Objective To observe the value of grey-level histogram analysis based on T2WI for differentiating consistency of meningioma.Methods Data of 109 patients with meningioma were retrospectively analyzed.The patients were ...Objective To observe the value of grey-level histogram analysis based on T2WI for differentiating consistency of meningioma.Methods Data of 109 patients with meningioma were retrospectively analyzed.The patients were divided into hard group(n=71)and soft group(n=38)according to the consistency of tumors.Tumor ROI was outlined on axial T2WI showing the largest tumor section,gray levels were extracted and histogram analysis was performed.The value of each histogram parameter were compared between groups.Then receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficiency for differentiating soft and hard meningioma.Results P 1,P 10,P 50,P 90,P 99 and the mean grey levels on T2WI in soft group were all higher than those in hard group(all P<0.05),while the variance,the kurtosis and the skewness were not significantly different between groups(all P>0.05).The differentiating efficiency of P 1,P 10,P 50,P 90,P 99 and the mean grey levels on T2WI were all fine,with AUC of 0.774 to 0.833,and no significant difference was found(all P>0.05).Conclusion Parameters of grey-level histogram analysis such as P 1,P 10,P 50,P 90,P 99 and the mean values based on T2WI were all valuable for differentiating soft and hard meningioma.展开更多
Dual-layer spectral detector CT is a new spectrum CT imaging technology based on detector being able to obtain both images similar to true plain and spectral images in one time scanning.The reconstructed multi-paramet...Dual-layer spectral detector CT is a new spectrum CT imaging technology based on detector being able to obtain both images similar to true plain and spectral images in one time scanning.The reconstructed multi-parameter spectral images can not only improve image quality,enhance tissue contrast,increase the visualization and detection ability of occult lesions,but also provide qualitative and quantitative analysis of the lesions,so as to provide more imaging information and multi-dimensional diagnostic basis.The research progresses of dual-layer spectral detector CT for preoperative evaluation on colorectal cancer were reviewed in this article.展开更多
Objective To explore the correlations of transcranial sonography of substantia nigra(SN-TCS)characteristics with MRI iron deposition on substantia nigra in patients with Parkinson disease(PD).Methods Data of SN-TCS an...Objective To explore the correlations of transcranial sonography of substantia nigra(SN-TCS)characteristics with MRI iron deposition on substantia nigra in patients with Parkinson disease(PD).Methods Data of SN-TCS and craniocerebral MRI in 120 PD patients were retrospectively analyzed.The patients were divided into iron deposition positive group(positive group,n=46)and iron deposition negative group(negative group,n=74)according to quantitative susceptibility mapping(QSM)value.Then parameters of SN-TCS and MRI were compared between groups(both P<0.05),and correlation analysis were also performed.Results The proportion of high echo positive,strong echo area and QSM value of substantia nigra,as well as of hyper-substantia nigra area/midbrain area(S/M)in positive group were all higher than those in negative group(all P<0.001).No significant difference of midbrain area was found between groups(P>0.05).Strong echo area of substantia nigra and S/M based on SN-TCS were both low-medium positively correlated with substantia nigra QSM value showed on MRI(r=0.497,0.529,both P<0.001).Conclusion SN-TCS characteristics of PD patients were correlated with MRI iron deposition on substantia nigra,among which strong echo area and S/M were valuable for evaluating iron deposition on substantia nigra.展开更多
In the present study, we aimed to investigate the underlying mechanism of acetaminophen(APAP)-induced hepatotoxicity by measuring the expression levels of liver transporters and concentrations of bile acids(BAs) i...In the present study, we aimed to investigate the underlying mechanism of acetaminophen(APAP)-induced hepatotoxicity by measuring the expression levels of liver transporters and concentrations of bile acids(BAs) in rat plasma and liver. SD rats(42) were randomly assigned into six groups, including 6-h control group, APAP 6-h group, 12-h control group, APAP 12-h group, 24-h control group and APAP 24-h group. The estimation study of BAs in plasma and liver was performed on LC-MS/MS. The levels of bile salt export pump(Bsep), multidrug resistant protein 2(Mrp2), multidrug resistant protein 4(Mrp4), Na+/taurocholate cotransporting polypeptide(Ntcp) and organic anion transporting polypeptide 2(Oatp2) in the liver were analyzed by Western blotting analysis. Compared with the corresponding control