Fructus Psoraleae,which is commonly consumed for the treatment of osteoporosis,bone fracture,and leucoderma,induces liver injury.This study investigated the pathogenesis of the ethanol extract of Fructus Psoraleae(EEF...Fructus Psoraleae,which is commonly consumed for the treatment of osteoporosis,bone fracture,and leucoderma,induces liver injury.This study investigated the pathogenesis of the ethanol extract of Fructus Psoraleae(EEFP)-induced liver injury in rats.EEFP(1.35,1.80,and 2.25 g·kg^–1)was administrated to Sprague Dawley(SD)rats for 30 d.We measured liver chemistries,histopathology,and quantitative isobaric tags for relative and absolute quantitation(iTRAQ)-based protein profiling.EEFP demonstrated parameters suggestive of liver injury with changes in bile secretion,bile flow rate,and liver histopathology.iTRAQ analysis showed that a total of 4042 proteins were expressed in liver tissues of EEFP-treated and untreated rats.Among these proteins,81 were upregulated and 32 were downregulated in the treatment group.KEGG pathway analysis showed that the drug metabolic pathways of cytochrome P450,glutathione metabolism,glycerolipid metabolism,and bile secretion were enriched with differentially expressed proteins.The expression of key proteins related to the farnesoid X receptor(FXR),i.e.,the peroxisome proliferators-activated receptor alpha(PPAR-α),were downregulated,and multidrug resistance-associated protein 3(MRP3)was upregulated in the EEFP-treated rats.Our results provide evidence that EEFP may induce hepatotoxicity through various pathways.Furthermore,our study demonstrates changes in protein regulation using iTRAQ quantitative proteomics analysis.展开更多
Psoraleae Fructus(PF)is an important traditional herbal medicine with a long history of clinical application.It is widely used to treat various diseases,such as osteoporosis,leucoderma and diarrhea.As a traditional no...Psoraleae Fructus(PF)is an important traditional herbal medicine with a long history of clinical application.It is widely used to treat various diseases,such as osteoporosis,leucoderma and diarrhea.As a traditional nontoxic herb,it has aroused worldwide concern about the potential risks due to increasing adverse reaction events.This article reviews the botany,ancient records of medical uses,adverse reactions,toxicological research advance and detoxification methods of PF.According to clinical studies,liver injury is the most predominant in PF-related adverse reactions.The underlying mechanisms include bile acid metabolism and transport disorders,oxidative stress,mitochondrial damage,inhibition of liver cell regeneration and inflammatory reactions.Furthermore,the potential toxins of PF are summarized.Traditional methods of processing and compatibility will provide reference for reducing the toxicity of PF,which requires further research.In sum,this work systematically summarizes the reserach progress on the safety of PF,which will provide comprehensive insights into the toxicity of PF and facilitate its safe use and future development.展开更多
Pancreatic lipase(PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibi...Pancreatic lipase(PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae(FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL(IC50 < 10 μmol·L-1). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate(4-MUO) hydrolysis, with the Ki values of 1.61, 3.77 and 10.16μmol·L-1, respectively. Furthermore, docking simulations indicated that two chalcones(isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors.展开更多
Psoraleae Fructus(the dried fruits of Psoralea corylifolia), one of the most frequently used Chinese herbs in Asian countries, has a variety of biological activities. In clinical settings, Psoraleae Fructus or Psorale...Psoraleae Fructus(the dried fruits of Psoralea corylifolia), one of the most frequently used Chinese herbs in Asian countries, has a variety of biological activities. In clinical settings, Psoraleae Fructus or Psoraleae Fructus-related herbal medicines frequently have been used in combination with a number of therapeutic drugs for the treatment of various human diseases, such as leukoderma, rheumatism and dysentery. The use of Psoraleae Fructus in combination with drugs has aroused concern of the potential risks of herb-drug interactions(HDI) or herb-endobiotic interactions(HEI). This article reviews the interactions between human drug-metabolizing enzymes and the constituents of Psoraleae Fructus;the major constituents in Psoraleae Fructus, along with their chemical structures and metabolic pathways are summarized, and the inhibitory and inductive effects of the constituents in Psoraleae Fructus on human drug-metabolizing enzymes(DMEs), including target enzyme(s), its modulatory potency, and mechanisms of action are presented. Collectively, this review summarizes current knowledge of the interactions between the Chinese herb Psoraleae Fructus and therapeutic drugs in an effort to facilitate its rational use in clinical settings, and especially to avoid the potential risks of HDI or HEI through human DMEs.展开更多
The qualitative and quantitative analysis of active constituents in Fructus Psoraleae is presented by high-performance liquid chromatography(HPLC)coupled with different detections.Extracts of Fructus Psoraleae were ex...The qualitative and quantitative analysis of active constituents in Fructus Psoraleae is presented by high-performance liquid chromatography(HPLC)coupled with different detections.Extracts of Fructus Psoraleae were examined by HPLC with ion trap mass spectrometry(IT-MS)and 18 major compounds of coumarins,benzofuran glycosides,flavonoids,and meroterpene were identified.The determination of four major constituents including bavachin,isobavachalcone,bavachinin,and bakuchiol was accomplished by HPLC with UV,MS,and electrochemical detection(ECD).These methods were evaluated for a number of validation characteristics(repeatability,LOD,calibration range,and recovery).ECD obtained a high sensitivity for analysis of the four components;MS provided a high selectivity and sensitivity for determination of bavachin,isobavachalcone,and bavachinin in negative-ion mode.After optimization of the methods,separation,identification.and quantification of the four components in Fructus Psoraleae were comprehensively tested by HPLC with UV,MS,and ECD.展开更多
A simple, sensitive and selective method of high-performance liquid chromatography （HPLC） has been successfully developed for separation of bavachinin enantiomers in Fructus Psoraleae and rat plasma. The separation ...A simple, sensitive and selective method of high-performance liquid chromatography （HPLC） has been successfully developed for separation of bavachinin enantiomers in Fructus Psoraleae and rat plasma. The separation and detection conditions of HPLC were optimized. Chiral bavachinin were separated with the mobile phase of methanol and water （70：30, v/v） at a flow rate of 1.0 mL/min. The linear ranges were in the range of 20-1000 μg/mL. The detection limits were tested as 4 ng/mL and 6 ng/mL for （＋）-bavachinin and （-）-bavachinin, respectively. The method has been applied to analyze chiral bavachinin in rat plasma. HPLC-MS method was used to test the accuracy.展开更多
