Researchers discovered that betulinic acid, a natural compound found in plants, might help prevent and reverse liver scarring (fibrosis). The study used computer modeling, lab experiments, and mouse models to show that betulinic acid blocks a specific protein involved in liver damage. When mice with liver fibrosis received betulinic acid, their liver scarring improved significantly without causing harmful side effects. This research suggests a new natural approach to treating liver disease, though human studies are still needed to confirm these promising results.

The Quick Take

  • What they studied: Whether a natural plant compound called betulinic acid could stop and reverse liver scarring by blocking a specific protein that causes damage
  • Who participated: Laboratory mice with liver damage, human cells grown in dishes, and computer simulations—no human patients were directly tested
  • Key finding: Betulinic acid successfully reduced liver scarring in mice and prevented damage to liver cells in laboratory tests, working by blocking a protein called AT1R
  • What it means for you: This research is early-stage and promising, but it’s not yet ready for human treatment. It suggests a potential new natural therapy for liver disease, though more research in humans is needed before doctors could recommend it

The Research Details

Scientists used three main approaches to test betulinic acid. First, they used advanced computer programs to predict how betulinic acid would attach to and block a harmful protein called AT1R. Second, they tested this in laboratory dishes using human cells and mouse cells to see if it actually worked. Third, they gave betulinic acid to mice with liver damage to see if it improved their condition.

The researchers created liver damage in mice using a combination of an unhealthy diet and a chemical that harms the liver. They then treated some mice with betulinic acid and compared them to untreated mice. They also tested the compound on human cells in dishes to understand exactly how it works at the cellular level.

This multi-layered approach—combining computer predictions, lab tests, and animal studies—helps scientists understand both how a treatment works and whether it’s actually effective before testing it in humans.

This research approach is important because it follows the proper scientific steps before human testing. By first using computer modeling and lab cells, scientists can quickly identify promising candidates. Then testing in animals shows whether the treatment actually works in a living body and whether it causes harmful side effects. This careful progression helps ensure that only the safest and most effective treatments move forward to human studies.

The study used well-established scientific methods including computer modeling with advanced AI tools, molecular testing, and animal models. The researchers measured multiple markers of liver health and damage. However, this is early-stage research—no human patients were tested, so we don’t know if results will be the same in people. The study was published in a peer-reviewed journal, meaning other scientists reviewed it for quality. The main limitation is that animal studies don’t always translate to human medicine.

What the Results Show

Computer modeling showed that betulinic acid binds strongly and stably to the AT1R protein, which is a key driver of liver damage. This prediction was confirmed when researchers tested it in mice that had the AT1R gene removed—the betulinic acid still worked, proving it targets this specific protein.

When mice with liver fibrosis (scarring) received betulinic acid by mouth for an extended period, their liver scarring significantly improved. The treated mice showed better liver function and less damage compared to untreated mice. Importantly, the compound didn’t cause harmful effects to the liver, kidneys, or other organs, and blood tests remained normal.

In laboratory tests with human cells, betulinic acid prevented the harmful transformation of endothelial cells (cells that line blood vessels) into scar-forming cells. This transformation is a key step in how liver scarring develops. The researchers identified that betulinic acid works by affecting a specific cellular pathway called PI3K-AKT, which controls whether cells become scar-forming cells or remain healthy.

The study found that betulinic acid was well-tolerated with no signs of toxicity in major organs. Blood tests showed normal kidney and liver function even with long-term treatment. The compound appeared to work by preventing the activation of the harmful cellular pathway that turns normal cells into scar-forming cells. This suggests betulinic acid might have multiple protective effects in the liver beyond just blocking AT1R.

Previous research identified that AT1R is involved in liver scarring and that blocking this protein could be therapeutic. This study is the first to show that betulinic acid, a natural compound, can effectively block AT1R. Other AT1R-blocking drugs exist but are synthetic chemicals; this research suggests a natural alternative might work similarly. The finding that EndMT (the transformation of blood vessel cells into scar cells) is a key mechanism in liver fibrosis aligns with recent discoveries in the field.

This research was conducted only in mice and laboratory cells—results may not be identical in humans. The study didn’t compare betulinic acid to existing liver fibrosis treatments, so we don’t know if it’s better or worse. The exact dose and duration needed for human treatment is unknown. The mechanism of action was identified in laboratory conditions, which may differ from the complex environment inside a human body. No human safety or effectiveness data exists yet.

The Bottom Line

Based on this research alone, betulinic acid cannot yet be recommended as a treatment for liver disease. This is early-stage research showing promise in animals. Anyone with liver disease should continue following their doctor’s current treatment plan. Future human clinical trials are needed to determine if betulinic acid is safe and effective in people. Confidence level: Low (early-stage animal research only).

This research is most relevant to people with liver fibrosis or chronic liver disease, though they should not change their treatment based on this study alone. Researchers and pharmaceutical companies developing new liver disease treatments should pay attention. People interested in natural medicine approaches to disease may find this interesting, but it’s not yet ready for use. This research is NOT appropriate for self-treatment or replacing current medical care.

If betulinic acid moves forward to human testing, it typically takes 5-10 years before a new treatment becomes available to patients. First, small safety studies would be needed, followed by larger effectiveness studies. Even if human trials begin soon, patients shouldn’t expect this treatment to be available for several years.

Want to Apply This Research?

  • Users with liver disease could track liver function markers (ALT, AST, bilirubin levels from blood tests) monthly or quarterly to monitor their liver health status over time, creating a baseline for comparison if this treatment becomes available
  • Users could use the app to set reminders for regular liver function blood tests and doctor appointments, and log lifestyle factors that affect liver health (alcohol consumption, diet quality, exercise) to understand their personal liver disease progression patterns
  • Establish a long-term tracking system that records liver function test results, symptoms (fatigue, abdominal swelling), and medication adherence. This creates a personal health record useful for discussing new treatments with doctors as they become available

This research is early-stage laboratory and animal studies only—no human patients have been tested. Betulinic acid is not currently approved as a medical treatment for liver disease. Anyone with liver disease should continue their current medical treatment and consult their doctor before making any changes. Do not attempt to self-treat liver disease with betulinic acid or any supplement based on this research. This information is for educational purposes only and should not replace professional medical advice. Always speak with your healthcare provider before starting any new supplement or treatment.