Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120, Heidelberg, Germany.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Sci Rep. 2018 Jun 19;8(1):9343. doi: 10.1038/s41598-018-27452-8.
The potential hepatoprotective activities of two Lannea species were explored in vivo. Furthermore, the binding activities of their main polyphenols to the antiapoptotic protein Bcl-2 were investigated. Based on HPLC-MS/MS results, 22 secondary metabolites were characterized in L. stuhlmannii (mainly tannins), while 20 secondary metabolites (mainly sulphated tannins) were identified in L. humilis. Both extracts exhibited substantial antioxidant activities in vitro and counteracted D-galactosamine induced intoxication in rats in vivo and increased the total antioxidant capacity (TAC) of liver tissues. In addition to reducing the elevated levels of AST and total bilirubin, both extracts significantly attenuated the deleterious histopathologic changes in liver after D-galactosamine-intoxication. Also, both extracts protected hepatocytes from apoptotic cell death and increased the expression of the anti-apoptotic protein Bcl-2. The identified compounds from both extracts can bind to the Bcl-2: Bim (BH3) interface with an appreciable binding free energy. Hydrogen and ionic bonds and hydrophobic interactions with amino acid residues in the hydrophobic face of Bim (BH3) domain were discovered. To sum up, L. humilis and L. stuhlmanni exhibited promising hepatoprotective activities in vivo against D-GalN-induced liver injury and their hepatoprotection is due to the antioxidant and anti-apoptotic effects of tannins and proanthocyanidins.
两种腊莲属植物的潜在保肝活性在体内进行了探索。此外,还研究了它们主要多酚类物质与抗凋亡蛋白 Bcl-2 的结合活性。基于 HPLC-MS/MS 结果,在腊莲(主要为单宁)中鉴定了 22 种次生代谢物,而在矮腊莲(主要为硫酸单宁)中鉴定了 20 种次生代谢物。两种提取物均表现出较强的体外抗氧化活性,并在体内拮抗 D-半乳糖胺诱导的中毒,增加肝组织总抗氧化能力(TAC)。除了降低升高的 AST 和总胆红素水平外,两种提取物均显著减轻 D-半乳糖胺中毒后肝脏的组织病理学损伤。此外,两种提取物均可防止肝细胞发生凋亡性细胞死亡,并增加抗凋亡蛋白 Bcl-2 的表达。两种提取物中的鉴定化合物可与 Bcl-2:Bim(BH3)界面结合,具有可观的结合自由能。发现了氢键和离子键以及与 Bim(BH3)结构域疏水面上氨基酸残基的疏水相互作用。综上所述,矮腊莲和腊莲在体内对 D-GalN 诱导的肝损伤具有显著的保肝活性,其保肝作用归因于单宁和原花青素的抗氧化和抗凋亡作用。