Dr. Chris Siow
Innovative Therapy Research Laboratory, Canadian Centre for Agri-Food Research in Health and Medicine
Department of Physiology, University of Manitoba
We aim to develop innovative strategies for health maintenance and disease management through innovative value-added agri-food products.
Our research interests: (1) Evidence-based agri-food: Elucidation of the biochemical and molecular mechanisms of extracts or compounds isolated from agri-food and herbal medicine, using cell culture and animal models; (2) Analyses: ORAC, chromatographic fingerprinting and bioassays; (3) Knowledge translation and promotion of science-based agri-food and Chinese medicine in prevention of diseases.
Why is this work important?
The population of Canada and the rest of the world are ageing. With ageing, an increasing incidence of chronic diseases will be expected. In a 2013 Conference Board of Canada report (Health Matters: An Economic Perspective http://www.conferenceboard.ca/e-library/abstract.aspx?did=5309) prepared for Canadian Alliance for Sustainable Health Care (CASHC), it was recognized that chronic diseases contributed to significant and growing costs of healthcare in Canada. In addition, the outcomes of chronic diseases affected both the labour force participation and productivity, thereby impacting the tax base that helps sustain the Canadian economy which in turn funds the healthcare system. While some of these chronic diseases are genetically-linked, many are lifestyle and diet-related. These latter ones are preventable to a certain extent. Besides changing their lifestyle and eating healthier food, consumers have also resorted to self-administration of natural health products (NHP). To encourage the healthier living lifestyle of consumers, many food producers have also introduced added-value agri-food products into the marketplace. Our laboratory aims to provide the science behind the claims of these agri-food products and NHPs so that Canadians can make informed choices.
What techniques and equipment are used in this laboratory?
Using ultra-performance liquid chromatography (UPLC) and the available chemistries, we continue to develop protocols to identify bio-active compounds found in various agricultural and medicinal herb extracts. The UPLC system provides significant improvements in resolution, speed and sensitivity when compared to traditional high performance liquid chromatography.
Our laboratory is also capable of routinely measuring the antioxidant capacity of a compound or an extract, using a microplate-based assay system. Two parameters will be measured: total phenolics and oxygen radical absorbency capacity (ORAC), using gallic acid and trolox as controls, respectively.
Identified bio-active compounds and standardized agricultural and medicinal herb extracts will be used to study its protective effects on ischemia/re-perfusion using a few different model systems.
About Chris Siow
Dr. Siow earned a PhD in Biochemistry from University of Manitoba. He did his first post-doctoral research training with Nobel laureate Paul Greengard at The Rockefeller University in New York and then a second post-doctoral training at University of British Columbia. Dr. Siow began his independent research in the Department of Pharmacology,The University of Hong Kong and returned to Canada in 2003. He was appointed an Assistant Professor in the Department of Physiology, University of Manitoba. In 2007, Dr. Siow became a Research Scientist with Agriculture and Agri-Food Canada and was concurrently appointed as an Adjunct Professor in Physiology, University of Manitoba. Dr. Siow’s research is funded by many public and private agencies. He has extensive experience working with industry and has led a university-industry collaborative government-funded multimillion-dollar project to assist the industry partner to modernize and provide a scientific basis for one of their herbal medicine based therapeutic products. He has published over 70 papers in international peer-reviewed scientific journals and is serving as an Associate Editor of the Canadian Journal of Physiology and Pharmacology. He is a Founding Board Member and currently a Regional Director of the Canadian Institute of Chinese Medicinal Research.
For more information, please contact:
Dr. Chris Siow
Tel. (204) 235-3457
Dramatic progress has been made in unravelling the multitude of signal transduction pathways in the cell. Abnormalities in these signalling pathways are demonstrated in many diseases. These include proliferative diseases like atherosclerosis, cancer, psoriasis and restenosis, inflammatory diseases such as rheumatoid arthritis, sepsis and tissue rejection, and degenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis (Lou Gehrig’s Disease). Drugs that intervene at these signalling processes represent a novel type of therapy for cardiovascular diseases. The goal of our research is to develop innovative preventative and therapeutic approaches based on agricultural and herbal medicine that target cell signalling processes. We will use innovative strategies to identify the mechanisms and accelerate the subsequent development of standardized natural health product and therapeutic formulations based on agricultural and medicinal herbs.
Ischemia/reperfusion is a cellular process that can lead to cellular damage/death. Ischemia occurs when there is a blockage of blood vessels supplying oxygen and nutrients to particular region of an organ or parts of a tissue. If it occurs in the heart, it is known as myocardial infarct or heart attack. Reperfusion is established when there is restoration of blood flow through the blood vessels, upon successful surgical or drug intervention to remove the blockage. The ischemia/reperfusion process also causes cells to undergo stress and produce to undergo stress and generate oxygen free radicals and other cellular metabolites. All of these can cause an extremely rapid increase in cell death by a programmed and active mechanism of cell death known as apoptosis. Intervention by pharmacological means can prevent cellular damage/death.
Our present model for study is simulated ischemia/reperfusion in a cell culture model. The endpoint of the model system is apoptotic cell death following simulated ischemia/reperfusion. Apoptosis is determined by measurement of nucleosomal formation by quantitative in vitro determination of cytoplasmic histone-associated-DNA-fragments. The nucleosomal formation during the reperfusion period will also be assessed. Apoptosis will also be confirmed by simultaneous TUNEL-based apoptosis detection and morphological localization under a light microscope and by performing Western blots using antibodies specific for poly(ADP-ribose) polymerase (PARP).
