Inhibition of Protein Denaturation by Fatty Acids, Bile Salts and Other Natural Substances: A New Hypothesis for the Mechanism of Action of Fish Oil in Rheumatic Diseases

Saso, Luciano; Valentini, Giovanni; Casini, Maria Luisa; Mattei, E.; Braghiroli, L.; Mazzanti, Gabriela; Panzironi, Claudio; Grippa, Eleonora; Silvestrini, Bruno

doi:10.1254/jjp.79.89

Cited by 26 publications

(16 citation statements)

References 23 publications

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“…Studies on the stabilization induced by different chemical agents are of considerable importance. [14][15][16][17]21,[57][58][59] We performed a study on the stabilization effect of a NSAID, the ibuprofen. To verify the protective action of the ibuprofen, an analysis with SAXS, DLS, CD and fluorescence techniques was carried out on a set of solutions with urea concentrations between 0.00 and 9.00 M.…”

Section: Discussionmentioning

confidence: 99%

“…Saso et al 15,16 reported the stabilization activity of numerous drugs, studying the variation of absorbance (turbidimetric method) or the aggregation (HPLC technique) of HSA:ligand solutions in heat-induced denaturation conditions. These works show that FA, NSAIDs and a surfactant, the sodium dodecyl sulfate, are the more active compounds.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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Human serum albumin binding ibuprofen: A 3D description of the unfolding pathway in urea

Galantini¹,

Leggio²,

Konarev³

et al. 2010

Biophysical Chemistry

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT2 AbstractSmall angle X-ray scattering (SAXS) technique, supported by light scattering measurements and spectroscopic data (circular dichroism and fluorescence) allowed us to restore the 3D structure at low resolution of defatted human serum albumin (HSA) in interaction with ibuprofen. The data were carried out on a set of HSA solutions with urea concentrations between 0.00 and 9.00 M. The SingularValue Decomposition method, applied to the complete SAXS data set allowed us to distinguish three different states in solution. In particular a native conformation N (at 0.00 M urea), an intermediate I1(at 6.05 M urea) and an unfolded structure U (at 9.00 M urea) were recognized. The low resolution structures of these states were obtained by exploiting both ab initio and rigid body fitting methods. In particular, for the protein without denaturant, a conformation recently described (Leggio & al., PCCP, 2008, 10, 6741-6750), very similar to the crystallographic heart shape, with only a slight reciprocal movement of the three domains, was confirmed. The I1 structure was instead characterized by only a closed domain (domain III) and finally, the recovered structure of the U state revealed the characteristic feature of a completely open state. A direct comparison with the free HSA pointed out that the presence of the ibuprofen provokes a shift of the equilibrium towards higher urea concentrations without changing the unfolding sequence. The work represents a type of analysis which could be exploited in future investigations on proteins in solution, in the binding of drugs or endogenous compounds and in the pharmacokinetic properties as well as in the study of allosteric effects, cooperation or anticooperation mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

Human serum albumin binding ibuprofen: A 3D description of the unfolding pathway in urea

Galantini¹,

Leggio²,

Konarev³

et al. 2010

Biophysical Chemistry

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“…Increasing the amount of EPA in membrane phospholipids not only reduces the level of arachidonic acid (AA) available for metabolism by lipoxygenases and cyclooxygenases, but also competes with AA for metabolism to form metabolites of less proinflammatory than the AA derived metabolites, thereby taming the inflammatory reaction (Calder, 2006). Long chain fatty acids have been reported to have anti-denaturant activity that protects against protein denaturation, which might be beneficial in rheumatoid arthritis and other rheumatic conditions (Saso et al, 1999). This is may be another mechanism of action of primrose oil and fish oil due to their long chain fatty acid contents.…”

Section: Discussionmentioning

confidence: 99%

Preparation and evaluation of functional foods in adjuvant arthritis

Al‐Okbi¹,

Mohamed²

2012

Grasas y Aceites

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Adjuvant arthritis is an animal model that closely resembles rheumatoid arthritis in humans. It is a successful working model used to study new anti-inflammatory agents. In previous studies (animal and clinical) we have shown that evening primrose oil, fish oil and the methanol extract of date fruits and fenugreek seeds have anti-inflammatory activity and that the methanol extract of dates has an antioxidant effect. Based on these studies, the aim of the present study was to prepare 7 functional foods containing such bioactive fractions separately or in combination and to evaluate them in adjuvant arthritis in rats, study the stability of bioactive ingredients and evaluate their sensory properties. The studied biochemical parameters were erythrocyte sedimentation rate, erythrocyte superoxide dismutase, glutathione peroxidase and plasma copper, zinc and interlukin 2. Nutritional parameters, including body weight gain, food intake and food efficiency ratio were monitored during the feeding of the functional foods. The bioactive ingredients assessed were total phenolic contents and fatty acids. The results showed improvement in the biochemical parameters, body weight gain and food efficiency ratio of arthritic rats fed on the functional foods with different degrees. All the prepared functional foods were sensory accepted. The active ingredients showed stability during storage. In conclusion, all the tested functional foods showed promising antiinflammatory activity and were determined to be acceptable through sensory evaluation which means that their potential beneficial use as dietary supplements in rheumatoid arthritis patients may be recommended.<br><br>La artritis adyuvante es un modelo utilizado en animales y se caracteriza por ser muy parecida a la artritis reumatoide en humanos. Se trata de un modelo de trabajo utilizado con éxito para estudiar nuevos agentes anti-inflamatorios. En estudios previos (animales y clínica) hemos demostrado que el aceite de onagra, el aceite de pescado y los extractos metanólicos de semillas de fenogreco o alholva y de dátiles tienen actividad anti-inflamatoria y que el extracto metanólico de dátiles tiene efecto antioxidante. Basado en estos estudios, el objetivo del presente trabajo consistió en preparar alimentos funcionales con siete fracciones bioactivas por separado y conjuntamente y evaluarlas en artritis adyuvante en ratas, estudiar la estabilidad de los principios bioactivos y evaluar sus propiedades sensoriales. Los parámetros bioquímicas estudiados fueron la velocidad de sedimentación globular, la enzima superóxido dismutasa eritrocitaria, la glutatión peroxidasa, cobre plasmático, y la zinc interleucina-2. Los parámetros nutricionales, incluyendo ganancia de peso corporal, la ingesta de alimentos y la relación de eficiencia alimentaria se han seguido durante la ingesta de los alimentos funcionales. Los ingredientes bioactivos evaluados fueron el contenido de fenoles totales y ácidos grasos. Los resultados mostraron una mejoría de los parámetros bioquímicos,...