AIM： To observe the effect of Fructus Psoraleae on motility of isolated gallbladder muscle strips of guinea pigs and its mechanism. METHODS： Guinea pigs were hit to lose consciousness and the whole gallbladder was r...AIM： To observe the effect of Fructus Psoraleae on motility of isolated gallbladder muscle strips of guinea pigs and its mechanism. METHODS： Guinea pigs were hit to lose consciousness and the whole gallbladder was removed quickly. Two or three smooth muscle strips （8 mm×3mm） were cut along a longitudinal direction. The mucosa was gently removed. Every longitudinal muscle strip was suspended in a tissue chamber which was continuously perfused with 5 mL Krebs solution （37℃）, pH 7.4, and aerated with 950 mL/L 02 and 50 mL/L CO2. The isometric response was recorded with an ink-writing recorder. After 2 h equilibration under i g-load, 50 μL Fructus Psoraleae （10, 20, 70, 200, 700, 1000 g/L） was added cumulatively into the tissue chamber in turn every 2 rain to observe their effects on gallbladder muscle strips （cumulating final concentration of Fructus Psoraleae was 0.1, 0.3, 1.0, 3.0, 10.0, 20.0 g/L）. The antagonists, including 4-DAMP, benzhydramine, hexamethonium, phentolamine, verapamil and idomethine were given 2 min before Fructus Psoraleae respectively to investigate the mechanisms involved. RESULTS： Fructus Psoraleae dose-dependently increased the resting tension （r=0.992, P〈0.001）, decreased the mean contractile amplitude （r=0.970, P〈0.001） and meanwhile increased the contractile frequency of the gallbladder muscle strip in vitro （r=0.965, P〈0.001）. The exciting action of Fructus Psoraleae on the resting tension could be partially blocked by 4-DAMP （the resting tension decreased from 1.37 ± 0.41 to 0.70 ± 0.35, P〈0.001）, benzhydramine （from 1.37 ±0.41 to 0.45±0.38, P〈0.001）, hexamethonium （from 1.37 ± 0.41 to 0.94 ± 0.23, P〈0.05）, phentolamine （ from 1.37±0.41 to 0.89±0.22, P〈0.01） and verapamil （from 1.37±0.41 to 0.94±0.26, P〈0.05）. But the above antagonists had no significant effect on the action of Fructus Psoraleae-induced mean contractile amplitude （P〉0.05）. Moreover, the increase of the contractile frequency due to Fructus Psoraleae was inhibited by 4-DAMP （decreased from 8.3 ± 1.2 to 6.8 ± 0.5, P 〈 0.01） and hexamethonium （from 8.3 ±1.2 to 7.0 ± 0.9, P 〈 0.05）. Idomethine had no significant effect on the Fructus Psoraleae- induced responses （P〉 0.05）. CONCLUSION： Fructus Psoraleae enhances the motility of isolated gallbladder muscle strips from guinea pigs, in a dose-dependent manner. The effect of Fructus Psoraleae is partly related to M3, N receptor, α receptor, H1 receptor, Ca^2＋ channel, but not related to prostaglandin.展开更多
Objective:To study the effect of eucommia and fructus psoraleae treatment on the proliferation of osteoblasts cultured in vitro.Method:1-day-old SD rats were taken, the osteoblasts in exposed bone were separated, cult...Objective:To study the effect of eucommia and fructus psoraleae treatment on the proliferation of osteoblasts cultured in vitro.Method:1-day-old SD rats were taken, the osteoblasts in exposed bone were separated, cultured and divided into 4 groups, group A were treated with DMEM without drugs or serum, group B were treated with serum-free DMEM containing eucommia with final concentration 10 μg/L, group C were treated with serum-free DMEM containing fructus psoraleae with final concentration 10 μmol/L, and group D were treated with serum-free DMEM containing eucommia with final concentration 10 μg/L and fructus psoraleae with final concentration 10 μmol/L. 24 h after treatment, the mRNA expression of apoptosis genes and proliferation genes in cells were detected.Results: Bax, Fas, FasL and HSG mRNA expression in group B, group C and group D were significantly lower than those in group A while c-fos, c-jun, CyclinD1, Egr-1 and NDRG1 mRNA expression were significantly higher than those in group A;Bax, Fas, FasL and HSG mRNA expression in group D were significantly lower than those in group B and group C, and c-fos, c-jun, CyclinD1, Egr-1 and NDRG1 mRNA expression were significantly higher than those in group B and group C.Conclusion: Both eucommia and fructus psoraleae can promote the osteoblast proliferation, and the combination of the two drugs has synergistic effect.展开更多
Objective:Salt-processed Psoraleae Fructus(SPF)is widely used as a phytoestrogen-like agent in the treatment of osteoporosis.However,due to improper clinical use or misuse,resulting in liver damage.In this study,netwo...Objective:Salt-processed Psoraleae Fructus(SPF)is widely used as a phytoestrogen-like agent in the treatment of osteoporosis.However,due to improper clinical use or misuse,resulting in liver damage.In this study,network pharmacology was employed to analyze the mechanism of cholestatic liver damage.An adeno-associated virus overexpressing SULT1E1(rAAV8-SULT1E1)was constructed and the hepatotoxicity of SPF,psoralen,and isopsoralen was determined.Methods:By utilizing three databases inclding TCMSP,TCMID,and BATMAN-TCM,the targets of the three databases were summarized,and a total of 45 psoralen compounds were included.Network pharmacology analysis was then performed.The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo.SPF(10 g/kg),psoralen,and isopsoralen(50 mg/kg each)were intragastrically administered to mice for30 d.B-ultrasound and samples were collected and examined for follow-up experiments.Results:A total of 854 targets were predicted for 45 active components,with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF.A total of 126 pathways were enriched based on KEGG pathway analysis,with the"estrogen signaling pathway"identified as one of the top 20 pathways.In terms of pathological hepatic changes,treated mice had visually swollen hepatocytes,dilated bile ducts,and elevated serum biochemical markers,which were more prominent in mice treated with isopsoralen than in those treated with other compounds.Notably,the overexpression of SULT1E1 could reverse liver damage in each treatment group.B-ultrasound was used to observe the size of the gallbladder in vivo.The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-,psoralen-,and isopsoralen-treated groups,especially the SPF group.Compared with the expression levels in the negative control group(rAAV8-empty+con),the expression levels of FXR,Mrp2,Bsep,SULT1E1,SULT2A1,Ntcp,and Nrf2 decreased,whereas those of CYP7a1 and IL-6 increased in the SPF-,psoralen-,and isopsoralen-treated groups.Conclusion:The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators,indicating that SULT1E1 is an important target gene for SPF-induced liver damage.The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.展开更多
Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zh...Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zhuangguguanjiewan pills(ZGW),which contain EF and PF,could induce immune idiosyncratic liver injury according to clinical case reports and a nonhepatotoxic dose of lipopolysaccharide(LPS)model.This present study evaluated the liver injury induced by EF or PF alone or in combination and investigated the related mechanism by using the LPS model.Liver function indexes and pathological results showed that either EF or PF alone or in combination led to liver injury in normal rats;however,EF or PF alone could lead to liver injury in LPS-treated rats.Moreover,EF combined with PF could induce a greater degree of injury than that caused by EF or PF alone in LPS-treated rats.Furthermore,EF or PF alone or in combination enhanced the LPS-stimulated inflammatory cytokine production,implying that IL-1β,which is processed and released by activating the NLRP3 inflammasome,is a specific indicator of EF-induced immune idiosyncratic hepatotoxicity.Thus,EF may induce liver injury through enhancing the LPS-mediated proinflammatory cytokine production and activating the NLRP3 inflammasome.In addition,the metabolomics analysis results showed that PF affected more metabolites in glycerophospholipid and sphingolipid metabolic pathways compared with EF in LPS model,suggesting that PF increased the responsiveness of the liver to LPS or other inflammatory mediators via modulation of multiple metabolic pathways.Therefore,EF and PF combination indicates traditional Chinese medicine incompatibility,considering that it induces idiosyncratic hepatotoxicity under immunological stress conditions.展开更多
