13^th World Congress on Pharmacology and Toxicology November 14-15, 2018 | Mercure Albert Park | Melbourne, Australia

Biography:

Khalid Aftab has completed his PhD in Pharmacology, graduated from Department of Pharmacology, Faculty of Pharmacy and University of Karachi, Pakistan. He is currently working as a Professor and Head of Pharmacology in SMC, University of Health Sciences. He has published more than 50 papers in scientific journals of international repute and has participated in many conferences, gave lectures and poster presentations globally. His focus is on the biodiversity and pharmacological activities of marine organisms.

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Prof. B. Singh has a long teaching and research experience in the field of horticulture and forestry. During the past 30 years of his research he has contributed in the horticulture, agroforestry and forest resource utilization. He has been working on medicinal plant and their management in the Indian Eastern Himalayan region. He has completed some important projects on medicinal plant diversity distribution and mapping in north eastern of India. Visiting forest areas and exploration of resources for livelihood support to the rural communities are his prime focus presently

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Medicinal plants are one of the important forest resources under non timber forest producing plant species and because of their ethno medicinal and pharmacological values they are prioritized in management and conservation practices. The Indian eastern Himalayan is a rich floristic diversity region of the world and recognized as one of the biodiversity hotspot of the world. Because of the altitudinal variation, it harbors almost all the forest types viz. tropical subtropical, temperate and alpine forests. Medicinal plants form one of the important components of these forests and particularly the tropical and alpine forest form the habitat of a large number of high value medicinal plants having pharmacological potential. Many of the medicinal herb like Acorus calamus, Berberis aristata, Coptis teeta, Embelia ribes, Garcinia pedunculata, Homalomena aromatica, Illicium griffithii, , Podophyllum hexandrum, Piper peepuloides, P. mullesua, Sapindus mukorsii, Swertia chirayita, Taxuas wallichiana etc are distributed in the region. To understands their status of occurrence, ecological distribution, threats and conservation status, we have conducted various field studies during the past 10 years. Field survey and studies were conducted in various forest areas including tropical, subtropical and temperate forests. In this paper we discussed the present status of diversity, management and conservation aspects of some high value medicinal plants of eastern Arunachal Pradesh. 

Biography:

Dr. P. R. Gajurel hasbeen working in plant diversity and taxonomy of higher plants in the Eastern Himalayan region of India since past 20 years. During the past 10 years he has extensively working on medicinal plants and their management and conservation including the traditional knowledge systems. He has published more than 50 research article and presented paper in about 15 international conferences

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The north east India with its eastern Himalayan region is bestowed with diversified medicinal plants which include the globally significant medicinal herbs as well as the underutilized ethnomedicinal herbs. The region comprises of 8 administrative states including the biodiversity  rich states of Arunachal Pradesh and Sikkim of eastern Himalaya.  More than 200 ethnic communities are residing in the region and majority of them are still dependent on locally available plants species for curing the different health ailments. Understanding the traditional knowledge and practices of these tribes not only pave the way for identification of the medicinal plants but also for finding new pharmaceutical leads and formulation of valuable drugs. To understands the important ethnobotanical knowledge and the herbal practices adopted by the indigenous people, the authors have been exploring the region continuously for the few years. During the field visits and ethnobotanical data collection the authors could come across with many ethnomedicinal plants which are used for different diseases and ailments. Although some of the medicinal plants used by these communities are already known for their therapeutic potential but the complete bioactive properties of these plants yet to be explored. Moreover, the pharmacological relevance of some of these ethnomedicinal plants  need to be experimented. This will certainly benefit the mankind and also the poor communities through benefit sharing of the commercial outcomes. The present paper discussed the ethnobotanical uses and pharmacological potential of five medicinal plant species used by the local communities of north east India.

Biography:

Xiaolong Xu, who received a PhD degree from China Agriculture University (2012-2015), has his expertise in studying traditional Chinses herbal medicines with anti-inflammatory properties. He also engaged in pathogenesis of sepsis, psoriasis, and inflammatory diseases. He is now continuing his research work in Beijing Hospital of Traditonal Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, and Beijing Key Laboratory of Basic Research with  Traditional Chinese Medicine on Infectious Diseases.

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Current data have shown that punicalagin (PUN), an ellagitannin isolated from Pomegranate, possesses anti-inflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the first report that PTP1B serves as a direct target of PUN, with IC₅₀ value of 1.04 μM. Results from NPOI further showed that the K_on and K_off of PUN-PTP1B complex were 3.38e2 M^-1s^-1 and 4.13e-3 s^-1, respectively. Computation simulation by Autodock 4.0 predicted that PUN inhibited PTP1B via binding to Cys215, Arg221, and Arg24. Moreover, inhibition of PTP1B by PUN promoted an M2c macrophage polarization and enhanced anti-inflammatory expression, including IL-10 and M-CSF. Based on gene expression profile, we elucidated that PUN treatment significantly up-regulated 275 genes and down-regulated 1059 genes. M1 like macrophage marker genes, such as Tlr4, Irf1/2, Hmgb1, and Stat1 were down-regulated, while M2 marker genes, including Tmem171, Gpr35, Csf1, Il1rn, Cebpb, Fos, Vegfα, Slc11a1, and Bhlhe40 were up-regulated in PUN-treated macrophages. Hmox-1, a gene encoding HO-1 protein, was preferentially expressed with 16-fold change. Inhibition of HO-1 obviously restored PUN-induced M2 polarization and IL-10 secretion. In addition, phosphorylation of both Akt and Stat3 contributed to PUN-induced HO-1 expression. This study provided new insights into the mechanisms of PUN-mediated anti-inflammatory and anti-oxidant activities and provided new therapeutic strategies for inflammatory diseases.

