by Sharon Proctor
Photograpy by Greg Ehlers

Modern science looks to a traditional treatment

Imagine a family that boasts several artists, singers, writers, and literary types. Imagine another with a preponderance of chemists and pharmacists. It was the marriage of two such families that produced SFU’s Mario Pinto (above). And that marriage is why Pinto, his siblings, and all their children have such a variety of talents, including singing, acting, writing, and scientific curiosity. In the end young Mario chose a career in science. He became a chemical biologist, then an SFU faculty member, and eventually SFU’s vice-president of research. What’s intriguing is that one of his current research projects reflects back on his family history.

Mario Pinto was born in 1952 in Colombo, Sri Lanka. His mother’s family was the artistic one. She and her siblings excelled in such areas as art, singing, poetry, acting, music, and writing. Pinto’s maternal uncle, called “Tambi” by his friends, was a well-known poet, editor and critic. (Look him up on the Internet.) He was born in Sri Lanka, spent most of his adult life in England, and a few years in the U.S. In 1938 he founded and began publishing Poetry London. It became an important literary magazine during the World War II years for it featured many great poets and writers of the time. “He brought together W.H. Auden, Dylan Thomas, and T.S. Elliott,” says Pinto, “and each issue had a cover designed by a famous artist with Tambi’s insignia, the lyre bird.” Tambi also published original works by Lawrence Durrell, Henry Miller, Elizabeth Smart, Henry Moore, and Cleanth Brooks. As it happens, Tambi’s father (Pinto’s grandfather) suffered from “sugar in the blood.” We know it as “pre-diabetes.”

Pinto’s father was a chemist and immunologist who worked as a forensic scientist. And his father was a second-generation chemist. In the 1950s, young Mario would visit his paternal grandfather, who taught pharmacy to the university medical students and still prepared medications for patients in his garage laboratory. The boy found it fascinating to watch the older gentleman mix preparations by hand. “I would fake a cough every time I visited him so I could watch him mix up special cough lozenges.”

One of many useful ancient remedies
There’s an old traditional Sri Lankan remedy for “sugar in the blood.” It’s an extract made from the roots and stems of a woody shrub called Salacia reticulata. The wood of the plant is soaked in water for several hours, and if the resulting elixir is drunk before a high-carbohydrate meal, it acts to prevent the absorption of glucose into the bloodstream. Today Pinto and several students are studying the molecular structure of Salacia’s active ingredients. Their work, in fact, could lead to a safe and effective synthetic version for people with pre-diabetes or type 2 diabetes, or to a validation of the herbal remedy itself.

We North Americans are already using ancient remedies or their derivatives. Think of sipping echinacea tea, or swallowing aspirin, slippery elm, quinine or valerian, or even getting a penicillin shot.

Echinacea comes from the herb Echinacea. It’s an old Native American remedy for treating wounds and infections (boosting the immune system). Aspirin (acetylsalicylic acid) is derived from salicin, a substance in the bark and leaves of the willow tree (Salix). Early Egyptians, Sumerians, Assyrians, and Greeks used it to treat pain and fever. Valerian, from the root of the Valeriana plant, has been used to treat insomnia since ancient Greece and Rome. As for penicillin, it comes from the Penicillium mould. Thus, Salacia is in good company.

The problem of too much blood sugar
Assume you’ve just chewed and swallowed a delicious treat. It slides down a chute (the esophagus) and lands in your stomach. Here the various carbohydrates, proteins, cholesterol, spices, and other ingredients are broken down by enzymes. Next stop: the small intestine.

The inside wall of the small intestine is lined with microscopic “fingers,” called “villi.” Coating the villi surfaces are a-glucosidase molecules, enzymes that further break down carbohydrates and release the simple sugar, glucose, which passes through the intestinal wall into the bloodstream. In a healthy individual, insulin in the blood helps glucose enter cells. Insulin does the job of regulating the amount of glucose in the blood at any one time. But if you have diabetes, there’s either less (or no) insulin available or it’s lost much of its effectiveness. If you have pre-diabetes or type 2 diabetes, insulin production may be normal but transport of glucose from the blood into cells is compromised. Either way, after a high-carb meal you can end up with too much glucose moving freely in the bloodstream without any restraints.

