AIM: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 ...AIM: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.CONCLUSION:HM had a favorable therapeutic effect on DSS-induced ulcerative colitis,supporting its further development and clinical application in inflammatory bowel disease.展开更多
AIM:To evaluate the potential effectiveness of hydroxynaphthoquinone mixture(HM)in rats with 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced colitis.METHODS:Colitis was induced by intracolonic administration of TNBS...AIM:To evaluate the potential effectiveness of hydroxynaphthoquinone mixture(HM)in rats with 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced colitis.METHODS:Colitis was induced by intracolonic administration of TNBS(80 mg/kg,dissolved in 50%ethanol).Rats were treated daily for 7 d with HM(2.5,5,10 mg/kg)and mesalazine 100 mg/kg 24 h after TNBS instillation.Disease progression was monitored daily by observation of clinical signs and body weight change.At the end of the experiment,macroscopic and histopathologic lesions of rats were scored,and myeloperoxidase(MPO)activity was determined.We also determined inflammatory cytokine tumor necrosis factor(TNF)-αlevel by ELISA,Western blotting and immunochemistry to explore the potential mechanisms of HM.RESULTS:After intracolonic instillation of TNBS,animals developed colitis associated with soft stool,diarrhea and marked colonic destruction.Administration of HM significantly attenuated clinical and histopathologic severity of TNBS-induced colitis in a dose-dependent manner.It abrogated body weight loss,diarrhea and inflammation,decreased macroscopic damage score,and improved histological signs,with a significant reduction of inflammatory infiltration,ulcer size and the severity of goblet cell depletion(all P<0.05 vs TNBS alone group).HM could reduce MPO activity.In addition,it also decreased serum TNF-αlevel and down-regulated TNF-αexpression in colonic tissue.This reduction was statistically significant when the dose of HM was 10 mg/kg(P<0.05 vs TNBS alone group),and the effect was comparable to that of mesalazine and showed no apparent adverse effect.The underlying mechanism may be associated with TNF-αinhibition.CONCLUSION:These findings suggest that HM possesses favourable therapeutic action in TNBS-induced colitis,which provides direct pharmacological evidence for its clinical application.展开更多
Escin is a natural mixture of triterpenoid as- ponin isolated from the seed of the horse chestnut and demonstrates anti-oedematous and anti-inflammatory effects. As yet, the pre-cise mechanisms by which escin exerts i...Escin is a natural mixture of triterpenoid as- ponin isolated from the seed of the horse chestnut and demonstrates anti-oedematous and anti-inflammatory effects. As yet, the pre-cise mechanisms by which escin exerts its anti- inflammatory effects remain unclear. The data from current studies indicate that the anti-in-flammatory properties of escin were attributed to its ability to reduce the adhesiveness of neu-trophils and the associated release of inflam-matory mediators;its ability to decrease hista-minic and serotoninergic activities;its ability to inhibit phospholipase A2;its ability to decrease nuclear factor-κ B activation and down-regulate the expression of tumor necrosis factor-α. All these effects are similar to glucocorticoids. Mo- reover, escin depends on adrenal glands to ex-ert its anti-inflammatory effects. Also, our recent research showed that the serum corticosterone level in mice did not increase after a 7-day in-travenous injection of escin. The results sup-port the hypothesis that escin may exert a syn-ergistic anti-inflammatory effect with glucocor-ticoids. Confirming this hypothesis will play a role in elucidating the anti-inflammatory mech- anisms of escin.展开更多
基金Supported by Programs for Science and Technology Development and Plan of Yantai,No.2013ZH086
文摘AIM: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.CONCLUSION:HM had a favorable therapeutic effect on DSS-induced ulcerative colitis,supporting its further development and clinical application in inflammatory bowel disease.
基金Supported by National Program for Important New Drugs R and D,No.2011ZX9102-006-04Programs for Science and Technology Development and Plan of Yantai,No.2013ZH086
文摘AIM:To evaluate the potential effectiveness of hydroxynaphthoquinone mixture(HM)in rats with 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced colitis.METHODS:Colitis was induced by intracolonic administration of TNBS(80 mg/kg,dissolved in 50%ethanol).Rats were treated daily for 7 d with HM(2.5,5,10 mg/kg)and mesalazine 100 mg/kg 24 h after TNBS instillation.Disease progression was monitored daily by observation of clinical signs and body weight change.At the end of the experiment,macroscopic and histopathologic lesions of rats were scored,and myeloperoxidase(MPO)activity was determined.We also determined inflammatory cytokine tumor necrosis factor(TNF)-αlevel by ELISA,Western blotting and immunochemistry to explore the potential mechanisms of HM.RESULTS:After intracolonic instillation of TNBS,animals developed colitis associated with soft stool,diarrhea and marked colonic destruction.Administration of HM significantly attenuated clinical and histopathologic severity of TNBS-induced colitis in a dose-dependent manner.It abrogated body weight loss,diarrhea and inflammation,decreased macroscopic damage score,and improved histological signs,with a significant reduction of inflammatory infiltration,ulcer size and the severity of goblet cell depletion(all P<0.05 vs TNBS alone group).HM could reduce MPO activity.In addition,it also decreased serum TNF-αlevel and down-regulated TNF-αexpression in colonic tissue.This reduction was statistically significant when the dose of HM was 10 mg/kg(P<0.05 vs TNBS alone group),and the effect was comparable to that of mesalazine and showed no apparent adverse effect.The underlying mechanism may be associated with TNF-αinhibition.CONCLUSION:These findings suggest that HM possesses favourable therapeutic action in TNBS-induced colitis,which provides direct pharmacological evidence for its clinical application.
文摘Escin is a natural mixture of triterpenoid as- ponin isolated from the seed of the horse chestnut and demonstrates anti-oedematous and anti-inflammatory effects. As yet, the pre-cise mechanisms by which escin exerts its anti- inflammatory effects remain unclear. The data from current studies indicate that the anti-in-flammatory properties of escin were attributed to its ability to reduce the adhesiveness of neu-trophils and the associated release of inflam-matory mediators;its ability to decrease hista-minic and serotoninergic activities;its ability to inhibit phospholipase A2;its ability to decrease nuclear factor-κ B activation and down-regulate the expression of tumor necrosis factor-α. All these effects are similar to glucocorticoids. Mo- reover, escin depends on adrenal glands to ex-ert its anti-inflammatory effects. Also, our recent research showed that the serum corticosterone level in mice did not increase after a 7-day in-travenous injection of escin. The results sup-port the hypothesis that escin may exert a syn-ergistic anti-inflammatory effect with glucocor-ticoids. Confirming this hypothesis will play a role in elucidating the anti-inflammatory mech- anisms of escin.