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Michele Visentin is working in Department of Clinical Pharmacology and Toxicology at University Hospital Zurich, Switzerland

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Background: Colistin is a member of the polymyxin family, a class of fatty acyl peptide antibiotics isolated from different species of Bacillus polymyxa seventy years ago. Colistin was gradually discontinued from clinical practice due to the high incidence of nephrotoxicity, however, the emergence of Multidrug-resistant (MDR) have made colistin the main option of the last decade for the treatment of MDR gram-negative bacterial infections. Colistin administration remains extremely challenging due to the high incidence of nephrotoxicity even when the target concentration would only be associated with bactericidal activity for organisms at the lower end of the susceptibility range. The mechanism behind colistin-induced nephrotoxicity is unknown. Mice exposed to colistin for a week showed sign of mitochondrial stress at the kidney cortex level.

Aim: This work aims to study the mechanism underlying colistin-induced mitochondrial dysfunction.

Results: Primary cultured proximal tubule cells exposed to colistin for 48h showed reduction of rhodamine123 accumulation in mitochondria, indicating mitochondrial membrane potential depolarization. Freshly isolated mitochondria from mouse kidney experienced a rapid, dose-dependent, depolarization, in presence of colistin, suggesting that mitochondrial damage was a primary effect of colistin. Isolated mitochondria were fully protected from colistin-induced membrane depolarization by co-incubation with ADP, and only partially protected by cyclosporine A, suggesting that colistin induced mitochondrial membrane depolarization by inducing the opening of the mitochondrial permeability transition pore (MPTP). Activated free fatty acids (e.g. palmitoyl-CoA) inhibit the adenosine nucleotide translocase (ANT) and induce the MPTP opening. As colistin contains a fatty acid chain (C7), the effect of colistin on the mitochondrial uptake of radiolabelled nucleotides was assessed (cis-inhibition assay). Colistin was able to reduce the [³H]ATP uptake in isolated mitochondria and an IC₅₀ was computed to be 2.2 mM (95% CI 0.9 to 5.4).

Conclusions: Colistin induced mitochondrial membrane depolarization by inhibiting the adenosine nucleotide translocase (ANT) and, in turn, inducing the MPTP opening.

Biography:

Nader G Abraham is working in Departments of Medicine and Pharmacology at New York Medical College, New York

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We have previously reported that epoxyeicosatrienoic acid (EET) has multiple beneficial effects on vascular function, in addition to its anti-apoptotic action; it increases insulin sensitivity and inhibits inflammation. To uncover the signaling mechanisms by which EET reduces cardiomyopathy, we hypothesized that EET infusion might ameliorate obesity-induced cardiomyopathy by improving HO-1, Wnt1, thermogenic gene levels and mitochondrial integrity in cardiac tissues and improved pericardial fat phenotype. EET reduced levels of fasting blood glucose, and pro-inflammatory adipokines including NOV signaling while increasing echocardiographic fractional shortening and O₂ consumption. Of interest, we also noted a marked improvement in mitochondrial integrity, thermogenic genes, Wnt 1 and HO-1 signaling mechanisms.  Knockout of PGC1a in EET-treated mice resulted in a reversal of these beneficial effects including a decrease in myocardial Wnt1 and HO-1 expression and an increase in NOV. To further elucidate the effects of EET on pericardial adipose tissues, we observed EET treatment increases in adiponectin, PGC1α, pAMPK, insulin receptors phosphorylation and thermogenic genes resulting in a “Browning’ pericardial adipose phenotype under high fat diets. Collectively, these studies demonstrate that an EET-agonist increased Wnt1; HO-1 signaling whiles decreasing NOV pathways and the progression of cardiomyopathy. Furthermore, this report presents a portal into potential therapeutic approaches for the treatment of heart failure and metabolic syndrome.

New and Noteworthy

The mechanism by which EET acts on obesity-induced cardiomyopathy is unknown. We describe a previously unrecognized function of EET infusion that inhibits NOV levels and activates Wnt1, hence identifying NOV inhibition and enhanced Wnt1 expression as novel pharmacologic targets for the prevention and treatment of cardiomyopathy and heart failure.

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Hiroshi Maruta is working at PAK Research Center, Melbourne, Australia.

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Our research goal is to understand the synaptic mechanisms involved in the pathophysiology of chronic pain and psychiatric disorders. We try to understand how brain circuit modulates neuronal transmission in midbrain periaqueductal gray, which is an critical region of midbrain for controlling of pain and emotion. We also try to understand how the analgesic compounds and antidepressants regulate pain and depression leads to therapeutic efficacy in the brain, especially in the periaqueductal gray.

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Statement of the Problem: Major depressive disorder affecting more than 100 million people worldwide every year is a heterogeneous illness. To date, current pharmacotherapies require prolonged administration from several weeks to months for an appreciable response. This is particularly concerning given that suicide risk is elevated in subjects with depression.