Objective To analyze clinical feature and information of medication to explore the risk signals of preparations containing Psoraleae Fructus(BGZP)related with hepatobiliary adverse drug reactions(ADR),in order to rein...Objective To analyze clinical feature and information of medication to explore the risk signals of preparations containing Psoraleae Fructus(BGZP)related with hepatobiliary adverse drug reactions(ADR),in order to reinforce pharmacovigilance.Methods A retrospective study was conducted based on hepatobiliary ADR related with BGZP from the China Adverse Drug Reaction Monitoring System in years from January 2012 to December 2016.Serious and general ADRs were analyzed and assessed.Results There were 355 cases of hepatobiliary ADR related to BGZP.Both the amount of cases and the proportion of serious ADR showed an increasing growth by years(P<0.05).It was found that 10.43%of 355 cases may be involved with irrational drug use,including overdose,repeated medication,and combination of multiple drugs.There were 190 cases which used BGZP(non-combination),and they were mainly for common in diseases caused by abnormal immune activation(accounting for 40.53%of the total cases).Especially at the age group with the most cases with age of 41–50 years,the cases associated with immunological diseases of female were obviously more than that of male(P<0.05).The latency of hepatobiliary ADR related to BGZP ranged from 1 to 386 days,and the median latency was 27.5 days,along with the range of cumulative dose(0.45–520.02 g)as well as the daily dose(0.09–2.64 g/d)after the conversion.Conclusions Cases of hepatobiliary ADR related to BGZP showed significant individual differences,and there was no correlation between drug usage duration and dosage and the occurrence of hepatobiliary ADR.It may be similar with idiosyncratic drug-induced liver injury,and recommended that BGZP should be used with more caution under monitoring liver function,especially in female patients with immunological diseases.展开更多
Objective To evaluate the quality of Psoralea corylifolia collected from 12 provinces of China.Methods An HPLC-DAD-MS/MS method was used to identify,determine,and estimate 14 representative bioactive compounds in P.co...Objective To evaluate the quality of Psoralea corylifolia collected from 12 provinces of China.Methods An HPLC-DAD-MS/MS method was used to identify,determine,and estimate 14 representative bioactive compounds in P.corylifolia.Then on the basis of the content data,the chemometrics method was used to differentiate 20 samples from different regions.Results The quality of P.corylifolia from 12 different provinces of China was evaluated by this method.Though the samples showed similar profiles,content of the detected markers varied significantly in different regions and batches.According to the results of the hierarchical cluster analysis and principle component analysis,it can be concluded that the samples from different origins could be clustered reasonably into two groups,as well as successfully distinguished.Conclusion A simple and reliable new method which used HPLC-DAD-MS/MS and chemometrics has been developed to characterize,classify,and control the quality of P.corylifolia.展开更多
Objective To find direct effect of Chinese herbs Bu Gu Zhi (Psoralea corylifolia L) and Bai Zhi (Dahurian angelica root) Extracts on melanocyte adhesion and migration in vitro. Methods Ethanol extracts obtained from t...Objective To find direct effect of Chinese herbs Bu Gu Zhi (Psoralea corylifolia L) and Bai Zhi (Dahurian angelica root) Extracts on melanocyte adhesion and migration in vitro. Methods Ethanol extracts obtained from two kind of Chinese medicinable herbs were tested. Human melanocytes were obtained from neonatal foreskins and 48-well culture dish covered with fibronectin were used to perform melanocyte adhesion assay; Motility was assessed using the micropore filter method. Results: The extracts of Bu Gu Zhi(Psoralea corylifolia L), Bai Zhi(Dahurian angelica root) obviously showed an effect in increasing of human melanocyte adhesion and migration on fibronectin. Conclusion It is suggested that Buguzhi(Fructus Psoraleae) and Baizhi(Radix Angelicae Dahuricae) might induce melanocyte adhesion and/or migration in the treatment of vitiligo.展开更多
Background:Psoralea corylifolia L.(Buguzhi,BGZ),known for its efficacy in supporting pregnancy and preventing miscarriage,has been used in China for over 1000 years.Recently,BGZ has been identified as a potential caus...Background:Psoralea corylifolia L.(Buguzhi,BGZ),known for its efficacy in supporting pregnancy and preventing miscarriage,has been used in China for over 1000 years.Recently,BGZ has been identified as a potential cause of drug-induced liver injury.However,its safety during pregnancy remains unclear,which significantly hinders its routine clinical application.Objective:To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring.Methods:Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy,with BGZ withdrawal during the lactation period.Liver histopathology(hematoxylin-eosin staining),biochemical analysis,and evaluation of liver bile acid metabolism were per-formed after the lactation period.Results:BGZ administration at doses of 2.5 and 10 g/kg during pregnancy,followed by withdrawal during the lactation period,caused mild liver damage in both mothers and their 21-day-old offspring.Serum total bile acid(TBA)levels were elevated compared with those in the control group.Additionally,changes were observed in the levels and proportions of various bile acids(BAs)in the liver,suggesting mild effects on BA metabolism.Conclusion:BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring.This phenomenon may be associated with imbalanced BA metabolism in the liver.Based on the present study and the limited toxicological research on BGZ,pregnant women should avoid prolonged use of BGZ.If BGZ is administered dur-ing pregnancy,serum TBA levels should be monitored,and if elevated,BGZ should be discontinued.展开更多
Psoraleae Fructus(PF)is a well-known traditional herbal medicine in China,and it is widely used for osteoporosis,vitiligo,and other diseases in clinical settings.However,liver injury caused by PF and its preparations ...Psoraleae Fructus(PF)is a well-known traditional herbal medicine in China,and it is widely used for osteoporosis,vitiligo,and other diseases in clinical settings.However,liver injury caused by PF and its preparations has been frequently reported in recent years.Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury(IDILI),but the mechanism underlying its hepatotoxicity remains unclear.This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity.Bavachin boosts the secretion of IL-ip and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C),monosodium urate crystal,or intracellular lipopolysaccharide.Bavachin does not affect AIM2 or NLRC4 inflammasome activation.Mechanistically,bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome.Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-ip via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI.These results suggest that bavachin specifically enhances the ATP-or nigericin-induced activation of the NLRP3 inflammasome.Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity.Moreover,bavachin and PF should be evaded among patients with diseases linked to the ATP-or nigericin-mediated activation of the NLRP3 inflammasome,which may be a dangerous factor for liver injury.展开更多
