The natural world has been medicine's most effective arsenal, providing life-saving antibiotics and our most potent anti-cancer drugs. Although historically most drugs have had their roots in natural products, some scientists worry that the approach is in decline. Eimear Vize examines some of the latest medical research utilising natural ingredients and finds that the apothecary Earth is still dispensing.
When it comes to stocking pharmacy shelves with drugs to treat our ailments and illnesses, Mother Nature still is the ultimate medicinal chemist. An estimated 70 percent of drugs approved to treat infectious disease and cancer over the past 25 years are of natural origin - medicines obtained from sources such as plants and animals, derived from natural products or chemically designed to mimic natural products.
These natural medicines range from aspirin - originally obtained from the willow tree - to taxol, the anti-cancer drug discovered in the Pacific yew tree, and the anti-malaria drug artemisinin from the Chinese wormwood tree.
In recent times, a remarkable number of clinical trials have rediscovered the therapeutic significance of some ancient remedies and uncovered a few new ones from Nature’s extensive medicine cabinet.
Medicines from the Sea
The sea represents an oasis of potential medicines and healing substances. Earlier this year, Norwegian scientists managed to produce completely new antibiotics from marine bacteria. These ‘bioprospectors’ discovered eleven species of bacteria found in the sea, which create substances that kill cancerous cells, and three other bacteria that produce new antibiotics.
Behind the successful collaboration between Professor Sergey Zotchev of NTNU (Norwegian University of Science and Technology) and senior scientist Håvard Sletta of SINTEF (the largest independent research organisation in Scandinavia), lies a long and painstaking process of screening, cultivation, isolation and testing. However, it will still take some time before they can be sure that the process will continue to the phases of commercialisation and medicine production.
“Substances with a new chemical structure and, we hope, with a different mechanism of action than we already know of, could be extremely valuable, for example in fighting cancer. This is why we need more candidate structures. Not all of them can be developed into new medicines, but if we are successful with one or two of them, we will be quite happy,” says NTNU professor Sergey Zotchev.
Recent focus on a few selected bacteria has led to these exciting findings. In Bergen and Moscow, the 11 anti-cancer substances have been tested against leukaemia and stomach, colon and prostate cancers.
“We have found that cancerous cells have been killed, while normal cells survive, and that individual extracts act on different types of cancer cells,” says Håvard Sletta. “However, we still have not identified the active substances in the compounds produced by the bacteria”.
A wise man’s remedy for bladder cancer
Frankincense oil has been highly prized by traditional healers throughout the ages for its wealth of health supporting properties. Now, an enriched extract of the Somalian Frankincense herb Boswellia carteri has been shown to kill off bladder cancer cells, according to research presented recently in the open access journal, BMC Complementary and Alternative Medicine.
The investigators from the University of Oklahoma Health Sciences Center and Oklahoma City VA Medical Center examined the effects of the oil in two different types of cells in culture: human bladder cancer cells and normal bladder cells. Remarkably, they discovered for the first time that frankincense oil is able to discriminate between normal and cancerous bladder cells in culture, and specifically kill cancer cells.
Gene expression analyses were performed to determine how frankincense oil affects bladder cancer cell survival. It appears the oil suppresses cancer cell growth by arresting cell cycle progression and induces bladder cancer cell death by activating multiple cell death pathways.
Lead researcher, Dr Hsueh-Kung Lin remarked: “Frankincense oil may represent an inexpensive alternative therapy for patients currently suffering from bladder cancer.”
The healing cuppa
The traditional Chinese cure-all Green Tea has just added another notch to its therapeutic belt as a new study of patients with prostate cancer, who consumed the active compounds in green tea, demonstrated a significant reduction in serum markers predictive of prostate cancer progression.
"The investigational agent used in the trial, Polyphenon E, may have the potential to lower the incidence and slow the progression of prostate cancer," confirms lead researcher James A Cardelli, Professor and Director of Basic and Translational Research in the Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center-Shreveport.
This open-label, single-arm, phase II clinical trial included 26 men, aged 41 to 72 years, diagnosed with prostate cancer and scheduled for radical prostatectomy. Patients consumed four capsules containing Polyphenon E until the day before surgery - four capsules are equivalent to about 12 cups of normally brewed concentrated green tea, says to Prof Cardelli.
Findings revealed a significant reduction in serum levels of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and prostate specific antigen (PSA) after treatment, with some patients demonstrating reductions in levels of greater than 30 percent. Other biomarkers were also positively affected, according to the study published in Cancer Prevention Research, a journal of the American Association for Cancer Research.