Methodology & Theoretical Orientation: It is still unclear that whether ketamine metabolite (2R,6R-hydroxynorketamine; 2R,6R-HNK) rescues chronic stress-elicited depression-like behavior. Depression-like behavior in the rats were induced by learned helplessness (LH) procedure. Forced swim test (FST) and sucrose preference test (SPT) were used to study the depression-like behavior. Findings: Rats receiving learned helplessness procedure exhibited high failure rate in the escapable footshock test compared to control group. LH rats exhibited an increase in immobile time during the FST and a reduction in sucrose consumption. Intraperitoneal ketamine metabolite, 2R,6R-HNK, injection decreased immobile time during the FST and increased sucrose consumption in LH rats.

Conclusion & Significance: Ketamine metabolite 2R,6R-HNK rescues LH-induced depression-like behavior including despair behavior and anhedonia. These results may pave the foundation for a critical issue that ketamine metabolite, 2R,6R-HNK plays crucial roles in stress-induced depression-like behaviors and provides a new insight into depression management and development of antidepressants.

Biography:

Katrin Mae M. Ortega, a bonifide graduate in Master of Science in pharmacy at the age of 25 years from of University Of Santo Tomas last June 2017 wherein she was awarded a dsitinction of Cum Laude. During her graduate study, Ms Ortega exhibited top performance during written examination as well as oral examinations. She got a Meritus honor on her thesis entitled “Antiangiogenic and AMP-Activated Protein Kinase Activities of Gracilaria coronopifolia J.G. Agardh Extracts”. This study as awarded gold medal in the Technical Poster Competition during 2nd International Science Graduate Scholars” Conference in the theme “From Disccoveries Today to Innovating Tommorow” held at the Philippine International Convention  Center Pasay City.

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AMP-activated protein kinase (AMPK) is an intracellular energy sensor which is important in metabolic regulation, cell growth, and survival. Recently, dysfunction in AMPK is implicated to numerous angiogenesis-related diseases, however, the mechanism remains elusive. In this study, the antiangiogenic activity of the red alga, Gracilaria coronopifolia, was determined through cellular signaling pathway of AMPK. Chorioallantoic membrane (CAM) assay showed that all extracts of G. coronopifolia inhbited angiogenesis in a dose-dependent manner. Among them, dichloromethane extract exhibited the most potent antiangiogenic activity (IC50 =1.21 μg/mL, p=0.215) followed by hexane extract (IC50=3.08 μg/mL, p=0.479) and methanol extract (IC50=8.93 μg/mL, p= 0.042). Antiangiogenic activity was correlated to a low concentrations of Fe, Zn, and Cu of duck CAM determined using flame atomic absorption spectrometer (fAAS) and colorimetric assay. Likewise, In vitro AMPK signaling assay showed that all extracts activated AMPK, with dichloromethane extract having the lowest EC50 of 70.2 μg/mL. Thin layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS) revealed the active component of each extracts. Notably, this is the first report on the AMPK activity of G. coronopifolia related to new blood vessel formation and a colorimetric-based correlation of angiogenesis based on Fe, Zn, and Cu concentration in the duck chorioallantoic membrane.

Biography:

Poi Yee Cheong is currently pursuing her PhD degree at Monash University Malaysia. She has completed her Master degree in Medical Sciences at International Medical University, Malaysia. Her research interests focus on the characterization of the molecular mechanisms of benzyloxycarbonyl-phenylalanine-alanine-fluoromethylketone (z-FA-FMK) and benzyloxycarbonyl-phenylalanine-alanine-chloromethylketone (z-FA-CMK) induced toxicity in T cells. Both compounds are structurally similar; the former with fluorine in the methylketone group is immunosuppressive whereas the latter with chlorine induced cell death.

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The cathepsin B inhibitor, benzyloxycarbonyl-phenylalanine-alanine-fluoromethyl ketone (z-FA-FMK) was found to readily inhibit Jurkat T cell proliferation at non-toxic concentrations. We showed that z-FA-FMK treatment leads to a decrease in intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) levels in Jurkat T cells. The inhibition of Jurkat T cell proliferation induced by z-FA-FMK were abolished by the presence of low molecular weight thiol-containing antioxidants such as GSH, N-acetylcysteine (NAC), L-cysteine but not with D-cysteine, which cannot be metabolized to GSH. These results suggest that the depletion of intracellular GSH is the underlying cause of z-FA-FMK-induced inhibition of cell proliferation in Jurkat T cells. Similarly, L-buthionine-sulfoximine (BSO) which blocks GSH biosynthesis also inhibits Jurkat T cell proliferation. In the presence of BSO, NAC has no effect on the inhibition of cell proliferation mediated by z-FA-FMK. Taken together, these results demonstrated that the inhibition of Jurkat T cell proliferation induced by z-FA-FMK is due to oxidative stress via the depletion of GSH.

Biography:

Cao Donghua is a PhD candidate from Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences and  University of Chinese Academy of Sciences. Her Research Interest lies at the crossroads of chemistry and biology, and  endeavors to discover novel active natural products  from medicinal plant. She has published 3 papers in reputed journals .

