@article{panda_rathinasabapathy_metzger_dodson_hanson_griffiths_komarnytsky_2024, title={Efficacy and tolerability of full spectrum hemp oil in dogs living with pain in common household settings}, volume={11}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2024.1384168}, abstractNote={Lameness and restricted mobility are a significant concern in companion animals experiencing chronic pain, inflammation, or age-related pathologies. The growing awareness of health risks and side effects associated with the long-term use of prescription analgesics requires different management strategies to address these issues. In this study, we conducted a crossover evaluation of the effect of full spectrum hemp oil dosed orally at 2 mg/kg BID phytocannabinoids for 8 weeks in dogs ( n = 37) living with pain in common household settings. Owner-reported canine pain, home activity, accelerometer-based activity, walkway-based gait, and tolerability were assessed at each phase of the study. Secondary endpoints included changes in blood biochemistry, liver enzymes, inflammatory biomarkers, and plasma metabolites. The intervention was positively associated with a decrease in pain scores (−46.2%, p = 0.0016), increased ability to walk up and down the stairs (10.6–14.7%, p < 0.05), and improved daily activity (25.9%, p = 0.0038). Decreases in plasma levels of proinflammatory cytokines TNF-α, IL-6, and IL-8 were also observed. Taken together, these findings suggest that the benefits of nutritional supplementation with hemp oil could include control of pain, greater mobility, and an overall improvement in the animal wellbeing.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Panda, Chinmayee and Rathinasabapathy, Thirumurugan and Metzger, Brandon and Dodson, Sheila and Hanson, Dirk and Griffiths, Jody and Komarnytsky, Slavko}, year={2024}, month={Jul} } @article{grodsky_wilson_rathinasabapathy_komarnytsky_2024, title={Triptolide Administration Alters Immune Responses to Mitigate Insulin Resistance in Obese States}, volume={14}, ISSN={["2218-273X"]}, url={https://doi.org/10.3390/biom14040395}, DOI={10.3390/biom14040395}, abstractNote={Individuals who are overweight or obese are at increased risk of developing prediabetes and type 2 diabetes, yet the direct molecular mechanisms that connect diabetes to obesity are not clear. Chronic, sustained inflammation is considered a strong risk factor in these interactions, directed in part by the short-lived gene expression programs encoding for cytokines and pro-inflammatory mediators. In this study, we show that triptolide administration in the C57BL/6 diet-induced obese mice at up to 10 μg/kg/day for 10 weeks attenuated the development of insulin resistance and diabetes, but not obesity, in these animals. Significant reductions in adipose tissue inflammation and improved insulin sensitivity were observed in the absence of changes in food intake, body weight, body composition, or energy expenditure. Analysis of the core cluster of biomarkers that drives pro-inflammatory responses in the metabolic tissues suggested TNF-α as a critical point that affected the co-development of inflammation and insulin resistance, but also pointed to the putatively protective roles of increased COX-2 and IL-17A signaling in the mediation of these pathophysiological states. Our results show that reduction of diet-induced inflammation confers partial protection against insulin resistance, but not obesity, and suggest the possibility of achieving overweight phenotypes that are accompanied by minimal insulin resistance if inflammation is controlled.}, number={4}, journal={BIOMOLECULES}, author={Grodsky, Lyudmila and Wilson, Mickey and Rathinasabapathy, Thirumurugan and Komarnytsky, Slavko}, year={2024}, month={Apr} } @article{dantas araujo_xavier-santos_silva_lima_schlamb_fernandes-pedrosa_silva junior_araujo junior_rathinasabapathy_moncada_et al._2023, title={Gel formulated with Bryophyllum pinnatum leaf extract promotes skin wound healing in vivo by increasing VEGF expression: A novel potential active ingredient for pharmaceuticals}, volume={13}, ISSN={["1663-9812"]}, DOI={10.3389/fphar.2022.1104705}, abstractNote={Bryophyllumpinnatum(Crassulaceae) is used in traditional medicine for treating skin wounds. In our previous study, a topical gel containingB. pinnatumaqueous leaf extract showed a preclinical anti-inflammatory effect inin vivoacute edema models. In continuation, the present study aims to evaluate the phytochemical content and the stability of a formulation in gel containingB. pinnatumaqueous leaf extract and its healing properties and mechanism of action through an experimental model of induction of skin wounds in rats andin vitroassays. The animals were treated topically for 7 or 14 days with a formulation in gel containing extract at 5% or a placebo or Fibrinase®in cream. In addition, to establish some quality control parameters, the total phenolic content (TPC), total flavonoid content (TFC), and a study focusing on the phytochemical and biological stability of a gel for 30 days at two different conditions (room temperature and 40°C/75% RH) were performed. Gel formulation containing extract showed a TPC and TFC of 2.77 ± 0.06 mg of gallic acid/g and 1.58 ± 0.03 mg of quercetin/g, respectively. Regarding the stability study, the formulation in gel showed no significant change in the following parameters: pH, water activity, chromatographic profile, and the content of the major compound identified in the extract. The gel formulation containing extract stimulated skin wound healing while reducing the wound area, as well as decreasing the inflammatory infiltrate, reducing the levels of IL-1β and TNF-α, and stimulating angiogenesis with increased expression of VEGF, an effect similar to Fibrinase. In conclusion, the gel formulation containing extract exhibited relevant skin wound healing properties and, therefore, has the potential to be applied as a novel active ingredient for developing wound healing pharmaceuticals.}, journal={FRONTIERS IN PHARMACOLOGY}, author={Dantas Araujo, Edilane Rodrigues and Xavier-Santos, Jacinthia Beatriz and Silva, Valeria Costa and Lima, Juliana Bessa and Schlamb, Jade and Fernandes-Pedrosa, Matheus de Freitas and Silva Junior, Arnobio Antonio and Araujo Junior, Raimundo Fernandes and Rathinasabapathy, Thirumurugan and Moncada, Marvin and et al.}, year={2023}, month={Jan} } @misc{vong_rathinasabapathy_moncada_komarnytsky_2022, title={All Polyphenols Are Not Created Equal: Exploring the Diversity of Phenolic Metabolites}, volume={70}, ISSN={["1520-5118"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85125020392&partnerID=MN8TOARS}, DOI={10.1021/acs.jafc.1c07179}, abstractNote={Dietary intake of plant polyphenols is significant, and many of them enter a human body as a highly diverse pool of ring-fission phenolic metabolites arising from digestion and microbial catabolism of the parental structures. Difficulty in designing the uniform intervention studies and limited tools calibrated to detect and quantify the inherent complexity of phenolic metabolites hindered efforts to establish and validate protective health effects of these molecules. Here, we highlight the recent findings that describe novel complex downstream metabolite profiles with a particular focus on dihydrophenolic (phenylpropanoic) acids of microbial origin, ingested and phase II-transformed methylated phenolic metabolites (methylated sinks), and small phenolic metabolites derived from the breakdown of different classes of flavonoids, stilbenoids, and tannins. There is a critical need for precise identification of the individual phenolic metabolite signatures originating from different polyphenol groups to enable future translation of these findings into break-through nutritional interventions and dietary guidelines.