Naturally Occurring Cytotoxic [3'→8″]-Biflavonoids from Podocarpus nakaii

Pen-Ho Yeh; Yun-Dar Shieh; Li-Chun Hsu; Li-Ming Yang Kuo; Jhih-Hu Lin; Chia-Ching Liaw; Yao-Haur Kuo

doi:10.1016/s2225-4110(16)30103-1

Naturally Occurring Cytotoxic [3'→8″]-Biflavonoids from Podocarpus nakaii

J Tradit Complement Med. 2012 Jul;2(3):220-6. doi: 10.1016/s2225-4110(16)30103-1.

Authors

Pen-Ho Yeh¹, Yun-Dar Shieh², Li-Chun Hsu³, Li-Ming Yang Kuo⁴, Jhih-Hu Lin⁵, Chia-Ching Liaw⁵, Yao-Haur Kuo⁶

Affiliations

¹ Institute of Pharmacology, National Yang-Ming University, Taipei 112, Taiwan.
² Institute of Pharmacology, National Yang-Ming University, Taipei 112, Taiwan ; National Research Institute of Chinese Medicine, Taipei 112, Taiwan.
³ National Research Institute of Chinese Medicine, Taipei 112, Taiwan ; Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan.
⁴ National Research Institute of Chinese Medicine, Taipei 112, Taiwan ; School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
⁵ National Research Institute of Chinese Medicine, Taipei 112, Taiwan.
⁶ National Research Institute of Chinese Medicine, Taipei 112, Taiwan ; Graduate Institute of Integrated Medicine, China Medical University, Taichung 404, Taiwan.

Abstract

Bioassay-guided fractionation of the EtOH extract of the dried twigs of Podocarpus nakaii Hayata (Podocarpaceae), endemic plant in Taiwan has resulted in isolation of four [3'→8″]-biflavonoid derivatives, amenotoflavone (AF), podocarpusflavone-A (PF), II-4″,I-7-dimethoxyamentoflavone (DAF), and heveaflavone (HF). Their structures were determined by physical and extensive spectroscopic analyses such as (1)H, (13)C, (1)H-(1)H COSY, HMQC, and HMBC, as well as comparison with literature values. Compounds PF and DAF showed significant inhibitions against DLD, KB, MCF-7, HEp-2 tumor cell lines (ED50 ca. 4.56-16.24 μg/mL) and induced cell apoptosis in MCF-7 via mainly sub-G1/S phase arrest. Furthermore, these compounds exhibited moderate Topoisomerase I inhibitory activity.

Keywords: Apoptosis; Cytotoxicity; Podocarpus nakaii; Topoisomerase I; [3′→8″]-Biflavonoids.