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Meliaceous limonoids, characteristic chemical markers of the Meliaceae family, are natural products with both fascinating structures and potential bioactivities that have attracted interest from both natural products chemists and synthetic chemists in the past half century. As part of a continuing search for structurally interesting and biologically important limonoids from the Meliaceae family, the leaves and twigs of Trichilia sinensis collected from Xishuangbanna, Yunnan province of China were investigated. Trichilia sinensis Bentv, a shrub, is native to the south of China and Vietnam, and it has traditional applications for the treatment of several diseases such as abdominal pain caused by Ascaris lumbricoides, chronic osteomyelitis, scabies, and eczema in folk medicine. The three novel rearranged mexicanolide-type limonoids (Trichiliasinenoids A-C) with an unprecedented C-29-C-7 connecting carbon skeleton formed by migration of C-7 from C-6 to C-29 of a mexicanolide-type limonoid precursor were isolated from the leaves and twigs of Trichilia sinensis. Their structures were assigned by spectroscopic analysis, and the absolute configurations were determined by X-ray crystallography and CD calculation. A possible biosynthetic pathway of Trichiliasinenoids A was also proposed. The three new limonoids were evaluated for their cytotoxic activity against human myeloid leukaemia (HL-60), hepatocellular carcinoma (SMMC-7721), lung cancer (A-549), breast cancer (MCF-7), and colon cancer (SW480) cell lines by MTS assay. Trichiliasinenoid B showed cytotoxicity against HL-60 cells, SMMC-7721 with an IC₅₀ value of 5.2 mM and 30.6 mM, respectively, whereas other limonoids were inactive  and comparable to the cisplatin positive control (IC₅₀: 1.1–17.3 m M).

Biography:

Dr. Rishi Pal has completed Postgraduate degree in 2001 and Ph.D (Pharmacology) in 2007 from Faculty of Medicine, University of Delhi. He has awarded Postdoctoral training fellowship by University of Texas, MD Anderson Cancer Centre (UTMDACC), Houston, Texas, USA. He is Associate Professor, Department of Pharmacology & Therapeutics, King George’s Medical University, UP, Lucknow, India. He is supervising MD/PhD students for their thesis. He has published more than 25 research papers in journals of repute, one book, two book chapters and serving as reviewer of many scientific international journals.

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Introduction: Phosphodiesterase (PDE) inhibitors are known to increase cAMP/cGMP in the cellular compartment and leads to signal transduction process in the various cell system. Here we focused on the anti-inflammatory & immunomodulatory protective role of some cAMP/cGMP-PDE inhibitors theophylline, pentoxifylline, sildinafil & rolipram and their interactions with nitric oxide (NO) modulators in complete Freund's adjuvant induced rheumatoid arthritis in rats.

Method: Wistar rats (200-300 gm, n=6/group) of either sex were used in the study. On day '0' rats were injected with 0.2 ml of complete Freund’s adjuvant (CFA) in sub-planter region of right hind paw along with 0.1 ml of squalene to develop RA while controls received only vehicle. PDE inhibitors drug treatment alone and in combination with NO modulators was given from day '14' to '28'. Arthritic parameters a) arthritis index, b) ankle diameter c) paw volume and their body weight were noted to evaluate progression of RA on day 0, 7, 14, 21 and 28. On day '28' rats were sacrificed and their blood and paws were collected for TNF-α and IL-10 cytokine estimation, pathological examination and NF-kB expression. Data obtained was analysed using two-way ANOVA followed by Newman-Keul’s posthoc test and p<0.05 was considered for significance.

Result: It was found that CFA significantly increased arthritis-index, paw volume, ankle diameter and serum TNF-α and NF-kB levels while body weight and serum IL-10 levels was significantly decreased (P<0.05). These CFA-induced changes were significantly reversed by theophylline (10 & 20 mg/kg), P<0.0001; pentoxifylline (5 & 10 mg/kg), P<0.002; rolipram (1 & 2 mg/kg), P<0.05; sildenafil (50 & 50 mg/kg) alone and in combination with L-arginine (100 mg/kg) and or L-NAME (10 mg/kg) in dose dependent manner (p<0.005) in all parameters (1). The maximum protective effects was observed in theophylline > pentoxifylline > rolipram > sildinafil with L-NAME 10 mg/kg combination treatment group (p<0.001). The data obtained was substantiated histopathological analysis (2).

Conclusion: Results of this study are suggestive of the involvement & interaction of NO with different PDE inhibitors. cAMP/cGMP mediated PDE inhibition may have protective role in pathogenesis of rheumatoid arthritis. Further studies are required to dissect out the role of PDE inhibitors and nitric oxide (NO) modulators at cellular level in RA.

Biography:

Prakash Kinthada is a professor in chemistry at Sri Vidyanikethan Engineering college, JNTU University in Tirupathi, India.

