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Antidiarrheal effect of fractions from stem bark of Thespesia populnea in rodents:Possible antimotility and antisecretory mechanisms

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Asian Pacific Journal of Tropical Medicine 2011年第6期4卷 451-456页

作者： Gollapalle Lakshminaraya Shastry Viswanatha Shylaja Hanumanthappa nandakumar Krishnadas Srinath rangappa Department of Pharmacology PES College of PharmacyBangalore-560050 Department of Pharmacognosy PES College of PharmacyBangalore-560050 Department of Pharmacology Manipal College of Pharmaceutical sciencesManipal-576104

Objective:To evaluate antidiarrheal activity of the fractions of aqueous extract from stem barks of Thespesia populnea(Malvaceae).Methods:From the aqueous extract three fractions namely ethyl acetate fraction(EAF),methanolic fraction(MF) and residue fraction(rF) were made and stuthed for antidiarrheal *** activity of the fractions were evaluated in castor oil induced diarrhea,prostaglandin E_2(PG-E_2) induced diarrhea and charcoal meal test as in vivo models and the most potent fraction was further evaluated with in vitro models to determine the possible antimotility ***:In castor oil induced diarrhea model,the rF(10,25,50 and 100 mg/kg,po.) and MF(100 mg/kg,po.) has significantly reduced the cumulative wet faecal mass,where as the EAF have not shown any significant antidiarrheal activity,rF was found to be more potent than *** on these results and percentage yield,only rF was evaluated in PGE_2 induced enteropooling and charcoal meal ***(10,25 and 50 mg/kg) had shown significant inhibition of PG-E_2 induced secretions(antisecretory) and decreased the movement of charcoal in charcoal meal test indicating its antimotility ***,rF has showed significant inhibition of acetylcholine,histamine and BaCl_2 induced contractions on rat colon,guinea pig ileum and rabbit jejunum with EC_(50) values of 241.7,303.1 and 286.1μg/mL,respectively indicating the antimotility effect of *** phytochemical analysis of rF showed presence of gums and mucilages and the possible mechanism may be the combination inhibition of elevated prostaglandin biosynthesis and reduced propulsive movement of the ***: rF possesses good antidiarrheal activity comparing with other two fractions and the possible mechanism thought to be associated with combination of antisecretory and antimolity.

关键词： Antidiarrheal activity Castor oil Charcoal meal test Prostaglandin E_2 Thespesia populnea

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Cellulose nanocomposites:Fabrication and biomedical applications

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Journal of Bioresources and Bioproducts 2020年第4期5卷 223-237页

作者： Blessy Joseph Sagarika V K Chinnu Sabu nandakumar Kalarikkal Sabu Thomas International and Inter University Centre for Nanoscience and Nanotechnology Mahatma Gandhi UniversityKottayam-686560KeralaIndia Indian Institute of Science Education and research TirupatiMangalamTirupati-517507Andhra PradeshIndia College of Pharmaceutical Sciences Government Medical CollegeKozhikode-673008KeralaIndia School of Energy Materials Mahatma Gandhi UniversityKottayam-686560KeralaIndia

Cellulose is a linear biopolymer which is composed of nanofibrils,thus having a large surface *** low-cost,low-density,high-specific-surface-area,easily processable polymer is found in nature in the form of plants,bacteria and *** has outstanding characteristics including low cytotoxicity,biocompatibility,good mechanical properties,high chemical stability,and cost effectiveness which make them suitable candidates for biomedical *** ma-nipulation of cellulose at nanoscale resulted in nanocellulose having exceptional physicochem-ical ***,cellulose nanocomposite is a fascinating area of research which has applications in biomedical fields like wound healing,bone tissue engineering,three dimensional printing,drug carriers,medical implants *** review is mainly focused on the developments in the generation of cellulose nanocomposites and their potential applications in the biomedical field.

