproline II type conformation, suggesting a less compact structure. The PGO was found to scavenge hydroxyl radical (IC50 517.68 ± 3.60 µg/mL) and superoxide radical (IC50 586.21 ± 3.41 µg/mL), and possess total antioxidant capacity (9.64 ± 0.23 mg gallic acid equivalent/g). Overall, this work would exploit PGO as a new hydrocolloid source in the food and pharmaceutical industries.

Metabolite profiling and in-vitro colon cancer protective activity of Cycas revoluta cone extract.

The methanolic extract of Cycas revoluta cone (MECR) was analyzed by GC-MS and UHPLC for metabolite profiling and was evaluated for anti-colon cancer property by using in vitro assays like Cell Viability Assay, Colony Formation Assay, ROS Determination, Flowcytometry, DAPI staining assay, Tunel assay. GC-MS and HPLC analysis confirmed the presence of different phytochemicals in the extract of Cycas revoluta cone. In-vitro studies showed MECR extract showed significant anti-colon cancer activity by reducing proliferation and inducing apoptosis in colon cancer cell (HCT-8) line, but no such activity was seen in normal colon cell (CCD-18Co) line. The investigation confirms that MECR may be a promising candidate in colon cancer protection.

Antioxidant and anticancer activity of synthesized 4-amino-5-((aryl substituted)-4H-1,2,4-triazole-3-yl)thio-linked hydroxamic acid derivatives.

OBJECTIVES: The antioxidant and anticancer activity of twelve 5-substituted-4-amino-1,2,4-triazole-linked hydroxamic acid derivatives were evaluated. METHODS: Previously synthesized 2-((4-amino-5-substituted-4H-1,2,4-triazol-3-yl)thio)-N-hydroxyacetamide and 3-((4-amino-5-substituted-4H-1,2,4-triazol-3-yl)thio)-N-hydroxypropanamide (6a-6l) were evaluated for in vitro antioxidant and in vivo anticancer activity. MDA-MB-231, MCF-7 and HCT 116 cell lines were used to evaluate IC50 values, in vitro. Ehrlich ascites carcinoma (EAC)-induced mice model was used to evaluate in vivo anticancer potential. Different biological markers were examined for drug-related toxicities. KEY FINDINGS: Compound 6b revealed more potent antioxidant property among all tested compounds, even than the ascorbic acid. The IC50 values of compound 6b were found to be 5.71 ± 2.29 µg/ml (DPPH assay) and 4.12 ± 0.5 µg/ml (ABTS assay). Histopathology of liver sections of drug-treated mice was evaluated. Survival analysis showed that compound 6b could increase the life span as of the standard drug. CONCLUSIONS: After the assessment of all in vivo anticancer study related data, it was found that compound 6b possess superior anticancer potency in terms of efficacy and toxicity. From this experimental design, it could be concluded that further modification of this prototypical structure will lead to develop more potent antioxidant as well as an anticancer agent in the future.

Seasonal Variation of Phyto-Constituents of Tea Leaves Affects Antiproliferative Potential.

Objective: Tea (Camellia sinensis Linn.; family: Theaceae) is popular as a stimulant beverage across the globe and is also utilized as a functional antioxidant in alternative medicine. This study has evaluated the impact of seasonal variation on phyto-constituents of tea. Method: The antiproliferative potential of methanolic extracts of tea leaves collected in the rainy season (MECR) was compared with the extract of tea leaves collected in the autumn season (MECA) of the same mother plant. Evaluation of in vivo antitumor activity was carried out in adult female Swiss albino mice groups inoculated with Ehrlich ascites carcinoma (EAC) cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to compare efficacy of MECR with that of MECA in the EAC cell line. Both qualitative and quantitative tests for phytochemical constituents present in MECA and MECR were performed. Antitumor efficacy of both the extracts was determined by evaluating different tumor markers showing dose-dependent cytotoxicity. Results: Statistically significant reduction in EAC-induced tumor was observed in MECR treated mice compared to MECA treated ones. Cell decimation was significantly higher with MECR treatment, where restoration of different parameters including tissue structures returned to normal. Moreover, gas chromatography-mass spectrometry (GC-MS) study revealed the presence of cyclobarbital and benzazulene derivative in MECR, which is thought to be a novel source of these chemicals. Conclusions: To our knowledge, there is no report that has attempted to reveal nutritional changes in terms of efficacy and variation in anticancer constituents in tea leaves, plucked in two seasons. This study revealed a novel source of barbital and benzazulene derivative. The unique presence of cyclobarbital and benzazulene, as revealed from GC-MS data, in methanolic extract of tea leaves collected during the rainy season (MECR) may have contributed to its enhanced in vitro (adopting MTT assay) and in vivo (on EAC-infected Swiss albino mice) cytotoxicity vis-à-vis antiproliferative properties compared to methanolic extract of tea leaves collected during the autumn season (MECA). The nature of plucking leaves in the two selected seasons is different.