Objective:The compatibility of Eucommia ulmoides(Eu)and Psoralea corylifolia(Pc)on the pharmacokinetic(PK)properties in the rat was explored in this study.Methods:Eu extract,Pc extract and the combined extracts(crude ...Objective:The compatibility of Eucommia ulmoides(Eu)and Psoralea corylifolia(Pc)on the pharmacokinetic(PK)properties in the rat was explored in this study.Methods:Eu extract,Pc extract and the combined extracts(crude drug ratio was 2:1)was administered by gavage,respectively.Two PK experiments were conducted.In first one,the blood samples were collected via the occuli chorioideae vein to get the PK properties of the components.In second one,the blood samples were simultaneously collected via the internal jugular vein or portal vein at different time points and the concentrations of target ingredients were detected by LC/MS/MS to clear the location where the interaction of Eu and Pc took place in vivo.Results:Eight of 11 ingredients in Eu and Pc extract were determined in rat plasma.The exposure levels of geniposidic acid(GPA),aucubin(AU),geniposide(GP),pinoresinol diglucoside(PDG),psoralen glycosides(PLG)and isopsoralen glycosides(IPLG)were decreased 1/5–2/3 after administration of combined extracts.Comparing to the combined administration,the exposure of GPA and AU in plasma of single Eu administration collected via the portal vein were decreased 1/3–2/3,and the values of AUC0-24h and AUC0-∞ of GP collected from the portal vein or internal jugular vein were double increased.The other components’parameters were not significantly changed.Conclusion:In summary,the Pc and Eu combined administration could affect the exposure of the main components of Eu extract in rats due to the changed intestinal absorption.The research on the compatibility of Pc and Eu was helpful to guide the clinical administration of Eu and Pc simultaneously.展开更多
Psoralea corylifolia L.(PCL)is widely used in clinical practice and is commonly used in the treatment of osteoporosis,tumors,and dermatosis.However,in recent years,adverse reactions of PCL and its related preparations...Psoralea corylifolia L.(PCL)is widely used in clinical practice and is commonly used in the treatment of osteoporosis,tumors,and dermatosis.However,in recent years,adverse reactions of PCL and its related preparations have been frequently reported,and there are even case reports of acute liver injury caused by taking PCL alone,which seriously affects the safe and rational clinical application of PCL.In this paper,the main chemical components,pharmacology,and toxicology of PCL are analyzed and summarized,and the effect-toxicity relationship of PCL and its main active components are sorted out and compared.On this basis,the active components of PCL for treating osteoporosis and causing hepatotoxicity are further systematically compared and summarized,to clarify its effect-toxicity relationship,reduce the toxicity risk of PCL,increase the benefit/risk ratio and provide evidence for the safe clinical application of PCL.展开更多
Background:Mining new whitening ingredients from plants is an effective way to develop new cosmetic products.Bakuchiol,as one of the main active ingredients from the seeds of Psoralea corylifolia L,displays whitening,...Background:Mining new whitening ingredients from plants is an effective way to develop new cosmetic products.Bakuchiol,as one of the main active ingredients from the seeds of Psoralea corylifolia L,displays whitening,antioxidant,antiaging,and free radical-scavenging activities and attracts wide attention especially in the cosmetics industry.However,environmentally friendly extraction technologies with high efficiency and high product purity remain to be developed for the scale production of bakuchiol.Objective:In this study,a new approach(acetic acid–steaming–assisted technique)was developed to improve the extraction efficiency of bakuchiol.Methods:The factors influencing the extraction efficiency of bakuchiol,including seed powder granularity,acetic acid volume,temperature,and time,were optimized based on single-factor experiments.Results:The extraction conditions were optimized as steaming the seed powder(100 g)of 40–100meshes with acetic acid(50 mL)for 10 minutes,from which a crude extract(25.1 g)containing bakuchiol was obtained.High purity(99.1)of bakuchiol(6.02 g)was then prepared by silica gel column chromatography in a one-step process.The method established in this study had higher extraction rate than other methods.The antioxidant potential of bakuchiol was evaluated based on the ABTS free radical scavenging activity and ferric reducing antioxidant power.Furthermore,bakuchiol demonstrated stronger tyrosinase inhibitory activity than the positive control(arbutin).Conclusions:Compared with the available methods,the method established in this study has increased extraction rate of bakuchiol and is environmentally friendly and economical,demonstrating the potential for industrial production.展开更多
基金supported by the the National Key Research and Development Program, Specialized Research on Modernization of TCM (Nos. 2018YFC1708006 and 2018YFC1708003)National Major New Drug Creation Special Project “National Drug New Varieties Research and Development and Its Key Innovative Technology Topics” (No. 2017ZX09301060-005)+3 种基金the National Natural Science Foundation of China (No. 81320108029)Tianshan Cedar Plan (No. 2018XS21)National “Major Scientific and Technological Special Project for Significant New Drugs Creation” Project (No. 2015ZX09501004-002-004)Specific Fund for Pub-lic Interest Research of Traditional Chinese Medicine, Ministry of Finance of China (No. 201507004-002)。
文摘Fructus Psoraleae,which is commonly consumed for the treatment of osteoporosis,bone fracture,and leucoderma,induces liver injury.This study investigated the pathogenesis of the ethanol extract of Fructus Psoraleae(EEFP)-induced liver injury in rats.EEFP(1.35,1.80,and 2.25 g·kg^–1)was administrated to Sprague Dawley(SD)rats for 30 d.We measured liver chemistries,histopathology,and quantitative isobaric tags for relative and absolute quantitation(iTRAQ)-based protein profiling.EEFP demonstrated parameters suggestive of liver injury with changes in bile secretion,bile flow rate,and liver histopathology.iTRAQ analysis showed that a total of 4042 proteins were expressed in liver tissues of EEFP-treated and untreated rats.Among these proteins,81 were upregulated and 32 were downregulated in the treatment group.KEGG pathway analysis showed that the drug metabolic pathways of cytochrome P450,glutathione metabolism,glycerolipid metabolism,and bile secretion were enriched with differentially expressed proteins.The expression of key proteins related to the farnesoid X receptor(FXR),i.e.,the peroxisome proliferators-activated receptor alpha(PPAR-α),were downregulated,and multidrug resistance-associated protein 3(MRP3)was upregulated in the EEFP-treated rats.Our results provide evidence that EEFP may induce hepatotoxicity through various pathways.Furthermore,our study demonstrates changes in protein regulation using iTRAQ quantitative proteomics analysis.