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Cancer is a dreadful disease and any practical solution in combating this disease is of paramount importance to public health. Cancer patients have burdened by drug induced toxic effects, and no turned to seek help from the complementary and alternative medicine hoping for a better cure. Research on Platinum based drugs and Non Platinum based drugs is a Multi-Million Dollar Industry in USA and there is every need to produce safe drugs for the cure of this monstrous disease. Flavonoids have a long history of use in traditional medicines in many cultures. The phytochemical, curcumin is one of the major dietary flavonoid, belonging to a group of flavonol, Curcumin is a natural polyphenol. It is highly potential molecule capable of preventing and treating various cancers.  Various dietary chemo preventive agents, turmeric powder or its extract are broadly used as therapeutic preparations in Indian System of medicine. We provide a summarized synthesis and structural determination of Curcumin Oxime, Curcumin Thiosemicarbazone derivative of Gold (III) complex. The use of these analogs for prevention of cancer tumor progression and treatments of human malignancies. A pharmacologic agent for treating and/or preventing cancer, among other diseases and conditions, and particularly breast, prostate, and pancreatic cancer, in humans and animals. The novel pharmacologic agent is an isoflavonoid or isoflavonoid mimetic covalently attached to a cytotoxic pharmacophore that, preferably has the ability to conjugate with a metal salt to form a more potent metal complex, particularly a Au (III) complex and other complexes of Platinum, Palladium, Ruthenium, Copper etc.

Biography:

Anil Kumar is working in Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study (UGC-CAS), Panjab University, Chandigarh, India

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Therapeutic potential of berberine has been well documented in various neurological problems. However, neurological mechanism of berberine remains untapped in the light of its p-glycoprotein mediated gut efflux properties responsible for reduced bioavailability. The present study was designed to evaluate the neuroprotective mechanism of berberine and its effect on various behavioral alterations, oxidative stress, mitochondrial dysfunction, neuroinflammation and histopathological modifications in sporadic dementia of Alzheimer's type in rats. Berberine (25, 50 and 100 mg/kg) or verapamil (2.5 and 5 mg/kg) were used as a treatment drugs and memantine (5mg/kg) was used as a standard. In the present study, berberine and verapamil significantly attenuated behavioural, biochemical, cellular and histological alterations suggesting their neuroprotective potential. Further, treatment of berberine (25 and 50  mg/kg) with verapamil (2.5 and 5.0 mg/kg) combinations respectively significantly potentiated their neuroprotective effect which was significant as compared to their effect per se in ICV-STZ treated animals. The augmentative outcome of verapamil on the neuroprotective effect of berberine can be speculated due to the inhibition of P-gp efflux mechanism and the prevention of calcium homeostasis alteration. In addition, anti-inflammatory and antioxidant effects of both berberine and verapamil could also contribute in their protective effect.

Biography:

Nader G Abraham is working in Departments of Medicine and Pharmacology at New York Medical College, New York

Abstract:

The global epidemic of obesity continues unabated with sequelae of diabetes and metabolic syndrome. This review reflects the dramatic increase in research on the role of increased expression of heme oxygenase (HO)-1/HO-2, biliverdin reductase, and HO activity on vascular disease. The HO system engages with other systems to mitigate the deleterious effects of oxidative stress in obesity and cardiovascular disease.  Recent reports indicate that HO-1/HO-2 protein expression and HO activity have several important roles in hemostasis and ROS-dependent perturbations associated with metabolic syndrome. HO-1 protects tissue during inflammatory stress in obesity through the degradation of pro-oxidant heme and the production of CO and bilirubin, both of which have anti-inflammatory and anti-apoptotic properties. In contrast, repression of HO-1 is associated with increases of cellular heme and inflammatory conditions including hypertension, stroke and atherosclerosis. HO-1 is a major focus in the development of potential therapeutic strategies to reverse the clinical complications of obesity and metabolic syndrome.

Biography:

Dr. Hesham N. Mustafa has received his MD in basic medical sciences (Anatomy) from Ain Shams University, Cairo, Egypt at 2009. Currently, he is working as an associate professor in basic medical sciences (Anatomy) department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. He has published more than 15 papers in reputed journals and been serving as an editorial board member and a reviewer at many reputed Journals. He received Certificate for Highly Cited Paper from Elsevier in December, 2016 And Award of Excellence of Scientific Publication for the staff members, from Deanship of Scientific Research, King Abdulaziz University.

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Background. Renal ischemia-reperfusion injury (IRI) represents the main reason for acute kidney injury (AKI). Dexmedetomidine (Dex) and Benincasa cerifera (BC) have wide beneficial effects being anti-inflammatory and antioxidants. This study aims illustrate the protective effects of BC and Dex on renal IRI of diabetic model.

Methods. Sixty Male Albino Rats (Wistar strain), weighing 250-300 g. Rats were divided in to 4 groups; Sham group: Non-diabetic. DM+IRI group: STZ-diabetic rats exposed for renal IRI on days 30 after diagnosis of diabetes. DM+IRI+BC group: STZ-diabetic rats were treated with Benincasa Cerfera (500 mg/kg) for 30 days after diagnosis of diabetes then they exposed for renal IRI. DM+IRI+Dex group: STZ-diabetic rats were treated with Dex (100µg/kg intra-peritoneal) 5 minutes before induction of ischemia on day 30 after diagnosis of diabetes then they exposed for renal IRI. Biochemical parameters, histopathological examination and immunohistochemical markers were evaluated.

Results. Significant improvement of biochemical, histopathological and immunohistochemical parameters in (DM+IRI+BC) group while (DM+IRI+Dex) group showed an improving in renal IRI and dyslipidemia.

Conclusion. The present study demonstrated that oxidative stress plays a chief role in renal IRI in STZ-induced diabetic model. Treatment with BC achieved excellent ameliorative effects while treatment with DEX improves renal IRI.

