Protective Effect of Pinitol Against Inflammatory Mediators of Rheumatoid Arthritis via Inhibition of Protein Tyrosine Phosphatase Non-Receptor Type 22 (PTPN22)

Abstract

BackgroundThe aim of the current study was to explore the anti-arthritic effect of pinitol via assessing its effect on various inflammatory mediators and its possible mechanism of action.Material/MethodWe assessed the anti-arthritic effect of pinitol in a formaldehyde- and CFA-induced arthritic model in Wistar Swiss albino strain rats divided into 6 groups. The rats received different doses of pinitol and indomethacin for 28 days. The arthritic index and body weight were determined at regular intervals, together with hepatic, hematological, and antioxidant parameters. The expression of proinflammatory cytokines (e.g., IL-6, TNF-α, and IL-1β) and inflammatory mediators (e.g., COX-2 and VEGF) were also estimated with histopathological evaluation of the joint tissue of rats. A docking study of pinitol with PTPN22 was also carried out.ResultsThe CFA-induced model rats developed redness and nodules in the tail and front paws, and the arthritic control (AC) group rats showed similar symptoms, which were decreased by pinitol administration. The body weight of AC group rats was decreased, while pinitol-treated rats showed considerably increased body weight. Hematological, hepatic, and antioxidant parameters were altered by pinitol in a dose-dependent manner. Pinitol significantly decreased the elevated concentration of proinflammatory cytokines and inflammatory mediators, with improvement in histopathological condition. The docking study suggested that pinitol efficiently interacted with PTPN22 via Arg59, Tyr60, Leu106, and Lys138 by creating close interatomic hydrogen bonds and hydrophobic contacts.ConclusionsPinitol showed anti-arthritic effects via reduction of proinflammatory cytokines and inflammatory mediators via inhibition of PTPN22.

Pinitol attenuates LPS‐induced pneumonia in experimental animals: Possible role via inhibition of the TLR‐4 and NF‐κB/IκBα signaling cascade pathway

“…Previous reports used to determine the treatment doses of pinitol (5, 10, 20 mg/kg). [ 20,21 ] Rats were treated with either vehicle or dexamethasone or pinitol for 28 days after LPS administration.…”

“…[ 20 ] Furthermore, pinitol inhibited the release of proinflammatory cytokines (such as TNF‐α, and IL's) as well as inflammatory mediators (including cyclooxygenase‐II (COX‐II) and vascular endothelial growth factor to produce its antiarthritic potential against rheumatoid arthritis. [ 21 ] Clinically, pinitol proved its antidiabetic potential in patients with type 2 diabetes mellitus. [ 18 ] Recently, a 12‐week randomized, double‐blind, placebo‐controlled study reported the hepatoprotective potential of pinitol via inhibition of oxidative stress in patients with nonalcoholic fatty liver disorder.…”

Extraction approaches used for the determination of biologically active compounds (cyclitols, polyphenols and saponins) isolated from plant material

“…D‐pinitol (3‐O‐Methyl‐D‐chiro‐inositol) has also a substantial pharmacological importance . It has been successfully used in the treatment of hypertension, rheumatism, rheumatoid arthritis, cardiovascular diseases and neurological disorders . Therefore, inositols as pharmaceutical ingredients are in great demand world‐wide.…”

Effects of growth conditions and cultivability on the content of cyclitols in Medicago sativa

“…Myo-inositol efficiency in disorders like panic attacks, premenstrual dysphoric, depression, or obsessive-compulsive behavior was demonstrated and described in a review article (Al-Suod et al 2017). D-pinitol has been successfully used for treating hypertension, rheumatoid arthritis, cardiovascular or neurological disorders (Zheng et al 2017). Both D-chiro-inositol and myo-inositol proved efficacy in improving functionality of the ovaries, by increasing the ovulation rate in those women suffering from polycystic ovary syndrome (Cheang et al 2008;Costantino et al 2009).…”