Scientific Program

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Day 1 :

Keynote Forum

CEJ van Rensburg (Connie Medlen)

School of Medicine, University of Pretoria, South Africa

Keynote: Medicinal applications of fulvic acid

Time : 10:35-11:15

OMICS International Pharmacology 2016 International Conference Keynote Speaker CEJ van Rensburg (Connie Medlen) photo
Biography:

Connie Medlen completed her pre and postgraduate studies in the Faculty of Medicine at the University of Pretoria, South Africa. She worked in the Departments of Immunology and Pharmacology at the University for 35 years before her retirement in 2009. In 2014 she was appointed as research Mentor for the Faculty. She has published 132 papers in international journals, presented at 45 international congresses and is the inventor/co-inventor of 6 patents. She publishes under the name of CEJ van Rensburg.

Abstract:

Humic and fulvic acid are natural products derived from the humification process of plant materials. A state owned company, tasked to find medicinal applications for bituminous coal, found a way to produce humic and fulvic acid from coal. We were requested to test these products for applications in the medical field and we found both these products are effective as antiinflammatory products. Fulvic acid also possesses broad spectrum antimicrobial activity in vitro and is effective in the eradication of bacteria including those resistant to antibiotics. Because of the expensive process of converting bituminous coal to humic and fulvic acid, a pharmaceutical company developed a safe and effective potassium humate product from brown coal and a second company developed a process to convert a carbohydrate source to fulvic acid, called carbohydrate derived fulvic acid. rnrnIn preclinical studies we found that the fulvic acid product suppresses the cutaneous immune response in mice whereas, in a phase 1 study done by a PhD student of mine (JJ Gandy), we found the product to be safe at a dosage of 40ml of a 3.8% solution taken twice daily for 3 days. In this clinical study a prelimary skin prick test was also done on the participants. The allergen to which the participants were most allergic, together with histamine and a negative control, were applied at the start and end of the study. A decrease in the wheel and flare reactions was observed in the treatment group. In conclusion we found that the product is safe and effective as an antiinflammatory agent at oral dosages of up to 40ml taken twice daily for one week. rnrnTo evaluate the efficacy and safety of the product as a atopical treatment for eczema, patients were randomely selected to receive fulvic acid or placebo (emolient therapy). A significant improvement in the symptoms was observed in the group treated with the product. In conclusion, the product was well tolerated and effective as a topical treatment for eczema. rn

Keynote Forum

Karen Mulkijanyan

Tbilisi State Medical University, Georgia

Keynote: Biologically active compounds of plant origin and their synthetic derivatives: Prospective therapeutic agents

Time : 11:30-12:10

OMICS International Pharmacology 2016 International Conference Keynote Speaker Karen Mulkijanyan photo
Biography:

Karen Mulkijanyan is the Head of the Department of Pharmacology at Tbilisi State Medical University Institute of Pharmacochemistry and Adviser on Technology Commercialization to afore-named Institute’s Administration. He obtained his MS in Biochemistry in 1981 and PhD in Pharmacy in 2005. His research areas are pharmacology of anti-inflammatory, wound healing and microcirculatory drugs, analysis of SAR and prediction of bioactivity of natural, modified and synthesized compounds. He is the author and co-author of more than 90 papers in peer reviewed journals, about 30 presentations at international scientific meetings, and 2 patents.

Abstract:

Plant extracts are still among the most attractive sources for drug development as they are believed to have no or minor side effects and thus, considered safe for use in humans. However, chemical constituents of many extracts represent serious risks to the human health. Thus, it is necessary to justify biological effects that are present in the vegetal products which are obtained from medicinal plants. For years, our research group is focused on chemical and pharmacological investigation of comfrey (Symphytum asperum and S. caucasicum) and bugloss (Anchusa italica) in order to determine the principal constituents responsible for their diverse curative properties. We succeeded in detecting and obtaining novel biopolymer that is Poly[3-(3.4-Dihydroxyphenyl) Glyceric Acid] (PDGA) from Boraginaceae family representatives Symphytum asperum, S. caucasicum and Anchusa italic and synthesis of its Monomer3-(3, 4-Dihydroxyphenyl) Glyceric Acid (MDGA). Pharmacological properties of PDGA and MDGA were studied both in vitro and in vivo experiments for antioxidant, wound healing, anticancer, leucopoietic properties. The obtained results revealed that, in vitro antioxidant activity and anti-complementary activity due to the inhibition of Xanthine oxidase complement convertase, respectively, abrogation of melanoma cells adhesion to tumor conditioned medium and VEGF-activated endothelial cells and also inhibition of prostate cancer cells growth. Consistent with in vitro results, in vivo study showed strong inhibition of 22Rvl tumors growth without any toxicity, rapid burn and wound healing due to the shortening of the second phase of wound healing that is the inflammatory response and significant stimulation of leucopoiesis in mice drug-induced leucopenia. From the above observed effects, it suggests that PDGA and MDGA have high therapeutic potential.