}, number={7}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Vong, Chi In and Rathinasabapathy, Thirumurugan and Moncada, Marvin and Komarnytsky, Slavko}, year={2022}, month={Feb}, pages={2077–2091} } @misc{rathinasabapathy_sakthivel_komarnytsky_2022, title={Plant-Based Support of Respiratory Health during Viral Outbreaks}, volume={70}, ISSN={["1520-5118"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85125019950&partnerID=MN8TOARS}, DOI={10.1021/acs.jafc.1c06227}, abstractNote={Respiratory viruses are linked to major epidemic events that have plagued humans through recorded history and possibly much earlier, ranging from common colds, influenza, and coronavirus infections to measles. However, difficulty in developing effective pharmaceutical solutions to treat infected individuals has hindered efforts to manage and minimize respiratory viral outbreaks and the associated mortality. Here we highlight a series of botanical interventions with different and often overlapping putative mechanisms of action to support the respiratory system, for which the bioactive pharmacophore was suggested and the initial structure-activity relationships have been explored (Bupleurum spp., Glycyrrhiza spp., Andrographis spp.), have been proposed with uncertainty (Echinacea spp., Zingiber spp., Verbascum spp., Marrubium spp.), or remained to be elucidated (Sambucus spp., Urtica spp.). Investigating these metabolites and their botanical sources holds potential to uncover new mediators of the respiratory health outcomes as well as molecular targets for future break-through therapeutic interventions targeting respiratory viral outbreaks.}, number={7}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Rathinasabapathy, Thirumurugan and Sakthivel, Lakshmana Prabu and Komarnytsky, Slavko}, year={2022}, month={Feb}, pages={2064–2076} } @misc{komarnytsky_rathinasabapathy_wagner_metzger_carlisle_panda_le brun-blashka_troup_varadharaj_2021, title={Endocannabinoid System and Its Regulation by Polyunsaturated Fatty Acids and Full Spectrum Hemp Oils}, volume={22}, ISSN={["1422-0067"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85106251726&partnerID=MN8TOARS}, DOI={10.3390/ijms22115479}, abstractNote={The endocannabinoid system (ECS) consists of endogenous cannabinoids, their receptors, and metabolic enzymes that play a critical homeostatic role in modulating polyunsaturated omega fatty acid (PUFA) signaling to maintain a balanced inflammatory and redox state. Whole food-based diets and dietary interventions linked to PUFAs of animal (fish, calamari, krill) or plant (hemp, flax, walnut, algae) origin, as well as full-spectrum hemp oils, are increasingly used to support the ECS tone, promote healthy metabolism, improve risk factors associated with cardiovascular disorders, encourage brain health and emotional well-being, and ameliorate inflammation. While hemp cannabinoids of THC and CBD groups show distinct but complementary actions through a variety of cannabinoid (CB1 and CB2), adenosine (A2A), and vanilloid (TRPV1) receptors, they also modulate PUFA metabolism within a wide variety of specialized lipid mediators that promote or resolve inflammation and oxidative stress. Clinical evidence reviewed in this study links PUFAs and cannabinoids to changes in ECS tone, immune function, metabolic and oxidative stress adaptation, and overall maintenance of a well-balanced systemic function of the body. Understanding how the body coordinates signals from the exogenous and endogenous ECS modulators is critical for discerning the underlying molecular mechanisms of the ECS tone in healthy and disease states. Nutritional and lifestyle interventions represent promising approaches to address chronic metabolic and inflammatory disorders that may overlap in the population at risk. Further investigation and validation of dietary interventions that modulate the ECS are required in order to devise clinically successful second-generation management strategies.}, number={11}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Komarnytsky, Slavko and Rathinasabapathy, Thirumurugan and Wagner, Charles and Metzger, Brandon and Carlisle, Carolina and Panda, Chinmayee and Le Brun-Blashka, Sara and Troup, John P. and Varadharaj, Saradhadevi}, year={2021}, month={Jun} } @article{wilson_konda_heidt_rathinasabapathy_desai_komarnytsky_2021, title={Rheum rhaponticum Root Extract Improves Vasomotor Menopausal Symptoms and Estrogen-Regulated Targets in Ovariectomized Rat Model}, volume={22}, ISSN={["1422-0067"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85099592894&partnerID=MN8TOARS}, DOI={10.3390/ijms22031032}, abstractNote={Ovarian insufficiency and ovariectomy are characterized by deregulated heat loss mechanisms. Unlike hormone therapy, ERr 731 (a standardized botanical extract of Siberian rhubarb Rheum rhaponticum L. high in rhaponticin) acts like a selective estrogen receptor modulator for ERβ receptors and may offer a higher degree of safety while maintaining the desired efficacy profile. In this study, we examined the relationship between oral administration of ERr 731 and the underlying components of skin vasomotion responses in an ovariectomized (OVX) rat model. ERr 731 dose-dependently reduced tail skin temperature (Tskin) values by an average of 1 °C. The rapid onset of this effect was observed in 1 and 3 mg/kg/day ERr 731 groups as early as day 2 of administration, and remained in place for the duration of the treatment (2 weeks). Substituting ERr 731 after E2 withdrawal helped maintain body temperature similarly to E2 alone, suggesting the usefulness of ERr 731 for replacing existing hormonal therapy in humans. ERr 731 also acted as a highly selective agonist for ERβ in the hypothalamus of OVX rats, as well as in ERα/β cell-based reporter assays. These data validate the OVX/Tskin rat model as a suitable screening platform to evaluate botanical and pharmaceutical treatments of menopause, while providing further evidence for the efficacy of ERr 731 towards alleviating vasomotor menopausal symptoms and improving wellbeing during the menopausal transition.