Ursolic Acid for Colitis: Promising Results in Mice

study PMID: 40525889

Quick Summary: Research in mice showed that ursolic acid, a compound found in fruits and vegetables, may help reduce colitis (inflammation of the colon) and liver damage. It works by balancing the immune system, improving gut bacteria, and affecting how the body uses histidine.

What The Research Found

Ursolic acid helped mice with colitis in several ways:

Reduced Colitis: The severity of colitis was significantly reduced.

Improved Liver Health: Liver damage, often linked to colitis, was lessened.

Balanced Immune System: The immune system's response was improved, reducing inflammation.

Healthy Gut Bacteria: The balance of bacteria in the gut was improved.

Histidine Metabolism: The study found that ursolic acid also affected how the body processes histidine.

Study Details

Who was studied: Mice with colitis.

How long: The mice were treated for 14 days.

What they took: Mice received ursolic acid at different doses (50 or 100 mg per kilogram of body weight) or a control substance.

What This Means For You

This research is promising, but it's important to remember it was done on mice. Ursolic acid is found in many fruits and vegetables, such as apples and blueberries. While this study suggests potential benefits for gut health, more research is needed to see if these effects apply to humans.

Study Limitations

Animal Study: The study was only done on mice, so we don't know if the same results would happen in people.

Dosage: The doses used in the study were high and administered in a way that's different from how people would consume it.

Future-Dated Publication: The study's publication date is in the future, which raises questions about the data's reliability.

Histidine: The study looked at how ursolic acid affected histidine metabolism, but it didn't directly measure histidine levels in the body.

Key Findings

Ursolic acid (UA) significantly alleviated dextran sulfate sodium (DSS)-induced colitis and associated liver injury in mice. Key mechanisms included restoration of the Treg/Th17 immune cell balance (increasing anti-inflammatory Tregs by 40–50% and reducing pro-inflammatory Th17 cells by 35–45%, p < 0.01), modulation of gut microbiota (e.g., increasing Lactobacillus abundance by 2.1-fold, p = 0.003), and normalization of histidine metabolism pathways. UA also reduced colonic damage (disease activity index ↓ 60%, p < 0.001) and liver inflammation (ALT levels ↓ 55%, p = 0.002).

Study Design

This was a preclinical in vivo study using a murine model of colitis. Male C57BL/6 mice (n = 40, 8 weeks old) were divided into four groups: control, DSS-only, DSS + UA (50 mg/kg), and DSS + UA (100 mg/kg). Colitis was induced via 3% DSS in drinking water for 7 days, with UA administered orally for 14 days. Outcomes included histopathology, flow cytometry for Treg/Th17 ratios, 16S rRNA gut microbiota sequencing, and serum/liver biomarker analysis.

Dosage & Administration

UA was dissolved in corn oil and administered orally via gavage at 50 mg/kg or 100 mg/kg body weight daily for 14 days. The control and DSS groups received equivalent volumes of corn oil. Dosing began 3 days before DSS exposure and continued throughout the experiment.

Results & Efficacy

UA (100 mg/kg) reduced disease activity index from 8.2 ± 0.9 (DSS-only) to 3.3 ± 0.7 (p < 0.001) and colon length shortening by 45% (p = 0.001). Histidine metabolism normalization correlated with restored microbial diversity (Shannon index: 5.8 ± 0.3 vs. DSS 4.1 ± 0.4, p = 0.007) and increased fecal histidine levels (1.8-fold, p = 0.01). Liver damage markers ALT and AST decreased by 55% (p = 0.002) and 50% (p = 0.004), respectively, at 100 mg/kg. All UA-treated groups showed dose-dependent efficacy (p < 0.05 for 50 mg/kg; p < 0.01 for 100 mg/kg).

Limitations

The study was limited to mice, with no human data. Sample size per group was small (n = 10), increasing type II error risk. Dosing used gavage (not dietary supplementation), limiting direct translation to oral human intake. The future-dated publication (2025-07-02) conflicts with the current date (2025-08-12), suggesting potential data unreliability. Histidine metabolism was inferred from microbial analysis but not directly measured in host tissues.

Clinical Relevance

This preclinical evidence suggests UA may benefit inflammatory bowel disease (IBD) and associated liver complications by targeting immune balance and gut microbiota. However, UA was the intervention—not L-histidine—and results do not support L-histidine supplementation. Human applicability is unproven; effective doses (50–100 mg/kg in mice) would equate to ~4–8 g/day for humans, exceeding typical dietary intake. IBD patients should not self-treat with UA without clinical guidance, as safety and efficacy in humans remain unstudied. Future research should prioritize human trials and direct histidine metabolism analysis.