Biography:

Professor Natasa Petronijevic, MD, PhD, has finished her PhD thesis in 2001 at the School of Medicine, University of Belgrade, Serbia. She is a specialist of clinical biochemistry and laboratory medicine. She is a project leader of scientific projects financed by Serbian Government Ministry of Science and a reviewer in several respectable international journals. She is a course director of medical biochemistry and director of PhD studies of neuroscience at the School of Medicine, University of Belgrade. She is a president of  Section for Clinical biochemistry, Serbian Medical Society. She has pulished more than 45 papers in reputed journals.

Abstract:

Decreased bone mineral density, inflammation and dysregulation of hypothalamic–pituitary–adrenal (HPA) axis are described in schizophrenia (SCH). Long-term treatment with antipsychotics is often required for disease control. Perinatal phencyclidine (PCP) administration to rodents represents an animal model of SCH. The aim of this study was to assess the effects of chronic haloperidol and clozapine treatment on bone mass, concentrations of IL-6, TNF-α and corticosterone in serum and the expression of the glucocorticoid receptor (GR), phosphorilated GR (pGR), chaperone and co-chaperone proteins (HSP70, HSP90, FKBP51) and glucocorticoid metabolising enzyme (11β-HSD1) in the brain of adult rats perinatally treated with PCP. Male Wistar  rats were subcutaneously treated on 2^nd, 6^th, 9^th and 12^th postnatal day (PN), with either PCP or saline. Antipsychotics were apllied from PN35. Dual X-ray absorptiometry measurements were performed on PN98. Animals were sacrificed on PN100. Concentrations of corticosterone, TNF-α and IL-6 were measured in the serum using ELISA kits. Expressions of proteins were assessed by Western blot. Perinatal PCP administration caused a significant decrease in bone mass and deterioration in bone quality. It didn’t have influence on the interleukine and corticosterone consentrations but changed the expression of GR related proteins indicating increased sensitivity of GR signaling system. Haloperidol had deleterious, while clozapine had protective effect on bones. Both haloperidol and closapine caused decrease of the sensitivity of GR signaling system but clozapine caused significant increase of corticosterone and TNF-α concentrations. Taken together our results indicate that haloperidol affects bones while clozapine alters HPA axes and inflammatory markers.

Biography:

Naveen Y P is working in Department of Studies in Food Science and Nutrition, University of Mysore, Manasagangothri, Mysore, India.

Abstract:

Swietenia mahagoni is a medicinal plant used in various medicinal practices for the treatment of various human ailments. Present study evaluates the anti-diabetic potential of Swietenia mahagoni aqueous extract (MAE) in fructose induced diabetic rats with insulin resistance. Diabetes was induced in the rats by treating the rats with 20 % fructose (W/V) in drinking water for 40 days. Diabetes and hyperinsulinemic condition was confirmed by assessing the glucose and insulin levels in the blood of the experimental rats. After the confirmation of diabetic condition, rats were treated with the MAE and the standard drug metformin and one group left without any treatment and labelled as positive control. MAE treatment improved glucose levels, reduced Insulin levels, improved insulin sensitivity, improved glucose tolerance, improved pancreatic β-cell health, decreased glycated hemoglobin content, reduced lipid peroxides, improved glycogen content and activity of enzymes involved in the synthesis of glycogen in the liver. There was also overall improvement in anti-oxidant status (improved levels of vitamin C, SOD and Catalase and decreased amount of lipid peroxides) of the treated groups when compared with the diabetic control. The treatment also improved the lipid profile (improved HDL and lowered LDL and triglycerides) of diabetic rats. Results confirmed the anti-diabetic potential of MAE in animal model indicating its scope for use as diabetic adjuvant in T-2 diabetic subjects.

Biography:

Luiz Augusto da Silva has his expertise in exercise effects in diabetes factors. Sua principal linha de pesquisa é a análise do comportamento de substratos energéticos relacionados a efeitos da cafeína e do exercício físico, buscando alternativas coadjuvantes no tratamento do diabetes mellitus. Novas teorias foram implementadas em seus estudos, como respostas hormonais frente ao exercício físico para o quadro diabético.

Abstract:

Swietenia mahagoni is a medicinal plant used in various medicinal practices for the treatment of various human ailments. Present study evaluates the anti-diabetic potential of Swietenia mahagoni aqueous extract (MAE) in fructose induced diabetic rats with insulin resistance. Diabetes was induced in the rats by treating the rats with 20 % fructose (W/V) in drinking water for 40 days. Diabetes and hyperinsulinemic condition was confirmed by assessing the glucose and insulin levels in the blood of the experimental rats. After the confirmation of diabetic condition, rats were treated with the MAE and the standard drug metformin and one group left without any treatment and labelled as positive control. MAE treatment improved glucose levels, reduced Insulin levels, improved insulin sensitivity, improved glucose tolerance, improved pancreatic β-cell health, decreased glycated hemoglobin content, reduced lipid peroxides, improved glycogen content and activity of enzymes involved in the synthesis of glycogen in the liver. There was also overall improvement in anti-oxidant status (improved levels of vitamin C, SOD and catalase and decreased amount of lipid peroxides) of the treated groups when compared with the diabetic control. The treatment also improved the lipid profile (improved HDL and lowered LDL and triglycerides) of diabetic rats. Results confirmed the anti-diabetic potential of MAE in animal model indicating its scope for use as diabetic adjuvant in T-2 diabetic subjects.