}, number={3}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, publisher={MDPI AG}, author={Wilson, Mickey and Konda, Veera and Heidt, Kathryn and Rathinasabapathy, Thirumurugan and Desai, Anuradha and Komarnytsky, Slavko}, year={2021}, month={Feb} } @article{xiong_chan_rathinasabapathy_grace_komarnytsky_lila_2020, title={Enhanced stability of berry pomace polyphenols delivered in protein-polyphenol aggregate particles to an in vitro gastrointestinal digestion model}, volume={331}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85086513528&partnerID=MN8TOARS}, DOI={10.1016/j.foodchem.2020.127279}, abstractNote={Stability of protein-polyphenol aggregate particles, created by complexing polyphenols from blueberry and muscadine grape pomaces with a rice-pea protein isolate blend, was evaluated in an in vitro gastrointestinal model. Recovery index (RI; % total phenolics present post-digestion) was 69% and 62% from blueberry and muscadine grape protein-polyphenol particles, compared to 23% and 31% for the respective pomace extracts. Anthocyanins RI was 52% and 42% from particles (6% and 13% from pomace extracts), and proanthocyanidins RI was 77% and 73% from particles (25% and 14% from pomace extracts), from blueberry and grape, respectively. Protein-polyphenol particle digests retained 1.5 to 2-fold higher antioxidant capacity and suppressed the expression of pro-inflammatory cytokines, iNOS, IL6, and IL1β, compared to unmodified extract digests, which only suppressed IL6. Protein-polyphenol particles as a delivery vehicle in foods may confer better stability during gastrointestinal transit, allow protected polyphenols to reach the gut microbiota, and preserve polyphenol bioactivity.}, journal={Food Chemistry}, publisher={Elsevier BV}, author={Xiong, Jia and Chan, Yu Hsuan and Rathinasabapathy, Thirumurugan and Grace, Mary H. and Komarnytsky, Slavko and Lila, Mary Ann}, year={2020}, pages={127279} } @article{tanveer_wagner_haq_ribeiro_rathinasabapathy_butt_shehzad_komarnytsky_2020, title={Spicing up gastrointestinal health with dietary essential oils}, volume={19}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85081609089&partnerID=MN8TOARS}, DOI={10.1007/s11101-020-09664-x}, number={2}, journal={Phytochemistry Reviews}, publisher={Springer Science and Business Media LLC}, author={Tanveer, Mahwish and Wagner, Charles and Haq, Muhammad Ikram and Ribeiro, Nilton C. and Rathinasabapathy, Thriumurugan and Butt, Masood Sadiq and Shehzad, Aamir and Komarnytsky, Slavko}, year={2020}, pages={243–263} } @article{boudreau_poulev_ribnicky_raskin_rathinasabapathy_richard_stephens_2019, title={Distinct fractions of an Artemisia scoparia extract contain compounds with novel adipogenic bioactivity}, volume={6}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85067802090&partnerID=MN8TOARS}, DOI={10.3389/fnut.2019.00018}, abstractNote={Adipocytes are important players in metabolic health and disease, and disruption of adipocyte development or function contributes to metabolic dysregulation. Hence, adipocytes are significant targets for therapeutic intervention in obesity and metabolic syndrome. Plants have long been sources for bioactive compounds and drugs. In previous studies, we screened botanical extracts for effects on adipogenesis in vitro and discovered that an ethanolic extract of Artemisia scoparia (SCO) could promote adipocyte differentiation. To follow up on these studies, we have used various separation methods to identify the compound(s) responsible for SCO's adipogenic properties. Fractions and subfractions of SCO were tested for effects on lipid accumulation and adipogenic gene expression in differentiating 3T3-L1 adipocytes. Fractions were also analyzed by Ultra Performance Liquid Chromatography- Mass Spectrometry (UPLC-MS), and resulting peaks were putatively identified through high resolution, high mass accuracy mass spectrometry, literature data, and available natural products databases. The inactive fractions contained mostly quercetin derivatives and chlorogenates, including chlorogenic acid and 3,5-dicaffeoylquinic acid, which had no effects on adipogenesis when tested individually, thus ruling them out as pro-adipogenic bioactives in SCO. Based on these studies we have putatively identified the principal constituents in SCO fractions and subfractions that promoted adipocyte development and fat cell gene expression as prenylated coumaric acids, coumarin monoterpene ethers, 6-demethoxycapillarisin and two polymethoxyflavones.}, journal={Frontiers in Nutrition}, author={Boudreau, A. and Poulev, A. and Ribnicky, D.M. and Raskin, I. and Rathinasabapathy, T. and Richard, A.J. and Stephens, J.M.}, year={2019} } @article{mak_rathinasabapathy_sankaran_kandasamy_ling_balijepalli_sagineedu_pichika_2018, title={Edible foxtail millet flour stabilises and retain the invitro activity of blueberry bioactive components}, volume={53}, ISSN={["1365-2621"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85048519655&partnerID=MN8TOARS}, DOI={10.1111/ijfs.13762}, abstractNote={SummaryBlueberries, a functional food, are rich in bioactive polyphenols and anthocyanins. However, the shelf life is short and requires cold storage. This study provides evidence that edible foxtail millet flour (FMF) efficiently sorbs only blueberry bioactive components (polyphenols and anthocyanins) but not sugars, improves their stability and retains the activity. The concentration of blueberry polyphenols and anthocyanins sorbed to FMF ranged from 6 to 113 and 4 to 41 mg g−1, respectively. The concentration of bioactive components in one serving of blueberries (73 g) is equivalent to those present in 1.2 g of blueberry‐enriched foxtail millet flour (BFMF). The blueberry bioactive sorbed onto FMF remained stable for at least 16 weeks at 40 °C. BFMF eluates inhibited α‐glucosidase enzyme activity and scavenged the free radicals conferring that blueberry bioactive components in BFMF retained the activity. The sorption process described here provides a practical way of creating low glycemic protein‐rich edible flour enriched with plant bioactive compounds without sugars.}, number={7}, journal={INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY}, author={Mak, Kit-Kay and Rathinasabapathy, Thirumurugan and Sankaran, Shanta and Kandasamy, Murugesh and Ling, Elaine Chan Wan and Balijepalli, Madhu Katyayani and Sagineedu, Sreenivasa Rao and Pichika, Mallikarjuna Rao}, year={2018}, month={Jul}, pages={1771–1780} } @article{jackson_rathinasabapathy_esposito_komarnytsky_2017, title={Structural constraints and importance of caffeic acid moiety for anti-hyperglycemic effects of caffeoylquinic acids from chicory}, volume={61}, ISSN={["1613-4133"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85018313098&partnerID=MN8TOARS}, DOI={10.1002/mnfr.201601118}, abstractNote={SCOPE Chicory (Cichorium intybus L.) is a perennial herb often consumed as a vegetable, whereas the ground and roasted roots are blended as a coffee substitute. Caffeoylquinic or chlorogenic acids (CQA), the abundant intermediates of lignin biosynthesis in chicory, have been reported to improve glucose metabolism in humans, but the functional group in their structure responsible for this effect has not been yet characterized. METHODS AND RESULTS Here, we showed that three di-O-caffeoylquinic acids suppressed hepatic glucose production in H4IIE rat hepatoma cells by reducing expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), two key enzymes that regulate hepatic gluconeogenesis. Direct comparisons between CQAs and their metabolites (3-caffeoylquinic, caffeic, and quinic acids) revealed the caffeic acid moiety alone was responsible for the observed effects. Further analysis suggested the activation of PI3K and MAPK pathways as a method of controlling gene expression was shared between caffeoylquinic and caffeic acids. These compounds promoted increased mitochondrial respiration and cellular metabolism, in part by inducing oxidative phosphorylation and proton leak. CONCLUSION We concluded that the caffeic acid moiety was important for suppression of hepatic gluconeogenesis and hyperglycemia, ultimately strengthening the link between dietary interventions based on caffeic acid-containing plant foods and healthy glucose metabolism.