Hunting therapeutic molecules in the Jungles of Traditional Medicine
Dr. Muhammad Iqbal Choudhary Tests Herbal Extracts at the Crucible of Modern Science
Are the plants called medicinal medicinally effective? Well, the market is full of all kinds of ‘medicinal’ plants material with glossy packages and charming brand names. But do they actually work? “Medicinal plants have been the basis of traditional medicines since antiquity, and in contemporary era have played a central role as sources of new drugs,” says Dr. Muhammad Iqbal Choudhary, a biochemist of International Center for Chemical and Biological Sciences (ICCBS) at the University Of Karachi, Pakistan.
Dr. Choudhary has tested many medicinal plants for their effectiveness. “As a chemist, I have been truly fascinated by the immense chemical diversity present in plants,” he says. With the modern tools of science, combined with traditional knowledge of their uses, medicinal plants can serve as a sustainable and rich source of new drugs against prevailing and emerging diseases.
With all of its romanticist elements, getting back to nature has become a lifestyle in recent decades throughout the world. Using traditional herbal formulations instead of so-called ‘chemical’ pharmaceuticals, which many consider a product of modern civilization depravities, is a conspicuous aspect of this movement that is not confined to the East; the herbal drugs are widely consumed in many developed countries.
There are between 50,000 and 80,000 flowering plant species used for their medicinal properties worldwide. Medicinal plants are generally prescribed for a wide range of health benefits, from breaking up the bladder stones and lowering blood pressure to reducing the risk of diverse cancers and even curing depression.
How do these claims stand the test of science? There are several valid techniques developed by phytochemists and pharmacologists to ascertain the efficacy of such herbal formulations. Have traditional herbal remedies in general stand to the claims of traditional medicine? Are these plants more promising than any other random plant for pharmaceutical research? Are herbal drugs safe? Are they effective? What is the optimal dosage? How about their side effects and/or interactions with other drugs?
“Our work and work of other scientists have firmly established the importance of medicinal plants as the most important source of new drug entities, and in many cases scientifically substantiated their traditional uses,” says Dr. Choudhary. “It is interesting that not all medicinal plants, used in traditional medicines, pass through the strict scientific criteria of safety, efficacy, and consistency. However, the success rate of finding ‘drug-like molecules’ from medicinal plants is disproportionately higher than the random screening of plant extracts or chemical libraries.”
Dr. Choudhary’s team has worked on many medicinal plants used in traditional medicines, and isolated several bioactive lead compounds or potential drugs. For example, they used pygmy groundcherry (Physalis minima) against Leishmaniasis, a tropical disease caused by a protozoan parasite that affects over 12 million people in 97 countries. They have also discovered potent antiepileptic natural products from a species of larkspur (Delphinium denudatum). They have then synthesized it in the laboratory for more investigations. These plant constituents and their synthetic analogues are now being tested in clinical trials.
Though they have benefited immensely from the traditional knowledge in their research, Dr. Choudhary warns against misusing these herbals. It is important to use scientific methods to evaluate the efficacy and safety of traditional medicines. “Inherent variations in the quantities of bioactive chemicals present in plants make it a challenge to produce standardized plant-based products. Preclinical, toxicological, and clinical trials on standardized plant products are absolutely imperative for the development of ‘evidence-based medicine,’” he says.
Dr. Choudhary’s research interest has been centered on finding the biological activities of natural and synthetic compounds. His team’s research projects are focused on metabolic and neurological disorders. “We aim to find solutions to the unsolved and prevailing health challenges,” he says. They have successfully employed a deep understanding of chemical principles and biological processes in discovering a large number of fascinating molecules with potential therapeutic applications. The quality of their research is internationally recognized and has also attracted the attention of leading pharmaceutical industries.
One of the most fascinating groups of molecules is enzymes that modulate the entire machinery of life. Their overexpression leads to the onset of innumerable diseases. Enzymes must bind to a specific molecule, called substrate, to begin or accelerate a chemical reaction. Then to decrease or even stop an enzyme activity, you have to use a molecule that binds to the enzyme and prevents it from binding to the substrate. This is called the enzyme inhibition process. These molecules, known as enzyme inhibitors, work through several mechanisms, including a competition with the substrate upon binding to the active site of the enzyme.
“Our research group has studied and discovered novel inhibitors of clinically important enzymes, which can be used to halt the molecular cascade involved in the enzyme-related disorders, such as Alzheimer’s diseases, diabetes, and ER+ breast cancer,” says Dr. Choudhary. As a result, several new classes of lead molecules were introduced to the world literature, along with an associated understanding of their mechanisms of action.
The goal is to reduce as much as possible the final product that would otherwise be produced. And when the final product of the reaction facilitated by the enzyme is an unwanted detrimental compound leading to a physiological condition, its inhibitor may be called a drug. Many molecules considered as a drug, such as an erythromycin antibiotic, are actually enzyme inhibitors blocking an enzyme’s activity to destroy a pathogen or tip a physiological balance to our favor.
One of the internationally recognized discoveries of Dr. Choudhary’s research group is urease inhibitors. The inhibitors of the enzyme urease, for example, have been used as anti-ulcer drugs. The urease, produced profusely by the bacterium Helicobacter pylori in the human stomach, increase the acidity of the stomach mucosal lining by breaking down the urea molecule (its substrate). The increased acidity cut through the lining and develop to gastritis or stomach ulcer which in some cases may progress to cancer. Anything that can block the urease is thus a potential drug for ulcers.
Fortunately, various compounds could be used as urease inhibitors, but should we prescribe them as oral agents to patients with stomach ulcers? Does it matter that these substances are of plant or bacterial origin or have been synthesized? What about side effects? Is it specific enough to not bind to proteins other than the target enzyme? What factors make an enzyme inhibitor an effective drug? These are questions Dr. Choudhary’s research addresses.
The biological activity of a plant is based on the phytochemicals it possesses. These chemicals are biosynthesized by plants in response to biotic and abiotic stresses, and thus the same plant collected in different seasons and from different regions may have huge differences in its phytochemical profile and biological effects. This makes the entire field of botanicals and phytopharmaceuticals rather complex and uncertain.
“How to ensure that we correctly measure the quantities of thousands of these chemicals in plant extracts is one of the most enduring questions in my field of research. Despite major advances in spectroscopy, genomics, and metabolomics, the answer to this question is yet to be found,” says Dr. Choudhary. The answer to this problem will indeed be a breakthrough in the field. “Our group plan to develop rapid untargeted metabolomic methods which can compare the metabolomes of control plant (proven to be biologically active) with test plant,” he says.
Dr. Choudhary has a dream: to establish a multidisciplinary International Center for Tropical and Neglected Diseases. He wishes to have the time and energy to complete this mission soon. “This center will fulfill my dream of creating a world-class research facility with sustainable funding and global network of satellite laboratories to study the causes and treatment of innumerable tropical and neglected diseases,” he says. Neglected because these poor man diseases are “not in the priorities” of the global pharmaceutical business, even though they affect the lives of billions of people in the most impoverished regions of the world.