Day 2 :
Keynote Forum
Rudolf Lucas
Augusta University, USA
Keynote: Solnatide: Tackling pulmonary permeability edema from all angles
Time : 09:15-09:55
Biography:
Rudolf Lucas obtained his PhD in cellular and genetic biotechnology in 1993 summa cum laude from the Free University of Brussels, Belgium (VUB) and he currently holds a faculty position at the Medical College of Georgia. He is currently Chair of the American Heart Association Lung Fellowship Committee. His expertise mainly
lies in the development of novel therapeutic candidates to treat pulmonary edema. Over the past 20 years, his research has led to the discovery of a TNF-derived peptide, Solnatide, which is a direct activator of the epithelial sodium channel. This peptide has shown promising activities in two recently finalized phase 2a clinical trials in patients with acute lung injury and upon lung transplantation.
Abstract:
Efficient exchange of oxygen and carbon dioxide between the lung capillaries and the alveoli requires that the latter is kept dry. Vectorial Na+ transport through the apically expressed epithelial sodium channel (ENaC), and the basolaterally expressed Na+-K+-ATPase mediates Alveolar liquid Clearance (ALC) in type 1/2 alveolar epithelial cells. ENaC activity is defined by the product of its open probability time and its membrane surface expression. The alpha subunit of ENaC also associates with the acid-sensing ion channel to form the hybrid Non-Selective Cation (NSC) Channel, which also contributes to ALC. In conditions of ARDS and severe pneumonia, which are associated with intense pulmonary inflammation, ENaC function can become impaired. Moreover, pathogen-associated toxins, as well as pro-inflammatory cytokines can disrupt capillary endothelial barriers, causing fluid to leak from the capillaries into the alveolar space. The resulting Pulmonary Permeability Edema (PPE)
is a potentially lethal complication, for which no proven pharmacological treatment exists to date. The identification of novel
therapeutics for PPE is therefore of the utmost importance. Solnatide is a TNF-derived peptide that mimics the lectin-like domain of tumor necrosis factor, the latter of which is spatially distinct from the receptor binding sites1-4. Solnatide binds to the alpha subunit of ENaC and as such increases the open probability, as well as surface expression of the channel, even in the presence of bacterial toxins, such as Pneumolysin (PLY), the main virulence factor of Streptococcus pneumoniae. The peptide also prevents bacterial toxin-induced endothelial barrier dysfunction in lung microvascular endothelial cells, which express both ENaC and NSC channels and has potent anti-inflammatory actions. The therapeutic potential of Solnatide was recently evaluated in two phase clinical trials in patients with acute lung injury and lung transplantation. The results of the pre-clinical and clinical studies will be discussed in this contribution.
Keynote Forum
Shahid Husain Ansari
Jamia Hamdard University, India
Keynote: Stability studies on Triphala: A common ayurvedic formulation
Time : 09:55-10:35
Biography:
SH Ansari obtained his BPharm in 1979 from University of Delhi, MPharm in 1981 from Punjab University, Chandigarh and PhD in Pharmacognosy and Phytochemistry in 1997 from Jamia Hamdard. He was conferred Doctor of Science in 2002 by International University of Contemporary Studies, Washington, USA. Professor Ansari, having teaching and research experience of more than 36 years, has served Jamia Hamdard, in different capacities as Head, Department of Pharmacognosy and Phytochemistry, Dean School of Pharmaceutical Education and Research, Dean Students’ Welfare, and Director, School of Open and Distance learning and as Vice Chancellor as well. Presently working as Professor in Department of Pharmacognosy and Phytochemistry in School of Pharmaceutical Education and Research. He has been bestowed with “Best Young Pharmacy Teacher Award 1997-98”, “Life Time Achievement Award” by United Writers’ Association, Chennai, Pharma Ratan Award for Life Time Achievement by Rab Di Meher Society, 2016. “Gold Medal of Excellence” by the Open University of Complimentary Medicines, Colombo, Sri Lanka in 1998. Professor Ansari also has 215 research papers to his credit.