  • Pharmacology | Neuropharmacology | Psychopharmacology | Advances in Pharmacological Research
Location: Brunel Suite
Speaker

Chair

CEJ van Rensburg (Connie Medlen)

University of Pretoria, South Africa

Speaker

Co-Chair

Alexander Kulikov

Siberian Division of Russian Academy of Sciences, Russia

Speaker
Biography:

Walber Toma has completed his PhD from University of Campinas (Unicamp) from Brazil. He is the Researcher of the Department of Ecology from Santa Cecília University (Unisanta) and also from the Department of Pharmaceutical Sciences in São Camilo University (São Camilo). In Santa Cecília University, he is the main Researcher of a Laboratory of Natural Products that seeks ethnopharmacological informations from the south coast populations of São Paulo state. He is also the Director of a specialization course in Clinical Pharmacology at Unisanta. He has published more than 30 papers on the following subjects: ethnopharmacology, gastroprotective activity of plant extracts, toxicology and ecotoxicology assays from natural products.

Abstract:

Gastric ulcers are a significant medical problem and the development of complications lead to significant mortality rates worldwide. In Brazil, Carthamus tinctorius L., Asteraceae, seeds essential oil, the safflower oil, is currently used as a thermogenic compound and as treatment for problems related to the cardiovascular system. In this study, by Raman spectroscopy, it was shown that oleic and linoleic acids are the compounds present in higher concentrations in the safflower oil. We demonstrated that safflower oil (750 mg/kg, p.o.) decrease the ulcerogenic lesions in mice after the administration of hydrochloric acid-ethanol. The gastric ulcers induced by non-steroidal anti-inflammatory drug (NSAID) in mice treated with cholinomimetics were treated with four different doses of safflower oil, of which, the dose of 187.5 mg/kg (p.o.) showed significant antiulcerogenic properties (**p<0.01). Moreover, the safflower oil at doses of 187.5 mg/kg (i.d.) increased the pH levels, gastric volume (**p<0.01) and gastric mucus production (***p<0.001), and decreased the total gastric acid secretion (***p<0.001). The acute toxicity tests showed that safflower oil (5.000 mg/kg, p.o.) had no effect on mortality or any other physiological parameter. Ecotoxicological tests performed using Daphnia similis showed an EC50 at 223.17 mg/l, and therefore safflower oil can be considered “non-toxic” based on the directive 93/67/EEC on risk assessment for new notified substances by European legislation. These results indicate that the antiulcer activity of Safflower oil may be due to cytoprotective effects, which serve as support for new scientific studies related to this pathology.

Speaker
Biography:

Elisabetta Radice has completed her degree in Medicine in 1983 and Specialization in Digestive Apparatus Surgery and Digestive Endoscopy in 1988 at Naples University School of Medicine, Italy. She did her Fellowship at Colorectal Surgery Department Mayo Clinic Rochester (MN, USA) 1995-1997. She worked as Assistant Professor from 2001 at Department of Surgical Sciences, University of Turin, Italy.