关键词： Nanocellulose Mechanical property Tissue engineering Surface modification

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Oxidative stress-induced mitochondrial dysfunction in a normal colon epithelial cell line

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World Journal of Gastroenterology 2017年第19期23卷 3427-3439页

作者： nandakumar Packiriswamy Kari F Coulson Susan J Holcombe Lorraine M Sordillo Department of Large Animal Clinical Sciences College of Veterinary Medicine Michigan State University

AIM To determine how a normal human colon cell line reacts to microbial challenge as a way to study oxidative stress-induced responses associated with inflammatory bowel *** Normal human colon epithelial cells(ATCC?CrL.1790?)were stimulated with either heat killed *** or heat killed murine cecal contents(HKC)and examined for several relevant biomarkers associated with inflammation and oxidative stress including cytokine production,mitochondrial autophagy and oxidant ***α,IL-1βand IL-8 protein concentrations were measured within the *** microscopy was performed to quantify the production of reactive oxygen species(rOS)using an oxidation responsive fluorogenic *** morphology and mitochondrial membrane potential was assessed by dual staining using COXIV antibody and a dye concentrating in active *** rOS scavenger was used to determine the source of rOS in stimulated *** was detected by staining for the presence of autophagic *** controls for autophagy and rOS/rNS experiments were treated with rapamycin and *** morphology,rOS production and autophagy microscopy experiments were analyzed using a custom acquisition and analysis microscopy software(Image J).rESULTS Exposing CrL.1790 cells to microbial challenge stimulated cells to produce several relevant biomarkers associated with inflammation and oxidative *** killed cecal contents treatment induced a 10-12fold increase in IL-8 production by CrL.1790 cells compared to unstimulated controls at 6 and 12 h(Presulted in a4-5 fold increase in IL-8 compared to the unstimulated control cells at each time point(Probust rOS production at 6(Prial morphologic abnormalities were detected at 6 and12 h based on reduced mitochondrial circularity and decreased mitochondrial membr

关键词： Colon cancer cell line CrL.1790 cells Inflammation Mitochondria Microbial stimulation Interleukin-8 Autophagy

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Comparison of three different recombinant hepatitis B vaccines:GeneVac-B,Engerix B and Shanvac B in high risk infants born to HBsAg positive mothers in India

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World Journal of Gastroenterology 2007年第22期13卷 3084-3089页

作者： Vijayakumar Velu Subhadra nandakumar Saravanan Shanmugam Suresh Sakharam Jadhav Prasad Suryakant Kulkarni Sadras Panchatcharam Thyagarajan Department of Medical Microbiology Dr ALM PGIBMS University of Madras Chennai 600113 and National referral Centre for viral hepatitis India Vaccine Research Centre Department of Microbiology and Immunology Emory University Atlanta Georgia 30329 United States Department of Medical Microbiology Dr ALM PGIBMS University of Madras Chennai 600113 and National referral Centre for viral hepatitis India Department of Medical Microbiology Dr ALM PGIBMS University of Madras Chennai 600113 and National referral Centre for viral hepatitis India YRG Centre for AIDS Research and Education VHS campus Taramani Chennai 600113 India Serum Institute of India Ltd Pune India

AIM： To evaluate a low cost Indian recombinant hepatitis B vaccine GeneVac-B for its immunogenicity and safety in comparison to Engerix B and Shanvac B vaccine in high risk newborn infants born to （hepatitis B surface antigen） HBsAg positive mothers.METHODS： A total of 158 infants were enrolled in the study. Fifty eight infants were enrolled in the GeneVac-B group while 50 each were included for Engerix B and Shanvac B groups. A three-dose regimen of vaccination; at birth （within 24 h of birth）, 1st mo and 6 too. were adopted with 10 μg dosage administered uniformly in all the three groups. Clinical and immunological parameters were assessed for safety and immunogenicity of the vaccines, in all the enrolled infants.rESULTS： Successful follow up until seven months of age was achieved in 83% （48/58） for GeneVac-B, 76% （38/50） and 64% （32/50） for Engerix B and Shanvac B groups respectively. 100% seroconversion and seroprotection was achieved in all the three groups of infants. The geometric mean titers of anti-HBs one month after the completion of three dose of vaccination were 90.5, 80.9 and 72.5 mTU/mL in GeneVac-B, Engerix B and Shanvac B vaccine group respectively. Furthermore the level of anti-HBs increases with age of babies who were born to HBsAg positive mothers. The GMT values of anti-HBs were 226.7, 193.9 and 173.6 mIU/mL respectively in GeneVac-B, Engerix B and Shanvac B groups one year after the completion of the three doses of vaccine. No systemic reactions were reported in infants during the entire vaccination process of GeneVac-B and the other two vaccines. Clinical safety parameters remained within the normal limits throughout the study period.CONCLUSION： The study concludes that there is no significant difference between the three recombinant hepatitis B vaccines. Administration of these vaccines within 24 h of birth to babies, born to HBsAg positive mothers will reduce the incidence of HBV infection.