Abstract:
The global acceptability of herbal drugs and traditional medicines are still challenged due to its complex nature and quality control analysis. Due to this the stability analysis of herbal drugs, botanicals, and traditional medicine is very complicated and needs proper attention in this field. However uses of bioactive markers for the analysis stability of these drugs are in common practice, which gives an insight and at least an answer to the complexity in analysis. Use of biologically active molecules for analysis of stability, shelf life and pharmacokinetics is very useful for understanding biology and mechanism of action of these traditionally used drugs as well as makes it easy. Triphala is a very common drug used in traditional ayurvedic and unani medicines for the treatment of various diseases and very frequently used in Indian system of medicine. It is composed of powder fruits of Emblica officinalis, Termenalia chebula and Termenalia bellerica in a uniform ratio. The phenolic antioxidants like Gallic Acid, Tannic Acid (Termenalia chebula, Termenalia bellerica) and Quercetin (Emblica officinalis) are common biomarkers present in these fruits. Hence in present investigation the stability of Triphala was established using Gallic acid, Tannic acid and Quercetin by expressing the samples at different temperatures and humidity as per the WHO guidelines at bench top and at accelerated stability conditions. The results of the study showed that constant of these markers as much affected in stored conditions.
Keynote Forum
Hiroshi Kobayashi
Chiba University, Japan
Keynote: Innovative methods for exploitation of anti-cancer drugs working in acidified nests
Time : 11:00-11:40
Biography:
Hiroshi Kobayashi received his PhD in Biochemistry from University of Tokyo in 1974. After his postdoctoral training at Colorado University Medical Center, he started to study adaptation strategies of microorganisms to acidic environments at Chiba University in 1978. His research is focused on mammalian cell functions under acidic conditions from 1996 at Graduate School of Pharmaceutical Sciences, Chiba University. His current research interest is cancer chemotherapy with drugs specific to acidic nests. He retired in 2012 and is now a professor emeritus at Chiba University. He works as an associate editor of International Immunopharmacology published by Elsevier from 2014.
Abstract:
It is well known that cancer nests are often acidified. The acidity may affect anti-cancer chemotherapy and immune responses.
Our group found that the cytosolic pH decreased in cancer cells proliferating in acidic medium and approximately 700 genes were expressed at a higher level in such cells, leading us to suppose that an anti-cancer drug whose target is the product of such genes may work in acidic cancer nests with less of effects on alkaline normal tissues. We established the in vitro assay system for screening anti-cancer drugs working in acidic nests, and approximately 300 compounds were examined using various cancer cell lines. Among them, four compounds, Lovastatin, Cantharidin, Manumycin A, and Ionomycin, were found to have anti-cancer activity preferentially at acidic pH. Next, the anti-cancer activity of statins was focused. Promising results of statins as an anti-cancer drug have been reported in mouse models and cancer patients. Stains have been used in patients with hyperlipidemia and side effects have been reported in less than 1% patients, supporting that anti-cancer drugs working preferentially in acidic cancer nests have less of effects on normal tissues whose pH is slightly alkaline. Since alkaline medium has been used for screening of drugs, it would be highly possible that novel anti-cancer drugs with fewer side effects would be exploited using our methods. Our experimental system would be also useful for elucidation of immune functions in acidic cancer nests. It was shown with this method that TCR signaling does not work under acidic conditions.
Keynote Forum
Jing Wang
Institute of Neurosciences of Montpellier, France
Keynote: New strategies for improving the quality of life of cancer survivors: Reversible p53 inhibition
Time : 11:40-12:20
Biography:
After her MD from Medical school of University Kunming, China and her PHD thesis on inner ear cell degeneration and therapies from University of Montpellier, France. Jing Wang is the team leader of “Sensory loss and rescue” group at the Institute of Neurosciences of Montpellier, Montpellier, France. During her career, Jing Wang published 36 papers in international journals (web of science h-Index: 19, citations, 1040 citations), 9 book chapters and more than 150 communications or posters. She is member of the Editorial Boards of international journals. In addition to basic research, she took out 3 patents for tinnitus and deafness treatments and promoted translational research.