Abstract:

Dendritic cells (DCs), specialized antigen-presenting cells bridging innate and adaptive immunity, play a crucial role in determining specific immune response to tumors. Because of their potent immunoregulatory capacities, DCs have been exploited in anticancer vaccination, with limited success thus far. This pilot study compared low-dose interleukin (IL)-4 and IL-12 prepared by sequential kinetic activation (SKA) with standard doses of the same recombinant human cytokines on functional activity of ex vivo-generated monocyte-derived (Mo) DCs from colon carcinoma patients and normal subjects. MoDCs were exposed to medium alone, SKA-IL-4 (0.5 fg/ml), or SKA-IL-12 (2 fg/ml), alone or consecutively combined, in parallel with rhIL-4 (50 ng/ml) and rhIL-12 (1 ng/ml). Primary allogeneic one-way mixed lymphocyte reaction (MLR) was the end point to assess in vitro T-lymphocyte proliferation in response to MoDCs, and secreted IL-12p70 and interferon-γ in MLR supernatants measured by ELISA to assay for T-helper 1-promoting MoDC phenotype. No single agent enhanced the compromised allostimulatory activity of MoDCs from colon cancer patients, unlike healthy donors. However, MoDCs from nonmetastatic colon cancer patients, after sequential exposure to SKA-IL-4 (48 hours) and SKA-IL-12 (24 hours), displayed increased T-cell stimulatory capacity by MLR and acquired driving T-helper 1 polarization activity, although less markedly than the effects induced by recombinant human cytokines or found in normal subjects. These results point to an immunomodulatory capacity of low-dose SKA-IL-4 and SKA-IL-12 and encourage further investigation to provide clues for the rational development of new and more effective immunotherapeutic strategies against cancer.

Speaker
Biography:

Alexander Kulikov has completed his PhD in 1983 and SD in 2005 from Institue of Cytology and Genetics (ICG). At present, he is the Head of Department of Collection of Neurophathologies. He has published more than 200 papers in reputed journals and participated at many international conferences. He is interested in the genetic and molecular mechanisms as well as the development of mouse models of  psychopathologies. Moreover, he is a well known expert in 5-HT system and tryptophan hydroxylase 2. He is coauthor of 6 new mouse models of psychopathologies. He supervised of 5 PhD students.

Abstract:

Mice with hereditary disturbances of the behavior and the brain are effective tools for preclinical study of the mechanisms of psychotropic drug action. Catalepsy or exagerated freezing is a sign of grave brain dysfunctions. The main gene determining of about 20% of genetic variation of catalepsy has been mapped at the terminal fragment of mouse chromosome 13. This fragment has been transferred from the catalepsy-prone CBA/Lac line to the genome of a catalepsy-resistant AKR/J line and the AKR.CBA-D13Mit76 (D13) recombinant line has been bred. About 50% of D13 mice are cataleptics. Mice of this line show elevated expression of the Il-6 gene, coding the pro-inflammation cytokine interleukine-6, in the cortex and hippocampus and sensitivity to lipopolysaccharide. MRI revealed a reduction of the pituitary gland in D13 mice. Unlike AKR mice, D13 mice show a spatial learning deficit in the Morris water maze (MWM). An acute ivc administration of 300 ng of brain derived neurotrophic factor (BDNF) normalized the performance and memory retention in the MWM in D13 mice. These results indicated a possible association between the hereditary catalepsy, MWM performance, pituitary gland reduction, BDNF and level of Il-6 mRNA in the brain, although the relation between these characteristics seems to be more complex. Thus, AKR.CBA-D13Mit76 recombinant mouse line with deficit of spatial learning, is a promising model for study of the genetic and molecular mechanisms of learning disorders as well as for screening potential cognitive enhancers.

T.G. Borovskaya

Goldberg Research Institute of Pharmacology and Regenerative Medicine, Russia

Title: Experimental study of the effectiveness of antioxidant therapy in treating the most common diseases of the male reproductive system

Time : 14:10-14:30

Speaker
Biography:

T G Borovskaya has graduated from the Tomsk State Medical University and received MD degree and completed her Post-doctoral studies from the Goldberg Research Institute of Pharmacology. She is the Head of Laboratory of Pharmacology. She has published 3 monographs, more than 190 papers in reputed journals and is the author of 17 patents. The field of interests covers Toxicology, Andrology and Embryology. 

