Natural products and analogs as preventive agents for metabolic syndrome via peroxisome proliferator-activated receptors: An overview.

Autores de INCLIVA

• Carlos Villarroel Vicente

  Autor

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  Jordi Ferri Ciscar

  Autor

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  Diego Cortes Martinez

  Autor

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  Nuria Cabedo Escrig

  Autor

Participantes ajenos a INCLIVA

• Gutierrez-Palomo, Sergio

Grupos y Plataformas de I+D+i

• Grupo de Investigación en Inflamación

  

  Leading Researcher

  Maria Jesus Sanz Ferrando

Abstract

Natural products and synthetic analogs have drawn much attention as potential therapeutical drugs to treat metabolic syndrome. We reviewed the underlying mechanisms of 32 natural products and analogs with potential pharmacological effects in vitro, and especially in rodent models and/or patients, that usually act on the PPAR pathway, along with other molecular targets. Recent outstanding total syntheses or semisyntheses of these lead compounds are stated. In general, they can activate the transcriptional activity of PPARa, PPAR?, PPARa/?, PPARß/d, PPARa/d, PPAR?/d and panPPAR as weak, partial agonists or selective PPAR? modulators (SPPAR?M), which may be useful for managing obesity, type 2 diabetes (T2D), dyslipidemia and non-fatty liver disease (NAFLD). Terpenoids is the largest group of compounds that act as potential modulators on PPARs and are comprised from small lipophilic cannabinoids to lipophilic pentacyclic triterpenes and polar saponins. Shikimates-phenylpropanoids include polar heterocyclic flavonoids and phenolic compounds containing at least one C3-C6 unit and usually a double bond on the propyl chain. Quercetin (19), resveratrol (24) and curcumin (27), stand out from this group for exhibiting beneficial effects on patients. Alkaloids, the minor group of potential modulators on PPARs, include berberine (30), which has been widely explored in preclinical and clinical studies for its potential beneficial effects on T2D and dyslipidemia. However, large-scale clinical trials may be warranted for the promising compounds.

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Keywords

• Hepatic steatosis; Metabolic syndrome; Natural products; PPAR; Synthesis; Type 2 diabetes