ETHNOPHARMACOLOGICAL RELEVANCE:Psoraleae Fructus (PF) is a commonly used traditional Chinese medicine for treating osteoporosis. Previous studies elucidated the pharmacodynamic basis of its treatment for osteoporosis by analyzing the constituents in the blood, but their distribution in bone tissue was not taken into account, which had certain limitations. AIM OF THE STUDY:This study clarified the pharmacodynamic material basis of PF in the treatment of osteoporosis through a comprehensive analysis of its constituents distributed in plasma and bone tissue, along with the osteogenic activity of constituents distributed in the body. METHODS:This research was founded on a pre-established chemical library of PF. The plasma and bone tissues of rats were harvested, and UFLC-MS was employed to detect the constituents absorbed into the plasma and distributed into the bone tissues. The osteogenic activity of the combined constituents entering the body was investigated using MC3T3-E1 subclone cell. RESULTS:36 constituents absorbed into blood and 42 constituents distributed in bone tissue were identified, furthermore uncovering their plasm pharmacokinetic (PK) and bone tissue distribution (BTD) characteristics. Psoralen (5) and isopsoralen (6) exhibited the highest distribution levels in plasma and bone tissue, reaching 1000 ng/mL and 1000 ng/g. Although the Cmax of psoralenoside (45) and isopsoralenoside (46) in plasm were as high as 2068.86 ng/mL and 7486.24 ng/mL, their Cmax in bone tissue were only 194.91 ng/g and 310.26 ng/g, which was attributed to their characteristics of high polarity and being easily metabolized. Bakuchiol followed closely, with a plasma Cmax of 147.56 ng/mL and bone tissue Cmax of 483.05 ng/g. The coumarin compound psoralidin (4), and the prenylated flavonoid constituents, namely neobavaisoflavone (17), corylifol A (21), bavachin (28), bavachinin (29), and isobavachalcone (41), followed in distribution levels with the plasm Cmax mostly below 10 ng/mL and the bone tissue Cmax at 100-500 ng/mL. The distribution levels of other constituents in the body were mostly below 20 ng/g. The dosage of these constituents were relatively low and they belonged to the derivatives of the main flavonoids. Isopentenyl alterations appeared to enhanced the plasma exposure of the trace constituents. A principal component analysis showed these compounds could be clustered into four types: ''high dosage, high blood drug concentration, and high/medium tissue distribution'', ''high dosage, extremely low blood drug concentration, and medium tissue distribution'', ''high dosage, low blood drug concentration, and medium tissue distribution'', and ''low dosage, low blood drug concentration, and low tissue distribution'' based their dosage, Cmax of PK, Cmax of BTD and apparent volume of distribution. The main constituents of PF had a high/medium distribution in bone tissue. Furthermore, the main constituents were combined based on the distribution amount, and they could significantly increase the ALP activity and the formation of mineralized nodules, upregulate the mRNA expression levels of BSP and OCN. The western blotting suggested the combined constituents activated AKT signaling, along with the accumulation of β-catenin and the upregulation of Runx2. CONCLUSIONS:The above findings suggested that the main constituents distributed in bone tissue enhanced the osteogenic differentiation and mineralization by activating AKT/GSK-3β/β-catenin pathway, indicating them as the pharmacodynamic material basis of PF in the treatment of osteoporosis. Furthermore, this study on PK and BTD analyses of other non-main constituents was also possible to provide extremely crucial reference bases for them at multiple levels, including subsequent research, development, and application.

Berberine is a natural isoquinoline alkaloid with low toxicity, which exists in a wide variety of medicinal plants. Berberine has been demonstrated to exhibit potent prevention of indomethacin-induced gastric injury (GI) but the related mechanism remains unclear. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied for the first time to investigate the alteration of serum metabolites in the protection of berberine against indomethacin-induced gastric injury in rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-GI effect of berberine. The pharmacodynamic data indicated that berberine could ameliorate gastric pathological damage, inhibit the level of proinflammatory factors in serum, and increase the level of antioxidant factors in serum. The LC-MS-based metabolomics analysis conducted in this study demonstrated the presence of 57 differential metabolites in the serum of rats with induced GI caused by indomethacin, which was associated with 29 metabolic pathways. Moreover, the study revealed that berberine showed a significant impact on the differential metabolites, with 45 differential metabolites being reported between the model group and the group treated with berberine. The differential metabolites were associated with 24 metabolic pathways, and berberine administration regulated 14 of the 57 differential metabolites, affecting 14 of the 29 metabolic pathways. The primary metabolic pathways affected were glutathione metabolism and arachidonic acid metabolism. Based on the results, it can be concluded that berberine has a gastroprotective effect on the GI. This study is particularly significant since it is the first to elucidate the mechanism of berberine’s action on GI. The results suggest that berberine’s action may be related to energy metabolism, oxidative stress, and inflammation regulation. These findings may pave the way for the development of new therapeutic interventions for the prevention and management of NSAID-induced GI disorders.

