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1.
Ann Clin Lab Sci ; 53(3): 353-359, 2023 May.
Article in English | MEDLINE | ID: mdl-37437941

ABSTRACT

OBJECTIVE: The SARS-CoV-2 pandemic has reached to a state where populations across the world should ad-just to live with it like many other diseases. Regular serosurveys are essential for disease surveil-lance and policy decisions. In this study, we evaluated the analytical and clinical performance of two commercially available rapid antibody assays. METHODS: SARS-CoV-2 PCR positive patients (N=104) were recruited for method evaluation study of two commercially available lateral flow Rapid IgM and IgG assays; Edinburgh Genetics ActivXpress+ COVID-19 IgG/IgM Immunoassay Complete Testing Kit (EGCV0092L) and Abchek COVID-19 IgM/IgG Antibody Rapid Test (NUL/COV-19/R&D/001). We have tested all the participants for SARS-CoV-2 with a Rapid Anti-gen Test (Abchek) on the day of sample collection. Additionally, we analyzed vaccinated people (N=187) for seroprevalence of IgG. EP Evaluator version 12 and GraphPad Prism 9.5.0 were used for statistical analysis. RESULTS: The IgG seropositivity after 10-15 days of PCR positivity was 97.11% (Edinburg Genetics Assay) and 92.30% (Abchek Assay). The Rapid Antigen test was 100% negative with IgM negativity of 93.27% (Edinburg Genetics Assay) and 98.08% (Abchek Assay). The IgG seropositivity of vaccinated participants was 89.84% using both the assays. The IgG sero-positivity was 86.82% (Edinburg Genetics Assay, N=91) and 92.71% (Abchek Assay, N=96) in the study participants with post vaccination. CONCLUSIONS: These assays are robust and scalable. Both the assays can be used for serosurveys with desired scale and speed when a quick observation is needed for surveillance. These tests are cost effective, field deployable without need of any sophis-ticated instruments and large capital. IMPACT STATEMENT: During a public health emergency like the COVID-19 pandemic, regular sero-surveys are essential for disease surveillance and swift policy decisions. However, deployment of the gold standard methods like quantitative ELISA, neutralizing antibody assays for assessment of population based seroprevalence and immune status becomes logistically difficult, costly and time consuming. The point of care antibody assays are easily scalable, affordable and field deployable. The present study demonstrates that these tests are reliable in terms of analytical and clinical performance. These assays could be used when rapid observations are to be made by including large sample population.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Pandemics , Point-of-Care Systems , Seroepidemiologic Studies , COVID-19/diagnosis , Immunoglobulin G , Immunoglobulin M
2.
Metab Brain Dis ; 38(1): 61-68, 2023 01.
Article in English | MEDLINE | ID: mdl-36149588

ABSTRACT

Glioblastoma (GB) are aggressive tumors that obstruct normal brain function. While the skull cannot expand in response to cancer growth, the growing pressure in the brain is generally the first sign. It can produce more frequent headaches, unexplained nausea or vomiting, blurred peripheral vision, double vision, a loss of feeling or movement in an arm or leg, and difficulty speaking and concentrating; all depend on the tumor's location. GB can also cause vascular thrombi, damaging endothelial cells and leading to red blood cell leakage. Latest studies have revealed the role of single nucleotide polymorphisms (SNPs) in developing and spreading cancers such as GB and breast cancer. Many discovered SNPs are associated with GB, particularly in great abundance in the promoter region, creating polygenetic vulnerability to glioma. This study aims to compile a list of some of the most frequent and significant SNPs implicated with GB formation and proliferation.


Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Humans , Glioblastoma/genetics , Glioblastoma/pathology , Endothelial Cells/pathology , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain/pathology
3.
Oxid Med Cell Longev ; 2022: 6873874, 2022.
Article in English | MEDLINE | ID: mdl-35910833

ABSTRACT

A high incidence of dementia (60-80%) and a high rate of memory loss are two of the most common symptoms of Alzheimer's disease (AD), which affects the elderly. Researchers have recommended that traditional Chinese medicine (TCM) and Indian medicines can be used to prevent and cure AD. Several studies have linked neuroinflammation linked to amyloid-ß (Aß) deposition in the brain to the pathophysiology of neurodegenerative disorders. As a result, more research is needed to determine the role of inflammation in neurodegeneration. Increased microglial activation, cytokine production, reactive oxygen species (ROS), and nuclear factor kappa B (NF-κB) all play a role in the inflammatory process of AD. This review focuses on the role of neuroinflammation in neuroprotection and the molecular processes used by diverse natural substances, phytochemicals, and herbal formulations in distinct signaling pathways. Currently, researchers are focusing on pharmacologically active natural compounds with the anti-neuroinflammatory potential, making them a possible contender for treating AD. Furthermore, the researchers investigated the limits of past studies on TCM, Indian Ayurveda, and AD. Numerous studies have been carried out to examine the effects of medicinal whole-plant extracts on AD. Clinical investigations have shown that lignans, flavonoids, tannins, polyphenols, triterpenoids, sterols, and alkaloids have anti-inflammatory, antiamyloidogenic, anticholinesterase, and antioxidant properties. This review summarizes information about numerous medicinal plants and isolated compounds used in the treatment of AD and a list of further references.


Subject(s)
Alzheimer Disease , Biological Products , Plants, Medicinal , Aged , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Biological Products/pharmacology , Biological Products/therapeutic use , Humans , Phytochemicals/therapeutic use , Plants, Medicinal/metabolism , Polyphenols/pharmacology
5.
Int Immunopharmacol ; 38: 332-41, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27344639

ABSTRACT

Diagnosis of cancer and photothermal therapy using optoelectronic properties of noble metal nanoparticles (NPs) has established a new therapeutic approach for treating cancer. Here we address the intrinsic properties of noble metal NPs (gold and silver) as well as the mechanism of their potential antitumor activity. For this, the study addresses the functional characterization of tumor associated macrophages (TAMs) isolated from murine fibrosarcoma induced by a chemical carcinogen, 3-methylcholanthrene (MCA). We have previously shown antitumor activity of both gold nanoparticles (AuNPs) and silver nanoparticle (AgNPs) in vivo in a murine fibrosarcoma model. In the present study, it has been seen that AuNPs and AgNPs modulate the reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, suppressing the antioxidant system of cells (TAMs). Moreover, the antioxidant-mimetic action of these NPs maintain the ROS and RNS levels in TAMs which act as second messengers to activate the proinflammatory signaling cascades. Thus, while there is a downregulation of tumor necrosis factor-α (TNF-α) and Interleukin-10 (IL-10) in the TAMs, the proinflammatory cytokine Interleukin-12 (IL-12) is upregulated resulting in a polarization of TAMs from M2 (anti-inflammatory) to M1 (pro-inflammatory) nature.


Subject(s)
Fibrosarcoma/immunology , Macrophages/physiology , Metal Nanoparticles/administration & dosage , Animals , Cell Differentiation , Cells, Cultured , Fibrosarcoma/chemically induced , Gold/chemistry , Interleukin-10/metabolism , Interleukin-12/metabolism , Male , Metal Nanoparticles/chemistry , Methylcholanthrene/toxicity , Mice , Oxidative Stress , Phenotype , Reactive Oxygen Species/metabolism , Silver/chemistry , Tumor Necrosis Factor-alpha/metabolism
6.
J Biomed Sci ; 23: 40, 2016 Apr 16.
Article in English | MEDLINE | ID: mdl-27084510

