Betulinic acid is a natural pentacyclic triterpenoid compound and an inhibitor of eukaryotic topoisomerase I with an IC50 value of 5 μM[1]. Betulinic acid has anti-inflammatory, anti-malarial, anti-AIDS and anti-tumor activities[2]. Betulinic acid can inhibit α-glucosidase with an IC50 value of 10.6 μM[3].
In vitro, betulinic acid (7.5 μM) treatment of mouse hypothalamic cell line (mHypoE-46) neurons for 10 h significantly inhibited the enzymatic activity of protein tyrosine phosphatase 1B (PTP1B) by 35%[4]. Betulinic acid (10-160 μM) treatment of MDA-MB-231 cells for 24 or 48 h inhibited cell viability in a time- and dose-dependent manner, reduced Bcl-2 expression in cells, and induced ultrastructural changes in cells[5].
In vivo, oral administration of betulinic acid (50 mg/kg) to treat retinal ischemia model mice prevented retinal GCL cell loss and optic nerve axon loss, partially blocked retinal arteriolar endothelial dysfunction, inhibited ROS production in retinal blood vessels, and enhanced the mRNA expression of antioxidant enzymes SOD3 and HO-1[6]. Oral administration of betulinic acid (30 mg/kg) to treat colitis mice significantly prevented colon pathological changes such as diarrhea and bleeding, reduced nitrite, malondialdehyde, peroxidase and lipid peroxide levels, and increased superoxide dismutase, catalase and glutathione levels[7].
References:
[1] Chowdhury A R, Mandal S, Mittra B, 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[J]. Medical Science Monitor, 2002, 8(7): BR254-BR260.
[2] Drąg-Zalesińska M, Borska S. Betulin and its derivatives–precursors of new drugs[J]. World Scientific News, 2019, 127(3): 123-138.
[3] Ding H, Wu X, Pan J, et al. New insights into the inhibition mechanism of betulinic acid on α-glucosidase[J]. Journal of agricultural and food chemistry, 2018, 66(27): 7065-7075.
[4] Jin T, Yu H, Huang X F. Selective binding modes and allosteric inhibitory effects of lupane triterpenes on protein tyrosine phosphatase 1B[J]. Scientific Reports, 2016, 6(1): 20766.
[5] Gao Y, Ma Q, Ma Y B, et al. Betulinic acid induces apoptosis and ultrastructural changes in MDA-MB-231 breast cancer cells[J]. Ultrastructural Pathology, 2018, 42(1): 49-54.
[6] Musayeva A, Unkrig J C, Zhutdieva M B, et al. Betulinic acid protects from ischemia-reperfusion injury in the mouse retina[J]. Cells, 2021, 10(9): 2440.
[7] Kalra J, Lingaraju M C, Mathesh K, et al. Betulinic acid alleviates dextran sulfate sodium-induced colitis and visceral pain in mice[J]. Naunyn-Schmiedeberg's Archives of Pharmacology, 2018, 391: 285-297.
白桦脂酸（Betulinic acid）是一种天然的五环三萜类化合物，是真核细胞拓扑异构酶I的抑制剂，IC50值为5μM[1]。Betulinic acid具有抗炎，抗疟疾，抗艾滋病和抗肿瘤等活性[2]。Betulinic acid可以抑制α-葡萄糖苷酶，IC50值为10.6μM[3]。
在体外，Betulinic acid（7.5μM）处理小鼠下丘脑细胞系（mHypoE-46）神经元10h，显著抑制了蛋白酪氨酸磷酸酶1B（PTP1B）的酶活性，抑制率达35%[4]。Betulinic acid（10-160μM）处理MDA-MB-231细胞24或48h，以时间和剂量依赖性方式抑制了细胞活力，降低了细胞的Bcl-2表达，诱导了细胞的超微结构变化[5]。
在体内，Betulinic acid（50mg/kg）通过口服治疗视网膜缺血模型小鼠，可防止视网膜GCL细胞丢失和视神经轴突丢失，部分阻断视网膜小动脉内皮功能障碍，抑制视网膜血管中的ROS产生，并增强抗氧化酶SOD3和HO-1的mRNA 表达[6]。Betulinic acid（30mg/kg）通过口服治疗结肠炎小鼠，显著预防腹泻和出血等结肠病理变化，降低了亚硝酸盐、丙二醛、过氧化物酶和脂质过氧化物水平，提高了超氧化物歧化酶、过氧化氢酶和谷胱甘肽水平[7]。