In addition, researchers in Hong Kong are reporting new evidence that green tea may also help improve bone health. They found that the tea contains a group of chemicals that can help in the prevention and treatment of osteoporosis and other bone diseases that affect million worldwide. Their findings are in ACS' Journal of Agricultural and Food Chemistry.
And staying with the humble, yet apparently potent cuppa, two scientists at the University of Copenhagen are attempting to develop a new treatment for type-2 diabetic, with the help of a special African tea.
The tea is used as a treatment in traditional Nigerian medicine and is produced from the extract of Rauvolfia Vomitoria leaves and the fruit of Citrus aurantium. The scientists have recently tested the tea on 23 patients with type-2 diabetes over a four-month period and the results are very promising.
“The research subjects drank 750ml of tea each day. The cure appears to differentiate itself from other current type-2 diabetes treatments because the tea does not initially affect the sugar content of the blood. But after four months of treatment with tea we can, however, see a significant increase in glucose tolerance,' explains postdoc Joan Campbell-Tofte from the Department of Medicinal Chemistry.
She and her research partner Prof Per Mølgaard hope that new clinical tests and scientific experiments in the future will result in a new treatment for type-2 diabetics.
The sweet root to preventing colorectal cancer
Doctors at the Vanderbilt University Medical Center in Nashville, Tennessee, are also taking a new look at another ancient remedy – Liquorice - and coming up with some surprising results. Liquorice has been used therapeutically for centuries in both Eastern and Western medicine to treat various conditions. New research published in the Journal of Clinical Investigation has identified a chemical component of liquorice that may offer a new approach to preventing colorectal cancer without the adverse side effects of other preventive therapies.
Drs Raymond Harris and Ming-Zhi Zhang, and colleagues found that inhibiting the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) - either by treatment with glycyrrhizic acid, the main sweet-tasting component of liquorice, or by silencing the 11betaHSD2 gene - prevents colorectal cancer progression in mice predisposed to the disease.
Liquorice, Dr Harris notes, has been used as a nutraceutical for thousands of years for ailments ranging from coughs to constipation. But even liquorice is not without side effects; long-term consumption can lead to low blood potassium and increases in blood pressure - side effects linked to the inhibition of 11betaHSD2.
"These are relatively minor compared to the cardiovascular side effects of COX-2 inhibitors," Dr Harris says. "We didn't see [these side effects] in the mice we treated, but it would be something to be aware of, and something that could easily be treated with a diuretic."
Dr Zhang, an assistant professor of Medicine and of Cancer Biology, plans to look at the enzyme's role in lung cancer and other tumours.
Cherry picking for osteoarthritis
The one in four people in Ireland who suffer from osteoarthritis may find that pain relief can come with a cherry on top. According to researchers with the Dallas-based Baylor Research Institute, tart cherries, in pill form, are a promising pain-reliever for this common and debilitating form of arthritis.
Patients with osteoarthritis of the knees were enrolled in a pilot study to assess potential efficacy of the tart cherry pills. More than half of the patients experienced a significant improvement in pain and function after taking the cherry pills for eight weeks.
Made from Montmorency tart cherries, this preparation is made up of ground whole cherries and given as a soft gelatine capsule (marketed under the brand name CherryFlex).
"This specific type of tart cherry is one of the best studied natural products and anecdotally has been claimed to have a salutary effect on osteoarthritis and other types of arthritis as well," explains Dr John Cush, rheumatologist and principal investigator of the study.
Baylor Research Institute together with the Arthritis Care & Research Institute is currently enrolling patients in a second study, which will test cherry pills versus placebo in an eight-week double blind study.
Baking soda: For cooking, cleaning and ... kidney disease patients?
Baking soda – that common household essential used for cooking and cleaning – may now have an important role to play in kidney health. A study in the September edition of the Journal of the American Society of Nephrology (JASN) demonstrates that sodium bicarbonate can slow the decline of kidney function in some patients with advanced chronic kidney disease (CKD).
The study included 134 patients with advanced CKD and low bicarbonate levels, also called metabolic acidosis. One group received a small daily dose of sodium bicarbonate in tablet form, in addition to their usual care. For this group, the rate of decline in kidney function was greatly reduced—about two-thirds slower than in the other patients.
