Herb induced liver injury by Xianling Gubao Tablets: A case assessed for causality using updated RUCAM and integrated evidence chain

Objective:A typical case of Xianling Gubao(XLGB)Tablets-induced liver injury was systematically studied in the clinic and the laboratory.Methods:A patient with herb-induced liver injury(HILI)and a history of taking XLGB Tablets before disease onset was engaged as the study subject,and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method(RUCAM)and the integrated evidence chain(iEC)method recommended by the Guidelines for Diagnosis and Treatment of Herb-induced Liver Injury(HILI Guidelines).Results:Clinical history,biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral,alcoholic and autoimmune liver diseases on the diagnosis.Based on an investigation of the patient’s medication history,she was suspected to have HILI caused by XLGB Tablets,as the patient was only taking an oral preparation of XLGB Tablets,and the influence of other drugs on the diagnosis was excluded.This patient with alanine aminotransferase(ALT)3 upper limit of normal(ULN)and a calculated R of 6 was diagnosed with possible acute drug-induced hepatocellular injury.The relationship was considered“highly probable”(score of 9)using the updated RUCAM of 2016.Moreover,the fingerprint similarity between the preparation taken by the patient and a commercially available preparation was 0.99,suggesting that the patient was consuming XLGB Tablets rather than another drug.LC-MS technology and the Agilent Fake TCM-Drugs database were used to investigate the drug,and no chemical additions were found.Examination of the drug for pesticide residues,heavy metals,aflatoxins and other exogenous substances indicated compliance with the content limits of the Chinese Pharmacopoeia.Conclusion:In summary,the final diagnosis of XLGB-induced liver injury reached the clinical diagnosis of HILI and was acute severe hepatocellular injury type by the updated RUCAM and iEC.Therefore,this study provides scientific evidence regarding the causality evaluation of compound preparations of traditional Chinese medicines-induced liver injury.

Regulation of Quan Du Zhong capsule on VEGF/bFGF and expression of Bcl‑2/Bax and Caspase‑3 protein in the repairing process of canine femoral head necrosis

Objective:To explore the repair and treatment effect of Quan Du Zhong capsule on necrosis of femoral head in dogs.Methods:Totally 12 beagles were randomly divided into normal group,model group,Quan Du Zhong capsule group and Xianlinggubao capsule group,with three in each group.In addition to the normal group,the other groups established the femoral head necrosis model by liquid nitrogen alternative freezing.The normal group and the model group did not have any intervention during the modeling period,and the Quan Du Zhong group began to receive the Quan Du Zhong by gavage on the day of modeling;Xianlinggubao capsule group was given Xianlinggubao capsule by gavage once a day for 12 consecutive weeks on the day of modeling.The levels of VEGF and bFGF in the blood vessels of each group at the 12th week were compared,and the ratios of BMD,BS/BV,BV/TV,Tb.Th,Tb.N were measured by Micro CT,and the expressions of Bcl-2,Bax,Caspase-3 proteins were detected by immune reaction.Results:1.Compared with the normal group,the level of serum VEGF and bFGF in the model group decreased after 12 weeks of modeling(P<0.05);Compared with the model group,the levels of serum VEGF and bFGF water in the Xianlinggubao capsule group and the Quan Du Zhong capsule group increased on average at the 12th week of modeling,with statistical difference(P<0.05).The level of the Quan Du Zhong capsule group was the highest,followed by the Xianlinggubao capsule group.2.Compared with the normal group,BMD,BS/BV,BV/TV,Tb.Th and Tb.N in the model group were lower,and Tb.SP were higher,the results were statistically significant(P<0.05).Compared with the model group,the BMD,BV/TV,Tb.Th and Tb.N of Xianlinggubao capsule group and the total eucommia capsule group increased,while the BS/BV and Tb.SP decreased(P<0.05).3.The Quan Du Zhong capsule group and Xianlinggubao capsule group could significantly increase the expression of bcl-2 protein in the femoral head of dogs,which was significantly different from the model group(P<0.05).The expression of bax protein in the femoral head of dogs in the Quan Du Zhong capsule group and the Xianlinggubao capsule group was significantly reduced compared with the model group(P<0.05).The expression of caspase-3 protein in the femoral head of dogs was significantly reduced in the Quan Du Zhong capsule group and Xianlinggubao capsule group,which was significantly different from the model group(P<0.05).Conclusion:Quan Du Zhong capsule can increase the expression of VEGF and bFGF in serum,increase the expression of bcl-2,inhibit the expression of bax,and reduce the expression of caspase-3,which plays a synergistic role in the treatment of avascular necrosis of the femoral head,and has potential targets.

Effects of Different Extracts of Kanggushu(抗骨疏) on Osteoporosis in Model Rats and the Underlying Mechanisms

Objective： To investigate the preventive effects and possible underlying mechanism of different extracts of Kanggushu （抗骨疏） on osteoporosis in ovariectomized rats. Methods： One hundred and sixty- five female SD rats were divided into 11 groups： control, sham, model, Xianling Gubao Capsule （仙灵骨葆胶囊）, nilestriol, Kanggushu aqueous extract high-, medium-, and low-dose and suet extract high-, medium-, and low-dose groups. The osteoporosis model was made by ovariectomizing the rats. The latter 8 groups were administered intragastricly with Xianling Gubao Capsule, nilestriol, Kanggushu aqueous extract and suet extract for 12 weeks, respectively, while the other 3 groups were administered orally saline. The whole body bone mineral density, bone mineral content, organ coefficient of uterus, serum estradiol and alkaline phosphatase contents, blood calcium, phosphorus, interleukin 6 and bone Gla-protein levels after treatment were monitored. Additionally, three-point bending test of femur, HE staining, and scanning electron microscope were performed to explore the pharmacodynamics and underlying mechanisms. Results： In comparison with ovariectomized rats of model group, Kanggushu aqueous extract high-dose resulted in an increased bone mineral density, bone mineral content and organ coefficient of uterus, improved estradiol level, and improved maximum load and structural stiffness （P〈0.05 or P〈0.01）. Two-dimensional and thrae-dimensional trabecular structure was also observed under HE staining and scanning electron microscopy, and the number and thickness of trabecular bone in Kanggushu aqueous extract high-dose group was significantly increased compared to the model group, while the lipid droplets in bone marrow cavity were significantly less. However, there were no significant differences in blood calcium, total serum alkaline phosphatase and bone Gla protein among different treatment groups. Overall, the osteoprotective effects of Kanggushu aqueous extract were comparable to those of nilestriol and were significantly more effective than those of Xianling Gubao Capsule. Conclusion： The preventive effects of Kanggushu aqueous extract might be partly due to the increased estradiol level, accelerated restoration of bone trabecular reticulate structure, and accordingly increased bone mineral density in osteoporosis rats.