}, number={9}, journal={MOLECULAR NUTRITION & FOOD RESEARCH}, author={Jackson, Kimberly M. Palatini and Rathinasabapathy, Thirumurugan and Esposito, Debora and Komarnytsky, Slavko}, year={2017}, month={Sep} } @article{rathinasabapathy_palatini jackson_thor_buru_esposito_li_pichika_hamzah_komarnytsky_2017, title={Thiazolopyridines Improve Adipocyte Function by Inhibiting 11 Beta-HSD1 Oxoreductase Activity}, volume={2017}, ISSN={2090-9063 2090-9071}, url={http://dx.doi.org/10.1155/2017/3182129}, DOI={10.1155/2017/3182129}, abstractNote={Background. Glucocorticoid excess has been linked to clinical observations associated with the pathophysiology of metabolic syndrome. The intracellular glucocorticoid levels are primarily modulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme that is highly expressed in key metabolic tissues including fat, liver, and the central nervous system. Methods. In this study we synthesized a set of novel tetrahydrothiazolopyridine derivatives, TR-01–4, that specifically target 11β-HSD1 and studied their ability to interfere with the glucocorticoid and lipid metabolism in the 3T3-L1 adipocytes. Results. Based on the docking model and structure-activity relationships, tetrahydrothiazolopyridine derivatives TR-02 and TR-04 showed the highest potency against 11β-HSD1 by dose-dependently inhibiting conversion of cortisone to cortisol (IC50 values of 1.8 μM and 0.095 μM, resp.). Incubation of fat cells with 0.1–10 μM TR-01–4 significantly decreased cortisone-induced lipid accumulation in adipocytes and suppressed 11β-HSD1 mRNA expression. Observed reduction in adipocyte fat stores could be partially explained by decreased expression levels of adipogenic markers (PPAR-γ, aP2) and key enzymes of lipid metabolism, including fatty acid synthase (FAS), hormone sensitive lipase (HSL), and lipoprotein lipase (LPL). Conclusions. The tetrahydrothiazolopyridine moiety served as an active pharmacophore for inhibiting 11β-HSD1 and offered a novel therapeutic strategy to ameliorate metabolic alterations found in obesity and diabetes.}, journal={Journal of Chemistry}, publisher={Hindawi Limited}, author={Rathinasabapathy, Thirumurugan and Palatini Jackson, Kimberly Marie and Thor, Yiwen and Buru, Ayuba Sunday and Esposito, Debora and Li, Xu and Pichika, Mallikarjuna Rao and Hamzah, Ahmad Sazali and Komarnytsky, Slavko}, year={2017}, pages={1–10} } @book{prabu_suriyaprakash_kandasamy_rathinasabapathy_2015, title={Effective waste water treatment and its management}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84981501458&partnerID=MN8TOARS}, DOI={10.4018/978-1-4666-9734-8.ch016}, abstractNote={Worldwide there is an increasing industrialization leads to increased disposal of uncontrolled waste products into the environment which made the environment more pollute and creates hazards. Industrial wastewater is having a major role in the environmental pollution. The major physical, chemical and biological products of the wastewater are solid content, organic matter, in-organic compounds, detergents, soap, cleaning products, metals, gases, volatile compounds, numerous pathogenic microorganisms, nutrients and toxic compounds. Untreated wastewater can cause various environment pollutions problems such as eutrophication or oxygen depletion in the environment. Hence a effective wastewater treatment process and its management is necessary to reduce the contaminants in the permissible levels in the treated waste streams. The final outcome of an effective wastewater treatment and its management is to ensure and provide an appropriate environment protection to the living things and public human beings in the world.}, journal={Toxicity and Waste Management Using Bioremediation}, author={Prabu, S.L. and Suriyaprakash, T.N.K. and Kandasamy, R. and Rathinasabapathy, T.}, year={2015}, pages={312–334} } @article{prabu_suriyaprakash_thirumurugan_shanmugarathinam_2014, title={Process validation: A review}, volume={46}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84943603029&partnerID=MN8TOARS}, number={4}, journal={Pharma Times}, author={Prabu, S.L. and Suriyaprakash, T.N.K. and Thirumurugan, R. and Shanmugarathinam, A.}, year={2014}, pages={12–15} } @article{esposito_rathinasabapathy_schmidt_shakarjian_komarnytsky_raskin_2013, title={Acceleration of cutaneous wound healing by brassinosteroids}, volume={21}, ISSN={["1524-475X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84883490805&partnerID=MN8TOARS}, DOI={10.1111/wrr.12075}, abstractNote={AbstractBrassinosteroids are plant growth hormones involved in cell growth, division, and differentiation. Their effects in animals are largely unknown, although recent studies showed that the anabolic properties of brassinosteroids are possibly mediated through the phosphoinositide 3‐kinase/protein kinase B signaling pathway. Here, we examined biological activity of homobrassinolide (HB) and its synthetic analogues in in vitro proliferation and migration assays in murine fibroblast and primary keratinocyte cell culture. HB stimulated fibroblast proliferation and migration and weakly induced keratinocyte proliferation in vitro. The effects of topical HB administration on progression of wound closure were further tested in the mouse model of cutaneous wound healing. C57BL/6J mice were given a full‐thickness dermal wound, and the rate of wound closure was assessed daily for 10 days, with adenosine receptor agonist CGS‐21680 as a positive control. Topical application of brassinosteroid significantly reduced wound size and accelerated wound healing in treated animals. mRNA levels of transforming growth factor beta and intercellular adhesion molecule 1 were significantly lower, while tumor necrosis factor alpha was nearly suppressed in the wounds from treated mice. Our data suggest that topical application of brassinosteroids accelerates wound healing by positively modulating inflammatory and reepithelialization phases of the wound repair process, in part by enhancing Akt signaling in the skin at the edges of the wound and enhancing migration of fibroblasts in the wounded area. Targeting this signaling pathway with brassinosteroids may represent a promising approach to the therapy of delayed wound healing.