Acankoreagenin and acankoreosides, a family of lupane triterpenoids with anti‐inflammatory properties: an overview

Abstract

Acankoreagenin (ACK, also known as acankoreanogenin and HLEDA) and impressic acid are two lupane‐type triterpenes that can be isolated from various Acanthopanax and Schefflera species. They efficiently block activation of the NF‐κB signaling pathway and the release of proinflammatory cytokines and/or the action of inflammation mediators (HMGB1, iNOS, and NO). These effects are the basis for the antiviral and anticancer activities reported with these pentacyclic compounds or their various glycoside derivatives. More than 15 acankoreosides (Ack‐A to ‐O, and ‐R) and a few other mono‐ and bidesmosidic saponins (acantrifoside A and acangraciliside S) derive from the ACK aglycone. Compounds like Ack‐A and ‐B are remarkable anti‐inflammatory agents, inhibiting cytokine release from activated macrophages. Despite their effectiveness, ACK and impressic acid are far much less known and studied than the structurally related compounds betulinic acid and 23‐hydroxybetulinic acid (anemosapogenin). The structural differences (notably the R/S stereoisomerism of the 3‐hydroxyl group) and functional similarities of these compounds are discussed. The complete series of acankoreosides is presented for the first time. These natural products deserve further attention as anti‐inflammatory agents, and ACK is recommended as a template for the design of new anticancer and antiviral drugs.

Messagenin–based Chalcones: Synthesis, Modification and Perspectives of Antidiabetic Potency

“…They efficiently block activation of the NFÀ kB signaling pathway and the release of proinflammatory cytokines and/or the action of inflammation mediators (HMGB1, iNOS, and NO). [52] Finally, lupane-type triterpenes isolated as the active constituents from leaves of AGS (Acanthopanax gracilistylus W. W.Smith) described before have anti-inflammatory activities in LPS-induced RAW264.7 cells through inhibiting expression of proinflammatory cytokines and NFÀ kB activation and could be potentially used in treatment of inflammatory-related diseases in the future. [53] In this study, we determined the content of NO affected by compounds 6, 8 and 10 in the LPS-stimulated mouse murine macrophage RAW264.7 cell line with the IC 50 values of 3.03 � 0.18 μM, 2.33 � 0.21 μM and 4.0 � 0.5 μM being higher than N-(omega)-Monomethyl-L-Arginine Acetate as a positive control (IC 50 values of 5.98 � 0.31 μM) (Figure 9).…”

Saponins of Selected Triterpenoids as Potential Therapeutic Agents: A Review

“…& G. Forst. (Araliaceae; umbrella tree) species ( Figure 16 ) [ 74 ]. The antinociceptive and anti-inflammatory activities of Schefflera octophylla extracts are well known and have been characterized.…”

“…This compound reduced the production of the cytokine-stimulated inducible nitric oxide synthase (iNOS) and caused a limited activation of the transcription factor NF-κB in cells. The inhibition of the NF-κB pathway prevents iNOS expression in vitro [ 74 ]. The compound 16a displayed anti-inflammatory activity both in vitro and in vivo, reducing the serum levels of inflammatory cytokines (TNF-α and IL-1β) and the release of the protein HMGB1, a pro-inflammatory cytokine, in a dose-dependent way [ 74 ].…”

“…The inhibition of the NF-κB pathway prevents iNOS expression in vitro [ 74 ]. The compound 16a displayed anti-inflammatory activity both in vitro and in vivo, reducing the serum levels of inflammatory cytokines (TNF-α and IL-1β) and the release of the protein HMGB1, a pro-inflammatory cytokine, in a dose-dependent way [ 74 ].…”

“…The structural differences (notably the R / S stereoisomerism of the C(3)-OH group of the triterpenoid skeleton) and functional similarities of these compounds were investigated. The complete series of acankoreosides was presented for the first time in the paper by Bailly [ 74 ]. These natural products were also investigated as anti-inflammatory agents, and acankoreosides have been recommended as templates for designing new anticancer and antiviral drugs.…”