基金supported by the Major Program of National Natural Science Foundation of China(Nos.82192910 and 82192911).
文摘Psoraleae Fructus(PF)is an important traditional herbal medicine with a long history of clinical application.It is widely used to treat various diseases,such as osteoporosis,leucoderma and diarrhea.As a traditional nontoxic herb,it has aroused worldwide concern about the potential risks due to increasing adverse reaction events.This article reviews the botany,ancient records of medical uses,adverse reactions,toxicological research advance and detoxification methods of PF.According to clinical studies,liver injury is the most predominant in PF-related adverse reactions.The underlying mechanisms include bile acid metabolism and transport disorders,oxidative stress,mitochondrial damage,inhibition of liver cell regeneration and inflammatory reactions.Furthermore,the potential toxins of PF are summarized.Traditional methods of processing and compatibility will provide reference for reducing the toxicity of PF,which requires further research.In sum,this work systematically summarizes the reserach progress on the safety of PF,which will provide comprehensive insights into the toxicity of PF and facilitate its safe use and future development.
基金the National Key Research and Development Program of China (Nos.2017YFC1700200,2017YFC1702000)NSF of China (Nos.81922070, 81973286, 81973393, 81773687)+4 种基金Natural Science Foundation of Liaoning Province (No.20180530025)Program of Shanghai Academic/Technology Research Leader (No. 18XD1403600)Shuguang Program (No. 18SG40) supported by Shanghai Education Development Foundation and Shanghai Municipal Education CommissionInnovative Entrepreneurship Program of High-level Talents in Dalian (No. 2017RQ121)Undergraduate Training Program for Innovation and Entrepreneurship from Shanghai University of Traditional Chinese Medicine (No. 2017101419803010904)。
文摘Pancreatic lipase(PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae(FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL(IC50 < 10 μmol·L-1). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate(4-MUO) hydrolysis, with the Ki values of 1.61, 3.77 and 10.16μmol·L-1, respectively. Furthermore, docking simulations indicated that two chalcones(isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors.
基金supported by the NSF of China(Nos.81922070,81973286,81773687)the National Key Research and Development Program of China(No.2017YFC1700200,2017YFC1702000)+3 种基金Program of Shanghai Academic/Technology Research Leader(No.18XD1403600)Shuguang Program(No.18SG40)Program for applied basic research of Qinghai Provincial Science and Technology Department(No.2017-ZJ-713)Program for Innovative Leading Talents of Qinghai Province(2018&2019)
文摘Psoraleae Fructus(the dried fruits of Psoralea corylifolia), one of the most frequently used Chinese herbs in Asian countries, has a variety of biological activities. In clinical settings, Psoraleae Fructus or Psoraleae Fructus-related herbal medicines frequently have been used in combination with a number of therapeutic drugs for the treatment of various human diseases, such as leukoderma, rheumatism and dysentery. The use of Psoraleae Fructus in combination with drugs has aroused concern of the potential risks of herb-drug interactions(HDI) or herb-endobiotic interactions(HEI). This article reviews the interactions between human drug-metabolizing enzymes and the constituents of Psoraleae Fructus;the major constituents in Psoraleae Fructus, along with their chemical structures and metabolic pathways are summarized, and the inhibitory and inductive effects of the constituents in Psoraleae Fructus on human drug-metabolizing enzymes(DMEs), including target enzyme(s), its modulatory potency, and mechanisms of action are presented. Collectively, this review summarizes current knowledge of the interactions between the Chinese herb Psoraleae Fructus and therapeutic drugs in an effort to facilitate its rational use in clinical settings, and especially to avoid the potential risks of HDI or HEI through human DMEs.
基金supported by the National Mega Project on Major Drug Development(No.2009ZX09301-014-1)the National Scientific Foundation of China(Nos.90817103,20775055,30973672)+1 种基金the start-up funds for ZC’s Luojia chair professorship of Wuhan University(Nos.306276216,306271159)the Fundamental Research Funds for the Central Universities
文摘The qualitative and quantitative analysis of active constituents in Fructus Psoraleae is presented by high-performance liquid chromatography(HPLC)coupled with different detections.Extracts of Fructus Psoraleae were examined by HPLC with ion trap mass spectrometry(IT-MS)and 18 major compounds of coumarins,benzofuran glycosides,flavonoids,and meroterpene were identified.The determination of four major constituents including bavachin,isobavachalcone,bavachinin,and bakuchiol was accomplished by HPLC with UV,MS,and electrochemical detection(ECD).These methods were evaluated for a number of validation characteristics(repeatability,LOD,calibration range,and recovery).ECD obtained a high sensitivity for analysis of the four components;MS provided a high selectivity and sensitivity for determination of bavachin,isobavachalcone,and bavachinin in negative-ion mode.After optimization of the methods,separation,identification.and quantification of the four components in Fructus Psoraleae were comprehensively tested by HPLC with UV,MS,and ECD.