Baicalin concentration is concerned in manufacture of scutellaria spray drying powder as a traditional Chinese medicine, and the quality control based on high-performance liquid chromatography is inconvenience. In this study, terahertz time domain spectroscopy was employed to achieve quality control of scutellaria spray drying powder; however, an acute difficulty was found that terahertz spectra overlapped due to the disturbance in both content matrix and measurement error. In this study, similar terahertz spectra of scutellaria spray drying powder were classified with the help of Gaussian mixture model and built a classifier based on probability feature instead of spectral features conventionally employed in previous investigations. To explore the feasibility of GMM, principal component analysis was given, indicating that it is possible to train GMM with original features and proper principal components. Probable advantage of training GMM based on PCA feature was discussed and so it was with the capacity of the model to identify the linear combined spectra by comparing the performance of GMM and a decision tree model. Above all, the reason why GMM shows potential in the analysis of TCM terahertz spectra was illustrated by comparing the thought of discriminative model and generative model. This study implied that generative model may have natural advantage of overcoming the inherent disturbance of terahertz spectroscopy, which would be promising in future studies.

Objective: To determine the content of ginsenosides in fresh ginseng crystal and understory ginseng by ultra-high performance liquid chromatography-mass spectrometry， so as to study the difference of ginsenosides in fresh ginseng crystal and understory ginseng， and to provide a scientific basis for the nutritional effect of fresh ginseng crystal. Methods: Fresh ginseng crystal and understory ginseng samples were ultrasonic-extracted with 70% methanol liqueous solution at room temperature. UFLC-MS/MS analysis was performed on Waters ACQUITY UPLC ? BEH Shield RP C 18 column （100 mm × 2.1 mm， 1.7 μm）， together with a gradient elution using acetonitrile and 0.5 mmol·L –1 ammonium formate in water as mobile phases. The flow rate was 0.35 mL·min –1 . Under the electrospray ion source， negative ion and multiple reaction monitoring mode， the contents of 39 ginsenoside analytes in fresh ginseng crystals and understory ginseng were determined by the external standard reference method. Results: After methodological verification， the analytical method established in this study met the requirements of quantitative analysis. The contents of total ginsenosides in 4 batches of understory ginseng and 1 batch of fresh ginseng crystals were 27.59-52.63 mg·g -1 and 52.26 mg·g -1 ， and the total contents of rare ginsenosides were 3.79-6.65 mg·g -1 and， 7.42 mg·g -1 ， respectively. The total contents of G-Rg 1 and G-Re in understory ginseng and fresh ginseng crystals were 0.72%-0.94% and 1.21%， while the contents of G-Rb 1 were 0.24%-0.53% and 0.43%， respectively. Conclusion: The total amount of G-Rg 1 and G-Re as well as the content of G-Rb 1 in fresh ginseng crystals and understory ginseng were in accordance with the current quality standards. The fresh ginseng crystals processed by modern technology are rich in ginsenosides， especially rare ginsenosides， which are almost the same as those in understory ginseng， although the content is different. This study provide a scientific basis for comprehensive evaluation of the quality and effect of fresh ginseng crystals and understory ginseng.