groups, no difference was found in the BA levels and the expressions of BA transporters in the plasma and liver after 6 h of APAP administration. While BA levels were significantly decreased in the plasma and increased in the liver after 12 h of APAP administration(P0.05); and the expressions of Bsep and Mrp2 were significantly reduced(P0.05). After 24 h of APAP administration, BA levels were both greatly increased in the plasma and liver(P0.05); and the expressions of Mrp4 and Oatp2 were significantly decreased(P0.05). In response to over-dose APAP, Bsep, Mrp2, Mrp4 and Oatp2 levels were reduced at different time points, causing the accumulation of BAs, and such accumulation may ultimately lead to the severe liver injury, which could be an underlying mechanism of the APAP-induced hepatotoxicity.展开更多
Quercetin, a phenolic phytochemical widely present in vegetables and fruits, has antioxidant, anti-inflammatory, antiviral, and immunomodulatory activities, and it has been successfully used in the treatment of acute ...Quercetin, a phenolic phytochemical widely present in vegetables and fruits, has antioxidant, anti-inflammatory, antiviral, and immunomodulatory activities, and it has been successfully used in the treatment of acute and chronic diseases. In the present study, we aimed to investigate the alleviation effect of quercetin on rat liver fibrosis and explore its mechanism of action. Healthy male SD rats were randomly divided into the normal group, model group, and quercetin group, with six rats in each group. Liver fibrosis was induced by intraperitoneal injection of 1 m L/kg carbon tetrachloride(50% v/v in olive oil) twice a week for 6 weeks, and quercetin(100 mg/kg/d) was administered orally in the 7th week until the end of the 12th week. Blood and liver samples were collected at 1 h after the last administration. Serum liver function parameters(AST, ALT, ALP, GGT, and TBA) were detected by an automatic biochemical analyzer. H&E, Masson, and Sirius red staining were used to observe the pathological morphology of liver tissue. Western blotting analysis was used to evaluate the expressions of liver fibrotic factors(TGF-β1, α-SMA, MMP2, and MMP9) and bile acid-related regulatory proteins(FXR, CYP7A1, CYP8B1, and CYP27A1). The oxidative stress markers(GSH, GSH-Px, GR, SOD, and MDA) in the liver tissue were detected using corresponding kits. The contents of bile acids in the liver tissue were determined by LC-MS/MS. The results showed that compared with the model group, quercetin treatment could significantly reduce serum AST, ALT, and TBA levels(P < 0.05). The fibrotic liver injury was significantly improved, and the expressions of fibrotic factors TGF-β1, α-SMA, MMP2, and MMP9 were significantly decreased(P < 0.05). Liver GSH, GSH-Px, GR, and SOD levels were significantly increased(P < 0.05), and the MDA level was significantly decreased(P < 0.05). The contents of hepatic bile acids were significantly decreased(P < 0.05), the expression of FXR was significantly increased(P < 0.05), and the expressions of CYP7A1 and CYP8B1 were significantly decreased(P < 0.05). This study suggested that quercetin could effectively alleviate carbon tetrachloride-induced liver fibrosis injury, and its mechanism of action was related to improving the liver’s ability to resist oxidative stress and reducing the expressions of fibrotic factors and bile acid synthesis.展开更多
Sorafenib remains the standard systemic treatment for advanced human hepatocellular carcinoma(HCC).However,the low response rate,high recurrence,and high progression limit the therapeutic efficacy.Therefore,a combinat...Sorafenib remains the standard systemic treatment for advanced human hepatocellular carcinoma(HCC).However,the low response rate,high recurrence,and high progression limit the therapeutic efficacy.Therefore,a combination therapy strategy was advanced to strengthen the antitumor effects of sorafenib.In the present study,we aimed to evaluate whether icaritin could enhance the inhibitory effects of sorafenib on HCC cells and clarify the underlying mechanism.The cell viability was evaluated via MTT assay,and the synergistic inhibitory effects of sorafenib and icaritin were verified by calculating the combination index(CI).Their combined effects on cell proliferation or apoptosis were investigated using colony formation assay and flow cytometry.Mitochondrial membrane potential(MMP)was detected by flow cytometric assay.The protein expressions associated with the apoptotic pathway were determined by Western blotting analysis.The data demonstrated that sorafenib and icaritin exerted synergistic inhibitory effects on cell viability(CI<1).Icaritin enhanced the inhibitory effect of sorafenib on colony formation and sorafenib-induced apoptosis of HCC cells.We discovered a reduced level of antiapoptotic Bcl-2 and an elevated level of proapoptotic protein Bax when the cells were exposed to the combination.The effect of cleaved and activated PARP was also enhanced.Cleaved caspase-9 and cleaved caspase-3 were increased markedly in the combination group.Furthermore,the combination of icaritin and sorafenib significantly increased the loss of MMP compared with the single treatment group and induced the release of cytochrome c from the mitochondria to the cytosol.These findings indicated that icaritin could enhance sorafenib-induced cytotoxicity and trigger sorafenib-induced apoptosis through a mitochondria-dependent pathway.展开更多
