2. Academic Validation
  3. Enantiomeric 8-O-4'-type neolignans from Crataegus pinnatifida exhibit cytotoxic effect via apoptosis and autophagy in Hep3B cells

Enantiomeric 8-O-4'-type neolignans from Crataegus pinnatifida exhibit cytotoxic effect via apoptosis and autophagy in Hep3B cells

  • Bioorg Chem. 2020 Nov;104:104267. doi: 10.1016/j.bioorg.2020.104267.
Xin-Yue Shang 1,  Rui Guo 1,  Xiao-Qi Yu 1,  Bin Lin 2,  Xiao-Xiao Huang 3,  Guo-Dong Yao 4,  Shao-Jiang Song 5
Affiliations

Affiliations

  • 1 Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
  • 2 School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, People's Republic of China.
  • 3 Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: [email protected].
  • 4 Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: [email protected].
  • 5 Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: [email protected].
PMID: 32920350 DOI: 10.1016/j.bioorg.2020.104267
Abstract

Crataegus pinnatifida has been famous for its nutritional purpose. However, systematic investigation on the bioactive constituents is still lacking, although this fruit has been reported for its cytotoxic effect before. In this study, two pairs of new lignan enantiomers (1a/1b, 2a/2b), which isolated using chiral chromatographic column from the fruits of C. pinnatifida were studied. The absolute configurations of enantiomers were determined by comparison between the experimental electronic circular dichroism (ECD) and calculated ECD spectra. Among them, 1a/1b exhibited a better cytotoxic effect in hepatocellular carcinoma Hep3B cells with an IC50 value of 34.97 ± 2.74 and 17.42 ± 0.71 μM, respectively. In addition, 1b induced much more apoptotic, autophagic cells than 1a in Hep3B cells. Furthermore, the underlying mechanism was demonstrated that p38 activation could promote 1b-induced Apoptosis and Autophagy. Moreover, 1b-induced Apoptosis was significantly decreased in the presence of autophagic inhibitor Bafilomycin A1 (Baf A1), suggesting that the induction of Autophagy enhanced apoptotic cell death in 1b-treated cells. In general, these findings provide a valuable basis for further understanding the effect of 8-O-4' Lignans in C. pinnatifida on cytotoxic effect.

Keywords

8-O-4′-type neolignans; Apoptosis; Autophagy; Crataegus pinnatifida; Enantiomers.

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