Amorfrutins Are Natural PPARγ Agonists with Potent Anti-inflammatory Properties

Abstract

Amorfrutins are isoprenoid-substituted benzoic acid derivatives, which were found in Amorpha fruticosa L. (bastard indigo) and in Glycyrrhiza foetida Desf. (licorice). Recently, amorfrutins were shown to be selective activators of the nuclear receptor PPARγ. Here, we investigated the effects and PPARγ-based mechanisms of reducing inflammation in colon cells by treatment with amorfrutins. In TNF-α-stimulated colon cells amorfrutin A (1) reduced significantly the expression and secretion of several inflammation mediators, in part due to interaction with PPARγ. These results support the hypothesis that amorfrutins may have the potential to treat inflammation disorders such as chronic inflammatory bowel diseases.

Ligands for the Nuclear Peroxisome Proliferator-Activated Receptor Gamma

“…5-Aminosalicylic acids are, for example, presently being used for treating inflammatory bowel disorders such as ulcerative colitis and Crohn's disease. Recently, amorfrutin A ( Figure 3, Table 1), which is structurally related to salicylic acid, was shown to exert mild anti-inflammatory effects in inflamed colon cells, at least in part via activation of PPARg [55]. Ongoing clinical studies are further investigating the effects of various PPARg-targeting compounds in the treatment of various inflammatory disorders including colitis and rheumatoid arthritis (updates can be found at https://clinicaltrials.…”

First Total Syntheses of Amorfrutin C and pseudo‐Amorfrutin A

“…[1] Amorfrutin A was first extracted from Glycyrrhiza acanthocarpa by Ghisalberti et al [2] Biological studies revealed that amorfrutin A has potent antimicrobial, [3] anticancer, [4] antiinflammatory, [5] and antidiabetes [6] activities. [1] Amorfrutin A was first extracted from Glycyrrhiza acanthocarpa by Ghisalberti et al [2] Biological studies revealed that amorfrutin A has potent antimicrobial, [3] anticancer, [4] antiinflammatory, [5] and antidiabetes [6] activities.…”

“…The amorfrutins are a family of compounds that contain a characteristic planar 2-hydroxybenzoic acid core with prenyl, benzyl, or alkyl residues, and a methoxy or hydroxy group attached at the C-4 position; they usually show diverse biological activities. [1] Amorfrutin A was first extracted from Glycyrrhiza acanthocarpa by Ghisalberti et al [2] Biological studies revealed that amorfrutin A has potent antimicrobial, [3] anticancer, [4] antiinflammatory, [5] and antidiabetes [6] activities. Mitscher et al extracted amorfrutin A and amorfrutin B from Amorpha fruticosa.…”

Amorpha fruticosa – A Noxious Invasive Alien Plant in Europe or a Medicinal Plant against Metabolic Disease?

“…Several previously unreported derivatives of dihydrostilbene (with various substitutions of the bibenzyl skeleton – depicted in Figure 3 ) have recently been isolated and received a lot of attention as potent antidiabetic agents (via binding to PPARγ, see section on pharmacology) (Weidner et al, 2012; Wang et al, 2014; Fuhr et al, 2015). Further, other phenylpropanoids have been identified as plant constituents along with volatile terpenoids and fatty oils.…”

“…Fuhr et al (2015) studied PPARγ-related anti-inflammatory effects of amorfrutins colon cells. Indeed it was observed that amorfrutin A reduces the expression of several inflammation mediators, at least in part due to activation of PPARγ.…”