Chronic renal failure(CRF)is a type of progressive chronic kidney disease with the alteration of substrates excretion.However,changes in renal excretion pathways remain unclear in CRF.This study aimed to evaluate the ...Chronic renal failure(CRF)is a type of progressive chronic kidney disease with the alteration of substrates excretion.However,changes in renal excretion pathways remain unclear in CRF.This study aimed to evaluate the changes in renal excretion pathways of exogenous and endogenous substrates in CRF rats.Results showed that the levels of cystatin C,creatinine,and urea nitrogen were dramatically increased in the adenine(50 or 100 mg/kg)-induced CRF rats.The levels of rOCT2 were dose-dependently up-regulated by adenine,and rMRP2 and rMATE1 levels were dose-dependently down-regulated,while rMRP4 was induced by adenine(50).Plasma concentrations of metformin,p-aminohippurate,and furosemide in the adenine(100)group were significantly increased compared with the control group.However,plasma concentrations of metformin and p-aminohippurate were slightly changed in the adenine(50)group.Consistently,urinary excretions of metformin and p-aminohippurate were unaffected.In addition,renal N1-methylnicotinamide uptakes were increased in rats treated with adenine,and renal phenyl-β-D-glucuronide and hippuric acid uptakes were induced by adenine(50).These results showed that adenine(100)-induced CRF caused the reduced function of GFR-r OCTs-r MATE1 and GFR-r OAT1/r OAT3-r MRP pathway,and oppositely the renal tubular transport pathways of rOCTs-r MATE1 and rOAT1-MRPs were induced in rats with the treatment of adenine(50).展开更多
Drug-induced liver injury(DILI)is associated with an imbalance in the homeostasis of bile salts(BAs).However,a clear connection between BAs and different types of DILI remains to be established.In the present study,ra...Drug-induced liver injury(DILI)is associated with an imbalance in the homeostasis of bile salts(BAs).However,a clear connection between BAs and different types of DILI remains to be established.In the present study,random forest(RF)machine learning prediction systems were deployed with 17 individual BAs for categorizing DILI.BAs were analyzed via LC-MS/MS in the serum using the model of seven known hepatotoxins(isoniazid,acetaminophen,bendazac,17α-ethinylestradiol,1-naphthylisothiocyanate,tetracycline,and ticlopidine),which caused cholestasis,steatosis,and necrosis in rats.The RF model was validated via leave-one-out cross-validation.The importance of each individual BA with respect to prediction ability was determined.The RF model achieved the best prediction performance,producing accuracy values of 0.98,0.97,and 1.00 for leave-one-out cross-validation,the training set,and the external test set,respectively.The order of descriptor‟s importance was obtained,which was TUDCA>GUDCA>TCA>THDCA.The specificity values for necrosis,cholestasis,and steatosis were 0.94,1.00,and 1.00,respectively.The results indicated the potential value of individual BA level in serum for categorizing DILI.The RF model in the present work was an inexpensive and readily available tool for categorizing DILI.展开更多
In the present study,we aimed to ascertain the metabolic detoxification routes of genipin via CYP3A4,SULT2 A1,and UGT1 A1 in Hepa RG cells.It was found that the hepatic CYP3A4,SULT2 A1,and UGT1 A1 synergistically medi...In the present study,we aimed to ascertain the metabolic detoxification routes of genipin via CYP3A4,SULT2 A1,and UGT1 A1 in Hepa RG cells.It was found that the hepatic CYP3A4,SULT2 A1,and UGT1 A1 synergistically mediated the metabolic detoxification of genipin,and the CYP3A4 was the limited enzyme.In detail,the pivotal detoxification pathway was CYP3A4-SULT2 A1/UGT1 A1,indicating that SULT2 A1 and UGT1 A1 further catalyzed the phase II detoxification metabolism followed by the genipin metabolization by CYP3A4 to the phase I metabolites with alleviated toxicity.Our findings provided valuable cues for future studies on the detoxification of genipin,even the compatibility detoxification of Zhi-zi.Moreover,these data facilitated the development and rational administration of genipin and Zhi-zi.展开更多
