HYPERTENSION, or high blood pressure, affects one billion people worldwide and if uncontrolled can lead to cardiovascular disease and death.
Resistant hypertension is when blood pressure remains high despite treatment with optimal doses of three different anti-hypertensive drugs. Current evidence estimates that it affects 14 to 16 per cent of all patients with hypertension, which is equal to 140 to 160 million people globally.
Currently, there is no single drug that can effectively treat this condition.
But, that may soon change.
Researchers from the University of Nottingham Malaysia (UNM) have discovered new natural compounds in a fig plant species native to Malaysia that could lead to improved treatment for resistant hypertension.
UNM’s Faculty of Science associate professor Dr Lim Kuan Hon, and his team have isolated a new class of natural compounds from the fig plant species that induce vasodilation in the aorta tissue, meaning the compounds have the ability to dilate the aorta tissue blood vessels.
“My research focuses on the discovery of natural chemical compounds that possess interesting or useful biological properties from Malaysian plants. Recently, we have isolated from a local fig plant a series of new natural compounds that dilate blood vessels, which has the potential application in decreasing blood pressure.
“We are also synthesising new chemical compounds that mimic the structures of the new natural compounds with the aim of discovering effective medicines to treat resistant hypertension — high blood pressure that doesn’t respond well to existing treatments,” said Lim, who is a natural product chemist by training.
Why synthesise compounds if they are abundant in nature?
“Humans have used plants as a natural remedy to treat many diseases for a long time. There were countless instances where natural compounds obtained from plants have been developed into useful medicines. However, in the context of my project, the natural compounds were only obtained in very small amounts from the fig plant, which does not represent a sustainable source,” Lim said.
The rare fig species was collected from a rainforest in Peninsular Malaysia. The location of the plant species is crucial as there may be differences in the plant’s chemical composition due to geographical variation.
“Finding these plant species is a challenge as they are often hidden in dense areas. So, when we do find them, we map their location carefully using global positioning system so that we can find them again if we need to. It took over 10kg of the dried fig leaves to produce just enough compounds for a few rounds of biological testing,” said Lim.
In addition to locating and collecting the plant, extracting and purifying the compounds from the plant is also painstaking.
The fig leaves were first air dried in the lab for two weeks before being ground down and then extracted with ethanol. Using solvent-solvent partitioning and chromatography techniques, the researchers then separated and purified the plant compounds and examined their chemical structures and properties. The researchers were only able to isolate 50mg of the most abundant new compound from 15kg of dried leaves.
When tested on rat aorta tissue, the purified compounds were found to induce significant vasodilation.
“From a sustainability point of view, it is better to synthesise the compounds in our labs than to isolate them from the harvested plants. We have to date successfully synthesised one of the new natural compounds in our lab and the synthetic compound showed equal potency to the natural one,” said Lim.
“We are also preparing many other molecules that mimic the structures of the bioactive new compounds with subtle differences among them with the aim to pinpoint which parts of the molecular structure are essential for bioactivity and eventually discover compounds with superior vasodilation activity.
“Nature has been providing remedies for numerous diseases and ailments for thousands of years, but it is impossible to know everything nature can offer us, so making a discovery like this is always exciting.
“With the help of our biological scientist colleagues we are on the verge of understanding exactly how the new compounds elicit their biological effect, and then hopefully we will have the knowledge and ingredients needed to create an effective drug for resistant hypertension.
“Currently there is no single medicine that can treat resistant hypertension. So, our research, should we be successful, has the potential to change many lives.”
Lim highlighted that collaboration is important in research work.
“Since research in drug discovery is highly multidisciplinary, it is only natural for us to collaborate with different research groups from and beyond the university so that scientists from different field of expertise can be pulled together to address different aspects of the research project.”
On advice he would give to someone starting out in research?
“Press on, don’t give up and let your passion to discover drive you forward. Try to do your best, whatever situation you are in.”