Therapeutic effect of a hydroxynaphthoquinone fraction on dextran sulfate sodium-induced ulcerative colitis.
OBJECTIVE
To evaluate the therapeutic effect of hydroxynaphthoquinone mixture (HM) on dextran sulfate sodium (DSS)-induced colitis and explore the underlying mechanisms.


METHODS
BALB/c mice received 3.5% DSS for 6 d to induce ulcerative colitis. Groups of mice were orally administered HM 3.5, 7 and 14 mg/kg and mesalazine 200 mg/kg per day for 7 d. During the experiment, clinical signs and body weight, stool consistency and visible fecal blood were monitored and recorded daily. A disease activity index score was calculated for each animal. At the conclusion of the experiment, the colonic histopathological lesions were evaluated. Myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) levels were determined. Protein expression levels of TNF-α, nuclear factor-κB (NF-κB) p65, inhibitor of κB (IκB) and phosphorylation of IκB (p-IκB) were analyzed by Western blot analysis.


RESULTS
Administration of 3.5% DSS for 6 d successfully induced acute colitis associated with soft stool, diarrhea, rectal bleeding, and colon shortening, as well as a loss of body weight. Administration of HM effectively attenuated the severity of colonic mucosa injury. For histopathological analysis, HM treatment improved histological alterations and lowered pathological scores compared with the DSS only group. This manifested as a reduction in the extent of colon injury and inflammatory cell infiltration, as well as the degree of mucosal destruction. In addition, HM at doses of 7 and 14 mg/kg significantly decreased MPO activity in colonic tissue (0.98 ± 0.22 U/g vs 1.32 ± 0.24 U/g, 0.89 ± 0.37 U/g vs 1.32 ± 0.24 U/g tissue, P < 0.05) and serum TNF-α levels (68.78 ± 7.34 ng/L vs 88.98 ± 17.79 ng/L, 64.13 ± 14.13 ng/L vs 88.98 ± 17.79 ng/L, P < 0.05). Furthermore, HM down-regulated the expression of TNF-α, NF-κB p65 and p-IκBα in colonic tissue while up-regulating IκBα protein expression. These results suggest that the significant anti-inflammatory effect of HM may be attributable to its inhibition of TNF-α production and NF-κB activation.


CONCLUSIONS
HM had a favorable therapeutic effect on DSS-induced ulcerative colitis, supporting its further development and clinical application in inflammatory bowel disease.
Zi-Liang Zhang, Ke Liu, College of Life Science, Jilin University, Changchun 130012, Jilin Province, China.
Zi-Liang
ZL
Zhang
Zi-Liang Zhang, Ke Liu, College of Life Science, Jilin University, Changchun 130012, Jilin Province, China.
Hua-Ying
HY
Fan
Zi-Liang Zhang, Ke Liu, College of Life Science, Jilin University, Changchun 130012, Jilin Province, China.
Ming-Yan
MY
Yang
Zi-Liang Zhang, Ke Liu, College of Life Science, Jilin University, Changchun 130012, Jilin Province, China.
Zuo-Kai
ZK
Zhang
Zi-Liang Zhang, Ke Liu, College of Life Science, Jilin University, Changchun 130012, Jilin Province, China.
Ke
K
Liu
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D028082:Boraginaceae / Q000737:chemistry; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005765:Gastrointestinal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009285:Naphthoquinones / Q000302:isolation & purification / Q000494:pharmacology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots; D010946:Plants, Medicinal; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D018836:Inflammation Mediators; D009285:Naphthoquinones; D010936:Plant Extracts; D016264:Dextran Sulfate
Arnebia euchroma (Royle) Johnst; Dextran sulfate sodium-induced ulcerative colitis; Hydroxynaphthoquinones; Inflammatory bowel disease; Nuclear factor-κB activation