A team led by researchers at the University of Toronto has discovered that a compound present in ginger selectively binds to and regulates a nuclear receptor involved in inflammatory bowel disease (IBD).
The preclinical study, published recently in the journal Nature Communications , found a strong interaction between the compound furanodienone (FDN), which researchers have been aware of FDN for decades, and the pregnane X receptor (PXR). In particular, the study showed that FDN reduced inflammation in the colon by activating PXR, which then suppressed the production of pro-inflammatory cytokines in the body.
Jiabao Liu, a research associate at U of T's Donnelly Centre for Cellular and Biomolecular Research, said the study suggests that oral injections of FDN could be used to reduce colon inflammation.
"Our discovery of FDN's target nuclear receptor highlights the potential of complementary and integrative medicine for IBD treatment," he said. "We believe natural products may be able to regulate nuclear receptors with more precision than synthetic compounds, which could lead to alternative therapeutics that are cost-effective and widely accessible."
IBD patients typically experience symptoms early in life, with about 25 per cent of patients diagnosed before the age of 20. There is currently no cure for IBD, so patients must adhere to lifelong treatments to manage their symptoms, which include abdominal pain and diarrhea. The condition can result in significant psychological and economic consequences.
While patients with IBD have found some relief through changes to their diet and herbal supplements, it is not clear which compounds in food and supplements are responsible for alleviating intestinal inflammation. With FDN now identified as a compound with potential to treat IBD, this specific component of ginger can be extracted to develop more effective therapies.
The research also shows that FDN can increase the production of tight junction proteins that repair damage to the gut lining caused by inflammation.
Furthermore, the effects of FDN in the study were limited to the colon, suggesting no unwanted side effects elsewhere in the body.
Nuclear receptors serve as sensors within the body for a wide range of molecules, including those involved in metabolism and inflammation. PXR specifically plays a role in the metabolism of foreign substances such as dietary toxins and pharmaceuticals. The binding between FDN and PXR needs to be carefully regulated because over-activating the receptor can lead to an increase in the metabolism and potency of other drugs and signalling metabolites in the body.
FDN is a relatively small molecule that only fills a portion of the PXR binding pocket. The study shows that this allows for additional compounds to bind simultaneously, thereby increasing the overall strength of the bond and its anti-inflammatory effects in a controlled manner.
"The number of people diagnosed with IBD in both developed and developing countries is on the rise due to a shift towards diets that are more processed and are high in fat and sugar," said Henry Krause, principal investigator on the study and professor of molecular genetics in U of T's Temerty Faculty of Medicine. "A natural product derived from ginger is a better option for treating IBD than current therapies because it does not suppress the immune system or affect liver function, which can lead to major side effects.
"FDN can form the basis of a treatment that is more effective while also being safer and cheaper."
The research was supported by the Canadian Institutes of Health Research; Agence Nationale de la Recherche SYNERGY; Key-Area Research and Development Program of Guangdong Province, China; U.S. National Institutes of Health; National Natural Science Foundation of China; Natural Sciences and Engineering Research Council of Canada and New Frontiers in Research Fund.