ABSTRACT

BACKGROUND: Breast cancer is considered as an increasing major life-threatening concern among the malignancies encountered globally in females. Traditional therapy is far from satisfactory due to drug resistance and various side effects, thus a search for complementary/alternative medicines from natural sources with lesser side effects is being emphasized. Andrographis paniculata, an oriental, traditional medicinal herb commonly available in Asian countries, has a long history of treating a variety of diseases, such as respiratory infection, fever, bacterial dysentery, diarrhea, inflammation etc. Extracts of this plant showed a wide spectrum of therapeutic effects, such as anti-bacterial, anti-malarial, anti-viral and anti-carcinogenic properties. Andrographolide, a diterpenoid lactone, is the major active component of this plant. This study reports on andrographolide induced apoptosis and its possible mechanism in highly proliferative, invasive breast cancer cells, MDA-MB-231 lacking a functional p53 and estrogen receptor (ER). Furthermore, the pharmacokinetic properties of andrographolide have also been studied in mice following intravenous and oral administration. RESULTS: Andrographolide showed a time- and concentration- dependent inhibitory effect on MDA-MB-231 breast cancer cell proliferation, but the treatment did not affect normal breast epithelial cells, MCF-10A (>80 %). The number of cells in S as well as G2/M phase was increased after 36 h of treatment. Elevated reactive oxygen species (ROS) production with concomitant decrease in Mitochondrial Membrane Potential (MMP) and externalization of phosphatidyl serine were observed. Flow cytometry with Annexin V revealed that the population of apoptotic cells increased with prolonged exposure to andrographolide. Activation of caspase-3 and caspase-9 were also noted. Bax and Apaf-1 expression were notably increased with decreased Bcl-2 and Bcl-xL expression in andrographolide-treated cells. Pharmacokinetic study with andrographolide showed the bioavailability of 9.27 ± 1.69 % with a Cmax, of 0.73 ± 0.17 µmol/L and Tmax of 0.42 ± 0.14 h following oral administration. AG showed rapid clearance and moderate terminal half lives (T1/2) of 1.86 ± 0.21 and 3.30 ± 0.35 h following IV and oral administration respectively. CONCLUSION: This investigation indicates that andrographolide might be useful as a possible chemopreventive/chemotherapeutic agent for human breast cancers.


Subject(s)
Apoptosis/drug effects , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Cell Cycle Checkpoints/drug effects , Cytotoxins/pharmacology , Diterpenes/pharmacology , Animals , Apoptosis/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Cycle Checkpoints/genetics , Female , Humans , MCF-7 Cells , Mice , Mice, Inbred BALB C
7.
BMC Cancer ; 16: 23, 2016 Jan 16.
Article in English | MEDLINE | ID: mdl-26772983

ABSTRACT

BACKGROUND: Betulinic acid (BA), a member of pentacyclic triterpenes has shown important biological activities like anti-bacterial, anti-malarial, anti-inflammatory and most interestingly anticancer property. To overcome its poor aqueous solubility and low bioavailability, structural modifications of its functional groups are made to generate novel lead(s) having better efficacy and less toxicity than the parent compound. BA analogue, 2c was found most potent inhibitor of colon cancer cell line, HT-29 cells with IC50 value 14.9 µM which is significantly lower than standard drug 5-fluorouracil as well as parent compound, Betulinic acid. We have studied another mode of PCD, autophagy which is one of the important constituent of cellular catabolic system as well as we also studied proteasomal degradation pathway to investigate whole catabolic pathway after exploration of 2c on HT-29 cells. METHODS: Mechanism of autophagic cell death was studied using fluorescent dye like acridine orange (AO) and monodansylcadaverin (MDC) staining by using fluorescence microscopy. Various autophagic protein expression levels were determined by Western Blotting, qRT-PCR and Immunostaining. Confocal Laser Scanning Microscopy (CLSM) was used to study the colocalization of various autophagic proteins. These were accompanied by formation of autophagic vacuoles as revealed by FACS and transmission electron microscopy (TEM). Proteasomal degradation pathway was studied by proteasome-Glo™ assay systems using luminometer. RESULTS: The formation of autophagic vacuoles in HT-29 cells after 2c treatment was determined by fluorescence staining--confirming the occurrence of autophagy. In addition, 2c was found to alter expression levels of different autophagic proteins like Beclin-1, Atg 5, Atg 7, Atg 5-Atg 12, LC3B and autophagic adapter protein, p62. Furthermore we found the formation of autophagolysosome by colocalization of LAMP-1 with LC3B, LC3B with Lysosome, p62 with lysosome. Finally, as proteasomal degradation pathway downregulated after 2c treatment colocalization of ubiquitin with lysosome and LC3B with p62 was studied to confirm that protein degradation in autophagy induced HT-29 cells follows autolysosomal pathway. CONCLUSIONS: In summary, betulinic acid analogue, 2c was able to induce autophagy in HT-29 cells and as proteasomal degradation pathway downregulated after 2c treatment so protein degradation in autophagy induced HT-29 cells follows autolysosomal pathway.


