Girija Kuttan

University of Calicut, Malappuram, Kerala, India

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Publications (209)408.06 Total impact

  • George K Gilcy · Girija Kuttan
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    ABSTRACT: Emilia sonchifolia (L.) DC is a widely distributed medicinal herb used mainly in the indigenous Ayurvedic system of medicine in India. This plant is one among the ten sacred plants of Kerala state in India, collectively known as Dasapushpam.
    No preview · Article · Dec 2015
  • Vishnu Priya Murali · Girija Kuttan
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    ABSTRACT: Background: Curculigo orchioides Gaertn is an ancient medicinal plant (Family: Amaryllidaceae), well known for its immunomodulatory and rejuvenating effects. Cyclophosphamide (CPA) is an alkylating agent widely used for treating a variety of human malignancies, but associated with different toxicities too. Our previous reports regarding the hemoprotective and hepatoprotective effects of the plant against CPA toxicities provide the background for the present study, which is designed to analyze the ameliorative effect of the methanolic extract of C orchioides on the urotoxicity and nephrotoxicity induced by CPA. Methods: CPA was administered to male Swiss albino mice at a single dose of 1.5 mmol/kg body weight to induce urotoxicity after 5 days of prophylactic treatment with C orchioides extract (20 mg/kg body weight). Mesna (2-mercaptoethanesulfonate) was used as a control drug. Serum, tissue, and urine levels of kidney function markers and antioxidant levels were checked along with the serum cytokine levels. Results: The plant extract was found to be effective in ameliorating the urotoxic and nephrotoxic side effects of CPA. Upregulation of serum interferon-γ and interleukin-2 levels were observed with C orchioides treatment, which was decreased by CPA administration. Besides these, serum tumor necrosis factor-α level was also downregulated by C orchioides treatment. Conclusion: Curculigo orchioides was found to be effective against the CPA-induced bladder and renal toxicities by its antioxidant capability and also by regulating the pro-inflammatory cytokine levels.
    No preview · Article · Oct 2015 · Integrative Cancer Therapies
  • George K Gilcy · Girija Kuttan
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    ABSTRACT: This study was performed in order to provide a scientific basis for the conventional use of Emilia sonchifolia in the traditional Indian Ayurvedic medicine possibly through modulation of the host immune defense. Emilia sonchifolia methanolic extract (25 mg/kg body weight) was administered intraperitoneally in mice, and hematological parameters, relative organ weights, bone marrow cellularity, and α-esterase activity were assessed. Humoral immune response was evaluated by hemagglutinating antibody (HA) titer and plaque forming cell (PFC) assay. Blastogenesis assays of lymphoid organs were done in the presence and absence of various mitogens such as phytohemagglutinin, concanavalin A, pokeweed mitogen, and lipopolysaccharide. Cytotoxic T lymphocyte (CTL) production was assessed by Winn's neutralization test. The levels of cytokines interleukin-2 (IL-2) and interferon-γ (IFN-γ) were evaluated by ELISA. Emilia sonchifolia significantly enhanced the total white blood cell count (9995±535 cells/mm3), bone marrow cellularity, α-esterase activity, and weight of lymphoid organs (p<0.001). The effect on humoral immune response was evident from the enhanced HA titer and increased number of PFCs (p<0.001). The blastogenic effects of mitogens were also stimulated to significant levels by E. sonchifolia treatment. Emilia sonchifolia treatment augmented cell-mediated immune response by enhancing the killing activity of CTLs and by enhanced production of IL-2 and IFN-γ. From these results, it was very evident that E. sonchifolia, an indigenous medicinal plant, is a potent immune response modulator, and the present report is so far the first study to demonstrate the immunoregulatory activity of E. sonchifolia.
