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Anti-arthritogenic and cardioprotective action of hesperidin and daidzein in collagen-induced rheumatoid arthritis

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Abstract

Atherosclerosis has been linked to chronic inflammatory processes. Changes in the levels of lipoproteins, especially low-density lipoprotein or its variants, as well as inflammatory markers are risk factors for the atherosclerosis. In the present study, an experimental model of rheumatoid arthritis was developed by administrating collagen suspension intradermally in the tail region of Wistar albino rats. At the same time, a suspension of hesperidin (50 mg/kg body weight) and daidzein (20 mg/kg body weight) was orally administrated. The compounds were given in the morning and evening for 21 days. Levels of inflammatory markers in the homogenate of knee joints of experimental rats as well as plasma lipoproteins were investigated. The administration of hesperidin and daidzein caused significant (p < 0.001) decrease in articular elastase activity, TNF-α, and malondialdehyde levels. Further, arthritis scoring and histological findings supported the anti-inflammatory actions of the test compounds. Interestingly, the test compounds also lowered the plasma low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglyceride but increased the level of high-density lipoprotein cholesterol. The test compounds thus ameliorated the risk factors of atherosclerosis. Furthermore, antioxidant roles of hesperidin as well as daidzein were evident from decrease in free radical load demonstrated as increase in total antioxidant level in plasma of arthritic animals treated with hesperidin and daidzein. In a separate in vitro experiment, enhanced free radical scavenging activity of hesperidin was demonstrated against 2,2-diphenyl-1-picrylhydrazyl and 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid. The anti-inflammatory, hypolipidemic, and antioxidant actions of the naturally occurring test compounds, particularly hesperidin, seem to be quite effective against rheumatoid arthritis and atherosclerosis. Thus, their consumption may be helpful in prevention or at least delaying the onset of these diseases in susceptible individuals.

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Abbreviations

ABTS·+ :

2,2-Azinobis-3-ethylbenzothiazoline-6-sulfonic acid

CAD:

Coronary artery disease

CD:

Conjugated diene

CHD:

Coronary heart disease

CIAD:

Daidzein-Treated Rheumatoid Arthritis

CIAH:

Hesperidin-Treated Rheumatoid Arthritis

CIRA:

Collagen-Induced Rheumatoid Arthritis Control

CTRL:

Normal Control

CVD:

Cardiovascular disease

DPPH· :

2,2-Diphenyl-1-picrylhydrazyl

HDL-C:

High-density lipoprotein cholesterol

Lb-LDL:

Large buoyant-LDL

LDL:

Low-density lipoproteins

MDA:

Malondialdehyde

NOS:

Nitric oxide synthase

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

RA:

Rheumatoid arthritis

Sd-LDL:

Small dense-LDL

TBARS:

Thiobarbituric acid reactive substances

TG:

Triglyceride

TNF- α:

Tumor necrosis factor-α

VLDL-C:

Very low-density lipoprotein cholesterol

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Acknowledgments

We acknowledge the Council of Science and Technology, Lucknow, India for providing financial assistance under the Young Scientist Project Scheme (Grant No. CST1239).

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Correspondence to Shafeeque Ahmad.

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Ahmad, S., Alam, K., Hossain, M.M. et al. Anti-arthritogenic and cardioprotective action of hesperidin and daidzein in collagen-induced rheumatoid arthritis. Mol Cell Biochem 423, 115–127 (2016). https://doi.org/10.1007/s11010-016-2830-y

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