Antiadipogenic effect of carnosic acid, a natural compound present in Rosmarinus officinalis, is exerted through the C/EBPs and PPARγ pathways at the onset of the differentiation program

Gaya, Mauro; Repetto, Victoria; Toneatto, Judith; Anesini, Claudia; Piwien-Pilipuk, Graciela; Moreno, Sílvia

doi:10.1016/j.bbagen.2013.03.021

Cited by 60 publications

(53 citation statements)

References 66 publications

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“…The main diterpenes isolated from S. pomifera leaves include salviol (6), pisiferic acid (7), carnosol (8), 12-methoxy-carnosic acid (9), O-methyl-pisiferic acid (10), and 2α-hydroxy-O-methyl-pisiferic acid (11) (Bottom). (B) The biosynthesis of tanshinone and carnosic acid begins with the cyclization of GGPP (12) by a class II diTPS to produce (+) copalyl diphosphate (CPP) (13), which is in turn converted to miltiradiene (14) by a class I diTPS. Spontaneous oxidation of 14 gives rise to abietatriene (15), which is oxidized to ferruginol (16) by a CYP enzyme.…”

Section: Resultsmentioning

confidence: 99%

“…Carnosic acid (1) and carnosol (8) are potent antioxidant (13), antiadipogenic (14), and anticancer agents (15,16), whereas several carnosic-acid-related diterpenes, such as 12-methoxy-carnosic acid (9) and pisiferic acid (7; Fig. 1A) have strong antiparasitic, antifungal, and antibacterial activities (17)(18)(19).…”

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confidence: 99%

“…Subsequent decoration of the various skeletons by modifying enzymes, such as cytochrome P450s (CYPs) (27), gives rise to a plethora of secondary metabolites (28,29). In Rosmarinus officinalis and Salvia fruticosa, carnosic acid and carnosol are synthesized from (+)-copalyl diphosphate (CPP; 13) through the intermediates miltiradiene (14), abietatriene (15), and ferruginol (16) (Fig. 1B) (30)(31)(32).…”

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confidence: 99%

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Carnosic acid biosynthesis elucidated by a synthetic biology platform

Ignea

Athanasakoglou

Iοannou

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

142

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Synthetic biology approaches achieving the reconstruction of specific plant natural product biosynthetic pathways in dedicated microbial “chassis” have provided access to important industrial compounds (e.g., artemisinin, resveratrol, vanillin). However, the potential of such production systems to facilitate elucidation of plant biosynthetic pathways has been underexplored. Here we report on the application of a modular terpene production platform in the characterization of the biosynthetic pathway leading to the potent antioxidant carnosic acid and related diterpenes in Salvia pomifera and Rosmarinus officinalis. Four cytochrome P450 enzymes are identified (CYP76AH24, CYP71BE52, CYP76AK6, and CYP76AK8), the combined activities of which account for all of the oxidation events leading to the biosynthesis of the major diterpenes produced in these plants. This approach develops yeast as an efficient tool to harness the biotechnological potential of the numerous sequencing datasets that are increasingly becoming available through transcriptomic or genomic studies.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Carnosic acid biosynthesis elucidated by a synthetic biology platform

Ignea

Athanasakoglou

Iοannou

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

142

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“…In one study, extracted carnosic acid was found to suppress adipocyte differentiation. This inhibition of adipogenesis can promote sustainable weight loss [45]. In another study, rosemary extract prevented weight gain by limiting lipid absorption in the intestine.…”

Section: Anti-obesity Activitymentioning

confidence: 99%

Rosmarinus Officinalis (Rosemary): A Novel Therapeutic Agent for Antioxidant, Antimicrobial, Anticancer,Antidiabetic, Antidepressant, Neuroprotective, Anti-Inflammatory, and Anti-Obesity Treatment

Hamidpour¹,

Hamidpour²,

Elias³

2017

BJSTR

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“…Carnosic acid alters mitotic clonal expansion (MCE) and the ratio of the different C/EBP forms, induces the loss of C/EBPb proper subnuclear distribution, and inhibits the expression of C/EBPa and PPARg. 20 Moreover, carnosic acid reduces lipid absorption in the gut of olive oil-loaded mice inhibiting the pancreatic lipase, therefore decreases body weight in vivo. 21 The molecular events that take place during the process of adipogenesis have been extensively studied on 3T3-L1, the mouse embryonic fibroblast cell line, since these cells have the ability to differentiate into cells that accumulate lipids, respond to insulin, and secrete leptin.…”

Section: -14mentioning

confidence: 99%

Effects ofRosmarinus officinalisextract on human primary omental preadipocytes and adipocytes

Stefanon

Pomari

Colitti

2015

Exp Biol Med (Maywood)

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The prevalence of obesity is increasing all over the world. Although it has been shown that natural substances influence fat metabolism, little is known about the effect on cellular and molecular mechanisms in human. In this in vitro study, the activity of Rosmarinus officinalis (RO) standardized extract in modulating human primary visceral preadipocytes differentiation, lipolysis, and apoptosis was investigated. Moreover, gene expression of key adipogenesis modulators and microRNAs-seq were evaluated. Preadipocytes treated with RO extract significantly reduced triglyceride incorporation during maturation in a dose-dependent manner without affecting cell viability. In addition, RO extract stimulated lipolytic activity in differentiating preadipocytes and mature adipocytes in treated cells compared to controls. Differentiating preadipocytes incubated in the presence of RO extract showed a decreased expression of cell cycle genes such as cyclin D1, cyclin-dependent kinase 4, cyclin-dependent kinase inhibitor 1A (p21, Cip1) and an increased expression of GATA binding protein 3, wingless-type MMTV integration site family, member 3A mRNA levels. Recent studies have demonstrated that some phytochemicals alter the expression of specific genes and microRNAs that play a fundamental role in the pathogenesis of obesity and related diseases. Interestingly, genes modulated in RO-treated cells were found to be validated miRNAs targets, such as let-7f-1, miR-17, and miR-143. The results indicated that RO extract modulates human adipocyte differentiation and significantly interferes with adipogenesis and lipid metabolism, supporting its interest as dietary supplement.

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Antiadipogenic effect of carnosic acid, a natural compound present in Rosmarinus officinalis, is exerted through the C/EBPs and PPARγ pathways at the onset of the differentiation program

Cited by 60 publications

References 66 publications

Carnosic acid biosynthesis elucidated by a synthetic biology platform

Carnosic acid biosynthesis elucidated by a synthetic biology platform

Rosmarinus Officinalis (Rosemary): A Novel Therapeutic Agent for Antioxidant, Antimicrobial, Anticancer,Antidiabetic, Antidepressant, Neuroprotective, Anti-Inflammatory, and Anti-Obesity Treatment

Effects ofRosmarinus officinalisextract on human primary omental preadipocytes and adipocytes

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