So what’s wrong with that?

Here’s the problem. While glucose is vital to our survival, and our bodies break it down to release the energy we need to stay alive, too much of it circulating freely in our bloodstream and entering living cells can sabotage important chemical processes inside the cells. So unless glucose is tightly controlled, too much of it in the blood, over time, can lead to heart problems, vascular disease, diabetic foot disease, nerve damage, blindness, and other complications.

An analogous example is oxygen. As with glucose, we can’t live without it. Also like glucose, free oxygen harms living cells if not tightly controlled. It’s the job of the red hemoglobin in our blood to seize all oxygen molecules absorbed by the lungs, transport them through the bloodstream, and hand them over to the metabolic workforce in cells.

Bringing Salacia into mainstream medicine
Remember the microvilli in the intestine wall? And the a-glucosidase molecules coating them? Drinking Salacia extract blocks the glucosidases from doing their job. “Certain compounds in Salacia, explains Pinto, “insert themselves directly into the active sites of glucosidases. This action blocks further breakdown of carbohydrates and keeps glucose from being released and entering the bloodstream.”
Happily this action is reversible. “You don’t want it to be permanent,” explains Pinto. “You just want to control sugar absorption after a meal. Eventually the Salacia compounds and the semi-digested carbohydrates pass through the intestine and out. It’s why the traditional extract has few (if any) side effects. It never enters the bloodstream.”

Mario Pinto has become a “synthetic chemist.” He seeks ways to artificially synthesize and modify natural substances in order to develop safer, more effective human applications. In this project, his current team includes two students from India – one a PhD candidate, the other a post-doctoral researcher – and another PhD candidate from Iran. “We’ve been pursuing the chemical structure of the active substances in Salacia,” says Pinto. “We’ve synthesized many compounds of similar composition, five of which occur in the plant, and two of which are especially active. And we’ve synthesized some variants that are more selective in their action. Now we’re determining precisely what part of their physical and/or chemical structure is responsible for blocking glucosidase activity.”

Of course, a single Salacia-based formula won’t work for everyone. Different human groups produce different enzymes for breaking down carbohydrates from different sources. It’s genetic. It’s also not clear why certain individuals who change from a traditional diet to a refined starchy one develop type 2 diabetes, obesity, or other complications. “We’re studying these human-enzyme differences,” says Pinto.

If one or more Salacia-based therapies can be developed, the result would be a godsend for millions of people. Not only would it help those with high blood sugar, it would relieve pressure on wild Salacia plants. Although Salacia is cultivated in Sri Lanka, India, Australia, and other countries, the growing demand for it outstrips the availability. And there’s another concern: “Sri Lankans have had to become very protectionist about Salacia,” says Pinto. “There are lawsuits underway against foreign companies who are trying to patent the natural extracts that Sri Lankans have used for a thousand years.”

Salacia and “curiosity-based” research
Mario Pinto’s Salacia project illustrates the importance of research that’s based solely on curiosity, with no planned objective. “It began as a pure discovery-based project,” he explains. “We were curious about the mechanism involved – about how the extract actually works to slow sugar absorption. While we ended up with a practical spinoff, that wasn’t the original goal.

“I think curiosity should guide knowledge creation. People come to work in my lab not because of the possible applications, but because they want to learn to think. They bring with them different expertise. I remember years ago my post-doctoral mentor saying that if you succeed in transferring all your knowledge to your students, you will have failed. It’s true. Why? Because then there’s no evolution of ideas. It’s better to pose a research question, then investigate it from different points of view. Sometimes innovation comes out of it in terms of a practical application; sometimes it doesn’t. Along the way, though, tremendous fundamental knowledge is created that other scientists can use – plus students are taught to think critically. That’s how science works.” aq

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