Nine new flavonoids dimers, psocorylins R-Z (1-9), were isolated from the fruits of Psoralea corylifolia L. (Psoraleae Fructus), a traditional Chinese medicine. The structures of these compounds were elucidated via multiple spectroscopic techniques and X-ray diffraction. Psocorylins R (1) and S (2) were rare cyclobutane-containing chalcone dimers, and psocorylins T-Z (3-9) were established by CC or COC bond of two flavonoid monomers. The structural-types, flavonoids dimers, were isolated from the plant for the first time, enriching the chemical diversity. The cytotoxicity assay suggested that compounds 1, 2, 4, 5, 6 and 8 exhibited cytotoxic activities against MCF-7 cells. Furthermore, compounds 1 and 8 significantly increased intracellular ROS levels, decreased MMP and induced apoptosis of MCF-7 cells. They markedly upregulated the expression of Bax and cleaved caspase-3, and suppressed Bcl-2 and caspase-3 levels, indicating their mechanism of Bcl-2/Bax/Cleaved caspase-3 pathway. Hence, our findings not only promoted the chemical investigation of Psoraleae Fructus, but also provided potential bioactive natural products for anti-cancer.

Oxidative damage and neuroinflammation are associated with numerous neurological diseases.In recent years,Psoraleae Fructus(dried fruits of Psoralea corylifolia L.),a traditional Chinese medicine,has been found to have medicinal properties in ameliorating central nervous system(CNS)injury.This study aimed to evaluate two neuroprotective compounds of Psoraleae Fructus:corylin and psoralidin,and reveal their underlying mechanisms.The results showed that corylin and psoralidin suppressed reactive oxygen species(ROS)production in H2O2-induced HT22 cells and nitric oxide(NO)production in lipopolysaccharide(LPS)-induced BV2 cells.Further mechanism research of corylin was carried out owing to its better safety and efficacy.In H2O2-induced HT22 cells,corylin significantly increased catalase(CAT),superoxide dismutase(SOD)activity,and glutathione(GSH)expression,while it inhibited mitochondrial membrane potential(MMP)reduction.Meanwhile,the expressions of Nrf2 and HO-1 were up-regulated.In LPS-induced BV2 cells,corylin markedly inhibited IL-1β,IL-6,and TNF-a expressions and specifically suppressed NF-κB p65 nuclear translocation.Furthermore,the docking analysis showed that corylin penetrated well into the hydrophobic pockets of Keap 1 and NF-κB protein.This study demonstrated that corylin alleviated oxidative damage and neuroinflammation by activating Nrf2/HO-1 and inhibiting NF-κB pathways,suggesting its potential ability to treat neurological diseases.

Triterpenoid saponins are the main bioactive components contributed to the nutritional value of ginseng, and different process conditions will affect their content and quality. To study the holistic characterization and dynamic changes of triterpenoid saponins in Asian ginseng (ASG) and American ginseng (AMG) during soaking and decoction, a UPLC-Triple TOF-MS/MS-based metabolomics strategy was used to characterize and discover differential saponin markers. In total, 739 triterpenoid saponins (including 225 potential new saponins) were identified from ASG and AMG in untargeted metabolomics. Based on PCA and OPLS-DA, 51 and 48 saponin markers were screened from soaked and decocted ASG and AMG, respectively. Additionally, targeted metab-olomics analysis and HCA of 22 ginsenoside markers suggested that decoction of ASG and AMG for 2 h to 4 h could significantly increase the contents of rare ginsenosides (G), such as G-Rg3, G-Rg5, G-F4. This study provides a scientific insight that high boiling combined with simmering enriches ASG and AMG extracts with rich rare ginsenosides that are more beneficial to human health.

Fuke Qianjin Formula， a well-known Chinese medicine compound effective in the treatment of gynecological inflammatory diseases， has been identified as a national protected species of Chinese medicine and included in the National Essential Medicine List. It has also been recorded in the 2020 edition of the Pharmacopoeia of the People’s Republic of China， which is divided into Fuke Qianjin Tablets and Fuke Qianjin Capsules. Fuke Qianjin Formula is composed of eight herbal drugs， including Moghaniae Radix， Rosae Laevigatae Radix， Andrographis Herba， Mahoniae Caulis， Zanthoxyli Radix et Caulis， Spatholobi Caulis， Codonopsis Radix， and Angelicae Sinensis Radix. Based on the research on chemical constituents， quality control， pharmacokinetics， and pharmacological actions of Fuke Qianjin Formula， as well as the theory of Chinese medicine quality markers， the prediction and analysis indicated that berberine， palmatine， jatrorrhizine， neoandrographiside， andrographolide， andrograpanin， 7-O-methylwogonin， genistin， ononin， genistein， naringenin， trans-ferulic acid， salicylic acid， and Z-ligustilide were considered potential quality markers of Fuke Qianjin Formula because of their good specificity and testability. The findings of this are expected to provide a scientific basis for quality control research on Fuke Qianjin Formula.

