Treatment of stress urinary incontinence by cinnamaldehyde, the major constituent of the chinese medicinal herb ramulus cinnamomi

Abstract

Stress urinary incontinence (SUI) is a common disorder in middle-aged women and the elderly population. Although surgical treatment of SUI has progressed, pharmacological therapies remain unelucidated. We screened potential herbal medicines against SUI with an ex vivo organ bath assay. Ramulus Cinnamomi and its major constituent cinnamaldehyde cause a high contractile force of the urethra and a low contractile force of blood vessels. Cinnamaldehyde dose-dependently reduced lipopolysaccharide-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. In the vaginal distension- (VD-) induced SUI model in mice, cinnamaldehyde significantly reversed the VD-induced SUI physical signs and reduced blood pressure. Cinnamaldehyde may offer therapeutic potential against SUI without the possible side effect of hypertension. The modulation of several SUI-related proteins including myosin, iNOS, survival motor neuron (SMN) protein, and superoxide dismutase 3 (SOD3) may play some crucial roles in the therapeutic approach against SUI. This information may offer clues to the pathogenesis of SUI and open additional avenues for potential therapy strategies.

Figure 1

Urethra and artery contraction in organ bath experiment. Representative original traces of the contractile responses to PE and cinnamaldehyde in female pig urethra (a) and artery (b). Contractions induced by 10⁻⁵ M of PE in the control media were taken as 100%. (c) Graphic representation of concentration-response curves.

Figure 2

(a) Raw 264.7 cell viability after culture with cinnamaldehyde for 24 h as determined by MTT assay. (b) Effects of cinnamaldehyde on LPS-induced NO production of RAW 264.7 macrophages. Cells were incubated for 24 h with 500 ng/mL of LPS in the absence or presence of cinnamaldehyde. Nitrite concentration in the medium was determined using Griess reagent. (c) Inhibition of iNOS protein expression by cinnamaldehyde in LPS-stimulated RAW 264.7 cells. (d) Modulation of myosin, iNOS, SMN, AdR1a, and SOD3 protein expressions in cinnamaldehyde-treated HBdSMCs. GADPH was used as a loading control. The calculated data were presented as mean ± SD for at least three different experiments. *P < 0.05, compared to control group. ^# P < 0.05, compared to LPS group.

Figure 3

(a) LPP, (b) MUCP, (c) BP, and (d) HR values on the sixth day after VD in the different groups. Each bar represents the mean ± SD of five individual mice. *P < 0.05, compared to control group. ^# P < 0.05, compared to VD group.

Figure 4

Myosin, iNOS, SMN, AdR1a, and SOD3 expressions on the sixth day after VD in the different groups. Each bar represents the mean ± SD of five individual mice. *P < 0.05, compared to control group. ^# P < 0.05, compared to VD group.