Abstract:

Studies of the last decade show a degradation of reproductive health of men. At the same time great attention is paid to oxidative stress as a factor that negatively affects the organs of reproduction. The purpose of this work is to evaluate the effectiveness of antioxidants from the group of 8-hydroxy-pyridine, flavonoids, sterically hindered phenols in experimental models of pathospermia and benign prostatic hyperplasia (BPH). The experiments were performed on Wistar rats. Pathospermia was induced by a single administration of the cytostatic drug Etoposide in the maximum tolerated dose. BPH was induced by long-time administration (during 2 months) of Sulpiride. The both models gave a significant decrease in the redox potential, which is estimated by chemiluminescence. In the case of pathospermia was the only antioxidant from the group of sterically hindered phenols was found to be effective. This redox-potential of the male germ cells was not different from that of intact animals. The model of BPH showed statistically significant decrease of the area of epithelial acini under the introduction of all the studied antioxidants. But significant increase of the stromal-epithelial rate was found only on the background of the antioxidants from the group of hindered phenols. Redox-potential of prostate in this group of animals did not differ from the baseline values.

Speaker
Biography:

Ali Sheikh Md Sayed has completed his MD and PhD in Cardiology from Xiangya School of Medicine, Central South University. He is the Visiting Professor of Hunan Traditional Medical University. He has published more than 13 papers in reputed journals.

Abstract:

Acute myocardial infarction (AMI) is the leading cause of sudden cardiac death (SCD) in the world and remains a significant unsolved clinical issue. Prevalence of AMI event will increase ≈18% by 2030. Though, in 20th century, enormous progress has been made in the diagnosis, treatment, and prognosis of AMI but still there is a clinical demand for a novel diagnostic, prognostic biomarker and new therapeutic interventions to decrease the AMI incidence. The purpose of this study was to evaluate the diagnostic and prognostic value of circulating miRNAs as a biomarker for AMI patients, and therapeutic effect of miR-208b or miR-378 in cardiac cell during hypoxia-reoxygenation (HR) injury. In our study, we enrolled AMI patients, 12 week-old C57BL/6 mice AMI and H9c2 cells. Total RNA was isolated from plasma and H9c2 cells by using TRIZOL reagent. Circulating miRNAs levels were measured by quantitative real-time polymerase chain reaction. We found that circulating miR-208b, miR-499 and miR-765 levels were significantly up-regulated, whereas miR-149, miR-378 and miR-424 levels were markedly down-regulated both in AMI patients and Mice model of AMI compared with controls, (p<0.01). Plasma levels of these miRNAs were returned towards normal at 96 h after PCI (p<0.01). However, inhibition of miR-208b and over expression of miR-378 were dramatically increased cell survival through negative regulation of their targets in HR-induced cardiomyocyte injury cell. Our study demonstrated that circulating miRNAs represent as novel diagnostic and prognostic biomarkers for AMI patients, and also represents a new therapeutic approach for ischemic heart disease.

Speaker
Biography:

Fleisher-Berkovich S has completed her PhD from Ben-Gurion University of the Negev. She is an Associate Professor in the Department of Clinical Biochemistry and Pharmacology. She has published papers and book chapters in reputed journals and serves as a reviewer of repute journals. She also received highly competitive national and international grants.

Abstract:

The pathology of Alzheimer's disease (AD) is associated with brain inflammation, which includes the involvement of glial cells e.g., microglia and astrocytes. Microglial activation by amyloid β (Aβ) (component of AD plaque) results in the production of various inflammatory mediators, oxidative radicals, and neurotoxic cytokines, which contribute to synaptic impairment and neuronal damage. Accumulating evidence indicate that the renin-angiotensin system (RAS) may contribute to the brain inflammation associated with AD pathology. Angiotensin II (Ang II) is considered as the major RAS effector, and acts mainly via stimulation of the angiotensin type 1 receptor (AT1R). Specific inhibition of brain RAS has been suggested as a potential therapeutic strategy for AD. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and to understand the possible implications for brain inflammation and AD in vitro and in vivo. Long term exposure of BV2 microglia to telmisartan (1-5 mM) decreased by about 50% the lipopolysaccharide (LPS)-induced nitric oxide (NO), inducible NO synthase (iNOS) and tumor necrosis factor  a (TNF- a) synthesis. Telmisartan did not affect the basal synthesis of these pro-inflammatory mediators in non-stimulated BV2 cells. Cell  viability was not altered following telmisartan treatment. Intranasal administration of telmisartan (1 mg/kg/day) for up to two months significantly reduced amyloid burden and microglia/macrophages activation in the cortex and hippocampus of five familial Alzheimer’s disease (5XFAD) mouse model. Based on these results, it is suggested that telmisartan act as an anti-inflammatory and a neuroprotective agent in the brain through modulation of microglial activation and of amyloid pathology.