Effect of Morphology and Concentration on Crossover between Antioxidant and Pro-oxidant Activity of MgO Nanostructures.

The toxicity of nanomaterials can sometimes be attributed to photogenerated reactive oxygen species (ROS), but these ROS can also be scavenged by nanomaterials, yielding opportunities for crossover between the properties. The morphology of nanomaterials also influences such features due to defect-induced properties. Here we report morphology-induced crossover between pro-oxidant activity (ROS generation) and antioxidant activity (ROS scavenging) of MgO. To study this process in detail, we prepared three different nanostructures of MgO (nanoparticles, nanoplates, and nanorods) and characterized them by HRTEM. These three nanostructures effectively generate superoxide anions (O2•-) and hydroxyl radicals (•OH) at higher concentrations (>500 µg/mL) but scavenge O2•- at lower concentrations (40 µg/mL) with successful crossover at 200 µg/mL. Nanorods of MgO generate the highest levels of O2•-, whereas nanoparticles scavenge O2•- to the highest extent (60%). Photoluminescence studies reveal that such crossover is based on the suppression of F2+ and the evolution of F+, F2+, and F23+ defect centers. The evolution of these defect centers reflects the antibacterial activity of MgO nanostructures which is initiated at 200 µg/mL against Gram-positive S. aureus ATCC 29737 and among different bacterial strains including Gram-positive B. subtilis ATCC 6633 and M. luteus ATCC 10240 and Gram-negative E. coli ATCC K88 and K. pneumoniae ATCC 10031. Nanoparticles exhibited the highest antibacterial (92%) and antibiofilm activity (17%) against B. subtilis ATCC 6633 in the dark. Interestingly, the nitrogen-centered free radical DPPH is scavenged (100%) by nanoplates due to its large surface area (342.2 m2/g) and the presence of the F2+ defect state. The concentration-dependent interaction with an antioxidant defense system (ascorbic acid (AA)) highlights nanoparticles as potent scavengers of O2•- in the dark. Thus, our findings establish guidelines for the selection of MgO nanostructures for diverse therapeutic applications.

Novel fused oxazepino-indoles (FOIs) attenuate liver carcinogenesis via IL-6/JAK2/STAT3 signaling blockade as evidenced through data-based mathematical modeling.

AIMS: To potentiate the well-documented tumor protecting ability of paullones, literatures demand for rational modifications in paullone ring structure and exploration of a precise mechanism underlying their antitumor effects. Thus, recently we synthesized novel paullone-like scaffold, 5H-benzo [2, 3][1,4]oxazepino[5,6-b]indoles, where compounds 13a and 14a attenuated the growth of liver cancer specific Hep-G2 cells in vitro and formed stable binding complex with IL-6. Henceforth, we hypothesized that this action is probably due to the blockade of IL-6 mediated JAK2/STAT3 signaling cascade. MAIN METHODS: A preclinical study was conducted using NDEA-induced HCC rat model by oral administration of FOIs at 10 mg/kg dose for 15 days. The molecular insights were confirmed through ELISA, qRT-PCR, western blot analyses. The study was further confirmed by data-based mathematical modeling using the quantitative data obtained from western blot analysis. 1H NMR based metabolomics study was also performed to unveil metabolite discriminations among various studied groups. KEY FINDINGS: We identified that the HCC condition was produced due to the IL-6 induced activation of JAK2 and STAT3 which, in turn, was due to enhanced phosphorylation of JAK2 and STAT3. The treatment with FOIs led to the significant blockade of the IL-6 mediated JAK2/STAT3 signaling pathway. Besides, FOIs showed their potential ability in restoring perturbed metabolites linked to HCC. In particular, the anticancer efficacy of compound 13a was comparable or somewhat better than marketed chemotherapeutics, 5-flurouracil. SIGNIFICANCE: These findings altogether opened up possibilities of developing fused oxazepino-indoles (FOIs) as new candidate molecule for plausible alternative of paullones to treat liver cancer.

