Metabolic Syndrome is a group of factors or traits that increase a person's risk of developing cardiovascular disease (and related conditions, such as stroke and type 2 diabetes). The five major factors with the most prognostic significance for clinicians and high-risk patients are 1) abdominal fat, 2) high triglycerides in the blood, 3 )low HDL levels (good fats), 4) high blood pressure and 5) high fasting blood sugar.
The co-morbid symptoms which result in the most adverse outcomes are: 1) obesity, 2) inactive lifestyle and 3 )insulin resistance. For patients with a unique genetic predisposition, exercise and healthy diet simply are not enough to maintain healthy fat and sugar levels in the blood.
Medications are often required for certain populations. The class most frequently prescribed are statins, which are used to lower cholesterol levels. Saponins, a naturally-occurring alternative, also effectively reduce cholesterol levels. This glycoside has a distinctive foaming ability and prevents serum cholesterol absorption once excreted into the bile.
Studies in hamsters and rabbits show serum cholesterol lowering abilities of 17-75%. Scientists have recently demonstrated that saponins can directly inhibit PPARgamma agonists responsible for adipocyte (fat cell) development. This is clinically significant, as it can be used to manage fatty tissue build up for patients with metabolic syndrome.
PPARgamma partial agonists and inhibitors are a popular modulation concept for metabolic syndrome. PPARgamma binding affinity is important in determining the agonistic versus inhibitory function resulting in either disease promoting or inhibiting affects. PPAR partial agonists activity are key; therefore studying the binding affinity and kinetics of these agonists will provide critical information for clinicians evaluating viable treatment options.
On the other hand, PPAR inhibitors reduce lipid synthesis and lipocyte differentiation. Saponins have shown incredibly diverse responses in modulating PPARgamma in both ways. They have the ability to increase insulin sensitivity and stabilize diabetes through partial agonist activity. Conversely, other forms of saponins have shown inhibitory lipogenesis and lipid accumulation.
Montanari et al.'s 2016 paper in Scientific Reports shows how SPR can be used to screen different saponins to find the optimal binding activity. Twenty-four compounds are tested using SPR. Compounds #1-17 are classified as saponins and 18-24 as sapogenins. Compound #18 (echinocistic acid) clearly showed different binding characteristics compared to all other compounds.
The real-time binding kinetics data obtained using SPR that #18 binding fits to a 2:1 molecular interaction model. Montanari et al. observed that two molecules of #18 can bind simultaneously to ligand binding domain (LBD) of PPARgamma. Compound #18 also showed a slow kinetics of association and dissociation consistent with other known PPARgamma antagonist.
More investigation is needed to determine if #18 is capable of inhibiting lipogenesis. Interestingly, Montanari et al. also found that #18 is capable of killing human cancer cells suggesting a possible role as anti-tumor therapy. With the application of SPR technology, compound #18 could lead to advances in metabolic syndrome and cancer research.
Metabolic syndrome will overtake smoking as a leading cause of cardiopathy in the next decade. Successful research into preventative therapies could therefore significantly improve patient health and reduce annual healthcare expenditures.
An estimated 25% of the global population has metabolic syndrome. This demographic has a five-fold greater chance of developing type II diabetes.
Exercise and healthy eating are essential to fighting the syndrome. Fresh foods that contain saponins and sapogenins (such as beans, peanuts, soy, potatoes and tomatoes) are vital to metabolic syndrome patients' well-being. Plant sources of high saponins (quinoa and ginseng) are already in vaccine research due to their extraordinary therapeutic characteristics. SPR technology will be essential to future saponin screening and research.