Abstract:
In recent years, with the improvement of cancer survival through more effective treatment, the emphasis has been in trying to minimize the side effects caused by chemo and radiotherapy, to ensure that patients have the best quality of life throughout their cancer journey. The tumour suppressor p53 is widely implicated in a broad range of cancers. Indeed, p53 is either mutated or inactivated in the majority of cancers. Abundant evidence indicates that toxicity caused by DNA-damaging anticancer therapies in normal tissues is also mainly mediated by p53. p53 accumulates in the cells shortly after anticancer challenges and acts as a nuclear transcription factor that modulates the expression of numerous p53-responsive genes (e.g. p21Waf1, 14- 3-3-σ, Mdm2, cyclin G, Bax). This initiates a cascade of events leading to massive programmed cell death in specific normal tissues during the systemic genotoxic stress associated with chemo and radiotherapies. This makes p53 a target for therapeutic suppression: An approach to reduce side effects associated with treatment of p53-deficient cancers. Here I summarize the role of p53 and the possibilities of its manipulation to improve side effects during active treatment through survivorship.
- Herbal and Holistic Medicine | Pharmacokinetics and Pharmacodynamics | Phytochemical Studies of Medicinal Plants and Plant Extracts | Medicinal Chemistry | Phytochemistry and Phytopharmaceuticals | Entrepreneurs Investment Meet | Cancer Pathophysiologies | Cancer Therapeutic Modalities Factors Affecting Clinical Outcomes | Types of Cancers
Location: Concord A/B
Chair
Shahid Husain Ansari
Jamia Hamdard University, India
Co-Chair
Daniel Dan Motlhanka
Botswana University of Agriculture and Natural Resources, Botswana
Session Introduction
Mohammad Ahmad
King Saud University, Saudi Arabia
Title: Attenuating effects of Nigella sativa on cognitive dysfunction, hippocampal oxidative stress and neurodegeneration following status epilepticus in young male rats
Biography:
Mohammad Ahmad has worked with many experimental models to carry out research studies on various neurological diseases of human health importance. His particular interest lies in correlating his research findings in perspective of Nursing care and infusing more interest in Nursing research activities. After doing his Ph.D. he visited Queen's University of Belfast, UK. to persuade his Post-Doctoral studies on the ultrastructural anatomy and neurophysiology of helminth parasites of health importance. He has a vast experience of research and teaching. At present, he is an Associate Professor in Medical Surgical Department of Nursing College, King Saud University teaching courses of Anatomy and Physiology, Pathophysiology, Infectious Diseases, Infection Control and Medical Microbiology. He has published more than 60 papers and is in the Editorial and Review Boards of many international journals of repute and high impact factors.
Abstract:
Statement of the Problem: The lithium-pilocarpine model of Status Epilepticus (SE) is most suitable and is frequently used for pathophysiological and management strategies in search of new, safe and effective therapeutic agents for SE. Recent studies have shown a significant potential of the pharmacological, prophylactic and therapeutic use of Nigella sativa (habba sauda) seed extract (NSE) for many beneficial activities in the body including neuroprotection from neurodegenerative diseases and have antioxidant property. Methodology: In the present study we investigated the effects of NSE on intensity and frequency of SE, cognitive behavioral dysfunction, hippocampal oxidative stress and histological abnormalities in the hippocampus of animals induced with SE by lithium (Li) in 3mgEq/ml/kg dose, i.e. followed 20h later by pilocarpine (Pc) in 20mg/ml/kg dose, s.c. NSE was administered intraperitoneally at the doses of 100, 200, and 400 mg/mL/kg, 30 minutes before Pc injection. Mortality (if any) within 24 hours was also recorded. Ethical approval was obtained from the ethics committee review board of the college, King Saud University, Riyadh, Saudi Arabia.
