Researchers identify betulinic acid as a promising new agent for treating hepatic fibrosis
04/14/2020 // Evangelyn Rodriguez // Views

Betulinic acid is a naturally occurring compound that can be found in the outer bark of various trees, particularly that of the white birch tree (Betula pubescens). It is classified as a triterpenoid and has demonstrated a wide range of beneficial properties in numerous studies.

Among the many activities of betulinic acid, the most notable ones include anti-retroviral, anti-malarial and anti-inflammatory properties. Recent reports also suggest that the compound has potent anti-cancer activity characterized by the inhibition of topoisomerase -- an enzyme responsible for winding and unwinding DNA during replication.

But in a recent study, researchers at Southern Medical University in China discovered another medicinal use of betulinic acid. In their article, which appeared in the Journal of Natural Medicines, they investigated the effects of betulinic acid on the expression of fibrosis- and autophagy-related markers.

The researchers found that betulinic acid can prevent unfavorable scarring by reducing the expression of relevant proteins and inducing autophagy. These mechanisms of action make the compound a promising agent for the treatment of liver fibrosis.

Betulinic acid can help prevent liver fibrosis

Fibrosis refers to the overgrowth, hardening and scarring of tissue caused by a surplus in deposits of extracellular matrix (ECM) components, such as collagen. Fibrosis is triggered by chronic inflammatory reactions that follow various events, such as persistent infections, autoimmune reactions, allergic responses, exposure to chemicals or radiation and tissue injury.


In the case of liver fibrosis, excessive amounts of ECM components including collagen accumulate in the liver. This is due to activated hepatic stellate cells, portal fibroblasts and myofibroblasts producing too much collagen. Liver fibrosis is considered a pathological event that can eventually lead to liver cirrhosis and liver failure.

For their study, the researchers examined how betulinic acid can influence liver fibrosis by testing it on human hepatic stellate cells (fat-storing cells in the liver) in vitro and C57BL/6 mice in vivo. They focused on the changes in the expression of alpha smooth muscle actin, a marker of fibrosis, and autophagy-related proteins. Autophagy is a cell-regulated process of clearing out unnecessary or damaged cellular components.

The researchers found that betulinic acid can reduce the pathological damage associated with liver fibrosis by decreasing serum platelet-derived growth factor and serum hydroxyproline levels. The former is an important factor that facilitates the progression of liver fibrosis, while the latter is an amino acid component of collagen.

In the livers of mice, betulinic acid down-regulated the expression of alpha smooth muscle actin and type I collagen but up-regulated the expression of microtubule-associated protein light chain 3B (LC3) and autophagy-related gene 7. LC3 plays a central role in autophagy.

Meanwhile in vitro, betulinic acid also increased the expression of the autophagy marker, LC3II, but decreased the expression of alpha muscle actin in hepatic stellate cells. These results suggest that the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway may be involved in the effects of betulinic acid on liver fibrosis. The signaling pathway controls cell processes associated with fibrosis.

Based on these findings, the researchers concluded that the anti-liver fibrosis activity of betulinic acid is due to its ability to induce autophagy, which makes it a promising new agent for treating liver fibrosis.

Other health benefits of betulinic acid

The outer bark of birch trees, from which betulinic acid is obtained, has been used as a folk remedy for centuries. Birch bark oil is said to have healing properties and is used to treat skin diseases like eczema and psoriasis. Native Americans also used to make tea out of birch bark to treat digestive tract infections. (Related: Birch bark nutrient prevents obesity, diabetes and high cholesterol.)

Recent studies on birch bark has found that it has interferon-inducing activity both in vitro and in vivo. Interferons are naturally occurring proteins that can boost immune function and reduce the growth of cancer cells.

Betulinic acid, the active component of birch bark, has also shown anti-inflammatory, anti-malarial, anti-HIV and anti-tumor activities. In fact, betulinic acid has proven itself to be effective against melanoma, a dangerous form of skin cancer.

Learn more about betulinic acid and other medicinal plant compounds at

Sources include: 1 2

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