Diosbulbin B is the main hepatotoxic component of Dioscorea bulbifera L., exhibiting potent anti-tumor activity [1]. Diosbulbin B can significantly induce an increase in liver MPO enzyme activity and protein expression, reduce IκB expression and promote the increase in NF-κB p65 translocation, and lead to an increase in serum levels of TNF-α, IL-6 and IFN-γ[2]. Diosbulbin B has been widely used in establishing animal models of liver injury and inhibiting the tumor growth of xenograft models[3].
In vitro, Diosbulbin B treatment for 72h significantly inhibited the viability of A549 cells and PC-9 cells, with IC50 values of 44.61μM and 22.78μM, respectively[4]. Treatment with 200µM Diosbulbin B for 48 hours induced autophagy and apoptosis in L-02 cells, accompanied by an increase in the expression of LC3 II/I and Beclin-1, and a decrease in the expression of p62[5]. Treatment with 50µM Diosbulbin B for 48 hours induced G2/M phase arrest in CYP3A4-transfected L-02 cells and decreased the expression of CDK1[6].
In vivo, Diosbulbin B treatment via oral administration at a dose of 50mg/kg/day for 2 months led to hepatic infiltration of immune cells, swelling and necrosis of hepatocytes in mice, and promoted liver fibrosis in the mice[7]. Oral administration of 64mg/kg/day of Diosbulbin B for 12 consecutive days led to liver structure damage and extensive necrosis in mice, and caused oxidative stress injury[8].
References:
[1] Tan R, Hu Z, Zhou M, et al. Diosbulbin B: An important component responsible for hepatotoxicity and protein covalent binding induced by Dioscorea bulbifera L[J]. Phytomedicine, 2022, 102: 154174.
[2] Niu C, Sheng Y, Yang R, et al. Scutellarin protects against the liver injury induced by diosbulbin B in mice and its mechanism[J]. Journal of ethnopharmacology, 2015, 164: 301-308.
[3] Wang J, Sheng Y, Ji L, et al. Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo[J]. Journal of Zhejiang University-SCIENCE B, 2014, 15(6): 540-547.
[4] Zhao J Q, Zhou Q Q, Sun Y, et al. The anti-non-small cell lung cancer effect of Diosbulbin B: Targeting YY1 induced cell cycle arrest and apoptosis[J]. Phytomedicine, 2024, 130: 155734.
[5] Ye J, Xue M, Liu Y, et al. Diosbulbin B-induced mitochondria-dependent apoptosis in L-02 hepatocytes is regulated by reactive oxygen species-mediated autophagy[J]. Frontiers in Pharmacology, 2019, 10: 676.
[6] Yang R, Wei M, Yang F, et al. Diosbulbin B induced G2/M cell cycle arrest in hepatocytes by miRNA-186-3p and miRNA-378a-5p-mediated the decreased expression of CDK1[J]. Toxicology and Applied Pharmacology, 2018, 357: 1-9.
[7] Zhang Y, Miao H, Guan H, et al. Long-term diosbulbin B treatment induced liver fibrosis in mice[J]. Chemico-biological interactions, 2019, 298: 15-23.
[8] Ma Y, Niu C, Wang J, et al. Diosbulbin B-induced liver injury in mice and its mechanism[J]. Human & experimental toxicology, 2014, 33(7): 729-736.
Diosbulbin B是Dioscorea bulbifera L.的主要肝毒性成分，具有强效的抗肿瘤活性[1]。Diosbulbin B可显著诱导肝脏MPO酶活性和蛋白表达升高，降低IκB表达并促进NF-κB p65转位增加，同时导致血清中TNF-α、IL-6和IFN-γ水平升高[2]。Diosbulbin B已被广泛用于建立肝损伤动物模型和抑制异种移植模型的肿瘤生长[3]。
在体外，Diosbulbin B处理72小时显著抑制了A549细胞和PC-9细胞的活力，IC50值分别为44.61μM 和22.78μM[4]。使用200μM的Diosbulbin B处理L-02细胞48小时，诱导了自噬和凋亡，伴随LC3 II/I和Beclin-1表达增加，以及p62表达降低[5]。使用50μM的Diosbulbin B处理转染CYP3A4的L-02细胞48小时，诱导了G2/M期阻滞并降低了CDK1的表达[6]。
在体内，每日口服50mg/kg剂量的Diosbulbin B，持续2个月，导致小鼠肝脏免疫细胞浸润、肝细胞肿胀和坏死，并促进了小鼠肝纤维化[7]。连续12天口服64mg/kg/day剂量的Diosbulbin B，导致小鼠肝脏结构损伤和广泛坏死，并引起氧化应激损伤[8]。