Hepatocellular carcinoma (HCC) is a primary malignant tumor with very poor prognosis. To search for more effective compounds for HCC treatment, two new pairs of flavan enantiomers, daphnegiranol C₁/C₂ (1a/1b) and daphnegiranol D₁/D₂ (2a/2b), were isolated from the stem bark and roots of Daphne giraldii by using chiral chromatography. MTT assay was applied to evaluate their cytotoxicity against three hepatocarcinoma cell lines (Hep3B, MHCC97H, HepG2) as well as a normal liver cell line L02. The results showed that these compounds preferred to inhibit the growth of Hep3B cells (p53 null). Among them, 2a/2b (the IC₅₀ value was 4.87 and 3.35 μM, respectively) exhibited a stronger cytotoxic effect than sorafenib (IC₅₀ = 6.59 μM) in Hep3B cells. A further study demonstrated that 2a/2b could induce apoptotic cell death with an increase in reactive oxygen species (ROS) in Hep3B cells. In addition, the IC₅₀ values of 2a/2b in HepG2 and MHCC97H cells (both harbored p53 gene) were more than 10-folds greater when compared with Hep3B cells, indicating that 2a/2b selectively exhibited cytotoxicity in p53-null hepatocarcinoma cells. Moreover, inhibition of p53 increased the inhibitory effect in p53-wild hepatocarcinoma cells, as well as apoptotic cells and ROS generation. Taken together, flavan enantiomers 2a/2b selectively induced apoptosis in Hep3B cells because of p53 deficiency.

肝细胞癌（HCC）是原发性恶性肿瘤，预后很差。为了寻找更有效的用于HCC治疗的化合物，从茎皮和根的根中分离出两对新的黄烷对映体，达夫尼洛尔C ₁ / C ₂（1a / 1b）和达夫尼洛尔D ₁ / D ₂（2a / 2b）。达芙妮吉拉尔迪通过使用手性色谱法。应用MTT法评估其对三种肝癌细胞系（Hep3B，MHCC97H，HepG2）以及正常肝细胞系L02的细胞毒性。结果表明，这些化合物优选抑制Hep3B细胞的生长（p53为无效）。其中2a / 2b（IC ₅₀分别为4.87和3.35μM的 Hep3B细胞表现出比索拉非尼（IC ₅₀ = 6.59μM）更强的细胞毒性作用。进一步的研究表明2a / 2b可以诱导Hep3B细胞中的活性氧（ROS）增加，从而诱导细胞凋亡。此外，与Hep3B细胞相比，HepG2和MHCC97H细胞（均带有p53基因）中2a / 2b的IC ₅₀值高10倍以上，表明2a / 2b在p53无效的肝癌细胞中选择性表现出细胞毒性。此外，对p53的抑制作用增强了对p53野生肝癌细胞以及凋亡细胞和ROS生成的抑制作用。总的来说，黄烷对映体2a / 2b 由于p53缺乏，选择性诱导Hep3B细胞凋亡。