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从 中分离得到的二萜生物碱及其对肝细胞脂质积累的抑制作用。

Diterpenoid Alkaloids Isolated from and Their Inhibitory Effects on Hepatocytes Lipid Accumulation.

机构信息

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.

Institute of Tibetan Medicine, University of Tibetan Medicine, Lasa 850000, China.

出版信息

Molecules. 2022 Mar 30;27(7):2257. doi: 10.3390/molecules27072257.

Abstract

This research aimed to excavate compounds with activity reducing hepatocytes lipid accumulation from . Four novel diterpenoid alkaloids, brunodelphinine B-E, were isolated from together with eleven known diterpenoid alkaloids through a phytochemical investigation. Their structures were elucidated by comprehensive spectroscopy methods including HR-ESI-MS, NMR, IR, UV, CD, and single-crystal X-ray diffraction analysis. The inhibitory effects of a total of 15 diterpenoid alkaloids on hepatocytes lipid accumulation were evaluated using 0.5 mM FFA (oleate/palmitate 2:1 ratio) to induce buffalo rat liver (BRL) cells by measuring the levels of triglyceride (TG), total cholesterol (TC), alanine transaminase (ALT), aspartate transaminase (AST), and the staining of oil red O. The results show that five diterpenoid alkaloids-brunodelphinine E (), delbruline (), lycoctonine (), delbrunine (), and sharwuphinine A ()-exhibited significant inhibitory effects on lipid accumulation in a dose-dependent manner and without cytotoxicity. Among them, sharwuphinine A () displayed the strongest inhibition of hepatocytes lipid accumulation in vitro. Our research increased the understanding on the chemical composition of and provided experimental and theoretical evidence for the active ingredients screened from this herbal medicine in the treatment of the diseases related to lipid accumulation, such as non-alcoholic fatty liver disease and hyperlipidemia.

摘要

本研究旨在从 中挖掘具有抑制肝细胞脂质积累活性的化合物。通过植物化学研究,从 中分离得到了 4 种新型二萜生物碱,即 brunodelphinine B-E,以及 11 种已知的二萜生物碱。通过 HR-ESI-MS、NMR、IR、UV、CD 和单晶 X 射线衍射分析等综合光谱方法阐明了它们的结构。采用 0.5mM FFA(油酸/棕榈酸 2:1 比例)诱导水牛大鼠肝(BRL)细胞,评价了 15 种二萜生物碱对肝细胞脂质积累的抑制作用,通过测定三酰甘油(TG)、总胆固醇(TC)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)的水平和油红 O 的染色来评价。结果表明,5 种二萜生物碱——brunodelphinine E ()、delbruline ()、lycoctonine ()、delbrunine ()和 sharwuphinine A ()——以剂量依赖的方式显著抑制了脂质积累,且没有细胞毒性。其中,sharwuphinine A ()对肝细胞脂质积累的体外抑制作用最强。本研究增加了对 的化学成分的认识,并为从该草药中筛选出的与脂质积累相关疾病(如非酒精性脂肪肝和高脂血症)的活性成分提供了实验和理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21e/9000738/ae8eb96375f1/molecules-27-02257-g001.jpg

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