Troxerutin acts on complement mediated inflammation to ameliorate arthritic symptoms in rats

Abstract

Troxerutin (TXR), a phytochemical reported to possess anti-inflammatory and hepato-protective effects. In this study, we aimed to exploit anti-arthritic properties of TXR using an adjuvant induced arthritic (AIA) rat model. AIA induced rats showed highest arthritis score at disease onset and by oral administration of TXR (50, 100, 200 mg/kg body weight), reduced to basal level in a dose dependent manner. Isobaric tag for relative and absolute quantitative (iTRAQ) proteomics tool was employed to identify deregulated joint homogenate proteins in AIA and TXR treated rats to decipher probable mechanism of the TXR action in arthritis. iTRAQ analysis identified a set of 434 joint homogenate proteins with 65 deregulated proteins (log2 case/control ≥1.5) in AIA. Expressions of a set of important proteins (AAT, T-kininogen, vimentin, desmin, nucleophosmin) that could classify AIA from healthy were validated using Western blot analysis. Western blot data corroborated proteomics findings. In silico protein-protein interaction study of joint homogenate proteome revealed that complement component 9, the major building blocks of the membrane attack complex (MAC) responsible for sterile inflammation, gets perturbed in AIA. Our dosimetry study suggests that a TXR dose of 200 mg/kg body weight for 15 days is sufficient to bring the arthritis score to basal levels in AIA rats. We have shown the importance of TXR as an anti-arthritis agent in AIA model and after additional investigation its arthritis ameliorating properties could be exploited for clinical usability.

In Silico and In Vitro Anticoagulant Activity Detection of Quercetin, Rutin, and Troxerutin as New Potential Inhibitors of Factor Xa

“…It is possible to exclude natural compounds from Lipinski and Veber rules because of their high complexity and special conformational features, which is supported by recent studies [81]. Troxerutin, for example, is used as a medicine for the treatment of hemorrhoids, varicose veins, and other chronic vascular insufficiency diseases [67].…”

“…Whereas, Rutin (Rut) showed several pharmacological activities, including antioxidant, cellular protection, vascular protective, anticancer, neuroprotective, and cardioprotective activities [65,66]. Troxerutin (Trx) also known as vitamin P4, is one of the well-known and medicinally used flavonoids [67], it is a trihydroxyethylated derivative of Rutin. It has been used to treat chronic venous insufficiency (CVI) and many diseases.…”