We collaborate with other CCARM members with animal model systems for studies using the standardized agri-food or identified bio-active compounds from these products.
Using ultra-performance liquid chromatography (UPLC) coupled to an extended wavelength photodiode array (PDAD) detector, we can obtain a chromatographic profile of a natural product extract. The chromatographic profile of a raw natural product extract that insures the extract’s bio-active components are consistent from batch to batch. This profile (fingerprint) usually varies between plant species, although the intensities of the various peaks may vary depending on growing conditions, harvesting climate, region of cultivation, etc. This chromatographic profiling is a reliable approach for controlling quality. Our present system has been optimized to separate several major anti-oxidants (this class of compounds is what intrigues us now).
The phenolic content of a food product is known to account for its anti-oxidant activity. This activity is mainly due to the redox properties of phenolics which allow them to act as reducing agents, hydrogen donors, singlet oxygen quenchers and metal chelators. Total phenolics are determined using the Folin-Ciocalteau phenol reagent and has been adapted in our laboratory for use in a 96-well microplate format. Using gallic acid as a standard, results are expressed as mg Gallic Acid Equivalents (GAE).
The oxygen radical absorbance capacity (ORAC) measurement is also a widely used assay to measure antioxidant activity. It provides a measure of the degree and length of time it takes to inhibit the action of oxygen free radicals or reactive oxygen species. Therefore, the higher the ORAC value, the better the antioxidant capacity of the substance. These substances include natural products such as fruits, vegetables, and herbal medicines, beverages, dietary supplements, serum or other biological fluids. In our laboratory, we are using a microplate-based system for measuring the ORAC value of an extract. This value is determined based on the oxidation of fluorescein by 2,2–azobis amidino(propane) dihydrochloride, a peroxyl radical generator. The downward change in fluorescent intensity is followed kinetically and ORAC values are calculated from the decay in fluorescence. The presence of antioxidants will delay the oxidation of fluorescein, resulting in preservation of the fluorescent signal. Using Trolox as a standard, the results are expressed as mol Trolox equivalents.
The Way Forward
The research program in my laboratory (R2010) focuses on health benefits of agri-food and natural health products. Through interdisciplinary collaborations within CCARM and other research groups, isolated compounds will be screened in other models of disease states for beneficial bioactivities. We presently have several international collaborations and are working with local industries to explore the health benefits of regionally grown natural products. We innovate to support Buy Local, Eat Local and help to empower the locals to support the Canadian economy.
“More and more of our patients want us … to help them follow a path to health that includes less-toxic nutrients and herbs when appropriate, combining the best scientific knowledge with an open mind” Jane L. Murray, M.D., Editorial, American Family Physician, Feb 1, Vol. 73, pp396-8, 2006
“Agriculture is emerging as a solution to mitigating climate change, reducing public health problems and costs, making cities more liveable, and creating jobs in a stagnant global economy.” Danielle Nierenberg, Director of Worldwatch Institute’s Nourishing the Planet project, July 6, 2011 (http://www.worldwatch.org/world-population-day-agriculture-offers-huge-opportunities-planet-7-billion-1).
1. Siow YL (2014) Editorial: What do we need to know about your NHP? Can.J.Physiol. Pharmacol. 92(2): iii.
2. Ross, K.A., Siow, Y., Brown, D., Isaak, C., Fukumoto, L., and Godfrey, D. (2014) Characterization of water extractable crude polysaccharides from cherry, raspberry, and ginseng berry fruits: Chemical composition and bioactivity. Internat. J.Food Properties In Press.
3. Isaak CK and Siow YL (2013) The Evolution of Nutrition Research. Can J Physiol Pharmacol. 91(4): 257-267.
4. Wu N, Sarna L, Hwang SY, Zhu Q, Wang P, Siow YL, and O K (2013) Activation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase during high fat diet feeding. Biochim Biophy Acta 1832(10): 1560-8.
5. Isaak CK, Petkau JC, O K, Ominski K, Rodriguez-Lecompte JC, and Siow YL (2013) Seasonal variations in phenolic compounds and antioxidant capacity of Cornus stolonifera plant material: applications in agriculture. Can J Plant Sci. 93(4): 725-734.
6. Wang P, Zhu Q, Wu N, Siow YL, Aukema H, and O K (2013) Tyrosol attenuates ischemia-reperfusion induced kidney injury via inhibition of inducible nitric oxide synthase. J Agric Food Chem. 61(15): 3669-3675.
7. Sun L, Isaak CK, Zhou Y, Petkau JC, O K, Liu Y, and Siow YL (2012) Salidroside and tyrosol from Rhodiola protect H9c2 cells from ischemia/reperfusion-induced apoptosis. Life Sci. 91(5-6): 151-158.
8. Siow YL, Sarna L, and O K (2011) Redox regulation in health and disease – therapeutic potential of berberine. Food Res Internat. 44: 2409-2417.
Outstanding Researcher Award, University of Hong Kong
University of Hong Kong Research Fellow Award
Canadian Foundation for Innovation
Manitoba Research Innovation Fund
Heart & Stroke Foundation of Manitoba
Lotte and John Hecht Memorial Foundation
Natural Health Products Directorate (Health Canada)
Manitoba Medical Services Foundation
The Estate of Marguerite Germaine Jerome