BACKGROUND:Chronic ulcerative colitis (UC) is a lifelong disease, patients with chronic UC have a high prevalence of common mental disorders. The increasing interest in the role of gut-brain axis is seen in inflammatory bowel diseases.PURPOSE:Corylin is a representative flavonoid compound isolated from the Psoraleae Fructus. This study aimed to identify the effects and mechanism of corylin on the inflammation interactions and 5-HT synthesis between the gut and brain in chronic UC.METHODS:Dextran sulfate sodium (DSS) induced chronic UC mouse model was established to assess the therapeutic effect of corylin on chronic UC symptoms. The expression of inflammatory cytokines was detected in the colon and brain. The expression of tight junction (TJ) proteins of intestinal mucosal barrier and blood-brain barrier (BBB) and the ionized calcium-binding adaptor molecule 1 (Iba1) in the hippocampus were determined by western blotting and immunofluorescence staining. In addition, several tryptophan (Trp) metabolites and related neurotransmitters in faeces, colon, serum, and brain were detected by UPLC-MS/MS. The interaction between corylin and 5-hydroxytryptophan decarboxylase (5-HTPDC) was performed by molecular docking and surface plasmon resonance (SPR). Finally, the changes of gut microbiota composition were analyzed by 16S rRNA sequencing.RESULTS:Corylin significantly alleviated colitis symptoms and inhibited inflammatory response in the colon and brain of DSS-induced chronic UC mice. The TJ proteins of intestinal mucosal barrier and BBB were improved and the expression of Iba1 in the hippocampus was normalized after corylin treatment. In addition, corylin treatment increased the expression of neurotransmitters in the brain, especially 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP), but the expression of 5-HT in the colon was inhibited. Further study firstly proved that corylin could bind to the 5-HTDPC, and then inhibit the expression of 5-HTDPC and VB6, resulting in the 5-HT reduction and 5-HTP accumulation in the colon. Moreover, the intake of corylin transformed the diversity and composition of intestinal microbiota, Bacteroides, Escherichia-Shigella, and Turicibacter were decreased but Dubosiella, Enterorhabdus, and Candidatus_Stoquefichus were increased.CONCLUSION:Corylin administration ameliorated DSS-induced colitis and inhibited intestinal inflammation and neuroinflammation via regulating the inflammation interactions across gut-brain axis and increasing 5-HTP generation in the colon.

Major chemical constituents in medicinal materials are often used as the marker compounds of traditional Chinese medicine (TCM) for treating various diseases. For spatholobi caulis (SPC), it contains a variety of flavones, phenolic acid esters, and lignans which exert many pharmacological effects. However, the absorption and permeability properties of these constituents of SPC are still unclear and require further investigation. Different types and major compounds of SPC were chosen as representative constituents to study their absorption and transepithelial transport characteristics in the human intestinal epithelium-like Caco-2 cell monolayer model. 35 constituents of SPC were evaluated by using ultra fast liquid chromatography combined with electrospray ionization triple quadrupole tandem mass spectrometry (UFLC-MS/MS) method, acetonitrile and water containing with 0.5 mM ammonium acetate were used as mobile phase, these analytes with good linear relationships (R2 was within 0.9967-0.9998), precision (CV values were less than 10.23 %, LLOQ was less than 13.69 %), accuracy (Mean of inter- and intra-day were within 85.02 %-111.61 % and 85.50-112.97 %, respectively) and stability (The mean was within 85.07 %-113.93 %), among which 16 analytes showed good permeability, 5 analytes were considered to be poorly permeable compounds, and the other 14 analytes were assigned for the moderately absorbed compounds in Caco-2 cell monolayer model. The further results showed that the absorption mechanism of 7 well absorbed compounds, 8-O-methylretusin (1), genistein (7), spasuberol B (16), naringenin (18), isoliquiritigenin (19), 4-hydroxy-3-methoxy cinnamic acid methyl ester (23) and (+)-epipinoresinol (31) in SPC was mainly passive diffusion, their bidirectional transport rate was correlated with the concentration and transport time. The chemical structures of these compounds could affect the permeability properties on the cell monolayer. This study demonstrated the utility of Caco-2 cell monolayer model for evaluating the absorption properties and initial mechanisms of compounds in SPC in vitro, and provided important basis for predicting oral bioavailability of SPC compounds.