"In fact, in patients taking sodium bicarbonate, the rate of decline in kidney function was similar to the normal age-related decline," says principle researcher Dr Magdi Yaqoob, MD, from the Royal London Hospital.
Low bicarbonate levels are common in patients with CKD and can lead to a wide range of other problems. "This is the first randomised controlled study of its kind," adds Dr Yaqoob. "A simple remedy like sodium bicarbonate, when used appropriately, can be very effective."
The hepatitis healing power of blueberry leaves
A chemical found in blueberry leaves has shown a strong effect in blocking the replication of the Hepatitis C virus, opening up a new avenue for treating chronic HCV infections, which affect 200 million people worldwide and can eventually lead to cirrhosis and liver cancer.
Among the areas of especially high Hepatitis C incidence is the Miyazaki prefecture of southern Japan, a trend that led Dr Hiroaki Kataoka and colleagues at the University of Miyazaki and elsewhere in Japan on a search for better treatment options.
They screened nearly 300 different agricultural products for potential compounds that suppress HCV replication and uncovered a strong candidate in the leaves of rabbit-eye blueberry. They purified the compound and identified it as proanthocyandin - a polyphenol similar to the beneficial chemicals found in grapes and wine.
While proanthocyandin can be harmful, Kataoka and colleagues noted its effective concentration against HCV was 100 times less than the toxic threshold, and similar chemicals are found in many edible plants, suggesting it should be safe as a dietary supplement. In the meantime, the researchers now hope to explore the detailed mechanisms of how this chemical stops HCV replication.
Hookworms in MS trial
Scientists from The University of Nottingham have begun studying the potential health benefits of parasitic worms in treatments for people with the autoimmune condition multiple sclerosis (MS).
Backed by funds of stg£400,000 from the MS Society, their three-year project aims to determine whether infection with a small and harmless number of the worms can lead to an improvement on the severity of MS over a 12-month period.
If the trial is successful, the worms have the potential to provide a simple, cheap, natural and controllable treatment for MS.
The WIRMS (Worms for Immune Regulation in MS) study is led by Professor Cris Constantinescu and Professor David Pritchard and is a randomised, placebo controlled, phase 2 study in people with relapsing remitting MS and will be carried out at multiple centres up and down the country.
The 25 worms are microscopic and are introduced painlessly through a patch in the arm. They are then flushed out after nine months.
“People are really interested in this form of potential therapy because it’s a natural treatment,” says Prof Constantinescu, Professor of Clinical Neurology. “It’s been tested for safety and we now need to study the potential benefits and any side effects.”
The Wisdom of the Ancients
Some scientists around the world are getting historical in their hunt for superior medicine. Researchers at the University of Pennsylvania are hoping to rediscover ancient healing wisdom using chemical tests to identify the herbs used medicinally in ancient Egypt.
By studying the residue of ingredients added to wine in ancient clay jars, these researchers hope to unlock some of the medical understanding held by physicians thousands of years ago.
Ancient Egypt was renowned for its prowess in the field of medicine, so much so that sick people travelled there from abroad in search of herbal remedies. Archaeologists know that the herbs were administered in a potent blend with wine. But the identity of many of those medicinal additives is a mystery - their names recorded in hieroglyphics that have resisted modern efforts at translation.
Now, two University of Pennsylvania scientists have begun to crack the puzzle with chemistry. In research published recently in the online edition of Proceedings of the National Academy of Sciences, the pair reported some of the earliest evidence of just what those long-ago physicians were prescribing.
One Egyptian clay jar, estimated to be more than 5,000 years old, yielded flaky residue that suggests a veritable apothecary of possible ingredients: coriander, senna, germander, balm, and savoury, among others. Samples scraped from the inside of a newer jar, just 1,500 years old, yielded compounds that likely came from rosemary.
These studies stem from more than just historical curiosity. Senior author Patrick McGovern, an "archaeochemist" at Penn's Museum of Archaeology and Anthropology, wants to know if the ancient herbalists came up with anything that really works.
And researchers at Penn's Abramson Cancer Center are similarly intrigued. They are already studying herbs identified in some of Mr McGovern's previous experiments. A derivative of the wormwood plant, found in a 3,200-year-old fermented beverage from China, has shown some promise against tumour cells in preliminary lab studies.
"I think people should be open-minded [about ancient remedies],” says Prof Wafik S El-Deiry, a Penn Professor of Medicine, Genetics, and Pharmacology, "because there may be hidden treasures."
