Plant compounds offer new clues about gut bacteria and cholestasis
Mouse study finds possible liver-protective effects from ferulic acid and wogonin
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Two plant-based compounds — ferulic acid and wogonin — may help protect the liver in cholestasis by influencing the growth of certain gut bacteria, according to a mouse study.
“These findings underscore the critical role of gut microbiota in cholestasis and suggest therapeutic potential for microbiota-targeted and natural compound-based interventions,” the researchers wrote.
The study, “Synergistic effects of ferulic acid and wogonin on cholestatic liver injury via gut microbiota modulation,” was published in npj Biofilms and Microbiomes.
Blocked bile flow can damage the liver
Cholestasis occurs when the flow of bile, a digestive fluid made in the liver, is blocked or slowed on its way to the small intestine. When bile builds up, it can damage the liver and leak into the bloodstream, leading to symptoms such as jaundice (yellowing of the skin and whites of the eyes) and itching.
Treatment often involves ursodeoxycholic acid (sold as Urso and Actigall), a medication that helps improve bile flow. However, some people respond only partially, which may increase the risk of liver failure and cirrhosis (permanent liver scarring).
Research increasingly shows that bile acids, the main components of bile, interact closely with the gut microbiota, the large community of bacteria and other microbes that live in the digestive tract. When this balance is disrupted, it may change the liver’s immune environment and contribute to liver disease.
“Treatments that adjust the crosstalk within the gut-liver bile acid system and microbial modulation of [bile acid] metabolism offer more effective interventions and therapeutic strategies for cholestasis-related diseases,” the researchers wrote.
Yinzhihuang (YZH) is a plant-based remedy used in China for liver injury. Two of its main natural components are ferulic acid and wogonin, two compounds thought to have antioxidant and anti-inflammatory properties.
Researchers test plant compounds in a mouse model
In this study, researchers in China tested YZH, along with its main compounds ferulic acid and wogonin, in mice with chemically induced cholestasis. They paid particular attention to how these treatments affected the gut microbiota.
First, mice with cholestasis that were treated with YZH showed significantly lower levels of liver injury biomarkers and fewer signs of liver tissue injury and scarring (fibrosis) than untreated mice. But when the mice were given antibiotics to deplete the gut bacteria, these benefits disappeared, suggesting the microbiota played a key role.
Further analyses showed that higher levels of the bacterium Alistipes putredinis (A. putredinis) were linked to significantly higher levels of liver damage biomarkers and worse liver fibrosis. In contrast, higher levels of Clostridium spp. (C. spp.) were associated with significantly lower signs of liver injury and fibrosis.
“These results suggest that A. putredinis could aggravate … cholestasis, while C. spp. has a therapeutic effect on cholestatic diseases,” the team wrote.
When the researchers tested the compounds individually, they found that ferulic acid suppressed the growth of A. putredinis, while wogonin promoted the growth and activity of C. spp.
Consistent with these findings, treatment with either ferulic acid or wogonin significantly reduced markers of liver injury and fibrosis, as well as pro-inflammatory signaling proteins.
Gut bacteria may either worsen or help protect the liver
Experiments showed that A. putredinis may damage the protective mucus barrier in the intestine, allowing bacteria to cross into the liver and worsen cholestasis. Treatment with ferulic acid helped protect the intestinal barrier and prevented bacteria from reaching the liver.
In another experiment, mice given C. spp. directly into the stomach showed lower levels of bile acids in the liver, but higher levels in stool, “suggesting that C. spp. promotes the excretion of [bile acids] in the intestine,” the team wrote. Similar results were seen when mice with induced cholestasis were treated with wogonin.
“Based on the interpretation of the mechanisms of YZH, C. spp. and A. putredinis, identified as probiotics and [disease-causing organisms] involved in cholestatic liver injury, were verified,” the researchers wrote. Probiotics are live microorganisms — found in foods such as yogurt and fermented products — that may support gut health.
Finally, the researchers tested a combination of ferulic acid, wogonin, and C. spp. They found that the combination provided greater liver protection than any single treatment alone.
“Our findings provide insights into the gut microbiota associated with cholestatic liver injury and highlight the therapeutic potential of probiotics and active compounds,” the researchers wrote.