This research was supported by the Israel Science Foundation (grant 101/11-16).

Speaker
Biography:

Myung Koo Lee,  Professor of College of Pharmacy, Chungbuk National University (CNU), has received his PhD degree from the Faculty of Pharmaceutical Sciences, Kyushu University in 1988 and Post-doctoral studies from the Lab of Molecular Neurobiology, Cornell University Medical School in 1991-1992. He has served as a Dean at the College of Pharmacy, CNU in 2002-2004, and as a President at the Society of Korean College of Clinical Pharmacy in 2010-2012. He has also served as the Director at the Research Center for Bioresource and Health, CNU in 2001-present. He has published more than 190 papers in journals.

Abstract:

Parkinson’s disease (PD) causes by the degeneration of dopamine neurons in the substantia nigra. L-3,4-Dihydroxyphenylalanine (L-DOPA) is the most frequently prescribed drug for controlling the symptoms of PD. However, the high levels of L-DOPA lead to cell death by generating reactive oxygen species in dopamine neurons and PC12 cells. The intracellular levels of cyclic AMP (cAMP) increase in response to cytotoxic concentrations of L-DOPA in PC12 cells, and multiple treatments with non-toxic L-DOPA (MT-LD) reduce dopamine biosynthesis in PC12 cells. We therfore investigated the effects of L-DOPA on ERK1/2 and JNK1/2-c-Jun systems. MT-LD (10 and 20 µM) induced cell survival via PKA-transient ERK1/2 activation in PC12 cells. MT-LD also induced differentiation via the Epac-sustained ERK1/2-c-Jun system, which subsequently led to the activation of the cell death process. In addition, SE and GP-EX enhanced dopamine biosynthesis and L-DOPA-induced increase in dopamine levels by inducing TH activity and TH gene expression in PC12 cells. SE and GP-EX protected L-DOPA-induced cytotoxicity through the modulation of the oxidative stress-induced cell death signaling pathways in PC12 cells. SE and GP-EX also showed the prophylactic and adjuvant therapeutic effects on long-term L-DOPA therapy in 6-hydroxydopamine-lesioned rat model of PD, suggesting that SE and GP-EX might serve as an adjuvant phytonutrient for PD. Taken together, it has been proposed that chronic treatment of L-DOPA led to the neurotoxic process via the cAMP-sustained ERK-c-Jun system and the modulation of ERK activity might be applied for screening the anti-neurodegenerative agents. 

  • Ethnopharmacology | Toxicology | Drug Screening and Discovery
Location: Brunel Suite
Speaker

Chair

CEJ van Rensburg (Connie Medlen)

University of Pretoria, South Africa

Speaker

Co-Chair

Hui-Hui Xiao

The Hong Kong Polytechnic University, PR China

Speaker
Biography:

P Brindha has completed her PhD from University of Madras and Post-doctoral research in Traditional Ayurveda and Siddha Herbal Drugs at Captain Srinivasamurthi Drug Research Institute, Chennai under the Ministry of Health and Family Welfare, Govt. of India. Presently, she is the Associate Dean and Co-ordinator for Centre for Advanced Research in Indian System of Medicine (CARISM), School of Chemical and Biotechnology, SASTRA University, Thanjavur, Tamilnadu, India. She has published more than 240 papers in reputed journals and has guided 25 PhDs in Herbal Science.

