Noscapine hydrochloride (benzyl-isoquinoline alkaloid) effectively prevents protein denaturation through reduction of IL-6, NF-kB, COX-2, Prostaglandin-E2 in rheumatic rats

Abstract

Noscapine hydrochloride (benzyl-isoquinoline antitussive alkaloid) is an opium derivative and generally used as a cough suppressant. Numerous studies on noscapine hydrochloride have reported that it has potent anti-inflammatory activity. However, the mechanisms by which it exerts an anti-inflammatory function is not well understood. Protein denaturation is the primary step that leads to the organ destruction and permanent arthritic disability. The above-mentioned facts provided the ground to plan this study using different in-vitro and in-vivo approaches. RT-qPCR and ELISA assays were used to assess the inflammatory markers related to protein denaturation in complete adjuvant persuaded rheumatism in Sprague - Dawley rats. The results were collected as paw volume and body weight changes, arthritic scoring and serum antioxidant enzymes assays. These findings demonstrated that all doses of noscapine hydrochloride (10, 20 and 40 mg/kg) studied in this study, significantly (p < 0.001) decreased the protein denaturation by preventing the increase in levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear factor-kB (NF-kB), cyclooxygenase-2 (COX-2) and prostaglandin E2. Noscapine hydrochloride significantly reduced the paw volume (p < 0.001), arthritic scoring and reversed the body mass as compared to arthritic control diseased rats.

Keywords: Antioxidant; Benzylisoquinoline alkaloids; Pro- and anti-inflammatory cytokines; Protein denaturation.

Graphical abstract

Fig. 1

Effect of noscapine hydrochloride at 10, 20 and 40 mg/kg doses on formaldehyde persuaded arthritis. Results are recorded as (n = 5, mean ± SEM) followed by Two-way ANOVA (^*** p < 0.001, *p < 0.05) statistically significant versus arthritic control.

Fig. 2

Effect of noscapine hydrochloride different doses on body mass of rats in CA persuaded arthritis. Two-way ANOVA was done by following Bonferroni post-test while ^*** p < 0.001, *p < 0.05 and ns presents non-significant (n = 5), statistically significant versus arthritic control.

Fig. 3

Effect of noscapine hydrochloride 10, 20 and 40 mg/kg on arthritic scoring of rats in CFA induced arthritis. Two way ANOVA was done by following Bonferroni posttest, whereas ^*** p < 0.001, ^**p < 0.01, *p < 0.05 and ns presents non-significant (n = 5), statistically significant versus arthritic control.

Fig. 4

Effect of Noscapine hydrochloride at increasing doses for 28 days on IL-1β, TNF-α, IL-6, COX-2, NF-kB in CFA-induced arthritic rats. Values are summarized as mean ± S.E.M, using one- way ANOVA followed by Dunnett’s post-test (^***p < 0.001), statistically significant versus arthritic control.

Fig. 5

Augmentation of IL-4 and IL-10 by noscapine hydrochloride (at 10, 20 and 40 mg/kg dose orally for 28 days) in contrast to CFA arthritic diseased control rats. Values are summarized as mean ± S.E.M, using one- way ANOVA followed by Dunnett’s post-test (^***p < 0.001), statistically significant versus arthritic control.

Fig. 6

Effect of noscapine hydrochloride at 10, 20 and 40 mg/kg orally for 28 days on PGE2 in CFA-induced arthritic model versus arthritic control. Results were analyzed by Mean ± SEM followed by one way ANOVA and results were statistically significant where (^***p < 0.001).

Fig. 7

Effect of noscapine hydrochloride at 10, 20 and 40 mg/kg orally for 28 days on antioxidant enzymes activity (CAT, SOD and POD) in CFA-induced arthritic model versus arthritic control.