}, number={5}, journal={WOUND REPAIR AND REGENERATION}, publisher={Wiley-Blackwell}, author={Esposito, Debora and Rathinasabapathy, Thirumurugan and Schmidt, Barbara and Shakarjian, Michael P. and Komarnytsky, Slavko and Raskin, Ilya}, year={2013}, month={Sep}, pages={688–696} } @article{komarnytsky_esposito_rathinasabapathy_poulev_raskin_2013, title={Effects of Pregnane Glycosides on Food Intake Depend on Stimulation of the Melanocortin Pathway and BDNF in an Animal Model}, volume={61}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf3033649}, DOI={10.1021/jf3033649}, abstractNote={Pregnane glycosides appear to modulate food intake by possibly affecting the hypothalamic feeding circuits; however, the mechanisms of the appetite-regulating effect of pregnane glycosides remain obscure. Here, we show that pregnane glycoside-enriched extracts from swamp milkweed Asclepias incarnata at 25-100 mg/kg daily attenuated food intake (up to 47.1 ± 8.5% less than controls) and body weight gain in rats (10% for males and 9% for females, respectively) by activating melanocortin signaling and inhibiting gastric emptying. The major milkweed pregnane glycoside, ikemagenin, exerted its appetite-regulating effect by decreasing levels of agouti-related protein (0.6-fold) but not NPY satiety peptides. Ikemagenin treatment also increased secretion of brain-derived neurotropic factor (BDNF) downstream of melanocortin receptors in the hypothalamus (1.4-fold) and in the C6 rat glioma cell culture in vitro (up to 6-fold). These results support the multimodal effects of pregnane glycosides on feeding regulation, which depends on the activity of the melanocortin signaling pathway and BDNF.}, number={8}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Komarnytsky, Slavko and Esposito, Debora and Rathinasabapathy, Thirumurugan and Poulev, Alexander and Raskin, Ilya}, year={2013}, month={Feb}, pages={1841–1849} } @article{graziose_rojas-silva_rathinasabapathy_dekock_grace_poulev_lila_smith_raskin_2012, title={Antiparasitic compounds from Cornus florida L. with activities against Plasmodium falciparum and Leishmania tarentolae}, volume={142}, ISSN={["1872-7573"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84862853930&partnerID=MN8TOARS}, DOI={10.1016/j.jep.2012.05.017}, abstractNote={The objective of this study was to identify the antiplasmodial constituents from the bark of Cornus florida L., a plant traditionally used in North America for the treatment of malaria.Dried and powdered bark was extracted with 95% ethanol. The resultant extract was subjected to in vitro antiplasmodial-guided fractionation against Plasmodium falciparum (D10 strain). Antiplasmodial IC(50) values were calculated for pure compounds. Compounds were also assayed against Leishmania tarentolae, and rat skeletal myoblast L6 cells to assess antileishmanial activity and cytotoxicity, respectively.Antiplasmodial-guided fractionation afforded 8 compounds: betulinic acid (1), ursolic acid (2), β-sitosterol (3), ergosta-4,6,8,22-tetraene-3-one (4), 3β-O-acetyl betulinic acid (5), 3-epideoxyflindissol (6), 3β-O-cis-coumaroyl betulinic acid (7), 3β-O-trans-coumaroyl betulinic acid (8), of which, (6) is for the first time here isolated from a natural product and (4), (7) and (8) are reported for the first time from this genus. In vitro IC(50) values against P. falciparum for (4) (61.0 μM) (6) (128.0 μM), (7) (10.4 μM), (8) (15.3 μM) are reported for the first time. Antileishmanial IC(50) values are reported here for the first time for (4) (11.5 μM), (6) (1.8 μM), (7) (8.3 μM) and (8) (2.2 μM). Cytotoxicity against L6 cells is reported for all compounds.The compounds isolated in this study, while displaying moderate in vitro antiplasmodial activity, do not fully support the historical importance of C. florida as an antimalarial remedy in North America. The traditional remedy may exert its well documented effects by mechanisms unrelated to direct antiplasmodial action. While not traditionally used to treat Leishmania, this work shows that several constituents of C. florida possess promising in vitro antileishmanial activity.}, number={2}, journal={JOURNAL OF ETHNOPHARMACOLOGY}, author={Graziose, Rocky and Rojas-Silva, Patricio and Rathinasabapathy, Thirumurugan and Dekock, Carmen and Grace, Mary H. and Poulev, Alexander and Lila, Mary Ann and Smith, Peter and Raskin, Ilya}, year={2012}, month={Jul}, pages={456–461} } @article{graziose_grace_rathinasabapathy_rojas-silva_dekock_poulev_lila_smith_raskin_2013, title={Antiplasmodial activity of cucurbitacin glycosides from Datisca glomerata (C. Presl) Baill}, volume={87}, ISSN={["0031-9422"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84872776315&partnerID=MN8TOARS}, DOI={10.1016/j.phytochem.2012.11.025}, abstractNote={The traditionally used antimalarial plant, Datisca glomerata (C. Presl) Baill, was subjected to antiplasmodial assay guided fractionation. This led to the isolation of seven cucurbitacin glycosides, datiscosides I-O, along with two known compounds, datiscoside and datiscoside B, from the aerial parts of D. glomerata. Their structures and relative stereochemistry were determined on the basis of mass spectrometry, 1D and 2D NMR spectroscopic data. Antiplasmodial IC(50) values were determined for all isolated compounds against a chloroquine sensitive strain of Plasmodium falciparum (D10), which were also evaluated in vitro for their antileishmanial activity against Leishmania tarentolae. Cytotoxicity was evaluated against rat skeletal muscle cells (L6) and Chinese ovarian hamster cells (CHO). The antiplasmodial activity of the compounds was moderate and ranged from 7.7 to 33.3 μM. None of the compounds showed appreciable antileishmanial activity. The compounds displayed cytotoxicity against L6 but not CHO mammalian cells.}, journal={PHYTOCHEMISTRY}, author={Graziose, Rocky and Grace, Mary H. and Rathinasabapathy, Thirumurugan and Rojas-Silva, Patricio and Dekock, Carmen and Poulev, Alexander and Lila, Mary Ann and Smith, Peter and Raskin, Ilya}, year={2013}, month={Mar}, pages={78–85} } @article{esposito_rathinasabapathy_poulev_komarnytsky_raskin_2011, title={Akt-Dependent Anabolic Activity of Natural and Synthetic Brassinosteroids in Rat Skeletal Muscle Cells}, volume={54}, ISSN={0022-2623 1520-4804}, url={http://dx.doi.org/10.1021/jm200028h}, DOI={10.1021/jm200028h}, abstractNote={Brassinosteroids are plant-derived polyhydroxylated derivatives of 5α-cholestane, structurally similar to cholesterol-derived animal steroid hormones and insect ecdysteroids. In this study, we synthesized a set of brassinosteroid analogues of a natural brassinosteroid (22S,23S)-homobrassinolide (HB, 1), including (22S,23S)-homocastasterone (2), (22S,23S)-3α-fluoro-homobrasinolide (3), (22S,23S)-3α-fluoro-homocastasterone (4), (22S,23S)-7-aza-homobrassinolide (5), and (22S,23S)-6-aza-homobrassinolide (6) and studied their anabolic efficacy in the L6 rat skeletal muscle cells in comparison to other synthetic and naturally occurring brassinosteroids (22R,23R)-homobrassinolide (7), (22S,23S)-epibrassinolide (8), and (22R,23R)-epibrassinolide (9). Presence of the 6-keto group in the B ring and stereochemistry of 22α,23α-vicinal hydroxyl groups in the side chain were critical for the anabolic activity, possibly due to higher cytotoxicity of the 22β,23β-hydroxylated brassinosteroids. All anabolic brassinosteroids tested in this study selectively activated PI3K/Akt signaling pathway as evident by increased Akt phosphorylation in vitro. Plant brassinosteroids and their synthetic derivatives may offer a novel therapeutic strategy for promoting growth, repair, and maintenance of skeletal muscles.