AIM:To find a rapid and efficient analysis method of gastrointestinal microflora in Pi-deficient(spleen-deficient) rats and to evaluate traditional Chinese drugs.METHODS:Enterobacterial repetitive intergenic consensus...AIM:To find a rapid and efficient analysis method of gastrointestinal microflora in Pi-deficient(spleen-deficient) rats and to evaluate traditional Chinese drugs.METHODS:Enterobacterial repetitive intergenic consensus-PCR(ERIC-PCR) based assay was performed to examine changes of intestinal microflora in two Pi-deficienct animal models and to evaluate the efficacy of four traditional Chinese drugs as well as a probiotic recipe and another therapy in Pi-deficient rats.RESULTS:A molecular marker was identified for Pi-deficiency in rats.The pharmacodynamic evaluation system,including identified molecular markers(net integral area and abundance of DNA bands),Shannon's index for diversity of intestinal microflora,and Sorenson's pairwise similarity coefficient,was established.The four major clinical recipes of traditional Chinese drugs for Pi-deficiency in rats,especially at their medium dose(equivalence to the clinical dose),produced more pronounced recovery activities in Pi-deficient rats,while higher doses of these recipes did not show a better therapeutic effect but some toxic effects such as perturbation deterioration of intestinal microflora.CONCLUSION:Both fingerprint analysis and identified marker can show Pi-deficiency in rats and its difference after treatment.The identified molecular marker may be applied in screening for the active compounds both in relative traditional Chinese drugs and in pharmacodynamic study of Pi-deficiency in rats.展开更多
Background:Bulleyaconitine A(BLA)is a diterpenoid alkaloid from the rhizomes of Aconitum bulleyanum Diels and has been clinically used for chronic pain treatment in China for many years.However,the newly reported adve...Background:Bulleyaconitine A(BLA)is a diterpenoid alkaloid from the rhizomes of Aconitum bulleyanum Diels and has been clinically used for chronic pain treatment in China for many years.However,the newly reported adverse events of BLA indicated that BLA still has potential safety issues.Materials and Methods:To assess the safety of BLA,analgesic tests,acute toxicity studies,repeated-dose oral toxicity studies,and tissue distribution studies after single and repeated administration of BLA were carried out.Results:Administration of 0.14 mg/kg BLA showed potent analgesic effects in both analgesic tests.In acute toxicity study,the LD50 value of BLA was calculated to be 3.4434 mg/kg.In the subchronic toxicity study,the no observed adverse effect level was 0.25 mg/kg,and the lowest observed adverse effect level was 0.5 mg/kg.The spleen,liver,and kidneys are newly identified target organs of BLA toxicity after long-term administration.Moreover,unlike a single BLA administration,repeated administration showed BLA redistribution from organs with an abundant blood supply to immune and metabolic organs.Conclusions:These results suggested that BLA itself would be nontoxic at a dosage of 0.25 mg/kg in rats and should be carefully used when combining BLA with medications that can cause spleen,liver,or kidney injury.展开更多
基金Supported by The National Natural Science Foundation of China,No.90209059Supported by The National Natural Science Foundation of China,No.90409018
文摘AIM:To find a rapid and efficient analysis method of gastrointestinal microflora in Pi-deficient(spleen-deficient) rats and to evaluate traditional Chinese drugs.METHODS:Enterobacterial repetitive intergenic consensus-PCR(ERIC-PCR) based assay was performed to examine changes of intestinal microflora in two Pi-deficienct animal models and to evaluate the efficacy of four traditional Chinese drugs as well as a probiotic recipe and another therapy in Pi-deficient rats.RESULTS:A molecular marker was identified for Pi-deficiency in rats.The pharmacodynamic evaluation system,including identified molecular markers(net integral area and abundance of DNA bands),Shannon's index for diversity of intestinal microflora,and Sorenson's pairwise similarity coefficient,was established.The four major clinical recipes of traditional Chinese drugs for Pi-deficiency in rats,especially at their medium dose(equivalence to the clinical dose),produced more pronounced recovery activities in Pi-deficient rats,while higher doses of these recipes did not show a better therapeutic effect but some toxic effects such as perturbation deterioration of intestinal microflora.CONCLUSION:Both fingerprint analysis and identified marker can show Pi-deficiency in rats and its difference after treatment.The identified molecular marker may be applied in screening for the active compounds both in relative traditional Chinese drugs and in pharmacodynamic study of Pi-deficiency in rats.
基金supported by Liao Ning Education Office(No.2019 LQN10)Shenyang Young and middle-aged science and technology innovation program(RC180308)
文摘Background:Bulleyaconitine A(BLA)is a diterpenoid alkaloid from the rhizomes of Aconitum bulleyanum Diels and has been clinically used for chronic pain treatment in China for many years.However,the newly reported adverse events of BLA indicated that BLA still has potential safety issues.Materials and Methods:To assess the safety of BLA,analgesic tests,acute toxicity studies,repeated-dose oral toxicity studies,and tissue distribution studies after single and repeated administration of BLA were carried out.Results:Administration of 0.14 mg/kg BLA showed potent analgesic effects in both analgesic tests.In acute toxicity study,the LD50 value of BLA was calculated to be 3.4434 mg/kg.In the subchronic toxicity study,the no observed adverse effect level was 0.25 mg/kg,and the lowest observed adverse effect level was 0.5 mg/kg.The spleen,liver,and kidneys are newly identified target organs of BLA toxicity after long-term administration.Moreover,unlike a single BLA administration,repeated administration showed BLA redistribution from organs with an abundant blood supply to immune and metabolic organs.Conclusions:These results suggested that BLA itself would be nontoxic at a dosage of 0.25 mg/kg in rats and should be carefully used when combining BLA with medications that can cause spleen,liver,or kidney injury.