Subject(s)
Autophagy/drug effects , Colonic Neoplasms/drug therapy , Proteasome Endopeptidase Complex/drug effects , Triterpenes/administration & dosage , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , HT29 Cells , Humans , Neoplasm Proteins/biosynthesis , Pentacyclic Triterpenes , Proteasome Endopeptidase Complex/genetics , Proteolysis/drug effects , Signal Transduction/drug effects , Triterpenes/chemistry , Vacuoles/drug effects , Vacuoles/pathology , Betulinic Acid
8.
Cell Mol Immunol ; 13(2): 191-205, 2016 Mar.
Article in English | MEDLINE | ID: mdl-25938978

ABSTRACT

The use of nanotechnology in nanoparticle-based cancer therapeutics is gaining impetus due to the unique biophysical properties of nanoparticles at the quantum level. Silver nanoparticles (AgNPs) have been reported as one type of potent therapeutic nanoparticles. The present study is aimed to determine the effect of AgNPs in arresting the growth of a murine fibrosarcoma by a reductive mechanism. Initially, a bioavailability study showed that mouse serum albumin (MSA)-coated AgNPs have enhanced uptake; therefore, toxicity studies of AgNP-MSA at 10 different doses (1-10 mg/kg b.w.) were performed in LACA mice by measuring the complete blood count, lipid profile and histological parameters. The complete blood count, lipid profile and histological parameter results showed that the doses from 2 to 8 mg (IC50: 6.15 mg/kg b.w.) sequentially increased the count of leukocytes, lymphocytes and granulocytes, whereas the 9- and 10-mg doses showed conclusive toxicity. In an antitumor study, the incidence and size of fibrosarcoma were reduced or delayed when murine fibrosarcoma groups were treated by AgNP-MSA. Transmission electron micrographs showed that considerable uptake of AgNP-MSA by the sentinel immune cells associated with tumor tissue and a morphologically buckled structure of the immune cells containing AgNP-MSA. Because the toxicity studies revealed a relationship between AgNPs and immune function, the protumorigenic cytokines TNF-α, IL-6 and IL-1ß were also assayed in AgNP-MSA-treated and non-treated fibrosarcoma groups, and these cytokines were found to be downregulated after treatment with AgNP-MSA.


Subject(s)
Cytokines/immunology , Fibrosarcoma/immunology , Immunologic Factors/pharmacology , Metal Nanoparticles/chemistry , Silver/pharmacokinetics , Animals , Fibrosarcoma/therapy , Immunologic Factors/chemistry , Mice , Silver/chemistry
9.
Eur J Med Chem ; 102: 93-105, 2015 Sep 18.
Article in English | MEDLINE | ID: mdl-26248310

ABSTRACT

A novel family of betulinic acid analogues, carrying a triazole unit at C-3 attached through a linker, was synthesized by the application of azide-alkyne "Click reaction". These were screened for their anticancer activity against different cancer cells and normal human PBMC by MTT assay. Compound 2c [(3S)-3-{2-(4-(hydroxymethyl-1H-1,2,3-triazol-1-yl)acetyloxy}-lup-20(29)-en-28-oic acid] was found as the most potent inhibitor of cell line HT-29 with IC50 value 14.9 µM. Its role as an inducer of apoptosis was investigated in this cell line by Annexin-V/PI binding assay and by following its capability for ROS generation, depolarization of mitochondrial transmembrane potential, activation of caspases, PARP cleavage, nuclear degradation and expression of pro- and anti-apoptotic proteins. It exhibited much higher cytotoxicity than the standard drug 5-fluorouracil but showed negligible cytotoxicity towards normal PBMC. Elevated level of ROS generation, activation of caspase 3 and caspase 9, DNA fragmentation, higher expression of Bax and Bad, lower expression of Bcl2 and Bcl-xl, and increased level of Bax/Bcl-xl ratio identified 2c as a promising inducer of apoptosis that follows a mitochondria dependent pathway. Bio-physical studies indicate that compound 2c acts as a minor groove binder to the DNA.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Triterpenes/chemistry , Triterpenes/pharmacology , Antineoplastic Agents/chemistry , Cell Line , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HT29 Cells , Humans , Molecular Structure , Pentacyclic Triterpenes , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Betulinic Acid
10.
Eur J Med Chem ; 97: 214-24, 2015 Jun 05.
Article in English | MEDLINE | ID: mdl-25982330