关键词： GeneVac-B Maternal screening High riskinfants Infant vaccination

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Electrospun poly（vinylidene fluoride-trifluoroethylene）/ zinc oxide nanocomposite tissue engineering scaffolds with enhanced cell adhesion and blood vessel formation

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Nano research 2017年第10期10卷 3358-3376页

作者： robin Augustine Pan Dan Alejandro Sosnik nandakumar Kalarikkal Nguyen Tran Brice Vincent Sabu Thomas Patrick Menu Didier rouxel Laboratory of Pharmaceutical Nanomaterials Science Department of Materials Science and Engineering Technion-lsrael Institute of Technology De-Jur Building Technion City Haifa 3200003 Israel Intemationaland Inter University Centre for Nanoscience and Nanotechnology Mahatma Gandhi University Kottayam Kerala 686560 India Ingenierie Moleculaire et Physiopathologie Articulaire UMR 7365 CNRS-Universite de Lorraine Vandoeuvre-Ies Nancy F-54500 France School of Pure and Applied Physics Mahatma Gandhi University Kottayam Kerala 686560 India School of Surgery Faculty of Medicine Universite de Lorraine Vandoeuvre-Ies-Nancy F-54500 France Institut Jean Lamour UMR 7198 CNRS-Universite de Lorraine Vandoeuvre-Ies-Nancy F-54500 France School of Chemical Sciences Mahatma Gandhi University Kottayam Kerala 686560 India

Piezoelectric materials that generate electrical signals in response to mechanical strain can be used in tissue engineering to stimulate cell proliferation. Poly （vinylidene fluoride-trifluoroethylene）（P（VDF-TrFE））, a piezoelectric polymer, is widely used in biomaterial applications. We hypothesized that incorporation of zinc oxide （ZnO） nanoparticles into the P（VDF-TrFE） matrix could promote adhesion, migration, and proliferation of cells, as well as blood vessel formation （angiogenesis）. In this study, we fabricated and comprehensively characterized a novel electrospun P（VDF-TrFE）/ZnO nanocomposite tissue engineering scaffold. We analyzed the morphological features of the polymeric matrix by scanning electron microscopy, and utilized Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry to examine changes in the crystalline phases of the copolymer due to addition of the nanoparticles. We detected no or minimal adverse effects of the biomaterials with regard to blood compatibility in vitro, biocompatibility, and cytotoxicity, indicating that P（VDF-TrFE）/ZnO nanocomposite scaffolds are suitable for tissue engineering applications. Interestingly, human mesenchymal stem cells （hMSCs） and human umbilical vein endothelial cells cultured on the nanocomposite scaffolds exhibited higher cell viability, adhesion, and proliferation compared to cells cultured on tissue culture plates or neat P（VDF-TrFE） scaffolds. Nanocomposite scaffolds implanted into rats with or without hMSCs did not elicit immunological responses, as assessed by macroscopic analysis and histology. Importantly, nanocomposite scaffolds promoted angiogenesis, which was increased in scaffolds pre-seeded with hMSCs. Overall, our results highlight the potential of these novel P（VDF-TrFE）/ZnO nanocomposites for use in tissue engineering, due to their biocompatibility and ability to promote cell adhesion and angiogenesis.

关键词： scaffolds electrospinning poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) ZnO angiogenesis cell adhesion stem cells

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Antioxidant and antimutagenic activities of bark extract of Terminalia arjuna

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Asian Pacific Journal of Tropical Medicine 2010年第12期3卷 965-970页

作者： Gollapalle Lakshminarayana shastry Viswanatha Santosh Kumar Vaidya ramesh C nandakumar Krishnadas Srinath rangappa Department of Pharmacology PES College of PharmacyBangalore-560050 India Department of Pharmacology St.John's College of PharmacyBangalore-560040 India Department of Pharmacology Manipal College of Pharmaceutical SciencesManipal-576104 India