}, number={12}, journal={Journal of Medicinal Chemistry}, publisher={American Chemical Society (ACS)}, author={Esposito, Debora and Rathinasabapathy, Thirumurugan and Poulev, Alexander and Komarnytsky, Slavko and Raskin, Ilya}, year={2011}, month={Jun}, pages={4057–4066} } @article{panneer_ramkanth_thirumurugan_kumar_raji_2011, title={Design and evaluation of buccoadhesive bi-layer tablet of atenolol}, volume={2}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79955369086&partnerID=MN8TOARS}, number={2}, journal={International Journal of Research in Pharmaceutical Sciences}, author={Panneer, K. and Ramkanth, S. and Thirumurugan, R. and Kumar, K. and Raji, S.}, year={2011}, pages={100–103} } @article{graziose_rathinasabapathy_lategan_poulev_smith_grace_lila_raskin_2011, title={Antiplasmodial activity of aporphine alkaloids and sesquiterpene lactones from Liriodendron tulipifera L.}, volume={133}, ISSN={["0378-8741"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-78650679847&partnerID=MN8TOARS}, DOI={10.1016/j.jep.2010.08.059}, abstractNote={The objective of this study was to isolate and characterize the active constituents of the traditionally used antimalarial plant Liriodendron tulipifera by antiplasmodial-assay guided fractionation. Bark and leaves were extracted with solvents of increasing polarity. Fractions were generated using flash chromatography, counter current chromatography and preparative HPLC and subjected to in vitro antiplasmodial and cytotoxicity assays. Active fractions were subjected to further fractionation until pure compounds were isolated, for which the IC50 values were calculated. Six known aporphine alkaloids, asimilobine (1), norushinsunine (2), norglaucine (3), liriodenine (4), anonaine (5) and oxoglaucine (6) were found to be responsible for the antiplasmodial activity of the bark. Leaves yielded two known sesquiterpene lactones, peroxyferolide (7) and lipiferolide (8) with antiplasmodial activity. The antiplasmodial activity of (2) (IC50 = 29.6 μg/mL), (3) (IC50 = 22.0 μg/mL), (6) (IC50 = 9.1 μg/mL), (7) (IC50 = 6.2 μg/mL) and (8) (IC50 = 1.8 μg/mL) are reported for the first time. This work supports the historical use of Liriodendron tulipifera as an antimalarial remedy of the United States and characterizes its antiplasmodial constituents.}, number={1}, journal={JOURNAL OF ETHNOPHARMACOLOGY}, author={Graziose, Rocky and Rathinasabapathy, Thirumurugan and Lategan, Carmen and Poulev, Alexander and Smith, Peter J. and Grace, Mary and Lila, Mary Ann and Raskin, Ilya}, year={2011}, month={Jan}, pages={26–30} } @article{sriram_yogeeswari_dinakaran_thirumurugan_2007, title={Antimycobacterial activity of novel 1-(5-cyclobutyl-1,3-oxazol-2-yl)-3-(sub)phenyl/pyridylthiourea compounds endowed with high activity toward multidrug-resistant Mycobacterium tuberculosis}, volume={59}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34447542173&partnerID=MN8TOARS}, DOI={10.1093/jac/dkm085}, abstractNote={OBJECTIVES The objective of this work was to synthesize 15 new 1-(5-cyclobutyl-1,3-oxazol-2-yl)-3-(sub)phenyl/pyridylthiourea compounds and evaluate their in vitro and in vivo antimycobacterial activities. METHODS 5-Cyclobutyloxazol-2-amine was reacted with 1,1'-thiocarbonyldiimidazole, followed by various substituted anilines and 2-amino pyridines to yield the 15 compounds, which were subjected to in vitro and in vivo evaluation against Mycobacterium tuberculosis H37Rv (MTB) and a clinical isolate of multidrug-resistant M. tuberculosis (MDR-TB). RESULTS Among the 15 compounds screened, 7 compounds inhibited both MTB and MDR-TB in vitro with MICs of < 1 microM. In the in vivo screening, compound 1-(5-cyclobutyl-1,3-oxazol-2-yl)-3-(2'-trifluoromethyl)phenylthiourea (compound 8) was equally active as isoniazid at the same dose level. CONCLUSIONS Compound 8 was found to be the most active, with an in vitro MIC of 0.14 microM and was 2.5 and 80 times more active than isoniazid against MTB and MDR-TB, respectively. Compound 8 was non-toxic to Vero cells up to 183 microM, with a selectivity index of > 1307. In the in vivo animal model, compound 8 decreased the mycobacterium load in lung and spleen tissues with 2.8 and 3.94 log(10) reductions, respectively.}, number={6}, journal={J Antimicrob Chemother}, author={Sriram, D. and Yogeeswari, P. and Dinakaran, M. and Thirumurugan, R.}, year={2007}, pages={1194–6} } @article{thirumurugan_sriram_saxena_stables_yogeeswari_2006, title={2,4-Dimethoxyphenylsemicarbazones with anticonvulsant activity against three animal models of seizures: synthesis and pharmacological evaluation}, volume={14}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33644982586&partnerID=MN8TOARS}, DOI={10.1016/j.bmc.2005.12.041}, abstractNote={Various 2,4-dimethoxyphenylsemicarbazones were synthesized starting from 2,4-dimethoxyaniline via a phenylcarbamate intermediate. The structures were confirmed by spectral and elemental analyses. The anticonvulsant activity of the synthesized compounds was established after intraperitoneal administration in three seizure models in mice which include maximal electroshock seizure, subcutaneous pentylenetetrazole, and subcutaneous strychnine-induced seizure screens. Nine compounds exhibited protection in all the three seizure models, and N1-(2,4-dimethoxyphenyl)-N4-(propan-2-one)semicarbazone (17) emerged as the most active compound with no neurotoxicity. These compounds were found to elevate γ-aminobutyric acid (GABA) levels in the midbrain and medulla oblongata regions equipotent to clobazam.}, number={9}, journal={Bioorg Med Chem}, author={Thirumurugan, R. and Sriram, D. and Saxena, A. and Stables, J. and Yogeeswari, P.}, year={2006}, pages={3106–12} } @article{sriram_yogeeswari_thirumurugan_pavana_2006, title={Discovery of new antitubercular oxazolyl thiosemicarbazones}, volume={49}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33745139827&partnerID=MN8TOARS}, DOI={10.1021/jm060339h}, abstractNote={Twenty 4-(5-cyclobutyloxazol-2-yl)thiosemicarbazones were synthesized and evaluated for preliminary in vitro and in vivo activity against Mycobacterium tuberculosis H37Rv (MTB) and multidrug-resistant Mycobacterium tuberculosis (MDR-TB). Among them, (4-bromophenyl)(phenyl)methanone N-(5-cyclobutyl-1,3-oxazol-2-yl)thiosemicarbazone 6q was found to be the most active compound in vitro with minimum inhibitory concentration of 0.05 microg/mL against MTB and MDR-TB. In the in vivo animal model 6q decreased the bacterial load in lung and spleen tissues with 2.1 log 10 and 3.72 log 10 protections, respectively, at 50 mg/kg body weight dose.