Dammarane-type saponins with proprotein convertase subtilisin/kexin type 9 inhibitory activity from Gynostemma pentaphyllum

Ya-Ping Huang; Yun-Shan Wang; Bi-Wen Liu; Zhe Song; Xiao-Shuang Liang; Yuan Teng; Jian Zhang; Zhi-Qi Yin; Ke Pan

doi:10.1016/j.phytochem.2021.113005

Dammarane-type saponins with proprotein convertase subtilisin/kexin type 9 inhibitory activity from Gynostemma pentaphyllum

Phytochemistry. 2022 Feb:194:113005. doi: 10.1016/j.phytochem.2021.113005. Epub 2021 Nov 16.

Authors

Ya-Ping Huang¹, Yun-Shan Wang², Bi-Wen Liu³, Zhe Song⁴, Xiao-Shuang Liang², Yuan Teng², Jian Zhang⁵, Zhi-Qi Yin⁶, Ke Pan⁷

Affiliations

¹ Department of TCMs Pharmaceuticals ＆ Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China; Cardiology Department, Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, 211200, People's Republic of China; Laboratory of Translational Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China.
² Department of TCMs Pharmaceuticals ＆ Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China; Laboratory of Translational Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China.
³ Cardiology Department, Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, 211200, People's Republic of China.
⁴ Instrumental Analysis Center of CPU, China Pharmaceutical University, Ministry of Education, Nanjing, 210009, People's Republic of China.
⁵ Laboratory of Translational Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China. Electronic address: zhangjian@jsatcm.com.
⁶ Department of TCMs Pharmaceuticals ＆ Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. Electronic address: cpu-yzq@cpu.edu.cn.
⁷ Department of TCMs Pharmaceuticals ＆ Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. Electronic address: kpan@cpu.edu.cn.

PMID: 34798409
DOI: 10.1016/j.phytochem.2021.113005

Abstract

Seven undescribed dammarane-type saponins, gypenosides LXXXI-LXXXVII, together with four known compounds, were isolated from the whole herb of Gynostemma pentaphyllum. The chemical structures of these undescribed compounds were elucidated on the basis of physical and spectroscopic analysis and comparison with literature data. All the isolates were evaluated for their proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitory activities in HepG2 cells. Among them, gypenosides LXXXII-LXXXVII, gynosaponin II, IV and VI suppressed the expression of PCSK9 in LPDS-induced HepG2 cells at 20 μM; gypenosides LXXXII, LXXXV and LXXXVII showed inhibitory activities against PCSK9 at 10 μM; notably, gypenoside LXXXII still exhibited inhibitory activity against PCSK9 at 5 μM.

Keywords: Cucurbitaceae; Dammarane-type saponin; Gynostemma pentaphyllum; PCSK9.

MeSH terms

Dammaranes
Gynostemma / chemistry*
Hep G2 Cells
Humans
PCSK9 Inhibitors / pharmacology*
Proprotein Convertase 9
Saponins* / pharmacology
Triterpenes / pharmacology*

Substances

PCSK9 Inhibitors
Saponins
Triterpenes
PCSK9 protein, human
Proprotein Convertase 9