文摘Objective To observe the value of grey-level histogram analysis based on T2WI for differentiating consistency of meningioma.Methods Data of 109 patients with meningioma were retrospectively analyzed.The patients were divided into hard group(n=71)and soft group(n=38)according to the consistency of tumors.Tumor ROI was outlined on axial T2WI showing the largest tumor section,gray levels were extracted and histogram analysis was performed.The value of each histogram parameter were compared between groups.Then receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficiency for differentiating soft and hard meningioma.Results P 1,P 10,P 50,P 90,P 99 and the mean grey levels on T2WI in soft group were all higher than those in hard group(all P<0.05),while the variance,the kurtosis and the skewness were not significantly different between groups(all P>0.05).The differentiating efficiency of P 1,P 10,P 50,P 90,P 99 and the mean grey levels on T2WI were all fine,with AUC of 0.774 to 0.833,and no significant difference was found(all P>0.05).Conclusion Parameters of grey-level histogram analysis such as P 1,P 10,P 50,P 90,P 99 and the mean values based on T2WI were all valuable for differentiating soft and hard meningioma.
文摘Dual-layer spectral detector CT is a new spectrum CT imaging technology based on detector being able to obtain both images similar to true plain and spectral images in one time scanning.The reconstructed multi-parameter spectral images can not only improve image quality,enhance tissue contrast,increase the visualization and detection ability of occult lesions,but also provide qualitative and quantitative analysis of the lesions,so as to provide more imaging information and multi-dimensional diagnostic basis.The research progresses of dual-layer spectral detector CT for preoperative evaluation on colorectal cancer were reviewed in this article.
文摘Objective To explore the correlations of transcranial sonography of substantia nigra(SN-TCS)characteristics with MRI iron deposition on substantia nigra in patients with Parkinson disease(PD).Methods Data of SN-TCS and craniocerebral MRI in 120 PD patients were retrospectively analyzed.The patients were divided into iron deposition positive group(positive group,n=46)and iron deposition negative group(negative group,n=74)according to quantitative susceptibility mapping(QSM)value.Then parameters of SN-TCS and MRI were compared between groups(both P<0.05),and correlation analysis were also performed.Results The proportion of high echo positive,strong echo area and QSM value of substantia nigra,as well as of hyper-substantia nigra area/midbrain area(S/M)in positive group were all higher than those in negative group(all P<0.001).No significant difference of midbrain area was found between groups(P>0.05).Strong echo area of substantia nigra and S/M based on SN-TCS were both low-medium positively correlated with substantia nigra QSM value showed on MRI(r=0.497,0.529,both P<0.001).Conclusion SN-TCS characteristics of PD patients were correlated with MRI iron deposition on substantia nigra,among which strong echo area and S/M were valuable for evaluating iron deposition on substantia nigra.
基金The National Natural Science Foundation of China(Grant No.81373494 and 81041086)Tianqing Liver Disease Rearch Fund(Grant No.TQGB20180088)
文摘In the present study, we aimed to investigate the underlying mechanism of acetaminophen(APAP)-induced hepatotoxicity by measuring the expression levels of liver transporters and concentrations of bile acids(BAs) in rat plasma and liver. SD rats(42) were randomly assigned into six groups, including 6-h control group, APAP 6-h group, 12-h control group, APAP 12-h group, 24-h control group and APAP 24-h group. The estimation study of BAs in plasma and liver was performed on LC-MS/MS. The levels of bile salt export pump(Bsep), multidrug resistant protein 2(Mrp2), multidrug resistant protein 4(Mrp4), Na+/taurocholate cotransporting polypeptide(Ntcp) and organic anion transporting polypeptide 2(Oatp2) in the liver were analyzed by Western blotting analysis. Compared with the corresponding control groups, no difference was found in the BA levels and the expressions of BA transporters in the plasma and liver after 6 h of APAP administration. While BA levels were significantly decreased in the plasma and increased in the liver after 12 h of APAP administration(P0.05); and the expressions of Bsep and Mrp2 were significantly reduced(P0.05). After 24 h of APAP administration, BA levels were both greatly increased in the plasma and liver(P0.05); and the expressions of Mrp4 and Oatp2 were significantly decreased(P0.05). In response to over-dose APAP, Bsep, Mrp2, Mrp4 and Oatp2 levels were reduced at different time points, causing the accumulation of BAs, and such accumulation may ultimately lead to the severe liver injury, which could be an underlying mechanism of the APAP-induced hepatotoxicity.