    No preview · Article · Aug 2015
  • A P Firdous · Girija Kuttan · Ramadasan Kuttan
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    ABSTRACT: Abstract Context: meso-Zeaxanthin (MZ) is a xanthophyll carotenoid with profound antioxidant activity. Objective: Oxidative stress plays a decisive role in numerous degenerative diseases including cancer. The present study evaluates anti-inflammatory effect of MZ. Materials and methods: Balb/c mice were treated with different doses of MZ (50 and 250 mg/kg b.wt, orally) 5 d before subcutaneous injection of carrageenan (1%), dextran (1%), and formalin (2%). Paw edema formation in MZ-treated and -untreated animals was measured using vernier calipers. Anti-inflammatory activity of MZ against lipopolysaccharide (LPS)-induced inflammatory model was studied by culturing macrophages in the presence and absence of LPS (5 μg/ml) and different concentrations of MZ (5, 10, and 25 μg/ml). After 24 h, the effect of MZ on pro-inflammatory cytokine levels in macrophages was analyzed by ELISA and its effect on various inflammatory genes was studied by RT-PCR. Results: MZ administration at different doses significantly (p < 0.001) inhibited paw edema induced by carrageenan, dextran, and formalin in mice. MZ also exhibited profound anti-inflammatory effect against LPS-induced inflammation in macrophages. Increased production of nitric oxide, C-reactive proteins, and various pro-inflammatory cytokines (TNF-α, interleukin-1β, and interleukin-6) in LPS-stimulated macrophages was significantly reduced by MZ treatment. Moreover, LPS-stimulated up-regulated mRNA expression of various inflammatory mediator genes like COX-2, TNF-α, and iNOS was down-regulated by MZ administration. Discussion and conclusion: MZ has potent anti-inflammatory effect which can be due to its down-regulated expression of various inflammatory mediator genes. Since cancer is considered as an inflammatory disease, the present study points towards the importance of MZ in chemo-preventive strategy.
    No preview · Article · Mar 2015 · Pharmaceutical Biology
  • Valsala Kumari Remya · Girija Kuttan
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    ABSTRACT: Our previous work suggests that Thuja occidentalis, Carcinosinum and Ruta graveolens have antineoplastic properties. The mechanism of this action has not previously been studied. We studied the hypothesis that the mechanism of action is through the immune modulation. We evaluated the effects of Thuja occidentalis, Carcinosinum and Ruta graveolens 1M, 200c and 30c on the immune system of Balb/c mice. The homeopathic preparations were administered orally for ten consecutive days. Haematological parameters (Total White Blood Cell (WBC) Count, Differential Count and Haemoglobin content), haematopoietic parameters (bone marrow cellularity and α-esterase positive cells) and immune parameters for antibody response and lymphoid cell proliferation were assessed using standard methods. Results were analysed by statistical comparison with the control. We observed significant enhancement of haematological parameters including total WBC count, haematopoietic parameters such as bone marrow cellularity and the number of α-esterase positive cells, other parameters of immune response such as circulating antibody titre and the number of plaque forming cells (PFC), particularly with higher dilutions of Thuja and Ruta. Enhanced proliferation of B and T lymphoid cells was also observed. No toxic effects were observed. The results suggest immunomodulatory activity of homeopathic preparations in high dilution. This may be a mechanism through which homeopathic preparations act. Copyright © 2014 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.
    No preview · Article · Mar 2015 · Homeopathy
  • Vishnu Priya Murali · Girija Kuttan
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    ABSTRACT: Cyclophosphamide (CTX) is a synthetic antineoplastic drug with severe and life-threatening side effects. Studies in search of protective agents, preferably natural products, that can alleviate these side effects are valuable because they can contribute to improve current chemotherapeutic treatment strategies. Curculigo orchioides Gaertn (family Hypoxidaceae) is well known for its medicinal use in the Indian Ayurvedic system of medicine, and various studies have been reported that proved its immunomodulatory and anti-inflammatory properties. In this study, the tumor reduction capacity of CTX in combination with C orchioides methanolic extract was studied using Dalton's lymphoma ascites-induced solid tumor models. Effect of C orchioides on the reversal of the damage induced by CTX administration (intraperitoneally) was also determined in this study. For this, solid tumor volume, serum cytokine levels, hematolological parameters, intestinal histopathology, and serum and tissue biochemical parameters (Glutathione [GSH], alkaline phosphatase [ALP], glutamate pyruvate transaminase [GPT], lipid peroxidation [LPO]) were analyzed. Immune suppression and increased serum proinflammatory cytokine levels caused by CTX administration (25 mg/kg body weight) were reversed by C orchioides (20 mg/kg body weight). The alcoholic extract enhanced the tumor reduction capacity of CTX and reduced GPT and ALP levels in liver and serum, which were elevated by CTX administration. The LPO level was also lower in the CTX-administered animals when treated with the C orchioides extract. In conclusion, the plant extract when administered in combination with CTX, can result in enhanced anticancer properties; it also ameliorates the toxic side effects of CTX. © The Author(s) 2015.