6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid attenuates colon carcinogenesis via blockade of IL-6 mediated signals.

In this study, we investigated the in vivo antiproliferative activity of 6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (M1) in dimethylhydrazine (DMH) induced colorectal carcinoma (CRC) using albino Wistar rats. M1 was administered to DMH induced CRC rats at 10 and 25 mg/kg doses for 15 days. Various physiological, oxidative parameters, histopathology, ELISA, gene and protein expression studies were conducted to evaluate the anti-CRC potential of M1. The histopathology and biochemical tests indicated the protective action of M1 in DMH-induced colon cancer. ELISA confirms that M1 reduced the increased concentration of IL-6 more prominently than those of IL-2 and COX-2. Gene expression analysis revealed that M1 attenuated the increased mRNA over-expression of IL-6, JAK2 and STAT3. The result obtained from quantitative western blot analysis demonstrated that the CRC condition was produced by the IL-6 induced activation/phosphorylation of JAK2 and STAT3 and further down-regulated with M1 treatment. This evidence was supported well with the application of data-based mathematical modeling. Applying the fitted model, we predicted the quantitative behavior of STAT3 populations not accessible to experimental measurement. Later, 1H NMR based serum metabolic profiling was carried out using rat sera to investigate the impact of M1 on CRC-induced metabolic alterations. M1 showed its ability to restore the perturbed metabolites in CRC condition. Altogether, our study provided the first time evidence that M1 exhibits anti-CRC potential through the blockade of IL-6/JAK2/STAT3 oncogenic signaling.

Novel 1,4-benzothazines obliterate COX-2 mediated JAK-2/STAT-3 signals with potential regulation of oxidative and metabolic stress during colorectal cancer.

1,4-benzothiazines have ameliorative effects through inhibition of COX-2 mediated STAT-3 pathways at G-protein couple receptor site. As per this scenario, we recently prepared and tested novel 1,4-benzothiazine derivatives against HT-29 human colon cancer cell line. Two compounds namely AR13 and AR15 showed higher inhibitions among all the synthesized compounds. In the present context, we conducted the in vivo antiproliferative action and identified the molecular mechanism associated to cytotoxic action of AR13 and AR15 in dimethylhydrazine (DMH) induced colorectal carcinoma (CRC) model. Various physiological, oxidative stress, histopathology, ELISA, qRT-PCR, western blot and NMR-based metabolomics were accomplished to evaluate the anticancer effect of titled compounds. Both compounds were subjected to histological and biochemical tests to observe the protective action of the compounds. ELISA showed potential role of these compounds to normalize increased levels of IL-2, IL-6 and COX-2 mediators. This action was more pronounced for COX-2 rather than IL-2 and IL-6. Gene expression analyses further revealed that both of them attenuated the over-expressed COX-2 gene. Furthermore, it was confirmed that these compounds exerted antitumor potential via preventing COX-2 induced JAK-2 and STAT-3 phosphorylation. This action was substansiated by immunohistochemistry using JAK2, p-JAK2, STAT3 and p-STAT3 targets in colon tissue. Finally, score plots of PLS-DA models exhibited significant metabolic discriminations between the treated and CRC groups, and both compounds showed ability to restore the imbalance of multiple metabolites during CRC. In conclusion, our study provided the evidence towards better antiproliferative effect of AR13 and AR15 in DMH-induced CRC through the blockade of COX-2/JAK-2/STAT-3 signal transduction pathway and could be demonstrated as useful anti-CRC candidate molecules for future anticancer therapy.

