Glabridin, an isoflavan from licorice root, upregulates paraoxonase 2 expression under hyperglycemia and protects it from oxidation

Yehuda, Itamar; Madar, Zecharia; Leikin-Frenkel, Alicia; Szuchman-Sapir, Andrea; Magzal, Faiga; Markman, Gilad; Tamir, Snait

doi:10.1002/mnfr.201500441

Cited by 29 publications

(21 citation statements)

References 55 publications

(90 reference statements)

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“…PON2 mRNA and protein downregulation under hyperglycemic conditions is supported by previous studies on macrophages and monocytes [37,49]. Moreover, a lower PON2 expression has been observed in liver and heart of hyperglycemic animal models [37,49].…”

Section: Discussionsupporting

confidence: 70%

“…In fact, a decrease of PON2 has been observed in Caco-2 cells oxidized by iron-ascorbate [27] or by treatment with H 2 O 2 [48]. PON2 mRNA and protein downregulation under hyperglycemic conditions is supported by previous studies on macrophages and monocytes [37,49]. Moreover, a lower PON2 expression has been observed in liver and heart of hyperglycemic animal models [37,49].…”

Section: Discussionmentioning

confidence: 70%

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Effect of High Glucose-Induced Oxidative Stress on Paraoxonase 2 Expression and Activity in Caco-2 Cells

Morresi

Cianfruglia

Cecati

et al. 2019

Cells

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1) Background: Hyperglycemia leads to several biochemical and physiological consequences, such as the generation of advanced glycation end products (AGEs) and reactive oxygen species (ROS), which are involved in the development of several human diseases. Intestinal cells are continuously exposed to pro-oxidants and lipid peroxidation products from ingested foods, and also to glyco-oxidative damage. It has been reported that free radical generation may be linked to the development of inflammation-related gastrointestinal diseases.(2) Methods: The effects of high glucose (HG) treatment (50 mM) were assessed in terms of free radical production, lipid peroxidation, and AGEs formation. Furthermore, the expression and the antiapoptotic and antioxidant activity of the paraoxonase-2 (PON2) enzyme in intestinal cells has been investigated. (3) Results: Caco-2 cells treated with media supplied with high glucose (HG) (50 mM) showed, with respect to physiological glucose concentration (25 mM), an increase in ROS production, lipid peroxidation, and AGEs formation. Moreover, a lower PON2 expression and activity in HG-treated cells was related to activation of the apoptotic pathways. (4) Conclusions: Our results demonstrated that high glucose concentrations triggered glyco-oxidative stress in intestinal cells; the downregulation of PON2 could result in a higher oxidative stress and might contribute to intestinal dysfunction.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 70%

Effect of High Glucose-Induced Oxidative Stress on Paraoxonase 2 Expression and Activity in Caco-2 Cells

Morresi

Cianfruglia

Cecati

et al. 2019

Cells

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“…Total RNA was isolated from THP-1 cells using the RNeasy Mini Kit including RNase-free DNase set (Qiagen, Hilden, Germany). Using the Transcriptor First-Strand cDNA Synthesis Kit (Roche Diagnostics, Mannheim, Germany), cDNA was synthesized from 2 μg of total RNA using oligo-dT (12)(13)(14)(15)(16)(17)(18) and 5 units of avian myeloblastosis virus reverse transcriptase at 50 C for 60 min, followed by heating to 85 C for 5 min. For further PCR amplification, an aliquot (1:10) of the realtime (RT) product was adjusted to contain 0.1 μg of each primer, and additional buffer was added to a final volume of 20 μL.…”

Section: Real-time Polymerase Chain Reaction Assaymentioning

confidence: 99%

“…Yang et al found that liquorice flavonoid can effectively enhance insulin secretion in high‐fat diet administered mice through JNK1‐dependent protein tyrosine phosphatase 1B (PTP1B) signaling. Glabridin, an isoflavan from liquorice root, has also been found in upregulating paraoxonase 2 expression and decreasing iNOS activity in saturated fatty acid‐fed diabetic mice . Besides, the natural compound of amorfrutins, extracted from Glycyrrhiza foetida , has showed powerful antidiabetic capacity by dramatically reducing insulin resistance, inflammatory phenomena, and without side effects such as hepatotoxicity by activating peroxisome proliferator‐activated receptor γ (PPARγ) .…”