}, number={12}, journal={J Med Chem}, author={Sriram, D. and Yogeeswari, P. and Thirumurugan, R. and Pavana, R. K.}, year={2006}, pages={3448–50} } @article{yogeeswari_sriram_ratan bal_thirumurugan_2006, title={Epibatidine and its analogues as nicotinic acetylcholine receptor agonist: an update}, volume={20}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33646414827&partnerID=MN8TOARS}, DOI={10.1080/14786410600604583}, abstractNote={Epibatidine (EPB) (1), an alkaloid isolated from the skin of the Ecuadorian poison frog, Epipedobates tricolor has attracted attention because of its exceptionally powerful analgesic properties: several hundred times greater than those of morphine, and the fact that it acts at nicotine rather than opiate receptors. Although the substance is toxic, it does serve as a lead compound in the development of drugs for pain relief as well as treatment of disorders whose pathogenesis involves nicotinic receptors. In this article, isolation, synthetic methods, effect on neuronal and neuromuscular nicotinic receptors, therapeutic potential, toxicity, nicotinic pharmacophore structural modifications related issues of 1 are discussed.}, number={5}, journal={Nat Prod Res}, author={Yogeeswari, P. and Sriram, D. and Ratan Bal, T. and Thirumurugan, R.}, year={2006}, pages={497–505} } @article{yogeeswari_sriram_thirumurugan_jeewanlal_jit_ragavendran_kavya_rakhra_saraswat_2006, title={Synthesis of N4-(2,4-dimethylphenyl) semicarbazones as 4-aminobutyrate aminotransferase inhibitors}, volume={56}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33748855540&partnerID=MN8TOARS}, number={3}, journal={Acta Pharm}, author={Yogeeswari, P. and Sriram, D. and Thirumurugan, R. and Jeewanlal, L. R. and Jit, S. and Ragavendran, J. V. and Kavya, R. and Rakhra, K. and Saraswat, V.}, year={2006}, pages={259–72} } @article{sriram_yogeeswari_thirumurugan_bal_2005, title={Camptothecin and its analogues: a review on their chemotherapeutic potential}, volume={19}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-19144361907&partnerID=MN8TOARS}, DOI={10.1080/14786410412331299005}, abstractNote={Topoisomerase I (Topo-I) is a major target for anticancer drug discovery and design. As a result, Topo-I inhibitors constitute an important class of the current anticancer drugs. To date, all of the Topo-I inhibitors that have been clinically evaluated are analogues of camptothecin (CPT), an extract of the Chinese tree Camptotheca acuminata. CPT has shown significant antitumor activity to lung, ovarian, breast, pancreas and stomach cancers. In this article the, phytochemical aspect, and various structural modifications are comprehensively reviewed as in rings A, B, C, D and E. Biological activity of camptothecin, other than anticancer, reported till the year 2003 has also been discussed.}, number={4}, journal={Nat Prod Res}, author={Sriram, D. and Yogeeswari, P. and Thirumurugan, R. and Bal, T. R.}, year={2005}, pages={393–412} } @article{yogeeswari_sriram_thirumurugan_raghavendran_sudhan_pavana_stables_2005, title={Discovery of N-(2,6-dimethylphenyl)-substituted semicarbazones as anticonvulsants: hybrid pharmacophore-based design}, volume={48}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-26444438132&partnerID=MN8TOARS}, DOI={10.1021/jm050283b}, abstractNote={Epilepsy is the most common primary neurological disorder known. In the past decade, various aryl semicarbazones have been designed that were structurally dissimilar from many common anticonvulsants containing the dicarboximide function (CONRCO), which may contribute to toxic side effects. In the present work various N4-(2,6-dimethylphenyl) semicarbazones were designed as pharmacophore hybrids between the aryl semicarbazones and ameltolide. A three-dimensional four-point pharmacophore model was developed for anticonvulsants, and the title compounds were found to match with ralitoline. All of the compounds exhibited anticonvulsant activity in the maximal electroshock test when administered by both intraperitoneal and oral routes. Compound N1-(2,6-dimethylphenyl)-N4-(2-hydroxybenzaldehyde) semicarbazone (9) emerged as a prototype with wide spectrum anticonvulsant agent active in five models of seizure with no neurotoxicity and hepatotoxicity. Compound 9 increased the 4-aminobutyric acid (GABA) level by 118% and inhibited the GABA transaminase enzyme both in vitro and ex vivo.}, number={20}, journal={J Med Chem}, author={Yogeeswari, P. and Sriram, D. and Thirumurugan, R. and Raghavendran, J. V. and Sudhan, K. and Pavana, R. K. and Stables, J.}, year={2005}, pages={6202–11} } @article{yogeeswari_ragavendran_thirumurugan_induja_sriram_stables_2006, title={Synthesis and structure-activity relationship on anticonvulsant aryl semicarbazones}, volume={2}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33746112596&partnerID=MN8TOARS}, DOI={10.2174/157340606775197778}, abstractNote={Seven series of various substituted aryl semicarbazones were synthesized and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure threshold tests. A comprehensive structure-activity relationship was derived comparing the substituents on the aryl ring and in the carbimino terminal. Generally the order of activity was 4-F > 2-Br = 3-Br = 4-Cl > 4-CH(3) > 4-Br > 3-Cl > 3-CH(3) with respect to the primary aryl group. Most of the compounds exhibited activity both in the MES and scPTZ screens. The 4-fluorophenyl substituted semicarbazones (5a-5y) emerged as the most potent compounds exhibiting anticonvulsant activity in mouse intraperitoneal (i.p.) and rat per oral (p.o.) MES, scPTZ and psychomotor seizure (6 Hz) screens.}, number={1}, journal={Medicinal Chemistry}, author={Yogeeswari, P. and Ragavendran, J.V. and Thirumurugan, R. and Induja, S. and Sriram, D. and Stables, J.P.}, year={2006}, pages={55–62} } @article{yogeeswari_thirumurugan_kavya_samuel_stables_sriram_2004, title={3-Chloro-2-methylphenyl-substituted semicarbazones: synthesis and anticonvulsant activity}, volume={39}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-3242746776&partnerID=MN8TOARS}, DOI={10.1016/j.ejmech.2004.03.008}, abstractNote={A series of 3-chloro-2-methylphenyl substituted semicarbazones (3–33) was synthesized and evaluated for anticonvulsant and CNS activities. After intraperitoneal injection to mice or rats, the semicarbazone derivatives were examined in the maximal electroshock seizure (MES), subcutaneous pentylenetetrazole (scPTZ), and subcutaneous strychnine (scSTY)-induced seizure and neurotoxicity screens. The aryl urea (1) and the semicarbazide (2) showed anticonvulsant activity in the MES and scPTZ screens with acute neurotoxicity, whereas the semicarbazone derivatives showed good anticonvulsant potency in the scSTY screen with moderate activity against MES and scPTZ screens. Compound 21 exhibited anticonvulsant potency against all the three screens with lesser neurotoxicity. Some titled compounds exhibited lesser CNS depression and neurotoxicity compared to phenytoin or carbamazepine as was evident from the CNS studies.