Effects of a novel tylophorine analog on collagen‐induced arthritis through inhibition of the innate immune response

Abstract

Objective. To test the effects of a novel tylophorine analog, DCB 3503, on the prevention and treatment of collagen-induced arthritis (CIA) and to elucidate its underlying mechanisms.Methods. DBA/1J mice were immunized with type II collagen, and in some cases, lipopolysaccharide (LPS) was used to boost the development of arthritis.

Interaction Studies of an Anticancer Alkaloid, (+)-(13aS)-Deoxytylophorinine, with Calf Thymus DNA and Four Repeated Double-Helical DNAs

“…1a) is a new phenanthroindolizidine alkaloid, originally extracted in our institute from the roots of Tylophora atrofolliculata and Tylophora ovata, which has a long history of being used as medicine to treat rheumatism and wounds in China [9]. Eleven phenanthroindolizidine alkaloids were isolated and screened.…”

A novel tylophorine analog NK-007 ameliorates colitis through inhibition of innate immune response

“…In our previous study, we demonstrated that DCB-3503 has an anti-inflammatory effect in CIA (collagen-induced arthritis) through inhibition of the innate immune response, and NK-007 (analog of DCB-3503, which exhibits better solubility) has therapeutic effects on CIA through suppressing TNF-α [20,21]. Here we investigated the role of NK-007 in both DSS-and acetic acid-induced colitis models, and the underlying molecular mechanism.…”

“…DCB-3503 (a tylophorine analog) has been commonly studied and showed antitumor activity [15,16] through mechanisms of inhibiting nucleic acid synthesis, RNA transcription, and protein synthesis [16][17][18]. Previously, DCB-3503 was reported to have anti-inflammatory effect in lupus and rheumatoid arthritis through suppressing innate immune response in our study [19,20]. In the current study, we synthesized (±)-tylophorine malate (NK-007), which had better water solubility (20 g/L at room temperature), whereas tylophorine (DCB-3503) could not be dissolved in water.…”

“…NK-007 (6 mg/kg) and distilled water (vehicle control) were administered through intraperitoneal injection once every other day from day 0 to day 6. This injection dose of NK-007 was determined from our optimizing animal study [20]. Body weight, stool consistency and fecal bleeding were monitored daily.…”

Inhibition of Lipopolysaccharide‐Induced Nitric Oxide Production by Antofine and Its Analogues in RAW 264.7 Macrophage Cells

“…Moreover, their anti-inflammatory activity was also reported recently. The phenanthroindolizidine alkaloid tylophorine inhibited the production of proinflammatory cytokines and the development and progression of collagen-induced arthritis [8]. Phenanthroindolizidine alkaloids, including tylophorine, inhibited LPS/IFN-g-induced NO production through the inhibition of AP-1 activation in macrophage cells [9].…”