Betulinic acid (Synonyms: Lupatic Acid, NSC 113090)

Betulinic acid is a natural pentacyclic triterpenoid, acts as a eukaryotic topoisomerase I inhibitor, with an IC50 of 5 μM, and possesses anti-HIV, anti-malarial, anti-inflammatory and anti-tumor properties.

Betulinic acid is a eukaryotic topoisomerase I inhibitor, with an IC50 of 5 μM, and prevents topoisomerase I-DNA interaction[1]. Betulinic acid (10, 20, 40, 80, and 160 µM) significantly suppresses MDA-MB-231 cell viability in a time- and dose-dependent manner after treatment for 24 or 48 h. Betulinic acid (20, 40 µM) causes decrease in Bcl-2 expression of MDA-MB-231 cells. Betulinic acid also induces morphological changes of MDA-MB-231 cells at 20 µM, and leads to ultrastructure changes of MDA-MB-231 cells at 40 µM[2]. Betulinic acid shows anti-HIV activities, with an EC50 of 1.4 µM in acutely infected H9 lymphocytes[4].

Betulinic acid (10 and 30 mg/kg, p.o.) significantly abrogates colon shortening, and reduces malondialdehyde (MDA) and lipid hydroperoxide levels in dextran sulfate sodium (DSS)-induced colitis in mice. Betulinic acid (30 mg/kg, p.o.) restores superoxide dismutase (SOD), catalase activity and glutathione (GSH) content to control levels in DSS-induced colitis in mice. Betulinic acid (30 mg/kg, p.o.) also inhibits the DSS-induced increase in inflammatory markers. Betulinic acid (3, 10, 30 mg/kg, p.o.) suppresses acetic acid-induced writhing responses and mustard oil (MO)-induced visceral nociception in mice[3].

Reference：
[1]. Chowdhury AR, et al. Betulinic acid, a potent inhibitor of eukaryotic topoisomerase I: identification of the inhibitory step, the major functional group responsible and development of more potent derivatives. Med Sci Monit. 2002 Jul;8(7):BR254-65.
[2]. Gao Y, et al. Betulinic acid induces apoptosis and ultrastructural changes in MDA-MB-231 breast cancer cells. Ultrastruct Pathol. 2018 Jan-Feb;42(1):49-54.
[3]. Kalra J, et al. Betulinic acid alleviates dextran sulfate sodium-induced colitis and visceral pain in mice. Naunyn Schmiedebergs Arch Pharmacol. 2017 Dec 26.
[4]. Hashimoto F, et al. Anti-AIDS agents--XXVII. Synthesis and anti-HIV activity of betulinic acid and dihydrobetulinic acid derivatives. Bioorg Med Chem. 1997 Dec;5(12):2133-43.