Ursolic Acid
Ursolic acid is a natural triterpene compound found in various plant foods and the herb Panax ginseng (covered in its own section). It modulates several pathways in the body that may prevent the development of chronic diseases. Among the many beneficial properties attributed to it, it exhibits anti-inflammatory, antioxidant, and neuroprotective effects1.
In a demyelination animal model of MS, ursolic acid 1 mg/ml of drinking water decreased demyelination and protected myelin-producing cells in the brain against the disease process. Treatment also improved spatial recognition memory compared to untreated controls2. In a similarly designed study, ursolic acid at 10% of feed suppressed demyelination and movement dysfunction3.
In an autoimmune animal model of MS, ursolic acid 25 mg/kg significantly decreased disease severity and CNS inflammation and demyelination, and promoted remyelination and neural repair.
In an inflammatory animal model of MS, basil essential oil (a concentrated source of ursolic acid) in doses of 100 and 200 mcl/kg significantly reduced neuroinflammation, as reflected in levels of pro-inflammatory cytokines (TNF-alpha and IL-6) in the brain. Treatment also significantly protected in brain mitochondrial function, integrity, and survival5.
In studies with pregnant rats, ursolic acid 10 mg/kg/day was observed to moderately decrease the risk of developmental defects in the fetus from gestational diabetes6, with no toxicity observed in mothers or offspring at 1000 mg/kg/day7.
The closely related ursodiol is naturally present in human milk. The very low levels observed after maternal supplementation translate to small amounts ingested by the breastfed infant that are not expected to cause any adverse effects8,9.
Food sources of ursolic acid include primarily herbs (e.g., basil, lavender, marjoram, oregano, peppermint, rosemary, thyme) and fruits (e.g., apple peel, bilberries, cranberries, prunes)10. It is generally found in supplements under the names “ursolic acid” or “holy basil.”
References
1.Seo DY, Lee SR, Heo JW, et al. Ursolic acid in health and disease. Korean J Physiol Pharmacol. May 2018;22(3):235-248. doi:10.4196/kjpp.2018.22.3.235
2.Honarvar F, Hojati V, Bakhtiari N, Vaezi G, Javan M. Myelin Protection by Ursolic Acid in Cuprizone-Induced Demyelination in Mice. Iran J Pharm Res. Fall 2019;18(4):1978-1988. doi:10.22037/ijpr.2019.112181.13582
3.Yamamoto S, Sakemoto C, Iwasa K, Maruyama K, Shimizu K, Yoshikawa K. Ursolic acid treatment suppresses cuprizone-induced demyelination and motor dysfunction via upregulation of IGF-1. J Pharmacol Sci. Nov 2020;144(3):119-122. doi:10.1016/j.jphs.2020.08.002
4.Zhang Y, Li X, Ciric B, et al. A dual effect of ursolic acid to the treatment of multiple sclerosis through both immunomodulation and direct remyelination. Proc Natl Acad Sci U S A. Apr 21 2020;117(16):9082-9093. doi:10.1073/pnas.2000208117
5.Garabadu D, Singh D. Ocimum basilicum attenuates ethidium bromide-induced cognitive deficits and pre-frontal cortical neuroinflammation, astrogliosis and mitochondrial dysfunction in rats. Metab Brain Dis. Mar 2020;35(3):483-495. doi:10.1007/s11011-020-00536-z
6.Dai S, Meng X, Cai X, et al. Therapeutic effect of ursolic acid on fetal development in pregnant rats with gestational diabetes mellitus via AGEs-RAGE signaling pathway. J Food Biochem. Apr 2021;45(4):e13651. doi:10.1111/jfbc.13651
7.Geerlofs L, He Z, Xiao S, Xiao ZC. Repeated dose (90 days) oral toxicity study of ursolic acid in Han-Wistar rats. Toxicol Rep. 2020;7:610-623. doi:10.1016/j.toxrep.2020.04.005
8.Ursodiol. Drugs and Lactation Database (LactMed(R)). 2006.
9.Simjak P, Petr T, Kaslova B, et al. Ursodeoxycholic acid use in lactating female patients is associated with clinically negligible concentrations of this bile acid in breast milk. Sci Rep. Nov 15 2022;12(1):19543. doi:10.1038/s41598-022-24253-y
10.Kashyap D, Tuli HS, Sharma AK. Ursolic acid (UA): A metabolite with promising therapeutic potential. Life Sci. Feb 1 2016;146:201-13. doi:10.1016/j.lfs.2016.01.017