Therapeutic and Prophylactic Effects of Zostera Marina on Dextran Sulfate Sodium-induced Colitis

Article information

J Korean Med. 2016;37(3):13-26

Publication date (electronic) : 2016 September 30

doi : https://doi.org/10.13048/jkm.16031

Woo-Hyeon Jeon ¹, Seok-Jae Ko ², Bongha Ryu ¹^,², Jae-Woo Park ¹^,²^,

¹Department of Clinical Korean Medicine, Graduate School, Kyung Hee University

²Department of Gastroenterology, College of Korean Medicine, Kyung Hee University

Correspondence to: 박재우 (Jae-Woo Park), 서울시 동대문구 경희대로 26 경희대학교 한의과대학 비계내과학교실, Tel: +82-2-440-6219, Fax: +82-2-440-7143, E-mail: pjw2907@khu.ac.kr

Received 2016 July 15; Revised 2016 September 06; Accepted 2016 September 06.

Abstract

Objectives

Inflammatory bowel disease (IBD) is chronic inflammatory disorders of the intestines. Due to limitation of conventional treatment including steroids, herbal medicines have emerged as possible therapeutic options for IBD. The purpose of the current study was to investigate the therapeutic and prophylactic effects and mechanisms of Zostera Marina water extract (ZME) on DSS-induced colitis.

Methods

Colitis was induced by DSS in Balb/c mice. In pre-treatment setting, ZME was administered 7 days before DSS treatment and in co-treatment setting, ZME was simultaneously administrated with DSS treatment. In both settings, ZME 100, 300 and 1000 mg/kg were orally administered twice a day, respectively. Mice weight and clinical findings were measured daily. Colon length, macroscopic findings and histological damages of colon mucosa were assessed at the end of experiments. The levels of cytokines including TNF-α, IFN-γ, IL-1β, IL-6, IL-10 and IL-17 were measured by Biometric Multiplex Cytokine Profiling method.

Results

In a dose dependent manner, ZME significantly inhibited the colon shortening, and improved macroscopic score and histological score. However, there were insignificant changes on inhibition of weight loss and improvement of clinical score. There were no significant differences of effects between co-treatment and pre-treatment settings. ZME 300 and 1000 mg/kg groups significantly inhibited IFN-γ. Only ZME 1000 mg/kg group significantly inhibited TNF-α, IL-1β and IL-6.

Conclusions

The current results show the possibility of therapeutic use and its prophylactic application of ZME on inflammatory bowel diseases. Future studies for targeted mechanisms of ZME are needed.

Keywords: Zostera Marina; Inflammatory bowel disease; Dextran sulfate sodium; Colitis; Cytokine

Fig. 1

The Prophylactic Effects of ZME on DSS-induced Colitis

(a) Body weight, (b) Colon length, (c) Clinical score, (d) Colon edema score and (e) Histological findings and scores (A, normal; B, control; C, positive control [Sulfasalazine 30 mg/kg]; D, E and F are ZME-treated groups. The whole colon tissue was stained by H&E. Center was distal part and boundary was proximal part of colon [×100]).

Data are expressed as mean ± S.E.M (n=8). Nor: normal group, Con: control group, P.C: positive control group (Sulfasalazine 30 mg/kg), ZME: Zostera Marina water Extract

***p<0.001, **p<0.01, *p<0.05 vs. control group by one-way ANOVA with Dunnett’s posthoc test.

Fig. 2

The Therapeutic Effects of ZME on DSS-induced Colitis

Data are expressed as mean ± S.E.M (n=8). Nor: normal group, Con: control group, P.C: positive control group (Sulfasalazine 30 mg/kg), ZME: Zostera Marina water Extract

***p<0.001, **p<0.01, *p<0.05 vs. control group by one-way ANOVA with Dunnett’s posthoc test.

Fig. 3

Cytokine Levels of Colon Mucosa

(a) IFN-γ, (b) TNF-α, (c) IL-1β, (d) IL-6, (e) IL-10 and (f) IL-17

Nor: normal group, Con: control group, ZME: Zostera Marina water Extract.

***p<0.001, **p<0.01, *p<0.05 vs. control group by one-way ANOVA with Dunnett’s posthoc test.

Table 1

Clinical score

Table 2

Macroscopic score

Notes

본 논문은 2013년도 경희대학교 대학원 박사학위논문임.

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Article information Continued

Fig. 1

The Prophylactic Effects of ZME on DSS-induced Colitis

Data are expressed as mean ± S.E.M (n=8). Nor: normal group, Con: control group, P.C: positive control group (Sulfasalazine 30 mg/kg), ZME: Zostera Marina water Extract

***p<0.001, **p<0.01, *p<0.05 vs. control group by one-way ANOVA with Dunnett’s posthoc test.

Fig. 2

The Therapeutic Effects of ZME on DSS-induced Colitis

Data are expressed as mean ± S.E.M (n=8). Nor: normal group, Con: control group, P.C: positive control group (Sulfasalazine 30 mg/kg), ZME: Zostera Marina water Extract

***p<0.001, **p<0.01, *p<0.05 vs. control group by one-way ANOVA with Dunnett’s posthoc test.

Fig. 3

Cytokine Levels of Colon Mucosa

(a) IFN-γ, (b) TNF-α, (c) IL-1β, (d) IL-6, (e) IL-10 and (f) IL-17

Nor: normal group, Con: control group, ZME: Zostera Marina water Extract.

***p<0.001, **p<0.01, *p<0.05 vs. control group by one-way ANOVA with Dunnett’s posthoc test.

Table 1

Clinical score

Score	Spontaneous behavior and posture	Coat and piloerection	Cleaning of perianal region
0	Moving[−] with hunching	Yellowish[light brown] and piloerection[+++]	Herniation with blood[+++]
1	Moving[±] with hunching	Dirty and yellowish[+++] and piloerection[++]	With stool[+++] and blood[+] trace
2	Moving[+] with hunching	Yellowish[++] with piloerection[+]	With stool[++] and blood[+] trace
3	Moving[++] without hunching	Clean and yellowish[+] without piloerection	With stool[+] trace
4	Moving[+++] without hunching	Normal state	Normal state

Table 2

Macroscopic score

Score	Macroscopic score
Score	Thickness of colon edema	Overall health state
0	+++, >0.35 mm	Fecal bleeding[+++] with tar stool[++]
1	++, 0.3–0.35 mm	Fecal bleeding[++] with tar stool[+]
2	+, 0.25–0.3 mm	Fecal bleeding[+] with pasty and semiformed stool
3	±, 0.2–0.25 mm	No bleeding with semiformed stool
4	0.1–0.2 mm	No bleeding with normal stool