Influence of Repeated Senna Laxative Use on Skin Barrier Function in Mice

Abstract

Background: Senna, one of the major stimulant laxatives, is widely used for treating constipation. Chronic senna use has been reported to be associated with colonic disorders such as melanosis coli and/or epithelial hyperplasia. However, there is no obvious information on the influence of chronic senna use on organs except for the intestine.

Objective: To clarify the influence of senna laxative use on skin barrier function by repeated senna administration.

Methods: Eight-week-old male hairless mice received senna (10 mg/kg/day) for 21 days. After administration, we evaluated transepidermal water loss (TEWL), and investigated the biomarkers in plasma and skin using protein analysis methods.

Results: Fecal water content on day seven was significantly increased; however, on day 21, it was significantly decreased after repeated senna administration. In the senna-administered group, TEWL was significantly higher compared to the control on days seven and 21. Plasma acetylcholine concentration and NO₂^-/NO₃^- were increased on days seven and 21, respectively. In skin, tryptase-positive mast cells and inducible nitric oxide synthase (iNOS)-positive cells were increased on days seven and 21, respectively. The increase of TEWL on days seven and 21 was suppressed by the administration of atropine and N(G)-nitro-L-arginine methyl ester, respectively.

Conclusion: It was suggested that diarrhea or constipation induced by repeated senna administration caused the impairment of skin barrier function. There is a possibility that this impaired skin barrier function occurred due to degranulation of mast cells via cholinergic signals or oxidative stress derived from iNOS.

Keywords: Acetylcholine; Nitric oxide synthase type II; Senna extract; Skin hydration; Transepidermal water loss.

Fig. 1. Effects of repeated senna administration on mice (A) body weight, (B) fecal weight, and (C) fecal water content. Blue circle is the control group. Red circle is the sennoside group. (D) H&E stain in control and sennoside group. ^*p<0.05 compared with the control. Scale bar=100 µm.

Fig. 2. Plasma concentration of (A) acetylcholine, (B) tumor necrosis factor alpha (TNF-α), (C) interferon gamma (IFN-γ), and (D) NO₂ ⁻/NO₃ ⁻. Blue circle is the control. Red circle is the sennoside group. ^*p<0.05 compared with the control.

Fig. 3. (A) Immunohistochemistry of mast cell tryptase (arrows) and the number of mast cell tryptase in the skin. (B) Immunohistochemistry of inducible nitric oxide synthase (iNOS) (arrows) and the number of iNOS-positive cells in the skin. Blue circle is the control. Red circle is the sennoside group. ^*p<0.05, ^**p<0.01 compared with the control. Scale bar=100 µm.

Fig. 4. Transition of (A) body weight, (B) fecal weight, (C) plasma acetylcholine, (D) tumor necrosis factor alpha (TNF-α), (E) NO₂ ⁻/NO₃ ⁻, (F) number of mast cell tryptase, and (G) inducible nitric oxide synthase (iNOS) positive cells. Blue circle is the control. Green square is the sennoside+atropine group. Red triangle is the sennoside+L-NAME group. ^*p<0.05 compared with the control. L-NAME: N(G)-nitro-L-arginine methyl ester.

Fig. 5. Transition of TEWL and the skin hydration level over 21 days. (A~C) Blue circle is the control. (A) Red circle is the sennoside group. (B) Green square is the sennoside+atropine group. (C) Open triangle is the sennoside+L-NAME group. ^*p<0.05 compared with the control. TEWL: transepidermal water loss, L-NAME: N(G)-nitro-L-arginine methyl ester.