Isolated mangiferin and naringenin exert antidiabetic effect via PPARγ/GLUT4 dual agonistic action with strong metabolic regulation.

In this study, we isolated two compounds from the leaves of Salacia oblonga (SA1, mangiferin and SA2, naringenin), and their structures were confirmed by infrared spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry. SA1 and SA2 were orally administered to streptozotocin-induced diabetic rats at 50 and 100 mg/kg daily for 15 days. Blood glucose level, serum lipid profile, oxidative stress parameters, histopathology, docking, molecular parameters, and NMR-based metabolic perturbation studies were performed to investigate the pharmacological activities of SA1 and SA2. Results suggested that both compounds reduced blood glucose level, restored body weight, and normalized lipid concentrations in the serum and oxidative stress biomarkers in the liver and pancreas. In addition, the docking study on several diabetes-associated targets revealed that both compounds had a strong binding affinity towards peroxisome proliferator-activated receptor gamma (PPARγ) and glucose transporter type 4 (GLUT4). Further real-time reverse transcription polymerase chain reaction and western blot analyses were performed to confirm the gene and protein expression levels of PPARγ and GLUT4 in the pancreatic tissues. Data obtained from the molecular studies showed that both compounds exhibited antidiabetic effects through dual activation of PPARγ/GLUT4 signaling pathways. Finally, the NMR-based metabolic studies showed that both compounds normalized the diabetogenic metabolites in the serum. Altogether, we concluded that SA1 and SA2 might be potential antidiabetic lead compounds for future drug development.

Sensitizing effects of an organovanadium compound during adjuvant therapy with cyclophosphamide in a murine tumor model.

Various epidemiological and preclinical studies have already established the cancer chemopreventive potential of vanadium. In addition, recent studies have also indicated the abilities of vanadium-based compounds to induce cell death selectively towards malignant cells. Therefore, the objective of the present investigation is to improve the therapeutic efficacy and toxicity profile of an alkylating agent, cyclophosphamide, by the concurrent use of an organovanadium compound, oxovanadium(IV)-l-cysteine methyl ester complex (VC-IV). In this study, VC-IV (1mg/kg b.w., p.o.) was administered alone as well as in combination with cyclophosphamide (25mg/kg b.w., i.p.) in concomitant and pretreatment schedules. The results showed that VC-IV in combination with cyclophosphamide resulted in an improved therapeutic efficacy as evidenced by reduction of tumor growth and prolongation of life span. The observed potentiation was mediated through generation of ROS in tumor cells, which ultimately led to significant DNA damage, and apoptosis in tumor cells. Further studies revealed that VC-IV sensitized tumor cells to cyclophosphamide therapy by down-regulating the anti-apoptotic protein Bcl-2 and by up-regulating molecules like p53, Bax, cytochrome c, caspases, which led to PARP cleavage and apoptosis. Significant inhibition of angiogenesis along with reduction in the levels of VEGF-A and MMP-9 in the tumor bed by VC-IV further contributed to the sensitization accomplished by VC-IV. Moreover, VC-IV ameliorated cyclophosphamide-induced hematopoietic, hepatic and genetic damages by modulating the antioxidant status in normal organs. Thus, the present study clearly demonstrated the sensitizing and protective efficacy of VC-IV and indicates it may serve as a promising adjuvant in cancer chemotherapy.

Vanadium(III)-l-cysteine enhances the sensitivity of murine breast adenocarcinoma cells to cyclophosphamide by promoting apoptosis and blocking angiogenesis.