Results: Treatment with NSE significantly ameliorated the frequency and severity of epileptic seizures in a dose-dependent manner. The cognitive dysfunctions were improved, hippocampal oxidative stress was ameliorated and neuronal cell loss and sprouting of mossy fibers in the hippocampus were also attenuated significantly and dose-dependently by NSE. Conclusion and Significance: Possibly, therapeutic application of Nigella sativa seed as an antiepileptic and as an antioxidant for the treatment of SE has a great potential and warrants further studies.
- Poster Presentations
Location: Concord A/B
Session Introduction
Jian-xin Liang
Jinan University, China
Title: Baicalin administration has a protective effect on hyperglycemia-Induced malformation of cardiovascular system
Biography:
Jian-Xin Liang has completed his undergraduate course from the Hubei University of Chinese Medicine. Now she is completing her master study in Jinan University School of Medicine. She has published 2 papers, including “Atg7-mediated autophagy is involved in the neural crest cell generation in chick embryo” Molecular Neurobiology, and “BRE modulates granulosa cell death to affect ovarian follicle development and atresia in the mouse.” Nearly for 2 years, she has been doing research about the impact of baicalin on the heart and vascular development of embryos, which are in the PGDM (previous gestational mellitus) environment.
Abstract:
Aims: Baicalin is a traditional Chinese medicine for tocolysis. Whether it can protects early embryonic cardiovascular development caused by gestational diabetes is obscure, and the mechanism remains unclear. In this research, early chicken embryo was used as a model to explore the molecular mechanism of baicalin in reducing the early cardiovascular developmental deformity caused by high glucose environment.
Methods: We found that 6μM baicalin administration can attenuate the death rate and retardation of chicken embryos caused by high glucose environment significantly. Thus, we observed the chick embryos in HH7, HH8, HH10, HH11stages, which are treated with simple saline, high glucose (50 mM) and/or Baicalin (6 μM). In this study, we used immunofluorescence,
situ hybridization, RT-PCR, Western blot, qPCR and others to observe the expression of the key transcription factors, and the changes of autophagy-related genes, apoptosis-related genes, ROS in the development of cardiovascular so that to study whether or not Baicalin could attenuate hyperglycemia-induced malformation of cardiovascular system and the mechanism. At the same time, we studied the mechanism involving ROS, autophagy and apoptosis, combined with HUVEC cell. In addition,
we also used Baicalin to treat the mice in diabetes model induced by Streptozotocin(STZ) and observed whether or not this has the protective impact on the blood glucose and other organs of diabetes mellitus mice.
Results: Hyperglycemia-enhanced cell apoptosis was reduced in embryos and HUVECs in the presence of Baicalin. Hyperglycemia-induced excessive ROS production was inhibited when Baicalin was administered. Analyses of classical antioxidant enzymes, MQAE and GABAA suggested Baicalin plays an antioxidant role in chick embryos possibly through
suppression of outwardly rectifying Cl(-) in the high-glucose microenvironment. What’s more, hyperglycemia-enhanced autophagy fell in the treatment of Baicalin, through affecting the ubiquitin of p62 and accelerating autophagy flux. Both Baicalin and Vitamin C could reduce apoptosis, but CQ did not, suggesting autophagy to be a protective function on the cell survival. In mice, Baicalin decreased the elevated blood glucose level caused by STZ.
Conclusions: In brief, these data suggest that hyperglycemia-induced embryonic cardiovascular malformation can be attenuated by Baicalin administration through suppressing the excessive production of ROS and autophagy. Baicalin could be a potential candidate drug for women suffering from gestational diabetes mellitus.