The root of Panax quinquefolius L. (RPQ) is considered as an important functional food and rich in bioactive components, ginsenosides. To comprehensively characterize ginsenosides and evaluate the quality of RPQ from different sources, UPLC-Triple TOF-MS coupled with UFLC-ESI-MS/MS was applied to untargeted metabolites and targeted analysis for the first time. In untargeted metabolites analysis, a total of 225 ginsenosides were identified from RPQ using UPLC-Triple TOF-MS combined with SWATH data-independent strategy. Furthermore, the contents of 39 targeted ginsenoside markers in 14 RPQ samples were analyzed by a rapid and sensitive UFLC-ESI-MS/MS method. In addition, the results of chemometric analysis showed the quality of American RPQ was distinguished from that of Chinese RPQ according to the amount of targeted ginsenosides. This newly developed approach provides a powerful tool for enriching the diversity of saponins database and assessing the quality of RPQ, which can be further extended to other ginseng products and functional foods.

The mature fruit of Psoralea corylifolia L. is a common traditional Chinese medicine used to tonify the kidney and yang, and as well as to treat osteoporosis. Systematic phytochemical investigations have established the most comprehensive constituent library to date, covering over 180 compounds. In this study, 109 chemical constituents containing 37 undescribed compounds were reported and incorrect structures of four known coumarins were corrected. The structures of these undescribed compounds were elucidated using spectroscopic methods, single-crystal X-ray diffraction, Rh2(OCOCF3)4 and Mo2(OAc)4-induced circular dichroism spectra. To identify potentially active compounds and investigate their structure-activity relationship (SAR), 89 constituents in the library were evaluated for their osteogenic differentiation and mineralisation activities in MC3T3-E1 cells. We found that coumarins, isoflavones, flavonones, and meroterpenoids were the material basis for Psoralea corylifolia-based treatment of osteoporosis, with some compounds exhibiting excellent activities. These compounds function via the estrogen receptor (ER) pathway and were natural phytoestrogen. Further SAR analysis showed that compounds with an intact isopentenyl replacement possessed superior activities, which was explained by their improved affinity with the ER.

目的 研究补骨脂Psoraleae Fructus 70％乙醇水提取物的环己烷溶性部分的化学成分.方法 采用硅胶、高效液相色谱等柱色谱方法进行分离纯化,通过化合物的谱学数据鉴定其结构.结果 从补骨脂70％乙醇水提取物的环己烷溶性部分分离出21个化合物,分别鉴定为补骨脂醚(1)、对羟基苯甲醛(2)、邻苯二甲酸二异辛酯(3)、补骨脂醚酚G(4)、补骨脂醚酚H(5)、双补骨脂酚V(6)、双补骨脂酚I(7)、双补骨脂酚H(8)、双补骨脂酚F(9)、双补骨脂酚D(10)、双补骨脂酚G(11)、豆甾醇(12)、补骨脂查耳酮(13)、补骨脂定(14)、补骨脂二氢黄酮甲醚(15)、异补骨脂素(16)、补骨脂素(17)、豆甾醇-3-O-β-D-吡喃葡萄糖苷-6'-O-棕榈酸酯(18)、4-羟基合生果素(19)、新补骨脂宁(20)和6-异戊烯基柚皮素(21).结论 化合物1、4、5和6为4个新的化合物.

Absorption is crucial to the resultant efficacy of oral drugs where the intestinal bacteria flora functions as one of the first-pass effects.The present study investigated the biotransformation of psoralenoside and isopsoralenoside in Chinese medicine Psoraleae Fructus(the dried fruit of Psoralea corylifolia) with the internationally recognized human intestinal bacteria flora model in vitro.Pso-ralenoside and isopsoralenoside were anaerobically incubated with human intestinal bacteria flora at 37 ℃, respectively, and biotransformation products were analyzed and identified using high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS) and comparison with reference standards.The main biotransformation products of psoralenoside were psoralen and a small amount of 6,7-furano-hydrocoumaric acid, and the main biotransformation products of isopsoralenoside were isopsoralen and a small amount of 5,6-furano-hydrocoumaric acid.