    No preview · Article · Jan 2015 · Integrative Cancer Therapies
  • Kodappully Sivaraman Siveen · Girija Kuttan
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    ABSTRACT: In this study, the antimetastatic potential of the ethanolic extract of Aerva lanata was evaluated using the B16F-10 melanoma-induced lung metastasis model. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Simultaneous treatment with A lanata inhibited tumor nodule formation in the lungs (70.53%), and there was a 65.3% increase in the survival rate of metastatic tumor-bearing animals. These results correlated with biochemical parameters such as lung collagen hydroxyproline, hexosamine, and uronic acid contents; serum sialic acid and γ-glutamyl transpeptidase levels; and histopathological analysis. In vitro studies using B16F-10 cells showed that A lanata inhibited migration of tumor cells, cell invasion through type-I collagen-coated polycarbonate filter and activation of matrix metalloproteinases. Treatment with A lanata induced apoptotic response, characterized by apoptotic morphology, a typical ladder of DNA fragmentation, and detection of 3' hydroxyl ends in DNA by TUNEL assay. There was an increase in the percentage of cells in the sub-G0/G1 phase indicating cell cycle arrest. A lanata treatment resulted in downregulation of bcl-2 and cyclin-D1 expression and upregulation of p53, bax, caspase-9, caspase-3, p21, and p27 gene expression in B16F-10 cells. Proinflammatory cytokine production and gene expression were also found to be downregulated in A lanata-treated cells.
    No preview · Article · Nov 2012 · Integrative Cancer Therapies
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    ABSTRACT: This study was carried out to determine the effect of herbal medication on the clinical status of HIV infected persons especially on their CD4 + T lymphocyte count and viral load. The toxicity of the medication was also studied. 25 HIV positive individuals were taken for the study. They were treated with a herbal formulation developed in our centre, for one year. Patients were evaluated for their clinical status every month and CD4 + T lymphocyte and viral load every six months. Other parameters assessed were body weight, hematological analysis and hepatic and renal function tests. Body weight was found to be increased in 20 patients out of 25 who have undergone treatment. CD4 +T lymphocyte count was increased in 15 patients and viral load was decreased in 20 patients. In six patients viral load was undetectable range. Administration of these medications significantly reduced, elevated interferon-γ and tumor necrosis factor in HIV patients. Medication did not produce any toxicity in HIV patients, as it did not show any significant change in hepatic function, renal function and haematology. Administration of herbal preparation was found to reduce clinical symptoms produced by HIV infection. This herbal formulation was found useful therapeutically for the management of HIV infection and did not produce any toxicity.
    No preview · Article · Jul 2012 · Indian Drugs
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    T P Hamsa · Girija Kuttan
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    ABSTRACT: The present study demonstrated the potential antimetastatic and antiinvasive effect of berberine using both in vivo mouse lung metastasis and in vitro models. Administration of berberine resulted in significant suppression of B16F-10 melanoma induced tumor nodule formation and enhanced the survival of tumor-bearing mice. Berberine treatment also decreased various biochemical parameters associated with lung metastasis. These inhibitory actions may be due to the significant suppression of several signaling molecules such as ERK1/2, NF-κB, ATF-2 and CREB involved in the transcription signaling pathways for MMP gene expression. It could also inhibit the migration and invasion of highly metastatic murine melanoma cells in a dose-dependent manner in vitro. The results clearly show that berberine could significantly inhibit experimental lung metastasis produced by intravenous injection of B16F-10 melanoma cells and this effect could be linked to the down-regulation of metastasis-related signaling molecules.