ABSTRACT

A novel water soluble five coordinate oxovanadium(IV) complex, [VO(C16H15N4O8S)HSO4] incorporating cefuroxime, a cephalosporin group of antibiotic have been prepared from an interaction of vanadyl sulfate and cefuroxime in aqueous solution. The compound was characterized by Fourier transform infrared spectroscopy (FTIR), CHN microanalyses, ultraviolet-visible spectroscopy (UV-Vis), fast atom bombardment (FAB) mass spectrometry and thermogravimetric analysis (TGA). Density Functional Theory (DFT) computation using Gaussian 09 program at B3LYP level revealed a distorted square pyramidal energy optimized geometry for the vanadyl(IV) complex. The molecular docking studies show that the interaction between the vanadium complex and protein receptor, clathrin is dominated by hydrophobic forces. The experimental (1)H nuclear magnetic resonance (NMR) features of the analogous Zn(II) complex matched well with the theoretically computed values further affirming the distorted square pyramidal geometry for the vanadyl(IV) complex. Cyclic voltammetry revealed a metal centered single-electron oxidation-reduction response for VO(IV)/VO(V) couple. The antioxidant activity of the vanadium(IV)-complex vis-à-vis the antibiotic has been assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. The vanadium complex showed comparatively better radical scavenging ability compared to the antibiotic cefuroxime. The antimicrobial activity of the compound has been assayed for five different microbial strains using minimum inhibitory concentration (MIC) method. Immunomodulatory studies carried out using phagocytosis index, myeloperoxidase release and cytokine assay indicated the vanadium(IV)-complex to be immunosuppressant. The cytotoxicity of the compound was evaluated by MTT (3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) reduction assay.


Subject(s)
Anti-Bacterial Agents/chemistry , Coordination Complexes/chemistry , Molecular Docking Simulation , Vanadium Compounds/chemistry , Water/chemistry , Animals , Anti-Bacterial Agents/pharmacology , Cefuroxime/chemistry , Cefuroxime/pharmacology , Cell Survival/drug effects , Coordination Complexes/chemical synthesis , Hydrophobic and Hydrophilic Interactions , Immunomodulation , Macrophages/drug effects , Mice , Microbial Sensitivity Tests , Molecular Structure , Solubility , Spectroscopy, Fourier Transform Infrared
11.
Asian Pac J Trop Med ; 7S1: S435-41, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25312164

ABSTRACT

OBJECTIVE: To investigate the antibacterial effect of Curcuma longa (C. longa), Zingiber officinale (Z. officinale) and Tinospora cordifolia (T. cordifolia) against Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Bacillus subtilis and Proteus mirabilis of clinical origin. METHODS: The antimicrobial efficacy of said medicinal plants and establishment of multidrug resistant character of these bacteria were carried out using disc diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods. RESULTS: The results of MIC and MBC showed that these clinical bacterial isolates were phenotypically multidrug resistant against standard antibiotics (>500 µg/mL). Compared to standard antibiotics, C. longa, Z. officinale and T. cordifolia were more effective in killing these microbes as evident from MIC and MBC values (5 to 125 µg/mL). Moreover, C. longa had highest antibacterial efficacy compared to Z. officinale and T. cordifolia. CONCLUSIONS: The result thus obtained suggests that bioactive principles of these plants can be used particularly against these multidrug resistant bacteria of clinical origin.