Although the functions of metabolic enzymes and nuclear receptors in controlling physiological homeostasis have been established, their crosstalk in modulating metabolic disease has not been explored. Genetic ablation of the xenobiotic-metabolizing cytochrome P450 enzyme CYP2E1 in mice markedly induced adipose browning and increased energy expenditure to improve obesity. CYP2E1 deficiency activated the expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) target genes, including fibroblast growth factor (FGF) 21, that upon release from the liver, enhanced adipose browning and energy expenditure to decrease obesity. Nineteen metabolites were increased in Cyp2e1-null mice as revealed by global untargeted metabolomics, among which four compounds, lysophosphatidylcholine and three polyunsaturated fatty acids were found to be directly metabolized by CYP2E1 and to serve as PPARα agonists, thus explaining how CYP2E1 deficiency causes hepatic PPARα activation through increasing cellular levels of endogenous PPARα agonists. Translationally, a CYP2E1 inhibitor was found to activate the PPARα–FGF21–beige adipose axis and decrease obesity in wild-type mice, but not in liver-specific Ppara-null mice. The present results establish a metabolic crosstalk between PPARα and CYP2E1 that supports the potential for a novel anti-obesity strategy of activating adipose tissue browning by targeting the CYP2E1 to modulate endogenous metabolites beyond its canonical role in xenobiotic-metabolism.

目的 建立复方苦参注射液的超高效液相色谱法(UPLC)指纹图谱,并同时测定其中6种指标成分的含量.方法 采用ACQUITY UPLC CSHTM C18(2.1 mm×100 mm,1.7 μm)色谱柱,以甲醇2 g·L-1磷酸二氢钾为流动相梯度洗脱,流速0.3 mL·min-1,柱温30℃,检测波长211 nm.结果 建立复方苦参注射液UPLC指纹图谱,确立了 9个共有峰,10批样品相似度均大于0.99.甲基氧化偶氮甲醇樱草糖苷、苦参碱、槐果碱、槐定碱、氧化槐果碱、氧化苦参碱6种成分在相应浓度范围内与峰面积的线性关系良好,平均加样回收率分别为100.42％、100.90％、101.45％、103.85％、99.95％、100.46％,相对标准偏差(RSD)值分别为1.96％、0.67％、1.60％、1.15％、1.02％、1.20％.结论 本研究建立的复方苦参注射液的UPLC指纹图谱及多成分含量测定方法,操作简单,重复性好,稳定可靠,为复方苦参注射液的质量标准研究提供更加全面的依据.

妇科千金片/胶囊在治疗妇科疾病的中成药领域享有盛誉.近10年来,国内医药工作者对妇科千金片/胶囊的基础药学和临床应用进行了大量研究,结果发现妇科千金片/胶囊具有抑菌、抗炎、镇痛、补益气血、提高免疫力等作用.临床单独应用或联合其他药物应用能治疗急慢性妇科炎症、气滞血瘀型原发性痛经等症,疗效确切,市场前景良好,已列入国家中药标准化提高项目.本文对妇科千金片/胶囊及原药材的化学成分、质量控制、现代药理作用和临床应用进行综述,为其进一步的开发和利用提供参考.

Evodiamine,rutaecarpine,and dehydroevodiamine have been demonstrated as the major alkaloids in the fruits of Euodia rutaecarpa,a well-known traditional Chinese medicine with central nervous system activities.To study their cerebrospinal fluid pharmacokinetics and cerebral nuclei distribution,the alkaloids were mixed at the weight ratio of 1∶1∶1 and orally administered via gavage to the rats at each dose of 15 mg/kg.A quick and reliable ultra-performance liquid chromatographic-tandem mass spectrometry method was developed and applied for the simultaneous analysis of the alkaloids in rat cerebrospinal fluid and cerebral nuclei collected at different time points.Non-compartmental pharmacokinetic profiles were calculated,and the distribution in cerebral nuclei was compared.All the tested compounds were absorbed into rat cerebrospinal fluid and distributed to the brain nuclei quickly.Their distribution in different nuclei varied,as evodiamine mainly in cerebellum and brainstem,rutaecarpine with its maximum in the brainstem,and dehydroevodiamine mostly in the cerebellum and hippocampus.They were eliminated from the brain rapidly without long-time accumulation.In summary,this study revealed the targeting discrepancy of evodiamine,rutaecarpine,and dehydroevodiamine in the brain,and highlighted the possibility for drug candidates in the encephalopathy treatment of the fruits of E.rutaecarpa.