基金Natural Science Foundations of China (Grant No. 81960680)Lanzhou Chengguan District Science and Technology Project (Grant No. 2019RCCX0039)Intra-hospital Fund of the First Hospital of Lanzhou University (Grant No. ldyyyn2018-10),China。
文摘Quercetin, a phenolic phytochemical widely present in vegetables and fruits, has antioxidant, anti-inflammatory, antiviral, and immunomodulatory activities, and it has been successfully used in the treatment of acute and chronic diseases. In the present study, we aimed to investigate the alleviation effect of quercetin on rat liver fibrosis and explore its mechanism of action. Healthy male SD rats were randomly divided into the normal group, model group, and quercetin group, with six rats in each group. Liver fibrosis was induced by intraperitoneal injection of 1 m L/kg carbon tetrachloride(50% v/v in olive oil) twice a week for 6 weeks, and quercetin(100 mg/kg/d) was administered orally in the 7th week until the end of the 12th week. Blood and liver samples were collected at 1 h after the last administration. Serum liver function parameters(AST, ALT, ALP, GGT, and TBA) were detected by an automatic biochemical analyzer. H&E, Masson, and Sirius red staining were used to observe the pathological morphology of liver tissue. Western blotting analysis was used to evaluate the expressions of liver fibrotic factors(TGF-β1, α-SMA, MMP2, and MMP9) and bile acid-related regulatory proteins(FXR, CYP7A1, CYP8B1, and CYP27A1). The oxidative stress markers(GSH, GSH-Px, GR, SOD, and MDA) in the liver tissue were detected using corresponding kits. The contents of bile acids in the liver tissue were determined by LC-MS/MS. The results showed that compared with the model group, quercetin treatment could significantly reduce serum AST, ALT, and TBA levels(P < 0.05). The fibrotic liver injury was significantly improved, and the expressions of fibrotic factors TGF-β1, α-SMA, MMP2, and MMP9 were significantly decreased(P < 0.05). Liver GSH, GSH-Px, GR, and SOD levels were significantly increased(P < 0.05), and the MDA level was significantly decreased(P < 0.05). The contents of hepatic bile acids were significantly decreased(P < 0.05), the expression of FXR was significantly increased(P < 0.05), and the expressions of CYP7A1 and CYP8B1 were significantly decreased(P < 0.05). This study suggested that quercetin could effectively alleviate carbon tetrachloride-induced liver fibrosis injury, and its mechanism of action was related to improving the liver’s ability to resist oxidative stress and reducing the expressions of fibrotic factors and bile acid synthesis.
文摘Sorafenib remains the standard systemic treatment for advanced human hepatocellular carcinoma(HCC).However,the low response rate,high recurrence,and high progression limit the therapeutic efficacy.Therefore,a combination therapy strategy was advanced to strengthen the antitumor effects of sorafenib.In the present study,we aimed to evaluate whether icaritin could enhance the inhibitory effects of sorafenib on HCC cells and clarify the underlying mechanism.The cell viability was evaluated via MTT assay,and the synergistic inhibitory effects of sorafenib and icaritin were verified by calculating the combination index(CI).Their combined effects on cell proliferation or apoptosis were investigated using colony formation assay and flow cytometry.Mitochondrial membrane potential(MMP)was detected by flow cytometric assay.The protein expressions associated with the apoptotic pathway were determined by Western blotting analysis.The data demonstrated that sorafenib and icaritin exerted synergistic inhibitory effects on cell viability(CI<1).Icaritin enhanced the inhibitory effect of sorafenib on colony formation and sorafenib-induced apoptosis of HCC cells.We discovered a reduced level of antiapoptotic Bcl-2 and an elevated level of proapoptotic protein Bax when the cells were exposed to the combination.The effect of cleaved and activated PARP was also enhanced.Cleaved caspase-9 and cleaved caspase-3 were increased markedly in the combination group.Furthermore,the combination of icaritin and sorafenib significantly increased the loss of MMP compared with the single treatment group and induced the release of cytochrome c from the mitochondria to the cytosol.These findings indicated that icaritin could enhance sorafenib-induced cytotoxicity and trigger sorafenib-induced apoptosis through a mitochondria-dependent pathway.