Various epidemiological and preclinical studies have already established the cancer chemopreventive potential of vanadium-based compounds. In addition to its preventive efficacy, studies have also indicated the abilities of vanadium-based compounds to induce cell death selectively toward malignant cells. Therefore, the objective of the present investigation is to improve the therapeutic efficacy and toxicity profile of an alkylating agent, cyclophosphamide, by the concurrent use of an organovanadium complex, vanadium(III)-l-cysteine. In this study, vanadium(III)-l-cysteine (1 mg/kg body weight, per os) was administered alone as well as in combination with cyclophosphamide (25 mg/kg body weight, intraperitoneal) in concomitant and pretreatment schedule in mice bearing breast adenocarcinoma cells. The results showed that the combination treatment significantly decreased the tumor burden and enhanced survivability of tumor-bearing mice through generation of reactive oxygen species in tumor cells. These ultimately led to DNA damage, depolarization of mitochondrial membrane potential, and apoptosis in tumor cells. Further insight into the molecular pathway disclosed that the combination treatment caused upregulation of p53 and Bax and suppression of Bcl-2 followed by the activation of caspase cascade and poly (ADP-ribose) polymerase cleavage. Administration of vanadium(III)-l-cysteine also resulted in significant attenuation of peritoneal vasculature and sprouting of the blood vessels by decreasing the levels of vascular endothelial growth factor A and matrix metalloproteinase 9 in the ascites fluid of tumor-bearing mice. Furthermore, vanadium(III)-l-cysteine significantly attenuated cyclophosphamide-induced hematopoietic, hepatic, and genetic damages and provided additional survival advantages. Hence, this study suggested that vanadium(III)-l-cysteine may offer potential therapeutic benefit in combination with cyclophosphamide by augmenting anticancer efficacy and diminishing toxicity to the host.

Ameliorative effects of pyrazinoic acid against oxidative and metabolic stress manifested in rats with dimethylhydrazine induced colonic carcinoma.

Pyrazinoic acid (PA) is structurally similar to nicotinic acid which acts on G-protein-coupled receptor (GPR109A). GPR109A expresses in colonic and intestinal epithelial sites, and involves in DNA methylation and cellular apoptosis. Therefore, it may be assumed that PA has similar action like nicotinic acid and may be effective against colorectal carcinoma (CRC). CRC was produced via subcutaneous injection of dimethylhydrazine (DMH) at 40 mg/kg body weight once in a week for 4 weeks. After that, PA was administered orally at 2 doses of 10 and 25 mg/kg daily for 15 d to observe the antiproliferative effect. Various physiologic, oxidative stress, molecular parameters, histopathology, RT-PCR and NMR based metabolomics were performed to evaluate the antiproliferative potential of PA. Our results collectively suggested that PA reduced body weight, tumor volume and incidence no. to normal. It restored various oxidative stress parameters and normalized IL-2, IL-6, and COX-2 as compared with carcinogen control. In molecular level, overexpressed IL-6 and COX-2 genes became normal after PA administration. Again, normal tissue architecture was prominent after PA administration. Score plots of PLS-DA models exhibited that PA treated groups were significantly different from CRC group. We found that CRC rat sera have increased levels of acetate, glutamine, o-acetyl-glycoprotein, succinate, citrulline, choline, o-acetyl choline, tryptophan, glycerol, creatinine, lactate, citrate and decreased levels of 3-hydroxy butyrate, dimethyl amine, glucose, maltose, myoinositol. Further the PA therapy has ameliorated the CRC-induced metabolic alterations, signifying its antiproliferative properties. In conclusion, our study provided the evidence that PA demonstrated good antiproliferative effect on DMH induced CRC and thus demonstrated the potential of PA as a useful drug for future anticancer therapy.

An oxovanadium(IV) complex protects murine bone marrow cells against cisplatin-induced myelotoxicity and DNA damage.