    Full-text · Article · Apr 2012 · Phytotherapy Research
  • K S Siveen · Girija Kuttan
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    ABSTRACT: Plant-derived natural products such as alkaloids, flavonoids, terpenoids, and polysaccharides have received considerable attention in recent years due to their diverse pharmacological properties such as immunomodulatory, anti-inflammatory, cytotoxic, cancer chemopreventive effects, and so on. 10-Methoxycanthin-6-one, a β-carboline alkaloid from the medicinal plant Aerva lanata, was assessed for immunomodulatory activity in Balb/c mice. Intraperitoneal administration of five doses of the compound at 0.5 mg/kg body weight was found to enhance the total WBC count (13,975.50 ± 324.27 cells/mm³ on the 12th day), bone marrow cellularity (23.08 ± 0.86 × 10⁶ cells/femur), and number of α-esterase-positive cells (1283.16 ± 21.10 cells/4000 cells). Treatment with the compound along with the antigen, sheep red blood cells, produced an enhancement in the circulating antibody titer (1024 on Days 12 and 15) and the number of plaque-forming cells (PFC) in the spleen. In treated group, maximum number of PFC (264.83 PFC/10⁶ spleen cells) was observed on the sixth day after antigen administration. At the same time, administration of 10-methoxycanthin-6-one could significantly reduce the elevated levels of proinflammatory cytokines and nitric oxide production by lipopolysaccharide (LPS)-stimulated macrophages. There was also a significant reduction in the mRNA levels of inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor alpha (TNF)-α, and interleukin (IL)-1β and IL-6 in LPS-stimulated macrophages after treatment with 10-methoxycanthin-6-one.
    No preview · Article · Feb 2012 · Immunopharmacology and Immunotoxicology
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    Poyil Pratheeshkumar · Girija Kuttan
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    ABSTRACT: Effect of Vernonia cinerea L. and vernolide-A on cell-mediated immune (CMI) response was studied in normal as well as tumor-bearing BALB/c mice. Administration of V. cinerea and vernolide-A significantly enhanced natural killer (NK) cell activity in both normal as well as tumor-bearing animals, and the activity was observed earlier than in tumor-bearing control animals. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement-mediated cytotoxicity (ACC) were also enhanced significantly in both normal as well as tumor-bearing animals after V. cinerea and vernolide-A administration compared with untreated control tumor-bearing animals. Extract and vernolide-A showed a significant increase in cytotoxic T lymphocyte (CTL) production in both the in vivo and in vitro models. The level of cytokines such as interleukin (IL)-2 and interferon (IFN)-γ were also enhanced by the treatment of V. cinerea and vernolide-A in both normal as well as tumor-bearing animals. This study demonstrated that V. cinerea extract and vernolide-A stimulate the CTL, NK cell, ADCC, and ADCC through enhanced secretion of IL-2 and IFN-γ.
    Full-text · Article · Feb 2012 · Immunopharmacology and Immunotoxicology
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    T P Hamsa · Girija Kuttan
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    ABSTRACT: Berberine, a naturally occurring isoquinoline alkaloid, is present in a number of important medicinal plants. Berberine has a wide range of biochemical and pharmacological effects, including anticancer effects. In this study, we elucidated the mechanism of antiangiogenic activity of berberine using in vivo and in vitro models. In vivo antiangiogenic activity was studied using B16F-10 melanoma cells and induced capillary formation in C57BL/6 mice. Berberine, at 10 mg/kg body weight, showed significant inhibition in tumor-directed capillary formation and in various proangiogenic factors, such as vascular endothelial growth factor (VEGF), and proinflammatory mediators, such as interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α), and granulocyte macrophage colony-stimulating factor (GM-CSF), which are involved in tumor angiogenesis. At the same time, it could also increase antitumor factors, such as IL-2 and tissue-inhibitor metalloproteinase (TIMP) levels in the serum. Berberine could also inhibit endothelial motility, migration, tube formation, and vessel sprouting from rat aortic ring in vitro. Further, berberine inhibited various transcription factors involved in tumor development and angiogenesis, such as NF-ĸB, c-Fos, CREB, and ATF-2. mRNA expression levels of proangiogenic factors, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and hypoxia-inducible factor (HIF), were also downregulated in tumor cells after treatment with berberine. Drastically elevated expressions of HIF and VEGF mRNA by tumor cells under hypoxic conditions were also decreased after treatment with berberine. This result clearly demonstrates that the antiangiogenic activity of berberine is mainly mediated through the inhibition of various proinflammatory and pro-angiogenic factors and the major ones are HIF, VEGF, COX-2, NO, NF-ĸB, and proinflammatory cytokines.