Abstract:

Peptic ulcer disease (PUD) develops when the defensive mechanisms of the gastrointestinal mucosa are devastated by the aggressive effects of gastric acid and pepsin. The transformation to plant derived drugs from synthetic modern drugs is mainly due to their side effects. Hence, in the present study attempts were made to develop an eco-friendly herbal drug taking leads from traditional herbal medicine practitioners. Based on the literature survey and interviews with local traditional healers, Caesalpinia sappan L., Cyclea peltata (Lam.) and Gmelina arborea Roxb. were selected and evaluated for their antiulcer potential.  Hydro-alcoholic extracts of the selected plants were used for the present study. C. peltata showed significant proton pump inhibitory activity. It was observed that C. sappan had better antioxidant activity in DPPH assay. In vitro acid neutralizing capacity was not observed for the three plants, which indicated that the plants cannot act as antacids. Acute oral toxicity studies on C. sappan, C. peltata and G. arborea extract showed no mortality in rats at doses up to 2 g/kg. In ethanol induced ulcer model, screening of cytoptotective activity revealed that C. sappan at the dose level of 500 mg/kg showed 92% ulcer protective index, whereas G. arborea and C. peltata showed 58% and 47% ulcer protective index respectively when compared with standard sucralfate (53%). In Pylorus ligation induced model, the maximum ulcer protection was observed in C. peltata and the probable antiulcer mechanism must be mediation through gastric secretion inhibition. Cysteamine induced duodenal ulcer model showed no activity. In NSAID induced gastric ulcer model, C. sappan (86%) showed maximum ulcer protection followed by C. peltata (75%) and G. arborea (66%) when compared with standard (74%). The bioactive extracts were subjected to LC-MS/MS analysis to detect the major phytoconstituents. Findings from in silico molecular docking studies further provided supporting evidences for their mechanisms of actions. It is concluded from the present study that C.sappan showed potent antiulcer effect mediated by increasing PGE2 level and promoting antioxidant status, thereby acting as a cytoprotective agent. C.peltata revealed significant antiulcer activity mediated through gastric juice inhibition and acting as an anti-secretory agent against gastric juice. G.arborea promoted ulcer healing through mucus secretions and protected the gastric mucosal damage against gastric acid secretions. A suitable combination of these three extracts can be used to formulate an antiulcer drug that could be useful in the management of any type of ulcers.

Speaker
Biography:

Aline Diogo Marinho has completed her Bachelor's in Pharmacy from Federal University of Ceara- UFC (2011) and Master's in Pharmacology from School of Medicine, UFC (2013). She is a Scholarship student of CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and Doctoral student in Pharmacology from UFC since 2014. She has experience in Pharmacology, with emphasis on Renal Pharmacology, focusing in the following topics: toxinology, venoms and renal alterations. She is a member of Laboratory of Pharmacology of Venoms, Toxins and Lectins (LAFAVET). Her related publications are: Bothropoides pauloensis venom effects on isolated perfused kidney and cultured renal tubular epithelial cells and Solanidane and iminosolanidane alkaloids from Solanum campaniforme.

Abstract:

Acute renal failure (ARF) is one of the most serious complications of Bothrops snake bites. Pathogenesis of ARF in snakebite envenomation may involve hemodynamic disturbances, immunologic reactions and direct nephrotoxicity, however, its pathogenesis remains obscure. Bothrops pauloensis is found in the State of São Paulo, Southeast region of Brazil. The aim of the work was to study Bothropos pauloensis venom (BpV) in rat isolated perfused kidneysand cytotoxicity on renal tubular cells Mardin-Darby Canine Kidney (MDCK). The renal effects were compared to a control group perfused with modified Krebs–Henseleit solution alone. BpV decreased the perfusion pressure (PP), renal vascular resistance (RVR),urinary flow (UF), glomerular filtration rate (GFR) and the percent sodium, potassium and chloride tubular transport (%TNa+, %TK+, %TCl). The treatment with BpV caused decrease in cell viability to the lowest concentration tested with an IC (50) of 7.5 μg/mL. Flow cytometry with annexin V and propidium iodide showed that cell death, suggesting the participation of apoptosis and late apoptosis on BpV-induced cell death. Through caspases 3 and 7 activation, mitochondrial membrane potential collapse and ROS overproduction. These findings demonstrated that BpV cytotoxicity on renal epithelial cells might be responsible for the nephrotoxicity observed in isolated kidney. The characterization of the effects in the isolated kidney and renaltubular cells gives strong evidences that the acute renal failure induced by this venom is a result of the direct nephrotoxicity which may involve the cell death mechanism.

