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Rheumatoid arthritis (RA) is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT), with methotrexate (MTX), the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA) in male Lewis rats. The experiment included healthy controls (CO), arthritic animals (AA), AA given N-f-5HT (AA-N-f-5HT), and AA given MTX (AA-MTX). N-f-5HT did not affect the body weight change and clinical parameters until the 14th experimental day. Its positive effect was rising during the 28-day experiment, indicating a delayed onset of N-f-5HT action. Administration of either N-f-5HT or MTX caused reduction of inflammation measured as the level of CRP in plasma and the activity of LOX in the liver. mRNA transcription of TNF-α and iNOS in the liver was significantly attenuated in both MTX and N-f-5HT treated groups of arthritic rats. Interestingly, in contrast to MTX, N-f-5HT significantly lowered the level of IL-1β in plasma and IL-1β mRNA expression in the liver and spleen of arthritic rats. This speaks for future investigations of N-f-5HT as an agent in the treatment of RA in combination therapy with MTX.

The quasi-steady-state approximation (QSSA) is commonly applied in chemical kinetics without rigorous justification. We provide details of such a justification in the ubiquitous case of reversible two-step bimolecular binding in which molecules as an intermediate step of the reaction form a transient complex. First, we justify QSSA in the regime that agrees with the results in the literature and is characterized by max{R₀, L₀} ≪ K(m). Here, R₀ and L₀ are the initial concentrations of reacting receptor and ligand, respectively, and K(m) is the Michaelis constant. We also validate QSSA under an alternative condition that can be viewed as partially irreversible binding, and it does not require a tight bound on R₀ and L₀ but rather requires k₂ + k₋₂ ≪ k₋₁. Here, k₋₁ is the rate constant of decomposition of the transient complex to the ligand and the receptor, and k₂ and k₋₂ are the forward and the reverse rate constants of transformation of the complex to the product, respectively. Furthermore, we provide arguments that QSSA can also be accurate in a regime when max{R₀, L₀} ≈ K(m) and k₂ + k₋₂ ≈ k₋₁ if |R₀ - L₀| ≪ K(m). The derived conditions may be of practical use as they provide weaker requirements for the validity of QSSA compared to the existing results.