Biography:

He is currently an assistant lecturer at Federal University Ndufu-Alike Ikwor,Ebonyi State,Nigeria.His bachelors degree is in Medicine and Surgery(MBBS).Currently he is running a masters degree in Pharmacology and Therapeutics in Ebonyi State University, Nigeria.

Abstract:

Therapeutic drug Monitoring is used to monitor a patient’s progress in the course of treatment and to enhance their therapeutic outcome of patients on Highly Active Antiretroviral Therapy(HAART). It is aimed at identifying drug dependent toxicity in other to adjust dose or change regime among these group of patient. This is extremely important  for drugs with narrow therapeutic index. Chromatography and Immunoassay can be employed in this process especially as because of its specificity and cost effectiveness in estimation of therapeutic drug monitoring. Although this requires expertise and highly trained personnel for this to be carried out. This is most crucial aspect of therapeutic drug monitoring. The setting up of therapeutic drug monitoring is capital intensive both in terms of equipment and personnel. Nigeria been a developing country suffers is its own set back as it requires political will to enable her carry out effective Therapeutic drug monitoring. Therapeutic drug monitoring team comprises of Medical officer,Pharmacologist,PharmarcistandNurse.Pharmacogentics,clinical toxicologist.Trainining and retraining is highly advocated for Doctors in clinical practice as clinical evidence on its own is not enough to determine toxicity. Regretably in most African Countries, this is not done hence the need for advocacy which  is the essence of this paper especially with regard to therapeutic drug monitoring of HAART among HIV patients who will be on life long treatment.

Biography:

Sunil Gowda S N is pursuing Ph D in Sastra University, India.

Abstract:

Radiotherapy is used to treat tumors of different origins and nature. Lung cancer patients significantly depend on radiotherapy for treatment but often lead to development of radioresistance and increase metastasis of cells. It is interesting that radiation induces the epithelial-mesenchymal transition (EMT), a process by which epithelial cells changes to mesenchymal property and gains enhanced tumor progression capability. Our study investigated the effect of Trichostatin A (TSA), a natural derivate isolated from Streptomyces, upon radiation-induced lung EMT and we tried to understand the role of signaling molecules in irradiated lung cancer cells A549. The cancer cells were irradiated at 8Gy of X-ray using LINAC. The cells were divided into four treatment group untreated control (C), Radiation alone (R), Radiation combined with TSA (R+T) and TSA 100nM (T). Radiation enhanced the migration of cancer cells whereas TSA treatment reduced the migration of cancer cells.  Radiation-induced lung EMT in A549 cells were evidenced by decreased expression of epithelial marker like E-cadherin, Zona occludin and increased expression of N-cadherin and vimentin. The Snail protein, a master regulator of EMT, was observed to be elevated after radiation treatment. In addition, TGF-ß1 signaling (smad2, 3, and 4) proteins were activated upon irradiation. Western blot data were supported by the altered m-RNA expression of E-cadherin. TGF-ß and Snail genes and this effect were reversed by TSA treatment. In addition to this as supportive evidence, we performed docking studies between snail protein and TSA using auto docking software and results suggested that less binding energy is needed for the putative binding of TSA on C-terminal domain of Snail protein. Based on our report, we suggest that TSA can effectively inhibit radiation- induced EMT (i) by altering epithelial and mesenchymal markers (ii) by modulating signaling molecules of TGFß1 pathway (iii) by inhibiting cancer cell migratory potential in A549 cells (iv) by effectively binding to Snail which is an enhancer of EMT. 

Biography:

He successfully completed  M. Pharm at the age of 25 years from Noakhali Science and Technology University with first position. He also completed  bachelor of pharmacy degree from this same institution with first position too. Presently he is working as a lecturer in pharmacy department of Atish Dipankar University of Science and Technology. He published more than 15 papers in reputed journals and have been serving as an editorial board member of American Journal of plant science.

Abstract:

Biography:

Ibrahim Malami has obtained his PhD from Universiti Putra Malaysia. He is a full time Faculty member and a Researcher at the Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria. His research interest emphasis on cancer research (of colorectal and breast) with focus on chemoprevention, biotherapeutics, and molecular biochemistry. He has published a quite number of papers in high impact journals of peer review process.

Abstract:

Uridine-cytidine kinase 2 is an enzyme that is overexpressed in abnormal cell growth and therefore, implicated in all types of cancers. Due to the selective expression of UCK2 in cancer cells, a selective inhibition of this key enzyme necessitates the discovery of its potential inhibitors for cancer chemotherapy. The present study was carried out to demonstrate the potentials of natural phytochemicals in inhibiting UCK2 enzyme activity useful for colorectal cancer therapy. Flavokawain B and alpinetin were isolated from the the rhizome of Alpinia mutica. These compounds were found to inhibit 50% cell proliferation at low IC₅₀ concentrations. Both compounds were found to reduce ADP production, possibly by inhibiting UCK2 activity using in vitro kinase assay. UCK2 was substantially downregulated in treated HT-29 cells both at gene and protein level. Subsequently, downregulation of 18S ribosomal RNA biosynthesis was confirmed using live cell fluorescence imaging. This study further suggested the possibility of p53 activation through MDM2 downregulation mediated by UCK2 enzyme inhibition. The expression of p53 protein induced p53 transactivation of targets genes that are essential in triggering cell cycle arrest and apoptosis of HT-29 cells. In this respect, apoptosis induction was further confirmed using DNA fragmentation analysis. Results from the in vitro studies have shown the ability of flavokawain B and alpinetin to target UCK2 enzyme specifically, inducing cell cycle arrest and subsequently leading to cancer cell death, possibly through interfering the MDM2-p53 signaling pathway. These phenomena have proven that the bioactive compounds could be useful for future therapeutic use in colorectal cancer.