    Full-text · Article · Jan 2012 · Drug and Chemical Toxicology
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    A Gulati · E S Sunila · G Kuttan
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    ABSTRACT: ETB receptor agonist, IRL-1620 (or SPI-1620) presently in US Phase 1 clinical trial, has been demonstrated to selectively and transiently increase tumor blood flow. The present study was conducted to determine the effect of IRL-1620 on radiation therapy in tumor bearing mice inoculated with Dalton's Lymphoma Ascites cells. Tumors were allowed to grow for 30 days to a size of 1.10-1.29 cm3 before starting the treatment. The animals with or without IRL-1620 treatment were exposed to radiation (4 Gy/dose) on every alternate day for a total of 5 doses. Tumor volume was determined twice every week till the end of study. Radiation alone did not affect the tumor volume; however, animals treated with IRL-1620 followed by radiation produced a significant (64%) reduction in tumor volume. Survival of mice improved from 0/10 at 56 days after tumor inoculation in vehicle plus radiation group to 6/10 at 70 days in IRL-1620 (9 nmol/kg) plus radiation group. It is concluded that IRL-1620 improves the efficacy of radiation treatment in tumor bearing mice. (These findings have been earlier presented as an abstract ).
    Full-text · Article · Jan 2012 · Arzneimittel-Forschung
  • K S Siveen · Girija Kuttan
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    ABSTRACT: Cell-mediated immunity offers protection against virus-infected cells and tumor cells, involves activation of natural killer (NK) cells, production of antigen-specific cytotoxic T-lymphocytes, and release of various cytokines in response to an antigen. Administration of an ethanolic extract of Aerva lanata was found to stimulate cell-mediated immunological responses in normal and tumor-bearing BALB/c mice. A significant enhancement in NK cell activity in both normal and tumor-bearing hosts was observed after administration of A. lanata. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement-mediated cytotoxicity (ACC) were significantly enhanced as well in both sets of treated hosts. In addition, in vivo production of IL-2 and IFNg were each significantly enhanced by extract treatment. The stimulatory effect of A. lanata on cytotoxic T-lymphocyte (CTL) production was determined by Winn's neutralization assay using CTL-sensitive EL4 thymoma cells. A. lanata treatment caused a significant increase in CTL production in both in vivo and in vitro models, in each case as indicated by a significant increase in the life-spans of tumor-injected mice. Taken together, all of these results in the murine model indicate that administration of an ethanolic extract of A. lanata could enhance the cell-mediated anti-tumor response.
    No preview · Article · Nov 2011 · Journal of Immunotoxicology
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    ABSTRACT: Cancer is a major public health problem in India and many other parts of the world. Its two main characteristics are uncontrolled cell growth and metastasis. Natural products represent a rich source of compounds that have found many applications in various fields of medicines and therapy including cancer therapy. Effective ingredients in several plant-derived medicinal extracts are terpenoid compounds and many terpenes have biological activities and are used for the treatment of human diseases. This review attempted to collect all available published scientific literature of eight naturally occurring terpenoids and their effect on inhibition of tumor progression. The present review is about eight potent naturally occurring terpenoids that have been studied for their pharmacological properties in our lab and this review includes 130 references compiled from all major databases. Literature survey revealed that triterpenoids, such as glycyrrhizic acid, ursolic acid, oleanolic acid, and nomilin, the diterpene andrographolide, and the monoterpenoids like limonene and perillic acid had shown immunomodulatory and antitumor activities. All of them could induce apoptosis in various cancer cells by activating various proapoptotic signaling cascades. Many of these terpenoids found to inhibit metastatic progression and tumor-induced angiogenesis. The molecular mechanisms that involved in these activities include inhibition of various oncogenic and anti-apoptotic signaling pathways and suppression or nuclear translocation of various transcription factors including nuclear factor kappa B (NF-κB). The chemopreventive and chemoprotective effects of these compounds point toward their possible role in modern anticancer therapies.