基金supported by the National Scientifc Foundation of China(NSFC nos.9081710330973672 and 20775055)+2 种基金Doctoral Fund of Ministry of Education of China(No 20110141110024)Hubei Provincial Scientifc Foundation(No 2011CDB475)the Fundamental Research Funds for the Central Universities
文摘A simple, sensitive and selective method of high-performance liquid chromatography （HPLC） has been successfully developed for separation of bavachinin enantiomers in Fructus Psoraleae and rat plasma. The separation and detection conditions of HPLC were optimized. Chiral bavachinin were separated with the mobile phase of methanol and water （70：30, v/v） at a flow rate of 1.0 mL/min. The linear ranges were in the range of 20-1000 μg/mL. The detection limits were tested as 4 ng/mL and 6 ng/mL for （＋）-bavachinin and （-）-bavachinin, respectively. The method has been applied to analyze chiral bavachinin in rat plasma. HPLC-MS method was used to test the accuracy.
基金Supported by Key Laboratory of Pre-clinical Study for New Drugs of Gansu Province and the Natural Science Foundation of Gansu Province, No.ZS021-A25-059-Y
文摘AIM： To observe the effect of Fructus Psoraleae on motility of isolated gallbladder muscle strips of guinea pigs and its mechanism. METHODS： Guinea pigs were hit to lose consciousness and the whole gallbladder was removed quickly. Two or three smooth muscle strips （8 mm×3mm） were cut along a longitudinal direction. The mucosa was gently removed. Every longitudinal muscle strip was suspended in a tissue chamber which was continuously perfused with 5 mL Krebs solution （37℃）, pH 7.4, and aerated with 950 mL/L 02 and 50 mL/L CO2. The isometric response was recorded with an ink-writing recorder. After 2 h equilibration under i g-load, 50 μL Fructus Psoraleae （10, 20, 70, 200, 700, 1000 g/L） was added cumulatively into the tissue chamber in turn every 2 rain to observe their effects on gallbladder muscle strips （cumulating final concentration of Fructus Psoraleae was 0.1, 0.3, 1.0, 3.0, 10.0, 20.0 g/L）. The antagonists, including 4-DAMP, benzhydramine, hexamethonium, phentolamine, verapamil and idomethine were given 2 min before Fructus Psoraleae respectively to investigate the mechanisms involved. RESULTS： Fructus Psoraleae dose-dependently increased the resting tension （r=0.992, P〈0.001）, decreased the mean contractile amplitude （r=0.970, P〈0.001） and meanwhile increased the contractile frequency of the gallbladder muscle strip in vitro （r=0.965, P〈0.001）. The exciting action of Fructus Psoraleae on the resting tension could be partially blocked by 4-DAMP （the resting tension decreased from 1.37 ± 0.41 to 0.70 ± 0.35, P〈0.001）, benzhydramine （from 1.37 ±0.41 to 0.45±0.38, P〈0.001）, hexamethonium （from 1.37 ± 0.41 to 0.94 ± 0.23, P〈0.05）, phentolamine （ from 1.37±0.41 to 0.89±0.22, P〈0.01） and verapamil （from 1.37±0.41 to 0.94±0.26, P〈0.05）. But the above antagonists had no significant effect on the action of Fructus Psoraleae-induced mean contractile amplitude （P〉0.05）. Moreover, the increase of the contractile frequency due to Fructus Psoraleae was inhibited by 4-DAMP （decreased from 8.3 ± 1.2 to 6.8 ± 0.5, P 〈 0.01） and hexamethonium （from 8.3 ±1.2 to 7.0 ± 0.9, P 〈 0.05）. Idomethine had no significant effect on the Fructus Psoraleae- induced responses （P〉 0.05）. CONCLUSION： Fructus Psoraleae enhances the motility of isolated gallbladder muscle strips from guinea pigs, in a dose-dependent manner. The effect of Fructus Psoraleae is partly related to M3, N receptor, α receptor, H1 receptor, Ca^2＋ channel, but not related to prostaglandin.
文摘Objective:To study the effect of eucommia and fructus psoraleae treatment on the proliferation of osteoblasts cultured in vitro.Method:1-day-old SD rats were taken, the osteoblasts in exposed bone were separated, cultured and divided into 4 groups, group A were treated with DMEM without drugs or serum, group B were treated with serum-free DMEM containing eucommia with final concentration 10 μg/L, group C were treated with serum-free DMEM containing fructus psoraleae with final concentration 10 μmol/L, and group D were treated with serum-free DMEM containing eucommia with final concentration 10 μg/L and fructus psoraleae with final concentration 10 μmol/L. 24 h after treatment, the mRNA expression of apoptosis genes and proliferation genes in cells were detected.Results: Bax, Fas, FasL and HSG mRNA expression in group B, group C and group D were significantly lower than those in group A while c-fos, c-jun, CyclinD1, Egr-1 and NDRG1 mRNA expression were significantly higher than those in group A;Bax, Fas, FasL and HSG mRNA expression in group D were significantly lower than those in group B and group C, and c-fos, c-jun, CyclinD1, Egr-1 and NDRG1 mRNA expression were significantly higher than those in group B and group C.Conclusion: Both eucommia and fructus psoraleae can promote the osteoblast proliferation, and the combination of the two drugs has synergistic effect.
基金supported by the National Natural Science Foundation of China(81973484 and 82304736)the 2022 Natural Science Foundation of Nanjing University of Chinese Medicine(XZR2021085)。
文摘Objective:Salt-processed Psoraleae Fructus(SPF)is widely used as a phytoestrogen-like agent in the treatment of osteoporosis.However,due to improper clinical use or misuse,resulting in liver damage.In this study,network pharmacology was employed to analyze the mechanism of cholestatic liver damage.An adeno-associated virus overexpressing SULT1E1(rAAV8-SULT1E1)was constructed and the hepatotoxicity of SPF,psoralen,and isopsoralen was determined.Methods:By utilizing three databases inclding TCMSP,TCMID,and BATMAN-TCM,the targets of the three databases were summarized,and a total of 45 psoralen compounds were included.Network pharmacology analysis was then performed.The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo.SPF(10 g/kg),psoralen,and isopsoralen(50 mg/kg each)were intragastrically administered to mice for30 d.B-ultrasound and samples were collected and examined for follow-up experiments.Results:A total of 854 targets were predicted for 45 active components,with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF.A total of 126 pathways were enriched based on KEGG pathway analysis,with the"estrogen signaling pathway"identified as one of the top 20 pathways.In terms of pathological hepatic changes,treated mice had visually swollen hepatocytes,dilated bile ducts,and elevated serum biochemical markers,which were more prominent in mice treated with isopsoralen than in those treated with other compounds.Notably,the overexpression of SULT1E1 could reverse liver damage in each treatment group.B-ultrasound was used to observe the size of the gallbladder in vivo.The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-,psoralen-,and isopsoralen-treated groups,especially the SPF group.Compared with the expression levels in the negative control group(rAAV8-empty+con),the expression levels of FXR,Mrp2,Bsep,SULT1E1,SULT2A1,Ntcp,and Nrf2 decreased,whereas those of CYP7a1 and IL-6 increased in the SPF-,psoralen-,and isopsoralen-treated groups.Conclusion:The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators,indicating that SULT1E1 is an important target gene for SPF-induced liver damage.The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.
