AIM:To investigate the effect of Scutellariae Radix extract(SRE)on ulcerative colitis(UC)in rats induced by dextran-sulfate sodium(DSS).METHODS:Colitis was induced in male Sprague-Dawley(SD)rats(170-180 g)by 4% dextra...AIM:To investigate the effect of Scutellariae Radix extract(SRE)on ulcerative colitis(UC)in rats induced by dextran-sulfate sodium(DSS).METHODS:Colitis was induced in male Sprague-Dawley(SD)rats(170-180 g)by 4% dextran sulfate sodium(DSS,wt/v;MW 54 000)in drinking water for 8 d.The treated rats received 4% DSS and SRE orally(100 mg/kg per day).Control rats received either tap water or SRE only.Macroscopic assessment which included body weight changes,fecal occult blood and stool consistency were determined daily.At the appointed time,the rats were sacrificed and the entire colons were removed.The colon length and the myeloperoxidase(MPO)activity were measured.The severity of colitis was graded by morphological and histological assessments.The ion transport activity of the colonic mucosa was assessed by electrophysiological technique.RESULTS:Rats treated with oral administration of 4% DSS regularly developed clinical and macroscopic signs of colitis.Treatment with SRE relieved the symptoms,including the reduction in body weight,shortening and ulceration of the colon.Administration of SRE also significantly reduced the histological damage induced by DSS.Moreover,the ISC responses of the colonic mucosato forskolin were suppressed after the induction of colitis.The stimulated ion transport activity of DSS-rats treated with SRE displayed significant improvement in the secretory responsiveness.CONCLUSION:SRE was effective in treating acute DSS-induced ulcerative colitis,as gauged by reduced clinical disease,improved macroscopic and histological damage scores,and enhanced recovery of normal colonic secretory function.展开更多
Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods Murine-derived tr...Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary glands.Sixty-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat pads.Starting from the day of tumor cell inoculation,tumors were grown for 6 days.The LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,respectively.The LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a week.The control group received daily oral gavage of 0.2 mL double-distilled water.The treatment period was 30 days.At the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota analysis.Results Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(P<0.05),altered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological activities.Moreover,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(P<0.05).4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective in activating the anti-tumor immune response(P<0.05).Conclusion The above results provide evidence for evaluating the immune regulating mechanisms of 4HF in breast cancer and support its clinical significance in its potential as an adjunctive therapeutic agent or immune supplement.展开更多
基金a direct grant for research from The ChineseUniversity of Hong Kong,No. 2041075 awarded to Wing-HungKo
文摘AIM:To investigate the effect of Scutellariae Radix extract(SRE)on ulcerative colitis(UC)in rats induced by dextran-sulfate sodium(DSS).METHODS:Colitis was induced in male Sprague-Dawley(SD)rats(170-180 g)by 4% dextran sulfate sodium(DSS,wt/v;MW 54 000)in drinking water for 8 d.The treated rats received 4% DSS and SRE orally(100 mg/kg per day).Control rats received either tap water or SRE only.Macroscopic assessment which included body weight changes,fecal occult blood and stool consistency were determined daily.At the appointed time,the rats were sacrificed and the entire colons were removed.The colon length and the myeloperoxidase(MPO)activity were measured.The severity of colitis was graded by morphological and histological assessments.The ion transport activity of the colonic mucosa was assessed by electrophysiological technique.RESULTS:Rats treated with oral administration of 4% DSS regularly developed clinical and macroscopic signs of colitis.Treatment with SRE relieved the symptoms,including the reduction in body weight,shortening and ulceration of the colon.Administration of SRE also significantly reduced the histological damage induced by DSS.Moreover,the ISC responses of the colonic mucosato forskolin were suppressed after the induction of colitis.The stimulated ion transport activity of DSS-rats treated with SRE displayed significant improvement in the secretory responsiveness.CONCLUSION:SRE was effective in treating acute DSS-induced ulcerative colitis,as gauged by reduced clinical disease,improved macroscopic and histological damage scores,and enhanced recovery of normal colonic secretory function.
基金Supported by the Funding of the State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants(The Chinese University of Hong Kong/CUHK)from Innovation and Technology Commission,Hong Kong,Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine,CUHK,Hong Kong and C.C.Wu Cultural Foundation。
文摘Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary glands.Sixty-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat pads.Starting from the day of tumor cell inoculation,tumors were grown for 6 days.The LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,respectively.The LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a week.The control group received daily oral gavage of 0.2 mL double-distilled water.The treatment period was 30 days.At the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota analysis.Results Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(P<0.05),altered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological activities.Moreover,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(P<0.05).4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective in activating the anti-tumor immune response(P<0.05).Conclusion The above results provide evidence for evaluating the immune regulating mechanisms of 4HF in breast cancer and support its clinical significance in its potential as an adjunctive therapeutic agent or immune supplement.