Speaker
Biography:

Hui-Hui Xiao is a Scientific Officer in The Hong Kong Polytechnic University. She received her PhD in Natural Product Chemistry from Shenyang Pharmaceutical University, China in 2011 and finished Post-doctoral studies from Jinan University in 2014. She has published more than 10 papers in reputed journals and obtained one authorized patent of invention. Her research interests are in the areas of preclinical study about the therapeutic effects of Traditional Chinese Medicine (TCM) on Osteoporosis, the chemical components of TCM and the involved mechanism in anti osteoporosis.

Abstract:

Sambucus williamsii Hance, as a fork herbal medicine has been used in China on treatment of bone and joint diseases for thousands of years. Our previous studies clearly demonstrated that a fraction composed of 50% and 95% ethanol eluate from S. williamsii exerted protective effects on trabecular bone and cortical bone without side effects on uterus in ovariectomized mice and rats. The fraction is rich in lignans and 55 lignans were isolated and identified in this fraction. Among them, 44 lignans were characterized as bioactive components by in vitro activity screening. In the present study, PPD, a typical norlignan was selected for mechanism investigation involved in the anabolic effects of S. williamsii. The results showed that PPD exerted beneficial effects in osteoblasts and its effects were abolished by co-incubation with ICI 182,780 or U0126. It failed to bind to either ERα or ERβ at the concentration up to 10-6 M and did not activate estrogen response element (ERE)-ludiferase activities via ER. PPD induced the phosphorylation of ERK and ERα at serine 118. The data indicated that PPD exerts oestrogen-like actions in ostoblast-like cells via ligand-independent, ERE-independent and mitogen-activated protein (MAP) Kinase-mediated rapid nongenomic ER signalling pathway. In order to elucidate the real bioactive components in body, we further study the metabolites of DDA, a major norlignan in the bioactive fraction. In rats model, 14 metabolites were identified in the plasma, urine and feces administrated with DDA. The final metabolite was enterodiol. However, the metabolic pathway was still in study.

Speaker
Biography:

Jiyoung Kim has completed her Ph.D from University of Georgia, GA, USA and postdoctoral studies from University of Wisconsin-Madison, WI, USA. She is the research assistant professor at Seoul National University, Seoul, Korea.  She has published more than 33 papers in reputed journals and 3 book chapters. Her papers “Naturally occurring phytochemicals for the prevention of Alzheimer's disease, Journal of Neurochemistry 2010 Mar: 112(6): 1415–1430” and “A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 2010 Aug 7: 690(1-2): 12-23” have been noted by more than 120 citation records.

Abstract:

Sulforaphane, an organosulfur compound present in cruciferous vegetables, has been shown to exert neuroprotective effects in experimental in vitro and in vivo models of neurodegeneration. To determine whether sulforaphane can preserve cognitive function, we examined its effects on scopolamine-induced memory impairment in mice using the Morris water maze test. Sulforaphane (10 or 50 mg/kg) was administered to C57BL/6 mice by oral gavage for 14 days (days 1–14), and memory impairment was induced by intraperitoneal injection of scopolamine (1 mg/kg) for 7 days (days 8–14). Mice that received scopolamine alone showed impaired learning and memory retention and considerably decreased cholinergic system reactivity in the hippocampus and frontal cortex, as indicated by a decreased acetylcholine (ACh) level and an increased acetylcholinesterase (AChE) activity. Sulforaphane significantly attenuated the scopolamine-induced memory impairment and improved cholinergic system reactivity, as indicated by an increased ACh level, decreased AChE activity, and increased choline acetyltransferase (ChAT) expression in the hippocampus and frontal cortex. These effects of sulforaphane on cholinergic system reactivity were confirmed in vitro. Sulforaphane (10 or 20 µM) increased the ACh level, decreased the AChE activity, and increased ChAT expression in scopolamine-treated primary cortical neurons. These observations suggest that sulforaphane might exert a significant neuroprotective effect on cholinergic deficit and cognitive impairment.