Compound found in honey reduced inflammation in PBC mice in lab
Scientists say galangin likely to have a protective effect on human liver
Galangin, a naturally occurring compound found in honey and certain plants, was shown to reduce inflammation and liver injury in a mouse model of primary biliary cholangitis (PBC), according to a new study from researchers in China.
The compound, known to have anti-inflammatory and antiscarring properties, was identified by the research team as a potential therapeutic candidate for PBC. That’s due to its ability to bind to ADORA2A, a receptor protein encoded by a gene the scientists say is likely to have a protective effect against PBC.
The scientists noted that more research is needed to “[lay] a more solid and comprehensive theoretical and practical foundation for PBC treatment,” and for “elucidating the mechanistic pathway of the galangin-ADORA2A interaction.”
Still, “these findings fully support the therapeutic potential of [galangin] in alleviating liver injury in PBC,” the team wrote.
Their study, “Identification of galangin as a therapeutic candidate for primary biliary cholangitis via systematic druggable genome-wide Mendelian randomization analysis and experimental validation,” was published in the journal Frontiers in Pharmacology.
PBC is marked by chronic inflammation of the bile ducts — the tubes that carry the digestive fluid bile from the liver to the intestines — within the liver. When these ducts become inflamed, bile accumulates in the liver, which may cause damage and progress to liver scarring, known as fibrosis, and liver failure.
About 40% of those with PBC fail to respond adequately to standard treatment
The standard first-line PBC therapy is ursodeoxycholic acid, called UDCA, marketed in the U.S. as Urso and Actigall, and available in generic versions. It improves bile flow and helps limit liver injury. However, about 40% of PBC patients do not respond adequately to UDCA, placing them at risk for liver failure, liver transplant, or death.
To investigate other options, a team of researchers from institutions in Shijiazhuang used Mendelian randomization to identify new therapeutic targets for PBC. The team’s goal was to predict and validate new drug candidates.
“Exploring novel therapeutic strategies is of great significance, and the continuous exploration of potential therapeutic targets for PBC has become a research focus,” the scientists wrote.
Mendelian randomization is a statistical technique that looks for relationships between an exposure and an outcome. In this case, the exposure concerned genetic variants that influence the activity of potential “druggable” genes and the outcome was PBC.
MR analysis was based on druggable gene data from blood and liver samples, as well as data from European genome-wide association studies (GWAS). GWAS are large-scale studies that collect genetic and clinical information from thousands of individuals to identify genetic variations associated with the risk of a specific clinical feature, such as a disease.
The analysis identified 15 genes that were significantly associated with PBC: 10 as potential protective genes and five as likely risk factors. These genes were linked with various biological processes, mainly immune responses, inflammation, and apoptosis, or programmed cell death.
Further analyses pointed to three genes, all thought to be protective against the disease, as potential PBC therapeutic targets. These were MYC, GPI, and ADORA2A.
The team then turned to computer-based drug prediction and drug-protein binding analyses.
In mice, galangin had similar results to first-line therapy UDCA
From those results, the researchers identified galangin as a promising drug candidate. Galangin, a naturally occurring compound with antioxidant, anti-inflammatory, and antifibrotic properties, is found in honey, a ginger-like root called galangal, and other plants.
In the analyses, the compound exhibited strong binding to ADORA2A, the cell surface receptor protein coded by the ADORA2A gene. ADORA2A, also known as the adenosine A2A receptor, has been implicated in suppressing immune cell activity, and thus protecting tissues from inflammation.
To validate these findings, the team tested galangin in a mouse model of PBC, which is generated by exposure to alpha-naphthyl isothiocyanate, a compound that causes liver damage, including bile duct injury.
An examination of the liver tissue under the microscope of untreated PBC mice found significant infiltration of inflammatory cells and abnormal bile ducts. These features were reduced in animals treated with either UDCA or galangin, of which medium and high doses showed more pronounced protective effects.
[The results suggest] that [galangin] may protect the liver by reducing liver injury and promoting bile secretion. … These findings provide new target directions and drug options for PBC treatment.
In blood tests, PBC mice had significantly higher levels of several liver injury biomarkers, including liver enzymes, bile acids (bile’s main component), and bilirubin. Treatment with either UDCA or galangin significantly lowered these elevated biomarkers.
Still, medium and high doses of galangin appeared to show more significant effects, “suggesting that [galangin] may protect the liver by reducing liver injury and promoting bile secretion,” the researchers wrote.
Lastly, PBC mice had markedly increased blood levels of pro-inflammatory signaling proteins, including IL-1-beta, IL-6, and TNF-alpha. Galangin treatment significantly reduced these protein levels, similar to UDCA, suggesting that galangin “may have anti-inflammatory properties and can alleviate liver inflammation,” the team wrote.
“These findings provide new target directions and drug options for PBC treatment,” the researchers concluded. “Future research will focus on gene function verification, multi-model verification, and in-depth clarification of the molecular mechanism underlying the [galangin-ADORA2A] interaction.”
About the Author