Objective:The alcoholic extract of stem bark of Terminalia arjuna（ALTA） was screened for antioxidant and antimutagenic（anticlastogenic） ***:Antioxidant property was determined by l,l,Diphynyl,2-Picryl hydrazyl（DPPH） assay,super oxide radical scavenging activity,lipid peroxidation assay and total polyphenolic content was determined by Folin-Ciocalteau’s *** activity was evaluated using micronucleus test in mice. results:The ALTA has shown potent antioxidant activity with EC50 of 2.491±0.160,50.110±0.150 & 71.000±0.250 in DPPH assay,superoxide radical scavenging activity and lipid peroxidation assay, which is comparable with ascorbic acid with EC50 of 2.471±0.140,40.500±0.390 and 63.000±0.360 *** micronucleus test,ALTA（100 & 200 mg/kg,p.o.） showed significant reduction in percentage of micronucleus in both polychromatic erythrocytes（PCE） and normochromatie erythrocytes（NCE） and also shown significant reduction in P/N ***:These results suggested that ALTA possess significant antioxidant and antimutagenic activity.

关键词： Terminalia arjuna Antioxidant activity Antimutagenic activity Micronuclease test

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Multi-layer 3D chirality:new synthesis,AIE and computational studies

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Science China Chemistry 2020年第5期63卷 692-698页

作者： Yangxue Liu Guanzhao Wu Zhen Yang Hossein rouh nandakumar Katakam Sultan Ahmed Daniel Unruh Zhonghua Cui Hans Lischka Guigen Li Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTexas 79409USA Institute of Chemistry and Biomedical Sciences School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210093China Institute of Atomic and Molecular Physics Jilin UniversityChangchun 130021China School of Pharmaceutical Sciences and Technology Tianjin UniversityTianjin 300072China Beijing National Laboratory for Molecular Sciences Beijing 100190China

New synthesis of multi-layer 3 D chiral molecules has been developed under novel conditions to give better *** aggregation-induced emission(AIE),UV irradiation/excitation,charge transfer(CT)and local excited(LE)ππ*transitions have been investigated on a representative individual enantiomer of pseudo C_2 asymmetry which was made possibly by differentiating moieties on phosphorous on N-phosphonyl ring of chiral sandwich ***,a new tandem C–N/C–C coupling reaction was unexpectedly rendered providing a novel access to special benzo[a]carbazoles.

关键词： multi-layer 3D chirality organo sandwich chirality architecture chirality aggregation-induced emission(AIE) charge transfer(CT)

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New therapeutic strategies targeting D1-type dopamine receptors for neuropsychiatric disease

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Frontiers in Biology 2015年第3期10卷 230-238页

作者： Young-Cho Kim Stephanie L. Alberico Eric Emmons nandakumar S. Narayanan Department of Neurology University of Iowa Iowa City IA 52242 USA Aging Mind and Brain Initiative Carver College of Medicine University of Iowa Iowa City IA 52242 USA

The neurotransmitter dopamine acts via two major classes of receptors, Dl-type and D2-type. D1 receptors are highly expressed in the striatum and can also be found in the cerebral cortex. Here we review the role of D1 dopamine signaling in two major domains： L-DOPA-induced dyskinesias in Parkinson＇s disease and cognition in neuropsychiatric disorders. While there are many drugs targeting D2-type receptors, there are no drugs that specifically target D1 receptors. It has been difficult to use selective Dl-receptor agonists for clinical applications due to issues with bioavailability, binding affinity, pharmacological kinetics, and side effects. We propose potential therapies that selectively modulate D1 dopamine signaling by targeting second messengers downstream of D1 receptors, aUosteric modulators, or by making targeted modifications to Dl-receptor machinery. The development of therapies specific to Dl-receptor signaling could be a new frontier in the treatment of neurological and psychiatric disorders.

关键词： D1Dr dopamine D1 receptor dyskinesia cognition

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Coinfection of hepatitis B and hepatitis C virus in HIV-infectedpatients in south India

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World Journal of Gastroenterology 2007年第37期13卷 5015-5020页

作者： Shanmugam Saravanan Vijayakumar Velu Nagalingeswaran Kumarasamy Subhadra nandakumar Kailapuri Gangatharan Murugavel Pachamuthu Balakrishnan Solomon Suniti Sadras Panchatcharam Thyagarajan Department of Microbiology Dr ALM PGIBMS University of Madras Chennai 600 113 and National Referral Centre for Viral Hepatitis India YRG Centre for AIDS Research and Education VHS campus Taramani Chennai 600 113 India Department of Microbiology Dr ALM PGIBMS University of Madras Chennai 600 113 and National Referral Centre for Viral Hepatitis India YrG Centre for AIDS research and Education VHS campus Taramani Chennai 600 113 India Department of Microbiology Dr ALM PGIBMS University of Madras Chennai 600 113 and National Referral Centre for Viral Hepatitis IndiaYRG Centre for AIDS Research and Education VHS campus Taramani Chennai 600 113 India

