title: Diosmin downregulates the expression of T cell receptors, pro-inflammatory cytokines and NF-κB activation against LPS-induced acute lung injury in mice.
abstract: Diosmin, a natural flavonoid glycoside present abundantly in the pericarp of various citrus fruits. Because of its anti-inflammatory and antioxidant properties, it can be used in many diseases. In this study, we investigated the possible protective mechanisms of the diosmin on LPS-induced lung injury through inhibition of T cell receptors, pro-inflammatory cytokines and NF-κB activation. Animals were pretreated with diosmin (50 and 100mg/kg, p.o.) for seven days prior to lipopolysaccharides (LPS) treatment. LPS administration increased neutrophils, monocytes, lymphocytes, total leukocyte count (TLC) and platelets which were decreased by diosmin. We observed that mice exposed to LPS showed increased malondialdehyde level and MPO activity whereas marked decrease in glutathione content. These changes were significantly reversed by treatment with diosmin in a dose dependent manner. Diosmin treatment showed a substantial reduction in T cell (CD4(+) and CD8(+)) receptors and pro-inflammatory (IL-2(+) and IL-17(+)) cytokines in whole blood. In addition, RT-PCR analysis revealed increased mRNA expression of IL-6, IL-17, TNF-α, and NF-κB in the LPS group, while reduced by treatment with diosmin. Western blot analysis confirmed the increased protein expression of IL-1β, TNF-α and NF-κB p65 in the LPS group and treatment of animals with diosmin reversed these effects. The levels of cytoplasmic p-IκB-α and p-NF-κB p65 expression also were mitigated by diosmin. The histological examinations revealed protective effect of diosmin while LPS group aggravated lung injury. These results support the potential for diosmin to be investigated as a potential agent for the treatment of lung injury and inflammatory diseases.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: fimam@ksu.edu.sa.
authors.forename: Faisal
authors.initials: F
authors.lastname: Imam
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Naif O
authors.initials: NO
authors.lastname: Al-Harbi
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Al-Harbi
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mushtaq Ahmad
authors.initials: MA
authors.lastname: Ansari
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Khairy M A
authors.initials: KM
authors.lastname: Zoheir
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Iqbal
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
authors.forename: Md Khalid
authors.initials: MK
authors.lastname: Anwer
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ali R
authors.initials: AR
authors.lastname: Al Hoshani
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Sabry M
authors.initials: SM
authors.lastname: Attia
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Sheikh Fayaz
authors.initials: SF
authors.lastname: Ahmad
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D004145:Diosmin / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D007376:Interleukin-2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D004145:Diosmin
keywords: Cytokines; Diosmin; Inflammatory mediators; Lipopolysaccharides; T cell receptors