Abstract Title:

Tocotrienols inhibit lipopolysaccharide-induced pro-inflammatory cytokines in macrophages of female mice.

Abstract Source:

Lipids Health Dis. 2010;9(1):143. Epub 2010 Dec 16. PMID: 21162750

Abstract Author(s):

Asaf A Qureshi, Julia C Reis, Christopher J Papasian, David C Morrison, Nilofer Qureshi

Article Affiliation:

Departments of Basic Medical Sciences, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA. [email protected]


BACKGROUND: Inflammation has been implicated in cardiovascular disease, and the important role of proteasomes in the development of inflammation and other macrophage functions has been demonstrated. Tocotrienols are potent hypocholesterolemic agents that inhibitβ-hydroxy-β-methylglutaryl coenzyme A reductase activity, which is degraded via the ubiquitin-proteasome pathway. Our objective was to evaluate the effect of tocotrienols in reducing inflammation. Lipopolysaccharide (LPS) was used as a prototype for inflammation in murine RAW 264.7 cells and BALB/c female mice.

RESULTS: The present results clearly demonstrate thatα-, γ-, or δ-tocotrienol treatments inhibit the chymotrypsin-like activity of 20 S rabbit muscle proteasomes (>50%; P<0.05). Chymotrypsin, trypsin, and post-glutamase activities were decreased>40% (P<0.05) with low concentrations (<80μM), and then increased gradually with concentrations of (80--640 μM) in RAW 264.7 whole cells. Tocotrienols showed 9--33% (P<0.05) inhibitions in TNF-α secretion in LPS-stimulated RAW 264.7 cells. Results of experiments carried out in BALB/c mice demonstrated that serum levels of TNF-α after LPS treatment were also reduced (20--48%; P<0.05) by tocotrienols with doses of 1 and 10μg/kg, and a corresponding rise in serum levels of corticosterone (19--41%; P<0.05) and adrenocorticotropic hormone (81--145%; P<0.02) was observed at higher concentrations (40μM). Maximal inhibition of LPS-induced TNF-α was obtained with δ-tocotrienol (10 μg/kg). Low concentrations of δ-Tocotrienols (<20μM) blocked LPS-induced gene expression of TNF-α, IL-1β, IL-6 and iNOS (>40%), while higher concentrations (40μM) increased gene expression of the latter in peritoneal macrophages (prepared from BALB/c mice) as compared to control group.

CONCLUSIONS: These results represent a novel approach by using natural products, such as tocotrienols as proteasome modulators, which may lead to the development of new dietary supplements of tocotrienols for cardiovascular diseases, as well as others that are based on inflammation.

Print Options

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2022 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.