Ursolic acid is a compound (a type of pentacyclic triterpene) that forms part of the waxy coating of certain fruits such as apples as well as the leaves of some culinary herbs such as rosemary. Ursolic acid has been reported to reduce cisplatin-induced inner ear damage. Now a new study has reported that ursolic acid also protects against cisplatin-induced liver injury.

Ursolic acid and breast cancer

Ursolic acid has been shown to inhibit tumor formation and growth in each of the major breast cancer receptor types (ER+/PR+, HER2+ and ER-/PR-/HER2-). Ursolic acid has also been reported to inhibit aromatase (the synthesis of estrogen from androgens within the body), thereby strengthening the treatment effects of aromatase inhibitors.
In addition, ursolic acid has been shown to reverse multidrug resistance in breast cancer cells. For example, one study found that ursolic acid reversed resistance to paclitaxel in paclitaxel-resistant triple negative breast cancer. Another study reported that ursolic acid resensitized multidrug resistant ER+/PR+ breast cancer cells to doxorubicin chemotherapy. Still another study demonstrated that ursolic acid increased the sensitivity of triple negative breast cancer cells to doxorubicin.

Food sources of ursolic acid

Ursolic acid is present in significant amounts in the following fruits and culinary herbs:
Sage is also a rich source of ursolic acid, but we do not recommend it for breast cancer patients and survivors because of its hormonal effects.

Organic apples are best

As noted above, ursolic acid is found in the waxy coating of the peels of apples of all varieties. Apple peels are the most abundant common fruit source of this compound. However, note that conventionally grown apples typically are produced using relatively high levels of pesticides. Such apples normally are washed after picking, which removes some of the pesticide residue, but also strips off some of the waxy cuticle. Food grade wax is then applied to the apples, which can seal in some of the remaining pesticide residue. Therefore, organically grown apples are best.

Latest research finds ursolic acid reduces cisplatin toxicity

The study referenced above was designed to investigate the potentially protective effects of ursolic acid in the livers of Swiss albino mice treated with cisplatin. Cisplatin chemotherapy is associated with systemic toxicities (including hepatotoxicity) that can limit its therapeutic use. Ferroptosis, a type of programmed cell death accompanied by iron accumulation and lipid peroxidation, appears to be involved in cisplatin-induced tissue damage. Ursolic acid has antioxidant qualities that have been proposed to help counteract cisplatin's toxic side effects.
To conduct the study, the authors divided 30 mice into five treatment groups: (1) untreated control; (2) cisplatin alone (10 mg/kg); (3) cisplatin + ursolic acid 1 (10 mg/kg+10 mg/kg); (4) cisplatin + ursolic acid 2 (10 mg/kg+40 mg/kg); and (5) ursolic acid alone (40 mg/kg). At the end of treatment, the mice were sacrificed and their liver tissues assessed for liver markers (ALT, AST, ALP), oxidative stress (ROS, antioxidant capacity), iron levels, and histopathological changes.
Mice given cisplatin gradually lost weight and experienced increasing levels of liver enzymes associated with liver damage. Cisplatin treatment also resulted in meaningful increases in ROS levels, iron accumulation, and histopathological damage in liver tissue. Mice in groups 3 and 4 (treated with both ursolic acid and cisplatin) experienced lowered ROS levels and liver enzymes, as well as restored antioxidant capacity, improved tissue structure, and reduced ferroptosis compared to group 2 (cisplatin alone). These findings support the hypothesis that ursolic acid has a protective role during cisplatin treatment. The authors conclude that ursolic acid may be a candidate treatment to help mitigate the systemic toxic effects of cisplatin.
Please see our article on foods to eat and avoid on cisplatin and the ursolic acid tag for more information.