Amal Y Aldhebiani
King Abdulaziz University, Saudi Arabia
Title: Antibacterial activity of Commiphora gileadensis and Abutilon bidentatum, collected from Al- Abwa region, Saudi Arabia
Biography:
Amal Y Aldhebiani, associate professor in Plant Taxonomy, Biological Sciences Dept. Jeddah, Kingdom of Saudi Arabia. PhD from University of Reading, United
Kingdom. Research interest in Flora of Saudi Arabia and medicinal plant in the country, their taxonomy and uses. Phytochemical compounds analysis and their
application. Genetic diversity among medicinal plant and how would that affect the chemical constituents and the environmental relation.
Abstract:
Different plants have been traditionally used in folkloric medicine to treat many diseases and disorders or to improve human health due to their secondary metabolites which have excellent antimicrobial activities. Commiphora gileadensis and Abutilon bidentatum were collected from Al-Abwa region, Saudi Arabia, identified, extracted and their antibacterial activity was determined by agar well diffusion method. Extraction by methanol, ethanol, acetone and hot water was carried out and some multidrug-resistant bacteria were used as test bacteria. Maximum activity was recorded for the methanolic
extract against all tested bacteria with inhibition zone diameter ranged from 31-35 mm and MIC was ranged 37.5 μg/ml. The lowest activities were recorded for the water extracts of the two plants Commiphora gileadensis, and Abutilon bidentatum. Abutilon bidentatum extract showed weaker antimicrobial activity against the tested bacteria compared to C. gileadensis leave extracts. It is noticed that C. gileadensis stem extracts showed stronger antimicrobial activity. The methanolic extracts of the two tested plants have no toxicity using Artemia salina as a test organism. In conclusion, C. gileadensis and A. bidentatum can
be traditionally and safely used against multidrug-resistant bacteria due to the efficient antimicrobial activities and low toxicity.
Jyothi Penta
Kakatiya University, India
Title: Assessment of herb drug interaction study of sitagliptin in combination with curcumin
Biography:
Abstract:
Curcumin is the principal curcuminoid of turmeric. It possesses antioxidant, antidiabetic, anticancer, antiviral, antifungal, antibacterial, and anti-aging activities. It is mainly metabolized by CYP3A4, CYP1A2, and CYP2C9 enzymes. Sitagliptin is an oral antihyperglycemic agent, belongs to class DPP-4 inhibitor. It is metabolized by CYP3A4 and CYP2C8 enzymes. In the drug interaction study of curcumin with sitagliptin, diabetes was induced in the albino wistar rats intraperitoneally using 55 mg/kg Streptozotocin (STZ). Then they were divided into four groups of six each. Group, I treated with sitagliptin (10 mg/ kg), group II treated with curcumin (80 mg/kg), group III treated with curcumin followed by sitagliptin and group IV treated with curcumin for 7 days and on the eighth day followed by sitagliptin. Blood samples were collected from an orbital puncture at time intervals between 0, 1, 2, 4, 8, 12, and 24hrs using heparinized capillaries. Different biochemical parameters were estimated by using respective methods for 28 days. The obtained pharmacokinetic data shows an increase in Cmax, Tmax, AUC total, AUC0-n, t½, MRT and decrease in Vd and CL in both normal and diabetic rats. In pharmacodynamic study group IV showed a decrease in serum glucose levels at all time points. There was a very significant (p<0.001) influence in the percentage of glucose reduction in diabetic rats under multiple dose treatment but less significant (p<0.05) influence in normal rats. Thus, the improved pharmacokinetic parameters of sitagliptin were more observed in the multiple dose treatment groups, and the improvement of pharmacodynamics was significant in only diabetic rats under multiple dose treatment. This may be due to the synergistic effect of curcumin and sitagliptin by inhibition of CYP3A4 in STZ induced diabetic rats. Hence sitagliptin dose may require special attention if used along with curcumin or herbal preparations containing curcumin to avoid complications.