Biography:

He completed Ph.D in microbiology. He published 8 research articles in high repute journals and also have 4.4 year experience as lab instructor in the department of bioscience, Integral University, Lucknow. His doctoral work has focused on heavy metal and multidrug resistant gram negative bacteria including E.coli, Enterobactor aerogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Serratia marcescens, Citrobacter amalonaticus and Proteus vulgaris from hospital wastewater. During his PhD tenure, apart from the main PhD theme, he also worked on some other areas which are significantly appealing to the global scientific community as they are fascinating to him.

Abstract:

The heavy metals are defined as any metallic chemical element that has a comparatively high density at low concentration; it is toxic or poisonous to all forms of life including bacteria. Hospital wastewater discloses the presence of molecules chlorinated in higher concentrations and in a punctual way the presence of heavy metals. Various studies have suggested that hospital wastewater receive inputs of heavy metals from the higher use of radionuclides, pharmaceuticals and antimicrobial solvents. Although some of these heavy metals are essential plant micronutrients and are required or are advantageous for plants and microbial development and growth (Zn, Cu, Fe, Mn, Ni, Mo, Co). The elevated amount and long-term presence of heavy metals, in environment are generally matter of due concern to society as they may adversely affect the quality of soil, water and concerned microbial population. Gram negative bacteria under heavy-metal stress are commonly resistant to their ions and the resistances can often be transferred by conjugation. The higher concentrations of heavy-metal ions form non specific complex compounds in the cell, which ultimately leads to toxic effects. Some heavy-metal cations, e.g. Hg²⁺ , Cd²⁺ and Ag²⁺, form strong toxic complexes, which makes them too dangerous for any physiological function. Therefore, the aim of this study is to reveal the facts as well as positive and negative interaction with gram negative bacteria and indicating the risk of environmental pollution and spread of heavy metal tolerance which may promote the development of resistance to drug among the pathogens. 

Biography:

Khalid AFTAB, PhD male, Pharmacologist, graduated from department of Pharmacology, Faculty of Pharmacy, University of Karachi, Pakistan in 1995. He worked for Pharmaceuticals industry as Quality Control & Quality Assurance professional and was actively involved in Research & Development of Pharmaceutical preparations. 

He has worked in few Medical & Dental Colleges & Universities as Assistant, Associate and became full Professor Pharmacology in 2006 and worked as visiting Professor in different Universities & research institutions. From 2009-2011, he has worked in Kingdom Saudi Arabia as a full Professor Pharmacology and currently working as Professor & HoD Pharmacology in SMC, University of Health Sciences.

Only Pakistani Pharmacologist who has got membership of American College of Clinical Pharmacology. Now he has published more than 50 papers in scientific journals of international repute and presented many lectures & poster presentations throughout the world, most awards to him was for the science and technology success. He was involved in drug discovery and the scientific evaluation of traditional remedies used in different disorders. His group has developed expertise in a wide range of activities and made valuable contributions on medicinal value of plants by providing pharmacological basis for their usefulness as antihypertensive, cardio-tonic, laxative, antispasmodic and anti-diarrheal. In recent year, he focused on the Biodiversity & Pharmacological activities of Marine organisms and got some important success.

Abstract:

Holarrhena pubescens belongs to the family Apocynacea, commonly known as “kurchi” is highly reputed in traditional medicine as a remedy for amoebic dysentery and other intestinal ailment. Bioassay-directed fractionation by chromatographic methods the ethanolic extract of Holarrhena pubescens resulted in the isolation of steroidal alkaloids i.e. Holamide and Pubscinine [1]. Holamide showed a three proton doublet at 1.45 (J=6.56 Hz) and two AB doubles at 3.17 and 3.00 each for on proton (J=12.06 Hz) in the 1H NMR spectrum suggested that it belongs to conanine series of alkaloid (A class of compound with the steroid nucleus and a five members heterocyclic ring with nitrogen). In contrast Pubscinine showed one methyl at 1.28 while the doublet is missing a three proton singlet was observed at 2.28 due to a vinylic methyl indicated a double bond in the 18,20 – epimino ring of the conanine series of alkaloids.

In anaesthetized rats, the Holamide and Pubscinine caused a fall in blood pressure in a dose-dependent manner. Pretreatment of animals Atropine completely abolished the hypotensive response of Acetycholine; whereas hypotensive effect of Holamide and Pubscinine were not modified by Atropine [1]. Similarly Acetylcholine produced contractile effect in guinea-pig ileum, which was antagonized by atropine, however both (Holamide and Pubscinine) failed to produced any stimulant response on guinea-pig ileum. These data indicate that the steroidal alkaloids i.e. Holamide and Pubscinine from Holarrhena pubescens mediated hypotensive response through a mechanism different to that of Acetycholine.