基金supported by the National Natural Science Foundation of China(Nos.81874368 and 81630100)the Beijing Nova Program(No.Z181100006218001)+2 种基金the National Key Technology R&D Program(No.2015ZX 09501-004-001-008)the National Key R&D Program of China(No.2018YFC1707000)the National TCM Industry Science and Technology Program(No.201507004-4-2).
文摘Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zhuangguguanjiewan pills(ZGW),which contain EF and PF,could induce immune idiosyncratic liver injury according to clinical case reports and a nonhepatotoxic dose of lipopolysaccharide(LPS)model.This present study evaluated the liver injury induced by EF or PF alone or in combination and investigated the related mechanism by using the LPS model.Liver function indexes and pathological results showed that either EF or PF alone or in combination led to liver injury in normal rats;however,EF or PF alone could lead to liver injury in LPS-treated rats.Moreover,EF combined with PF could induce a greater degree of injury than that caused by EF or PF alone in LPS-treated rats.Furthermore,EF or PF alone or in combination enhanced the LPS-stimulated inflammatory cytokine production,implying that IL-1β,which is processed and released by activating the NLRP3 inflammasome,is a specific indicator of EF-induced immune idiosyncratic hepatotoxicity.Thus,EF may induce liver injury through enhancing the LPS-mediated proinflammatory cytokine production and activating the NLRP3 inflammasome.In addition,the metabolomics analysis results showed that PF affected more metabolites in glycerophospholipid and sphingolipid metabolic pathways compared with EF in LPS model,suggesting that PF increased the responsiveness of the liver to LPS or other inflammatory mediators via modulation of multiple metabolic pathways.Therefore,EF and PF combination indicates traditional Chinese medicine incompatibility,considering that it induces idiosyncratic hepatotoxicity under immunological stress conditions.
基金Supported by the National Natural Science Foundation of China(No.81630100)Beijing Nova Program(No.Z181100006218001)Project of China PLA General Hospital(No.2019MBD-023)。
文摘Objective To analyze clinical feature and information of medication to explore the risk signals of preparations containing Psoraleae Fructus(BGZP)related with hepatobiliary adverse drug reactions(ADR),in order to reinforce pharmacovigilance.Methods A retrospective study was conducted based on hepatobiliary ADR related with BGZP from the China Adverse Drug Reaction Monitoring System in years from January 2012 to December 2016.Serious and general ADRs were analyzed and assessed.Results There were 355 cases of hepatobiliary ADR related to BGZP.Both the amount of cases and the proportion of serious ADR showed an increasing growth by years(P<0.05).It was found that 10.43%of 355 cases may be involved with irrational drug use,including overdose,repeated medication,and combination of multiple drugs.There were 190 cases which used BGZP(non-combination),and they were mainly for common in diseases caused by abnormal immune activation(accounting for 40.53%of the total cases).Especially at the age group with the most cases with age of 41–50 years,the cases associated with immunological diseases of female were obviously more than that of male(P<0.05).The latency of hepatobiliary ADR related to BGZP ranged from 1 to 386 days,and the median latency was 27.5 days,along with the range of cumulative dose(0.45–520.02 g)as well as the daily dose(0.09–2.64 g/d)after the conversion.Conclusions Cases of hepatobiliary ADR related to BGZP showed significant individual differences,and there was no correlation between drug usage duration and dosage and the occurrence of hepatobiliary ADR.It may be similar with idiosyncratic drug-induced liver injury,and recommended that BGZP should be used with more caution under monitoring liver function,especially in female patients with immunological diseases.
基金Ministry of Science and Technology of China(No 973:2005CB523404)
文摘Objective To evaluate the quality of Psoralea corylifolia collected from 12 provinces of China.Methods An HPLC-DAD-MS/MS method was used to identify,determine,and estimate 14 representative bioactive compounds in P.corylifolia.Then on the basis of the content data,the chemometrics method was used to differentiate 20 samples from different regions.Results The quality of P.corylifolia from 12 different provinces of China was evaluated by this method.Though the samples showed similar profiles,content of the detected markers varied significantly in different regions and batches.According to the results of the hierarchical cluster analysis and principle component analysis,it can be concluded that the samples from different origins could be clustered reasonably into two groups,as well as successfully distinguished.Conclusion A simple and reliable new method which used HPLC-DAD-MS/MS and chemometrics has been developed to characterize,classify,and control the quality of P.corylifolia.
文摘Objective To find direct effect of Chinese herbs Bu Gu Zhi (Psoralea corylifolia L) and Bai Zhi (Dahurian angelica root) Extracts on melanocyte adhesion and migration in vitro. Methods Ethanol extracts obtained from two kind of Chinese medicinable herbs were tested. Human melanocytes were obtained from neonatal foreskins and 48-well culture dish covered with fibronectin were used to perform melanocyte adhesion assay; Motility was assessed using the micropore filter method. Results: The extracts of Bu Gu Zhi(Psoralea corylifolia L), Bai Zhi(Dahurian angelica root) obviously showed an effect in increasing of human melanocyte adhesion and migration on fibronectin. Conclusion It is suggested that Buguzhi(Fructus Psoraleae) and Baizhi(Radix Angelicae Dahuricae) might induce melanocyte adhesion and/or migration in the treatment of vitiligo.
基金supported by the National Natural Science Foundation of China(82192913,82174073)the China Academy of Chinese Medical Sciences Innovation Fund(CI2021B016,CI2021A04801)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-040,ZXKT21028).