Cisplatin (CDDP) is one of the first-line anticancer drugs that has gained widespread use against various forms of human malignancies. But, the therapeutic outcome of CDDP therapy is limited due to its adverse effects including myelotoxicity and DNA damage which may lead to the subsequent risk of developing secondary cancer. Hence, in search of a suitable cytoprotectant, this study investigated the probable protective efficacy of an oxovanadium(IV) complex, namely oxovanadium(IV)-L-cysteine methyl ester complex (VC-IV) against CDDP-induced myelosuppression and genotoxic damage in the bone marrow cells of Swiss albino mice. CDDP was administered intraperitoneally (5 mg/kg b.w.) and VC-IV was administered orally (1 mg/kg b.w.) in concomitant and 7 d pretreatment schedule. Treatment with VC-IV in CDDP-treated mice significantly (p < 0.01) enhanced bone marrow cell proliferation and inhibited cell death in the bone marrow niche indicating improvement of CDDP-induced myelotoxicity. The organovanadium compound also significantly (p < 0.01) reduced the percentage of chromosomal aberrations, the frequency of micronuclei formation, and the extent of DNA damage. The observed chemoprotective effect of VC-IV was attributed to its anti-oxidant efficacy which significantly (p < 0.01) attenuated CDDP-induced generation of free radicals, and restored (p < 0.01) the levels of oxidized and reduced glutathione. Hence, VC-IV may serve as a promising candidate for future development to decrease the deleterious effects of CDDP in the bone marrow cells of cancer patients and associated secondary complications.

Ameliorative effect of an oxovanadium (IV) complex against oxidative stress and nephrotoxicity induced by cisplatin.

OBJECTIVE: The present study was designed to investigate the chemoprotective efficacy of an L-cysteine-based oxovanadium (IV) complex, namely, oxovanadium (IV)-L-cysteine methyl ester complex (VC-IV) against cisplatin (CDDP)-induced renal injury in Swiss albino mice. METHODS: CDDP was administered intraperitoneally (5 mg/kg body weight) and VC-IV was administered orally (1 mg/kg body weight) in concomitant and 7 days pre-treatment schedule. RESULTS: CDDP-treated mice showed marked kidney damage and renal failure. Administration of VC-IV caused significant attenuation of renal oxidative stress and elevation of antioxidant status. VC-IV also significantly decreased serum levels of creatinine and blood urea nitrogen, and improved histopathological lesions. Western blot analysis of the kidneys showed that VC-IV treatment resulted in nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) through modulation of cytosolic Kelch-like ECH-associated protein 1. Thus, VC-IV stimulated Nrf2-mediated activation of antioxidant response element (ARE) pathway and promoted expression of ARE-driven cytoprotective proteins, heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1, and enhanced activity of antioxidant enzymes. Interestingly, VC-IV did not alter the bioavailability and renal accumulation of CDDP in mice. DISCUSSION: In this study, VC-IV exhibited strong nephroprotective efficacy by restoring antioxidant defense mechanisms and hence may serve as a promising chemoprotectant in cancer chemotherapy.

Prebiotic potential of gum odina and its impact on gut ecology: in vitro and in vivo assessments.

The use of prebiotics to escalate certain gut flora is a current aspect of research for effective gut ecology. In the present study we appraise the efficacy of gum odina obtained from the bark of Odina wodier (Anacardiaceae), which is not fully degraded (16%) in the upper GI tract and becomes available to the lower region, as a prebiotic. An in vitro prebiotic activity assay established a quantitative score to describe the extent to which gum odina supports the selective growth of probiotics with a maximum of 5.60 ± 0.11 for Lactobacillus plantarum MTCC 6160. The polysaccharide, upon fermentation, also liberates lactic acid (0.46 ± 0.003 mg ml(-1)) and acetic acid (1.03 ± 0.003 mg ml(-1)). In vivo studies revealed that natural gum selectively stimulates Lactobacillus sp., and eliminates enteric pathogens with a C.F.U. of 384.48 ± 0.11 and 40.56 ± 0.17 respectively on the 8(th) day. The changes in the level of ß-galactosidase signify maturation of macrophages in the gut environment. It also boosts the immune system by increasing sIgA upon infection from the 5(th) day in the gut, when incorporated into the feed of mice. Moreover an increase in levels of IFNγ on the 5(th) day also manifest additional protection against various pathogen-induced primary and secondary infections. Thus, gum odina is a potential prebiotic which not only provides nutrition but also improves gut ecology.