    Full-text · Article · Oct 2011 · Pharmaceutical Biology
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    Kodappully S Siveen · Girija Kuttan
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    ABSTRACT: The antimetastatic potential of thujone, a naturally occurring monoterpene, was evaluated. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Administration of thujone (1 mg·(kg body weight)(-1)), prophylactically and simultaneously with tumor induction, inhibited tumor nodule formation in the lungs by 59.45% and 57.54%, respectively, with an increase in the survival rate (33.67% and 32.16%) of the metastatic tumor bearing animals. These results correlated with biochemical parameters such as lung collagen hydroxyproline, hexosamine and uronic acid contents, serum sialic acid and γ-glutamyl transpeptidase levels, and histopathological analysis. Treatment with thujone downregulated the production of proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and granulocyte-monocyte colony-stimulating factor. Thujone administration downregulated the expression of matrix metalloproteinase (MMP)-2, MMP-9, extracellular signal-regulated kinase (ERK)-1, ERK-2, and vascular endothelial growth factor (VEGF) and also upregulated the expression of nm-23, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 in the lung tissue of metastasis-induced animals. Treatment with thujone inhibited the activity of MMP-2 and MMP-9 in gelatin zymographic analysis. Thujone treatment significantly inhibited the invasion of B16F-10 melanoma cells across the collagen matrix in a Boyden chamber. Thujone also inhibited the adhesion of tumor cells to collagen-coated microtire plate wells and the migration of B16F-10 melanoma cells across a polycarbonate filter in vitro. These results indicate that Thujone can inhibit the lung metastasis of B16F-10 cells through inhibition of tumor cell proliferation, adhesion, and invasion, as well as by regulating expression of MMPs, VEGF, ERK-1, ERK-2, TIMPs, nm23, and levels of proinflammatory cytokines and IL-2 in metastatic animals.
    Full-text · Article · Sep 2011 · Canadian Journal of Physiology and Pharmacology
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    P Pratheeshkumar · Girija Kuttan
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    ABSTRACT: One of the major reasons for the rapid progression of cancers is the ability of tumor cells to escape from the immune surveillance mechanism of the body. Modulation of immune responses is highly relevant in tumor cell destruction. Effect of vernolide-A on the cell-mediated immune (CMI) response in metastatic condition was studied using C57BL/6 mice model. Administration of vernolide-A enhanced natural killer (NK) cell activity, antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent complement-mediated cytotoxicity (ACC) and the activity was observed in treated group much earlier compared with the metastatic tumor-bearing control. Administration of vernolide-A significantly enhanced the production of interleukin (IL)-2 and interferon-gamma (IFN-γ) in metastatic tumor-bearing animals. In addition, vernolide-A significantly down-regulated the serum levels of proinflammatory cytokines such as IL-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) during metastasis. All these results demonstrate that vernolide-A could enhance the immune response against metastatic progression of B16F-10 melanoma cells in mice.