}, number={8}, journal={Eur J Med Chem}, author={Yogeeswari, P. and Thirumurugan, R. and Kavya, R. and Samuel, J. S. and Stables, J. and Sriram, D.}, year={2004}, pages={729–34} } @article{sriram_yogeeswari_thirumurugan_2004, title={Antituberculous activity of some aryl semicarbazone derivatives}, volume={14}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-3042640435&partnerID=MN8TOARS}, DOI={10.1016/j.bmcl.2004.05.060}, abstractNote={During the course of our work on the synthesis and screening of new drugs for tuberculosis, we have identified N1-(4-acetamido phenyl)-N4-(2-nitro benzylidene) semicarbazone (1b), which inhibited in vitro Mycobacterium tuberculosis H(37)Rv; 100% inhibition at 1.56 microg/mL. This paper is first of its kind in which aryl semicarbazones are reported to possess antimycobacterials potency greater than p-aminosalicylic acid, ethionamide, ethambutol, ciprofloxacin and kanamycin.}, number={15}, journal={Bioorg Med Chem Lett}, author={Sriram, D. and Yogeeswari, P. and Thirumurugan, R.}, year={2004}, pages={3923–4} } @article{yogeeswari_ragavendran_thirumurugan_saxena_sriram_2004, title={Ion channels as important targets for antiepileptic drug design}, volume={5}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-4544375063&partnerID=MN8TOARS}, DOI={10.2174/1389450043345227}, abstractNote={Ion channels have a critical role in the function of the nervous system, where they instigate and conduct nerve impulses by asserting control over the voltage potential across the plasma membrane. Propagation of electrical impulses occurs by opening of voltage-gated ion channels. Ion channel blockers prevent this from occurring, and can therefore be used in the treatment of central nervous system disorders and neuropathic pain. Recent identification of ion channel gene mutations in Mendelian epilepsies suggests that genetically driven neuronal hyperexcitability plays an important role in epileptogenesis. Studies with animal seizure models have indicated that changes in temporal and spatial expression of voltage-gated sodium channels may be important in the pathology of epilepsy. This paper is aimed at elucidating the organization of the ion channels and covers a review on the antiepileptic drugs, both established and currently under development targeted to the ion channels in order to bring about effective seizure control.}, number={7}, journal={Current Drug Targets}, author={Yogeeswari, P. and Ragavendran, J.V. and Thirumurugan, R. and Saxena, A. and Sriram, D.}, year={2004}, pages={589–602} } @article{yogeeswari_sriram_veena_kavya_rakhra_ragavendran_mehta_thirumurugan_stables_2005, title={Synthesis of aryl semicarbazones as potential anticonvulsant agents}, volume={59}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-14644438358&partnerID=MN8TOARS}, DOI={10.1016/j.biopha.2004.04.013}, abstractNote={A series of 4-ethoxyphenyl semicarbazones (1–10) have been synthesized using an appropriate synthetic route and characterized by elemental analyses and spectral data. The anticonvulsant activity of all the synthesized compounds was evaluated against maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. All the test compounds were administered at doses of 30, 100, and 300 mg/kg body weight and the anticonvulsant activity was noted at 0.5 and 4 h time intervals after the drug administration. Among the compounds tested, compounds except 3, 4 and 10 showed protection from seizures in both the animal models. Compounds 6 and 8 were found to increase γ-aminobutyric acid (GABA) levels in the medulla oblongata region of the rat brain.}, number={1-2}, journal={Biomed Pharmacother}, author={Yogeeswari, P. and Sriram, D. and Veena, V. and Kavya, R. and Rakhra, K. and Ragavendran, J. V. and Mehta, S. and Thirumurugan, R. and Stables, J. P.}, year={2005}, pages={51–5} } @article{yogeeswari_sriram_saraswat_ragavendran_kumar_murugesan_thirumurugan_stables_2003, title={Synthesis and anticonvulsant and neurotoxicity evaluation of N 4-phthalimido phenyl (thio) semicarbazides}, volume={20}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0242270809&partnerID=MN8TOARS}, DOI={10.1016/j.ejps.2003.08.002}, abstractNote={The phenyl (thio) semicarbazide derivatives of phthalimido pharmacophore were synthesized and evaluated for their anticonvulsant and neurotoxic properties. Initial anticonvulsant screening was performed using intraperitoneal (i.p.), maximal electroshock-induced seizure (MES), subcutaneous pentylenetetrazole (scPTZ) and subcutaneous strychnine (sc STY)-induced seizure threshold tests in mice. Compound 2c afforded protection in all the three screens. Compounds except 1d, 2a and 2d showed no neurotoxicity up to 300 mg/kg. Compounds 1a, 1b, 2c, 2d, 2g and 2i were found to show oral MES activity. The compounds exhibited CNS depression and behavioral despair side effects, lesser than the conventional antiepileptic drugs.}, number={3}, journal={European Journal of Pharmaceutical Sciences}, author={Yogeeswari, P. and Sriram, D. and Saraswat, V. and Ragavendran, J.V. and Kumar, M.M. and Murugesan, S. and Thirumurugan, R. and Stables, J.P.}, year={2003}, pages={341–346} } @article{yogeeswari_sriram_saraswat_ragavendran_kumar_murugesan_thirumurugan_stables_2003, title={Synthesis and anticonvulsant and neurotoxicity evaluation of N4-phthalimido phenyl (thio) semicarbazides}, volume={20}, number={3}, journal={Eur J Pharm Sci}, author={Yogeeswari, P. and Sriram, D. and Saraswat, V. and Ragavendran, J. V. and Kumar, M. M. and Murugesan, S. and Thirumurugan, R. and Stables, J. P.}, year={2003}, pages={341–6} } @article{yogeeswari_sriram_brahmandam_sridharan_thirumurugan_stables_2003, title={Synthesis of novel aryl semicarbazones as anticonvulsants with GABA-mediated mechanism}, volume={12}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0347380971&partnerID=MN8TOARS}, number={2}, journal={Medicinal Chemistry Research}, author={Yogeeswari, P. and Sriram, D. and Brahmandam, A. and Sridharan, I. and Thirumurugan, R. and Stables, J.P.}, year={2003}, pages={57–68} } @article{thirumurugan_kavimani_srivastava_2000, title={Antitumour activity of Rhinacanthone against Dalton's ascitic lymphoma}, volume={23}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034530360&partnerID=MN8TOARS}, DOI={10.1248/bpb.23.1438}, abstractNote={The antitumour activity of Rhinacanthone (3,4-dihydro-3,3-dimethyl-2H-naphtho-[1,2-B] pyran-5,6-dione) has been evaluated against Dalton's ascitic lymphoma (DAL) in Swiss albino mice. A significant enhancement of mean survival time of tumour bearing mice and peritoneal cell count in normal mice was observed with respect to the control group. When these Rhinacanthone treated animals underwent i.p. inoculation with DAL cells, tumour cell growth was found to be inhibited. After 14 d of inoculation, Rhinacanthone was able to reverse the changes in the haemotological parameters, protein and packed cellular volume consequent to tumour inoculation.}, number={12}, journal={Biological and Pharmaceutical Bulletin}, author={Thirumurugan, R.S. and Kavimani, S. and Srivastava, R.S.}, year={2000}, pages={1438–1440} }