Details

Autor(en) / Beteiligte

• Liu, Liu
• Li, Haobin
• Hu, Kaiwen
• Xu, Qinglong
• Wen, Xiaoan
• Cheng, Keguang
• Chen, Caiping
• Yuan, Haoliang
• Dai, Liang
• Sun, Hongbin

Titel

Synthesis and anti-inflammatory activity of saponin derivatives of δ-oleanolic acid

Ist Teil von

• European journal of medicinal chemistry, 2021-01, Vol.209, p.112932-112932, Article 112932

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Pentacyclic triterpenes (PTs) are the active ingredients of many medicinal herbs and pharmaceutical formulations, and are well-known for their anti-inflammatory activity. On the other hand, anti-inflammatory effects of AMP-activated protein kinase (AMPK) have recently drawn much attention. In this study, we found that a variety of naturally occurring PTs sapogenins and saponins could stimulate the phosphorylation of AMPK, and identified δ-oleanolic acid (10) as a potent AMPK activator. Based on these findings, 23 saponin derivatives of δ-oleanolic acid were synthesized in order to find more potent anti-inflammatory agents with improved pharmacokinetic properties. The results of cellular assays showed that saponin 29 significantly inhibited LPS-induced secretion of pro-inflammatory factors TNF-α and IL-6 in THP1-derived macrophages. Preliminary mechanistic studies showed that 29 stimulated the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC). The bioavailability of 29 was significantly improved in comparison with its aglycon. More importantly, 29 showed significant anti-inflammatory and liver-protective effects in LPS/D-GalN-induced fulminant hepatic failure mice. Taken together, PTs saponins hold promise as therapeutic agents for inflammatory diseases. [Display omitted] •δ-Oleanolic acid was identified as a potent AMPK activator.•23 new saponin derivatives of δ-oleanolic acid were synthesized and biologically evaluated.•The bioavailability of saponins 29 and 33 was much better than their aglycon.•Saponin 29 exhibited significant in vitro and in vivo anti-inflammatory effects.