12.
Eur J Med Chem ; 85: 95-106, 2014 Oct 06.
Article in English | MEDLINE | ID: mdl-25078313

ABSTRACT

A new family of andrographolide analogues were synthesized and screened in vitro against kidney (HEK-293) and breast (MCF-7) cancer cells. The anti-cancer effects of the active analogues (2b, 2c and 4c) were determined by multiple cell based assays such as MTT, immunostaining, FACS, western blotting and transcriptional inhibition of NF-κB activity. Importantly, these compounds were found to possess higher anti-cancer potency than andrographolide and low toxicity to normal (VERO and MCF-10A) cells. Increased level of Bax/Bcl-xL ratio, caspase 3, and sub G1 population, higher expression level of tumor suppressor protein p53 and lower expression level of NF-κB suggested potent apoptotic property of the active analogues. Data revealed that the andrographolide derivative-mediated cell death in cancer cells was p53 dependent.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Diterpenes/chemical synthesis , Diterpenes/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Caspase 3/metabolism , Cell Line, Tumor , Chemistry Techniques, Synthetic , Diterpenes/chemistry , Diterpenes/metabolism , Glutathione/metabolism , Half-Life , Humans , Hydrolysis , NF-kappa B/metabolism , Transcription, Genetic/drug effects
13.
PLoS One ; 8(8): e71672, 2013.
Article in English | MEDLINE | ID: mdl-23967233

ABSTRACT

BACKGROUND: Identification of cytotoxic compounds that induce apoptosis has been the mainstay of anti-cancer therapeutics for several decades. In recent years, focus has shifted to inducing multiple modes of cell death coupled with reduced systemic toxicity. The plant Sesbania grandiflora is widely used in Indian traditional medicine for the treatment of a broad spectrum of diseases. This encouraged us to investigate into the anti-proliferative effect of a fraction (F2) isolated from S. grandiflora flowers in cancer cells and delineate the underlying involvement of apoptotic and autophagic pathways. PRINCIPAL FINDINGS: Using MTT based cell viability assay, we evaluated the cytotoxic potential of fraction F2. It was the most effective on U937 cells (IC50∶18.6 µg/ml). Inhibition of growth involved enhancement of Annexin V positivity. This was associated with elevated reactive oxygen species generation, measured by flow cytometry and reduced oxygen consumption - both effects being abrogated by anti-oxidant NAC. This caused stimulation of pro-apoptotic proteins and concomitant inhibition of anti-apoptotic protein expressions inducing mitochondrial depolarization, as measured by flow cytometry and release of cytochrome c. Interestingly, even with these molecular features of apoptosis, F2 was able to alter Atg protein levels and induce LC3 processing. This was accompanied by formation of autophagic vacuoles as revealed by fluorescence and transmission electron microscopy - confirming the occurrence of autophagy. Eventually, F2 triggered caspase cascade - executioners of programmed cell death and AIF translocation to nuclei. This culminated in cleavage of the DNA repair enzyme, poly (ADP-ribose) polymerase that caused DNA damage as proved by staining with Hoechst 33258 leading to cell death. CONCLUSIONS: The findings suggest fraction F2 triggers pro-oxidant activity and mediates its cytotoxicity in leukemic cells via apoptosis and autophagy. Thus, it merits consideration and further investigation as a therapeutic option for the treatment of leukemia.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Autophagy/drug effects , Flowers/chemistry , Plant Extracts/pharmacology , Sesbania/chemistry , Antineoplastic Agents, Phytogenic/toxicity , Caspases/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Chemical Fractionation , Dose-Response Relationship, Drug , Humans , Leukemia/metabolism , Microtubule-Associated Proteins/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Oxygen Consumption/drug effects , Plant Extracts/toxicity , Reactive Oxygen Species/metabolism , U937 Cells
14.
Cell Immunol ; 280(1): 92-100, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23295981