    Full-text · Article · Sep 2011 · Immunopharmacology and Immunotoxicology
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    K S Siveen · Girija Kuttan
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    ABSTRACT: Thujone, a naturally occurring monoterpene, was found to enhance the total WBC count, bone marrow cellularity, number of α-esterase positive cells, number of plaque forming cells in spleen and circulating antibody titer in Balb/c mice (1mg/kg body weight, intraperitoneally for 5 days). Thujone treatment enhanced proliferation of splenocytes and thymocytes, both in the presence and absence of specific mitogens. Administration of Thujone was found to stimulate the cell-mediated immunological response in normal and tumor bearing Balb/c mice. A significant enhancement in natural killer (NK) cell mediated cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement mediated cytotoxicity (ACC) in both normal as well as tumor-bearing animals was observed after the administration of Thujone. Production of cytokines such as IL-2 and IFN-γ was significantly enhanced by the administration of Thujone. The stimulatory effect of Thujone on cytotoxic T lymphocyte (CTL) generation was determined by Winn's neutralization assay using CTL sensitive EL4 thymoma cells. Thujone treatment showed a significant increase in CTL production in both the in vivo and in vitro models, as indicated by a significant increase in the life span of tumor bearing animals. All these results indicate that administration of Thujone could enhance the immune response of mice. There was a significant reduction in solid tumor development, mediated by the presence of alert immune responses during Thujone administration.
    Full-text · Article · Aug 2011 · International immunopharmacology
  • Poyil Pratheeshkumar · Girija Kuttan
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    ABSTRACT: Angiogenesis is a crucial step in the growth and metastasis of cancers. Antiangiogenic activity of nomilin was studied using in vivo as well as in vitro models. Nomilin significantly inhibited tumor directed capillary formation. Serum proinflammatory cytokines such as IL-1β, IL-6, TNF-α and GM-CSF and also serum NO levels were significantly reduced by the treatment of nomilin. Administration of nomilin significantly reduced the serum level of VEGF, a proangiogenic factor and increased the antiangiogenic factors IL-2 and TIMP-1. In vitro studies using rat aortic ring assay showed that administration of nomilin at non-toxic concentrations significantly inhibited microvessel sprouting. Studies using human umbilical vein endothelial cells clearly demonstrated that administration of nomilin significantly retarded endothelial cell proliferation, migration, invasion and tube formation. These data clearly demonstrate the antiangiogenic potential of nomilin by downregulating the activation of MMPs, production of VEGF, NO and proinflammatory cytokines as well as upregulating IL-2 and TIMP.
    No preview · Article · Aug 2011 · European journal of pharmacology
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    ABSTRACT: Homoeopathic medicines treat diseases, including cancer, using ultradiluted preparations. Earlier studies indicated that homoeopathic medicines are cytotoxic to tumor cells and reduced animal tumors. However, the mechanism of homoeopathic medicines at the cellular level is not known. The following drugs were used in the study: Ruta 200C, Carcinosinum 200C, Hydrastis 200C, Thuja 200C, and Thuja 1M. These drugs were tested for their ability to induce apoptosis as seen by morphology, DNA laddering, expression of genes related to apoptosis, and TUNEL assay. Similarly, the effect of homoeopathic medicines on apoptosis was measured by microarray analysis. Activity of Ruta 200C was compared with that of the mother tincture. Ruta 200C produced morphological changes in the Dalton's lymphoma ascites tumor cells and induced DNA laddering. Carcinosinum 200C increased apoptotic gene p53 and Ruta 200C decreased antiapoptotic gene Bcl2. Administration of potentiated homoeopathic drugs to tumor-bearing mice induced TUNEL-positive cells in the tumor, showing increased apoptosis of tumor cells. Microarray analysis of cells treated with homoeopathic drugs indicated that many enzymes related to apoptosis were increased by homoeopathic drugs. These data indicate that apoptosis is one of the mechanisms of tumor reduction of homeopathic drugs. A comparison of potentiated drugs with their mother tincture indicated that the potentiated drugs have biological activity similar to that of their mother tincture in spite of ultradilution.
    No preview · Article · Jul 2011 · Integrative Cancer Therapies

Publication Stats

6k Citations
408.06 Total Impact Points

Institutions

  • 2015
    • University of Calicut
      Malappuram, Kerala, India
  • 2009
    • Virginia Commonwealth University
      Ричмонд, Virginia, United States
  • 2007
    • Kerala Agricultural University
      • College of Veterinary and Animal Sciences
      Tiruvananantapuram, Kerala, India
  • 1999
    • Lions Cancer Hospital
      Vizag, Andhra Pradesh, India