基金The National Natural Science Foundation of China(Grant No.81803611)Innovation and Entrepreneurship Project of the First Clinical Medical College of Lanzhou University(Grant No.20190060133)。
文摘Chronic renal failure(CRF)is a type of progressive chronic kidney disease with the alteration of substrates excretion.However,changes in renal excretion pathways remain unclear in CRF.This study aimed to evaluate the changes in renal excretion pathways of exogenous and endogenous substrates in CRF rats.Results showed that the levels of cystatin C,creatinine,and urea nitrogen were dramatically increased in the adenine(50 or 100 mg/kg)-induced CRF rats.The levels of rOCT2 were dose-dependently up-regulated by adenine,and rMRP2 and rMATE1 levels were dose-dependently down-regulated,while rMRP4 was induced by adenine(50).Plasma concentrations of metformin,p-aminohippurate,and furosemide in the adenine(100)group were significantly increased compared with the control group.However,plasma concentrations of metformin and p-aminohippurate were slightly changed in the adenine(50)group.Consistently,urinary excretions of metformin and p-aminohippurate were unaffected.In addition,renal N1-methylnicotinamide uptakes were increased in rats treated with adenine,and renal phenyl-β-D-glucuronide and hippuric acid uptakes were induced by adenine(50).These results showed that adenine(100)-induced CRF caused the reduced function of GFR-r OCTs-r MATE1 and GFR-r OAT1/r OAT3-r MRP pathway,and oppositely the renal tubular transport pathways of rOCTs-r MATE1 and rOAT1-MRPs were induced in rats with the treatment of adenine(50).
基金supported by the Research Foundation of Education Bureau of Gansu Province,China(Grant No.2020B-013)the Foundation of the First Hospital Lanzhou University(Grant No.ldyyyn2018-10)the Engineering Research Centre of Prevention and Control for Clinical Medication Risk,Gansu Province.
文摘Drug-induced liver injury(DILI)is associated with an imbalance in the homeostasis of bile salts(BAs).However,a clear connection between BAs and different types of DILI remains to be established.In the present study,random forest(RF)machine learning prediction systems were deployed with 17 individual BAs for categorizing DILI.BAs were analyzed via LC-MS/MS in the serum using the model of seven known hepatotoxins(isoniazid,acetaminophen,bendazac,17α-ethinylestradiol,1-naphthylisothiocyanate,tetracycline,and ticlopidine),which caused cholestasis,steatosis,and necrosis in rats.The RF model was validated via leave-one-out cross-validation.The importance of each individual BA with respect to prediction ability was determined.The RF model achieved the best prediction performance,producing accuracy values of 0.98,0.97,and 1.00 for leave-one-out cross-validation,the training set,and the external test set,respectively.The order of descriptor‟s importance was obtained,which was TUDCA>GUDCA>TCA>THDCA.The specificity values for necrosis,cholestasis,and steatosis were 0.94,1.00,and 1.00,respectively.The results indicated the potential value of individual BA level in serum for categorizing DILI.The RF model in the present work was an inexpensive and readily available tool for categorizing DILI.
基金National Natural Science Foundation of China(Grant No.82174067,81960646 and 82004080)。
文摘In the present study,we aimed to ascertain the metabolic detoxification routes of genipin via CYP3A4,SULT2 A1,and UGT1 A1 in Hepa RG cells.It was found that the hepatic CYP3A4,SULT2 A1,and UGT1 A1 synergistically mediated the metabolic detoxification of genipin,and the CYP3A4 was the limited enzyme.In detail,the pivotal detoxification pathway was CYP3A4-SULT2 A1/UGT1 A1,indicating that SULT2 A1 and UGT1 A1 further catalyzed the phase II detoxification metabolism followed by the genipin metabolization by CYP3A4 to the phase I metabolites with alleviated toxicity.Our findings provided valuable cues for future studies on the detoxification of genipin,even the compatibility detoxification of Zhi-zi.Moreover,these data facilitated the development and rational administration of genipin and Zhi-zi.