Section: Introductionmentioning

confidence: 99%

“…Glabridin, an isoflavan from liquorice root, has also been found in upregulating paraoxonase 2 expression and decreasing iNOS activity in saturated fatty acid-fed diabetic mice. 11,12 Besides, the natural compound of amorfrutins, extracted from Glycyrrhiza foetida, has showed powerful antidiabetic capacity by dramatically reducing insulin resistance, inflammatory phenomena, and without side effects such as hepatotoxicity by activating peroxisome proliferator-activated receptor γ (PPARγ). 13 Matchkov et al 14 showed that 18β-GA blocks Ca 2+ signaling through the inhibition of voltage-sensitive Ca 2+ in the mesenteric small arteries.…”

Section: Introductionmentioning

confidence: 99%

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Novel findings of 18β‐glycyrrhetinic acid on sRAGE secretion through inhibition of transient receptor potential canonical channels in high‐glucose environment

Tung

Chen

et al. 2019

BioFactors

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Enhancing soluble receptor for advanced glycation endproducts (sRAGE) is considered as a potent strategy for diabetes therapy. sRAGE secretion is regulated by calcium and transient receptor potential canonical (TRPC) channels. However, the role of TRPC channels in diabetes remains unknown. 18β‐Glycyrrhetinic acid (18β‐GA), produced from liquorice, has shown antidiabetic properties. This study was aimed to investigate the effect of 18β‐GA on sRAGE secretion via TRPC channels in high glucose (HG)‐induced THP‐1 cells. HG treatment enhanced TRPC3 and TRPC6 expression and consequently caused reactive oxygen species (ROS) accumulation mediated through p47 nicotinamide‐adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase (iNOS) associated with uncoupling protein 2 (UCP2) decline and lower sRAGE secretion. Interestingly, 18β‐GA showed the dramatic effects similar to Pyr3 or 2‐aminoethyl diphenyl borinate inhibitors and effectively reversed HG‐elicited mechanisms including that blocking TRPC3 and TRPC6 protein expressions, suppressing intracellular [Ca2+] concentration, decreasing expressions of ROS, p47s, and iNOS, but increasing UCP2 level and promoting sRAGE secretion. Therefore, 18β‐GA provides a potential implication to diabetes mellitus and its complications.

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Recent advances on the synthesis of flavans, isoflavans, and neoflavans

Sreenivasulu

Dakoju

Satyanarayana

2020

Journal of Heterocyclic Chem

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Heterocyclic compounds are the omnipresent structural cores comprising many natural and pharmaceutical products of biological significance. Significantly, heterocyclic compounds are widely distributed in nature, and also have applications in agrochemicals, sanitizers, as dyestuff, as copolymers, etc. Among heterocyles, flavonoids are a class of compounds that are highly interesting and constitute many natural products. In general, all flavanoids contains a basic core of C6‐C3‐C6 of phenyl‐benzopyran backbone. The relative placement of the phenyl group on to the benzopyran core makes further classification into flavanoids, isoflavanoids and neoflavanoids. Flavans (2‐aryl chroman) are subclass of anthoxanthanes exhibits a broad spectrum of biological properties such as anti‐inflammatory, anti‐oxidant, and anti‐malarial properties. Some representative naturally occurring products possessing flavan core are apigenin, luteolin, tangeretin, scutellarein, etc. On the other hand, some of the notable isoflavan‐based natural products are glabridin and (S)‐(−)‐equol. Glabridin is isolated from Licorice roots, which regulates paraoxonase (PON2) levels. While the simple isoflavan (S)‐(−)‐equol, is produced from soy isoflavone intake. Also, natural products such as dalbergichromene, centchroman, and (+)‐myristinin A possess neoflavan (4‐aryl‐3,4‐dihydro‐2H‐chromenes) core structure. Owing to their broad biological and pharmacological properties, synthetic chemists are fascinated in developing new routes toward their synthesis. As a result, a decent number of reports have been established in the literature. Thus, for the past 5 years of time frame, many new methodologies have been witnessed, for the synthesis of various flavan systems. This review emphasizes most of the significant methods on accomplishing flavans, isoflavans and neoflavans and also focused on their applications to the synthesis of relevant natural as well as biologically active products.

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Glabridin, an isoflavan from licorice root, upregulates paraoxonase 2 expression under hyperglycemia and protects it from oxidation

Cited by 29 publications

References 55 publications

Effect of High Glucose-Induced Oxidative Stress on Paraoxonase 2 Expression and Activity in Caco-2 Cells

Effect of High Glucose-Induced Oxidative Stress on Paraoxonase 2 Expression and Activity in Caco-2 Cells

Novel findings of 18β‐glycyrrhetinic acid on sRAGE secretion through inhibition of transient receptor potential canonical channels in high‐glucose environment

Recent advances on the synthesis of flavans, isoflavans, and neoflavans

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