ABSTRACT

The present investigation was intended to study the immunostimulant properties of Curcuma longa (turmeric) and Zingiber officinale (ginger) rhizomes on splenic macrophages in carbon tetrachloride intoxicated male albino mice. The study was based on functional parameters like morphology, cell adhesion, phagocytosis, myeloperoxidase release, nitric oxide release and intracellular killing capacity of splenic macrophages. To elucidate the detailed mechanism of boosting of these cell functions, serum levels of TNF-α, and IFN-γ were quantified in different experimental mice groups. Carbon tetrachloride (CCl(4)) intoxication (0.5ml/kg body weight intraperitoneally) was found to affect the functional status of splenic macrophages as evident from these studies. Moreover, CCl(4) intoxicated mice also showed lower levels of cytokines TNF-α and IFN-γ. However, oral administration (singly) of polar fractions of C. longa (50mg/kg b.wt) and Z. officinale (120mg/kg b.wt) rhizomes ameliorated the affects of CCl(4), as evident from an increased functional status as well as the serum levels of these cytokines. Based on this study it can be suggested that, polar fractions of C. longa and Z. officinale rhizomes boost the immune system by altering the cytokine milieu of the immunosuppressed macrophages, thus modulating their functional status. Therefore, it can be inferred that dietary intake of C. longa and Z. officinale potentiates the non-specific host defenses against opportunistic infections.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Curcuma/chemistry , Phytotherapy , Plant Extracts/therapeutic use , Zingiber officinale/chemistry , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/pharmacology , Administration, Oral , Animals , Bacteriolysis , Carbon Tetrachloride Poisoning/immunology , Cell Adhesion/drug effects , Cell Differentiation/drug effects , Cells, Cultured/drug effects , Dose-Response Relationship, Immunologic , Drug Evaluation, Preclinical , Immunocompromised Host , Interferon-gamma/blood , Macrophages/immunology , Macrophages/metabolism , Macrophages/microbiology , Macrophages/ultrastructure , Male , Mice , Neutrophil Activation/drug effects , Nitric Oxide/metabolism , Phagocytosis/drug effects , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Plant Roots/chemistry , Respiratory Burst/drug effects , Spleen/pathology , Staphylococcus aureus , Tumor Necrosis Factor-alpha/analysis
15.
BMC Complement Altern Med ; 11: 102, 2011 Oct 28.
Article in English | MEDLINE | ID: mdl-22035196

ABSTRACT

BACKGROUND: The current practice of ingesting phytochemicals for supporting the immune system or fighting infections is based on centuries-old tradition. Macrophages are involved at all the stages of an immune response. The present study focuses on the immunostimulant properties of Tinospora cordifolia extract that are exerted on circulating macrophages isolated from CCl(4) (0.5 ml/kg body weight) intoxicated male albino mice. METHODS: Apart from damaging the liver system, carbon tetrachloride also inhibits macrophage functions thus, creating an immunocompromised state, as is evident from the present study. Such cell functions include cell morphology, adhesion property, phagocytosis, enzyme release (myeloperoxidase or MPO), nitric oxide (NO) release, intracellular survival of ingested bacteria and DNA fragmentation in peritoneal macrophages isolated from these immunocompromised mice. T. cordifolia extract was tested for acute toxicity at the given dose (150 mg/kg body weight) by lactate dehydrogenase (LDH) assay. RESULTS: The number of morphologically altered macrophages was increased in mice exposed to CCl(4). Administration of CCl(4) (i.p.) also reduced the phagocytosis, cell adhesion, MPO release, NO release properties of circulating macrophages of mice. The DNA fragmentation of peritoneal macrophages was observed to be higher in CCl(4) intoxicated mice. The bacterial killing capacity of peritoneal macrophages was also adversely affected by CCl(4). However oral administration of aqueous fraction of Tinospora cordifolia stem parts at a dose of 40 mg/kg body weight (in vivo) in CCl(4) exposed mice ameliorated the effect of CCl(4), as the percentage of morphologically altered macrophages, phagocytosis activity, cell adhesion, MPO release, NO release, DNA fragmentation and intracellular killing capacity of CCl(4) intoxicated peritoneal macrophages came closer to those of the control group. No acute toxicity was identified in oral administration of the aqueous extract of Tinospora cordifolia at a dose of 150 mg/kg body weight. CONCLUSION: From our findings it can be suggested that, polar fractions of Tinospora cordifolia stem parts contain major bioactive compounds, which directly act on peritoneal macrophages and have been found to boost the non-specific host defenses of the immune system. However, the molecular mechanism of this activity of Tinospora cordifolia on immune functions needs to be elucidated.


