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Review
. 2022 Dec 24;24(1):299.
doi: 10.3390/ijms24010299.

Anti-Obesity Effects of Isorhamnetin and Isorhamnetin Conjugates

Maitane González-Arceo  1 , Iván Gomez-Lopez  1   2   3 , Helen Carr-Ugarte  1 , Itziar Eseberri  1   2   4 , Marcela González  5 , M Pilar Cano  3 , María P Portillo  1   2   4 , Saioa Gómez-Zorita  1   2   4
Affiliations
Review

Anti-Obesity Effects of Isorhamnetin and Isorhamnetin Conjugates

Maitane González-Arceo et al. Int J Mol Sci. .

Abstract

Isorhamnetin is a plant-derived secondary metabolite which belongs to the family of flavonoids. This review summarises the main outcomes described in the literature to date, regarding the effects of isorhamnetin on obesity from in vitro and in vivo studies. The studies carried out in pre-adipocytes show that isorhamnetin is able to reduce adipogenesis at 10 μM or higher doses and that these effects are mediated by Pparγ and by Wnt signalling pathway. Very few studies addressed in rodents are available so far. It seems that treatment periods longer than two weeks are needed by isorhamnetin and its glycosides to be effective as anti-obesity agents. Nevertheless, improvements in glycaemic control can be observed even in short treatments. Regarding the underlying mechanisms of action, although some contradictory results have been found, reductions in de novo lipogenesis and fatty acid uptake could be proposed. Further research is needed to increase the scientific evidence referring to this topic; studies in animal models are essential, as well as randomised clinical trials to determine whether the positive results observed in animals could also be found in humans, in order to determine if isorhamnetin and its glycosides can represent a real tool against obesity.

Keywords: adipocytes; adipose tissue; animal models; isorhamnetin; isorhamnetin glucosides; obesity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structure of isorhamnetin.
Figure 2
Figure 2
Chemical structure of isorhamnetin 3-O-d-glucuronide (left) and isorhamnetin 3-O-β-glucopyranoside (right).
Figure 3
Figure 3
Mechanism of action underlying the effect of isorhamnetin on adipogenesis. αPR: progesterone receptor α; ACC: acetyl coA carboxylase; AP2: adipose fatty acid-binding protein 2; C/ebp: CCAAT-enhancer-binding protein; DKK: Dickkopf; FZD: frizzled class receptor; GLUT4: glucose transporter member 4; GSK-3β: glycogen synthase kinase-3 beta; PPARγ: peroxisome proliferator activated receptor γ; RXRα: retinoid X receptor alpha; SFRP: secreted frizzled related protein; SREBP1c: sterol regulatory element-binding protein 1c. Green arrows: upregulation by isorhamnetin; red arrows: downregulation by isorhamnetin.
Figure 4
Figure 4
Isorhamnetin glycosides found in Opuntia-ficus indica.
Figure 5
Figure 5
Mechanism of action underlying the effect of isorhamnetin on obesity in rodents. Acc: acetyl-CoA carboxylase; Cd36: cluster of differentiation 36; CHm; Chylomicrons; Lpl: lipoprotein lipase; NEFA: non-sterified fatty acids; PPARγ: peroxisomal proliferator-activated receptor γ; Scd-1: stearoyl-CoA desaturase-1; Srebp: sterol regulatory element binding protein; VLDL: very light density lipoproteins.
See this image and copyright information in PMC

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