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“…12 Saso et al, 1999 demonstrated that presence of PUFA such as AA, LA and ALA etc. inhibit heat induced protein denaturation 13,14 Hence, it becomes essential to assess the level of protein denaturation in presence of SBT seed oil to understand its potential in chronic inflammatory conditions.…”

Section: Inhibition Of Protein Denaturationmentioning

confidence: 99%

“…Hence, membrane stabilization was taken up as a measure of the anti-inflammatory property of SBT seed oil. Chronic inflammatory conditions may involve protein denaturation.12 Saso et al, 1999 demonstrated that presence of PUFA such as AA, LA and ALA etc. inhibit heat induced protein denaturation 13,14 Hence, it becomes essential to assess the level of protein denaturation in presence of SBT seed oil to understand its potential in chronic inflammatory conditions.…”

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confidence: 99%

Comparison of Fatty Acid Profiling and RBC Membrane Stabilization Activity of Seabuckthorn (Hippophae rhamnoides and Hippophae salicifolia) Seed Oil

Dubey¹,

Ramana²,

Mishra³

2017

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Background: Seabuckthorn (SBT) is one of the most important plants of higher altitude in India and China. SBT seed oil is rich in Poly Unsaturated Fatty Acid (PUFA) which is present in a peculiar ratio capable of combating inflammation. Objective: To compare the physicochemical characteristics, fatty acid profiling and Red Blood Cell (RBC) membrane stabilization activity between two species of SBT seed oil; Hippophae rhamnoides (HR) and Hippophae salicifolia (HS) collected from Ladakh and Sikkim, India, respectively. Materials and Methods: GC-MS analysis was performed and effect of SBT seed oil was evaluated against heat and hypotonicity induced haemolysis of RBC. Protein denaturation assay was also conducted to check its probable role in chronic inflammation. Results: GC-MS analysis confirmed the presence of PUFA viz. Alpha linolenic acid (ALA) and Linoleic acid (LA) in SBT seed oil. Both significantly (p<0.05) inhibited heat and hypotonicity induced membrane destabilization in a concentration dependant manner. Maximum percentage inhibition of protein denaturation was observed at 3.6 μg/ml after incubation period of 4 hours. Conclusion: HR and HS have been proved to inhibit membrane destabilization with almost equal efficacy. Their efficacy against heat induced protein denaturation indicates that they may be useful in prevention and/or treatment of chronic inflammation as well. These findings may be attributed to the presence of PUFA. This study has contributed in establishing some preliminary evidence about PUFAs being the mainstay of their anti-inflammatory efficacy. However, in vivo studies are required to further validate the results of this study. cellular concentrations by increased n-6 and decreased n-3 PUFA content of the modern western diet. HR and HS seed oil contains the 18-carbon n-3 fatty acid, ALA, which can be converted after ingestion to the 20-carbon n-3 fatty acid, EPA. EPA is believed to act as a competitive inhibitor of AA conversion to prostaglandin E2 and leukotriene B4, thereby, decreasing the synthesis of one or both of these eicosanoids. Similar to the effect of n-3 fatty acids, inclusion of the 20-carbon n-9 fatty acid, eicosatrienoic acid 5 and OA 6 in the diet also results in decreased synthesis of LTB4. Treatment of inflammation includes extensive use of non-steroidal anti-inflammatory agents (NSAIDs). However, their use makes the patients more vulnerable to gastrointestinal and liver toxicities.8 Therefore, new anti-inflammatory drugs having alternative mechanisms are being searched as substitutes to NSAIDs. 9 Inflammation is a complicated biological response of vascular tissues to external detrimental stimuli and can either be acute or chronic. At the onset of an inflammatory process, the cells undergo activation and release inflammatory mediators such as histamine and serotonin.10 These mediators collectively cause elevated vasodilatation and permeability of measured and reconstituted as a 40% v/v suspension with isotonic buffer solution (10 mM sodium phosphate buf...

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Inhibition of Protein Denaturation by Fatty Acids, Bile Salts and Other Natural Substances: A New Hypothesis for the Mechanism of Action of Fish Oil in Rheumatic Diseases

Cited by 26 publications

References 23 publications

Human serum albumin binding ibuprofen: A 3D description of the unfolding pathway in urea

Human serum albumin binding ibuprofen: A 3D description of the unfolding pathway in urea

Preparation and evaluation of functional foods in adjuvant arthritis

Comparison of Fatty Acid Profiling and RBC Membrane Stabilization Activity of Seabuckthorn (Hippophae rhamnoides and Hippophae salicifolia) Seed Oil

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