Subject(s)
Carbon Tetrachloride/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , Immunologic Factors/administration & dosage , Macrophages, Peritoneal/immunology , Plant Extracts/administration & dosage , Tinospora/chemistry , Animals , Cell Adhesion/drug effects , Cells, Cultured , Chemical and Drug Induced Liver Injury/immunology , Chemical and Drug Induced Liver Injury/physiopathology , Disease Models, Animal , Humans , Macrophages, Peritoneal/drug effects , Male , Mice , Phagocytosis/drug effects , Plant Stems/chemistry
16.
Org Biomol Chem ; 9(16): 5856-62, 2011 Aug 21.
Article in English | MEDLINE | ID: mdl-21743898

ABSTRACT

We report a general and facile method that provides rapid entry into 3-aryl substituted 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyrazines and their ring fused analogues in one-pot under palladium-copper catalysis. The methodology utilises simple and easily available substrates of broad range. The applicability of this reaction for the synthesis of optically active products has been demonstrated. A plausible reaction mechanism has also been proposed.


Subject(s)
Combinatorial Chemistry Techniques/methods , Pyrazines/chemical synthesis , Triazoles/chemical synthesis , Catalysis , Combinatorial Chemistry Techniques/economics , Copper/chemistry , Crystallography, X-Ray , Models, Molecular , Palladium/chemistry , Pyrazines/chemistry , Time Factors , Triazoles/chemistry
17.
Asian Pac J Trop Biomed ; 1(3): 193-9, 2011 Jun.
Article in English | MEDLINE | ID: mdl-23569758

ABSTRACT

OBJECTIVE: To evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl4 intoxicated Swiss albino mice. METHODS: First group of mice (n=5) received CCl4 treatment at a dose of 0.5 mL/kg bw (i.p.) for 7 days. Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for 15 days. The third group was given both the turmeric extract (for 15 days, orally) and CCl4 (for last 7 days, i.p.). The fourth group was kept as a control. To study the liver function, the transaminase enzymes (SGOT and SGPT) and bilirubin level were measured in the serum of respective groups. For assaying the immunotherapeutic action of Curcuma longa (C. longa), non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages were studied from the respective groups. RESULTS: The result of present study suggested that CCl4 administration increased the level of SGOT and SGPT and bilirubin level in serum. However, the aqueous extract of turmeric reduced the level of SGOT, SGPT and bilirubin in CCl4 intoxicated mice. Apart from damaging the liver system, CCl4 also reduced non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages. Administration of aqueous extract of C. longa offered significant protection from these damaging actions of CCl4 on the non specific host response in the peritoneal macrophages of CCl4 intoxicated mice. CONCLUSIONS: In conclusion, the present study suggests that C. longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity.


Subject(s)
Curcuma/chemistry , Immunologic Factors/pharmacology , Liver/drug effects , Plant Extracts/pharmacology , Protective Agents/pharmacology , Animals , Aspartate Aminotransferases/blood , Bilirubin/blood , Carbon Tetrachloride/toxicity , Cell Adhesion/drug effects , Cell Adhesion/immunology , Cytotoxicity, Immunologic/drug effects , Liver/metabolism , Liver/pathology , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Macrophages, Peritoneal/pathology , Male , Mice , Nitric Oxide/metabolism , Peroxidase/metabolism
18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-672853

ABSTRACT

Objective: To evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl4 intoxicated Swiss albino mice. Methods: First group of mice (n=5) received CCl4 treatment at a dose of 0.5 mL/kg bw (i.p.) for 7 days. Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for 15 days. The third group was given both the turmeric extract (for 15 days, orally) and CCl4 (for last 7 days, i.p.). The fourth group was kept as a control. To study the liver function, the transaminase enzymes (SGOT and SGPT) and bilirubin level were measured in the serum of respective groups. For assaying the immunotherapeutic action of Curcuma longa (C. longa), non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages were studied from the respective groups. Results: The result of present study suggested that CCl4 administration increased the level of SGOT and SGPT and bilirubin level in serum. However, the aqueous extract of turmeric reduced the level of SGOT, SGPT and bilirubin in CCl4 intoxicated mice. Apart from damaging the liver system, CCl4 also reduced non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages. Administration of aqueous extract of C. longa offered significant protection from these damaging actions of CCl4 on the non specific host response in the peritoneal macrophages of CCl4 intoxicated mice. Conclusions: In conclusion, the present study suggests that C. longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity.

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