AIM: To screen for the co-infection of hepatitis B (HBV) and hepatitis C virus (HCV) in human immunodeficiency virus (HIV) infected patients in southern India. METHODS: Five hundred consecutive HIV infected patients were screened for Hepatitis B Virus (HBsAg and HBV-DNA) and Hepatitis C virus (anti-HCV and HCV-rNA) using commercially available ELISA kits; HBsAg, HBeAg/ anti-HBe (Biorad laboratories, USA) and anti-HCV (Murex Diagnostics, UK). The HBV-DNA PCr was performed to detect the surface antigen region (pre S-S). HCV-rNA was detected by rT-PCr for the detection of the constant 5' putative non-coding region of HCV. rESULTS: HBV co-infection was detected in 45/500 (9%) patients and HCV co-infection in 11/500 (2.2%) subjects. Among the 45 co-infected patients only 40 patients could be studied, where the detection rates of HBe was 55% (22/40), antiHBe was 45% (18/40) and HBV-DNA was 56% (23/40). Among 11 HCV co-infected subjects, 6 (54.5%) were anti-HCV and HCV rNA positive, while 3 (27.2%) were positive for anti-HCV alone and 2 (18%) were positive for HCV rNA alone. CONCLUSION: Since the principal routes for HIV transmission are similar to that followed by the hepatotropic viruses, as a consequence, infections with HBV and HCV are expected in HIV infected patients. Therefore, it would be advisable to screen for these viruses in all the HIV infected individuals and their sexual partners at the earliest.

关键词： Hepatitis B virus Hepatitis C virus Humanimmunodeficiency virus Co-infection Hepatotrophicviruses HBV and HCV India HBV and HCV and HIV

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Small molecule SMU-CX24 targeting toll-like receptor 3 counteracts inflammation:A novel approach to atherosclerosis therapy

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Acta Pharmaceutica Sinica B 2022年第9期12卷 3667-3681页

作者： Xiaohong Cen Baoqu Wang Yuqing Liang Yanlin Chen Yu Xiao Shaohua Du Kutty Selva nandakumar Hang Yin Shuwen Liu Kui Cheng Guangdong Provincial Key Laboratory of New Drug Screening and State Key Laboratory of Organ Failure research School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Musculoskeletal Oncology the Third Affiliated Hospital of Southern Medical UniversityGuangzhou 510642China School of Pharmaceutical Sciences Beijing Advanced Innovation Center for Structural BiologyTsinghua-Peking Joint Center for Life SciencesTsinghua UniversityBeijing 100084China

Toll-like receptor 3(TLr3),as an important pattern recognition receptor(Prr),dominates the innate and adaptive immunity regulating many acute and chronic inflammatory *** is proved as an inflammatory disease,and inflammatory events involved in the entire process of initiation and ***,the contribution of TLr3 to atherosclerosis remains ***,we identified the clinical relevance of TLr3 upregulation and disease processes in human ***,activation of TLr3 also directly led to significant expression of atherogenic chemokines and adhesion ***,silencing TLr3 inhibited the uptake of oxLDL by macrophages and significantly reduced foam cell *** the aberrance in TLr3 functions on atherosclerosis progression,we hypothesized that TLr3 could serve as novel target for clinical atherosclerosis ***,we developed the novel ellipticine derivative SMU-CX24,which specifically inhibited TLr3(IC_(50)=18.87±2.21 nmol/L).In vivo,atherosclerotic burden was alleviated in Western diet fed ApoE^(−/−)mice in response to SMU-CX24 treatment,accompanying notable reductions in TLr3 expression and inflammation infiltration within atherosclerotic ***,for the first time,we revealed that pharmacological downregulation of TLr3 with specific inhibitor regenerated inflammatory environment to counteract atherosclerosis progression,thereby proposing a new strategy and probe for atherosclerosis therapy.

关键词： Toll-like receptor 3 Atherosclerosis Small molecule Inflammation Macrophage

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