文摘Background:Psoralea corylifolia L.(Buguzhi,BGZ),known for its efficacy in supporting pregnancy and preventing miscarriage,has been used in China for over 1000 years.Recently,BGZ has been identified as a potential cause of drug-induced liver injury.However,its safety during pregnancy remains unclear,which significantly hinders its routine clinical application.Objective:To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring.Methods:Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy,with BGZ withdrawal during the lactation period.Liver histopathology(hematoxylin-eosin staining),biochemical analysis,and evaluation of liver bile acid metabolism were per-formed after the lactation period.Results:BGZ administration at doses of 2.5 and 10 g/kg during pregnancy,followed by withdrawal during the lactation period,caused mild liver damage in both mothers and their 21-day-old offspring.Serum total bile acid(TBA)levels were elevated compared with those in the control group.Additionally,changes were observed in the levels and proportions of various bile acids(BAs)in the liver,suggesting mild effects on BA metabolism.Conclusion:BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring.This phenomenon may be associated with imbalanced BA metabolism in the liver.Based on the present study and the limited toxicological research on BGZ,pregnant women should avoid prolonged use of BGZ.If BGZ is administered dur-ing pregnancy,serum TBA levels should be monitored,and if elevated,BGZ should be discontinued.
基金This work has been supported by the Beijing Nova Program(No.Z181100006218001)the National Natural Science Foundation of China(Nos.81874368,81630100,81903891,and 81573676)+1 种基金the National Science and Technology Major Project “Key New Drug Creation and Manufacturing Program”(Nos.2017ZX09301022 and 2018ZX09101002-001-002)the Innovation Groups of the National Natural Science Foundation of China(No.81721002).
文摘Psoraleae Fructus(PF)is a well-known traditional herbal medicine in China,and it is widely used for osteoporosis,vitiligo,and other diseases in clinical settings.However,liver injury caused by PF and its preparations has been frequently reported in recent years.Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury(IDILI),but the mechanism underlying its hepatotoxicity remains unclear.This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity.Bavachin boosts the secretion of IL-ip and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C),monosodium urate crystal,or intracellular lipopolysaccharide.Bavachin does not affect AIM2 or NLRC4 inflammasome activation.Mechanistically,bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome.Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-ip via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI.These results suggest that bavachin specifically enhances the ATP-or nigericin-induced activation of the NLRP3 inflammasome.Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity.Moreover,bavachin and PF should be evaded among patients with diseases linked to the ATP-or nigericin-mediated activation of the NLRP3 inflammasome,which may be a dangerous factor for liver injury.
基金This study was funded by Key Program for National Natural Science Foundation of China(No.81630106)National Natural Science Foundation of China(No.81803691).
文摘Objective:The compatibility of Eucommia ulmoides(Eu)and Psoralea corylifolia(Pc)on the pharmacokinetic(PK)properties in the rat was explored in this study.Methods:Eu extract,Pc extract and the combined extracts(crude drug ratio was 2:1)was administered by gavage,respectively.Two PK experiments were conducted.In first one,the blood samples were collected via the occuli chorioideae vein to get the PK properties of the components.In second one,the blood samples were simultaneously collected via the internal jugular vein or portal vein at different time points and the concentrations of target ingredients were detected by LC/MS/MS to clear the location where the interaction of Eu and Pc took place in vivo.Results:Eight of 11 ingredients in Eu and Pc extract were determined in rat plasma.The exposure levels of geniposidic acid(GPA),aucubin(AU),geniposide(GP),pinoresinol diglucoside(PDG),psoralen glycosides(PLG)and isopsoralen glycosides(IPLG)were decreased 1/5–2/3 after administration of combined extracts.Comparing to the combined administration,the exposure of GPA and AU in plasma of single Eu administration collected via the portal vein were decreased 1/3–2/3,and the values of AUC0-24h and AUC0-∞ of GP collected from the portal vein or internal jugular vein were double increased.The other components’parameters were not significantly changed.Conclusion:In summary,the Pc and Eu combined administration could affect the exposure of the main components of Eu extract in rats due to the changed intestinal absorption.The research on the compatibility of Pc and Eu was helpful to guide the clinical administration of Eu and Pc simultaneously.
基金supported by the National Natural Science Foundation of China(No.82004057).
文摘Psoralea corylifolia L.(PCL)is widely used in clinical practice and is commonly used in the treatment of osteoporosis,tumors,and dermatosis.However,in recent years,adverse reactions of PCL and its related preparations have been frequently reported,and there are even case reports of acute liver injury caused by taking PCL alone,which seriously affects the safe and rational clinical application of PCL.In this paper,the main chemical components,pharmacology,and toxicology of PCL are analyzed and summarized,and the effect-toxicity relationship of PCL and its main active components are sorted out and compared.On this basis,the active components of PCL for treating osteoporosis and causing hepatotoxicity are further systematically compared and summarized,to clarify its effect-toxicity relationship,reduce the toxicity risk of PCL,increase the benefit/risk ratio and provide evidence for the safe clinical application of PCL.
文摘Background:Mining new whitening ingredients from plants is an effective way to develop new cosmetic products.Bakuchiol,as one of the main active ingredients from the seeds of Psoralea corylifolia L,displays whitening,antioxidant,antiaging,and free radical-scavenging activities and attracts wide attention especially in the cosmetics industry.However,environmentally friendly extraction technologies with high efficiency and high product purity remain to be developed for the scale production of bakuchiol.Objective:In this study,a new approach(acetic acid–steaming–assisted technique)was developed to improve the extraction efficiency of bakuchiol.Methods:The factors influencing the extraction efficiency of bakuchiol,including seed powder granularity,acetic acid volume,temperature,and time,were optimized based on single-factor experiments.Results:The extraction conditions were optimized as steaming the seed powder(100 g)of 40–100meshes with acetic acid(50 mL)for 10 minutes,from which a crude extract(25.1 g)containing bakuchiol was obtained.High purity(99.1)of bakuchiol(6.02 g)was then prepared by silica gel column chromatography in a one-step process.The method established in this study had higher extraction rate than other methods.The antioxidant potential of bakuchiol was evaluated based on the ABTS free radical scavenging activity and ferric reducing antioxidant power.Furthermore,bakuchiol demonstrated stronger tyrosinase inhibitory activity than the positive control(arbutin).Conclusions:Compared with the available methods,the method established in this study has increased extraction rate of bakuchiol and is environmentally friendly and economical,demonstrating the potential for industrial production.
