Anti‐atherogenic effect of statins: role of nitric oxide, peroxynitrite and haem oxygenase‐1

Obesity is a metabolic disorder characterized by the central distribution of abdominal fat, hyperglycemia, hyperlipidemia, and hypertension. A high-fat diet can lead to overnutrition and directly trigger inflammation in adipose tissue. Regulatory T cells (Tregs) are essential negative regulators of inflammation. Soybean (Glycine max L.) has a variety of beneficial health. It contains isoflavones, particularly daidzein and genistein which can be transformed using microbial and physical stimuli to enhance bioactivity. The aim of this study was to analyze the effect of elicited soybean extract (ESE) on Treg activity in high fat-fructose (HFFD) mice. Twenty-eight female Balb/C mice were divided into seven groups: normal diet (ND) only, ND + ESE 104 mg/kg BW, HFFD only, HFFD + Simvastatin 2.8 mg/kg, HFFD + ESE 78 mg/kg BW, HFFD + ESE 104 mg/kg BW, and HFFD + ESE 130 mg/kg BW. The high fat-fructose diet was given over a period of 20 weeks, and ESE was administered orally per day after 20 weeks for four weeks. At week 24, the animals were sacrificed and the spleen was collected. Tregs were labeled as CD4 + CD25 + CD62L + and the relative Treg number was measured using flow cytometry. The HFFD treatment significantly decreased Treg number (p < 0.05) compared to a normal diet. The ESE treatment in HFFD mice could improve Treg numbers compared to HFFD mice. Our results suggest that ESE has potential to be used as a supplement to suppress chronic inflammation via increased Treg number.

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“…Simvastatin could also activate Nrf2/HO-1 signaling pathway 35 . The ho-1 expression is correlated with Treg production.…”

Section: Resultsmentioning

confidence: 99%

Elicited soybean (Glycine max L.) extract improves regulatory T cell activity in high fat-fructose diet mice

Atho'illah

Widyarti

Rifa’i

2017

AIP Conference Proceedings

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“…Moreover, it has been established that atheroprotective effect of statins is mediated by restoring the normal NO/peroxynitrite balance (Heeba et al, 2009). The night dosing of simvastatin resulted in an increase of NO level compared to day treating.…”

Section: Discussionmentioning

confidence: 99%

Influence of Simvastatin Chronotherapy on Erythrocytes Nitric oxide Synthase Activity

Harisa¹,

Alanazi²,

Attia³

et al. 2015

International J. of Pharmacology

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A B S T R A C TThis study was undertaken to investigate the impact simvastatin chronotherapy on erythrocytes Nitric Oxide Synthase (NOS) activity. In the present study we select 24 adult human subjects have plasma total cholesterol high borderline (200-230 mg dLG 1 ). Subjects were administrated simvastatin (20 mg day time) for 2 months. Afterward, they were recommended for washout period (2 weeks), then subjects were administered the same dose at night time for additional 2 months. The present results showed that both day time and night time simvastatin treatment regimen significantly decrease plasma atherogenic index, malondialdehyde and protein carbonyl levels. However, paraoxonase-1 activity and total thiol level were significantly increased. Moreover, simvastatin therapy improved nitrite (NO marker) levels in both plasma and erythrocytes compared to baselines. As well, simvastatin day time and night time dosing significantly increased erythrocytes NOS activity (46 and 64%, respectively) compared to baselines. Night time dosing induced marked increase of NOS activity (19%) compared to day time. This study confirms that night time dosing boost hypocholesterolemic, antioxidant and NO modulating effects of simvastatin compared to day time.

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“…Therefore, the 70% MeOH extract from A. iwayomogi would be more suitable as a potent peroxynitrite scavenger than the other extracts tested. This extract could prevent atherosclerosis (Heeba et al, 2009) and hepatic (Han et al, 2012;Wang et al, 2012) or bowel (Singer et al, 1996) diseases that can be mediated through the excess production of peroxynitrite. The MeOH extract was prepared on a large scale, using the reflux method.…”

Section: Optimization and Validation Of The Hplc Methodsmentioning

confidence: 99%

Simultaneous quantification and validation of new peroxynitrite scavengers fromArtemisia iwayomogi

Nugroho

Lim

Karki

et al. 2014

Pharmaceutical Biology

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Context: Artemisia iwayomogi Kitamura (Compositae) has been very widely used for the treatment of acute or chronic hepatitis, jaundice, and gastritis. In the course of our continuing efforts to identify and quantify peroxynitrite scavengers from Compositae plants, A. iwayomogi was used in this study. Objective: The present study was aimed to identify and quantify the peroxynitrite scavengers of A. iwayomogi. Materials and methods: Silica gel and ODS were used for column chromatography. The isolated compounds were quantified using an HPLC equipped with a Capcell Pak C18 column (5 mm, 250 mm Â 4.6 mm i.d.), and the method was validated for the quality control. Peroxynitrite (ONOO À )-scavenging activities of the compounds and extracts were evaluated on the measurement of highly fluorescent rhodamine 123 converted from non-fluorescent dihydrorhodamine (DHR)-123 under the presence of peroxynitrite. Results: Based on the spectroscopic evidences, a new compound, 2 00 -O-caffeoylrutin (2 00 -O-trans-caffeic acid ester of quercetin 3-O-a-L-rhamnopyranosyl(1 ! 6)-b-D-glucopyranoside) was isolated and determined together with patuletin 3-O-glucoside, scopolin, scopoletin, rutin, 3,4-dicaffeoylquinic acid, and chlorogenic acid. All of them were potent peroxynitrite scavengers (IC 50 1.88 mg/mL). Discussion and conclusion: The peroxynitrite scavengers were mainly distributed in the EtOAc fraction rather than the ether and BuOH fractions. The 70% MeOH extract exhibited a high peroxynitrite-scavenging activity. Through the validation, the present HPLC method was verified to be sufficiently sensitive, accurate, precise, and stable. Therefore, this method can be used for the quality control of A. iwayomogi.

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Anti‐atherogenic effect of statins: role of nitric oxide, peroxynitrite and haem oxygenase‐1

Cited by 62 publications

References 39 publications

Elicited soybean (Glycine max L.) extract improves regulatory T cell activity in high fat-fructose diet mice

Elicited soybean (Glycine max L.) extract improves regulatory T cell activity in high fat-fructose diet mice

Influence of Simvastatin Chronotherapy on Erythrocytes Nitric oxide Synthase Activity

Simultaneous quantification and validation of new peroxynitrite scavengers fromArtemisia iwayomogi

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