Rooted in the traditional Chinese medicine theory of "flavor and meridian tropism," salt processing is widely applied to Achyranthis Bidentatae Radix to enhance its "kidney-tonifying and bone-strengthening" effects. However, the dynamic chemical changes and spatial redistribution of bioactive constituents during processing remain unclear, limiting mechanistic understanding. Here, we established an integrated multi-omics framework combining untargeted UPLC-QTOF-MS metabolomics, weighted gene co-expression network analysis (WGCNA), machine learning, and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Untargeted metabolomics profiled metabolites before and after salt processing, WGCNA identified processingassociated modules, and random forest modeling prioritized core differential metabolites. Guided by multivariate statistical analysis, MALDI-MSI enabled the first in situ visualization of seven key metabolites, revealing distinct localization and migration patterns within plant tissues. Mechanistically, salt processing remodeled metabolite abundance and spatial organization via dual "physical cell wall disruption" and "chemical modulation" pathways, driving enrichment in vascular tissues and metabolically active regions. This study provides the first systematic multi-omics elucidation of the dynamic transformation and spatial redistribution of bioactives in salt-processed Achyranthis Bidentatae Radix.

OBJECTIVE:This study evaluated the effects of Serfurosterone A (SSA) from Achyranthes bidentata Bl. on dexamethasone (DEX)-induced osteoblast dysfunction and its intestinal permeability. METHODS:The anti-osteoporotic effects of SSA were assessed by MTT assay, flow cytometry, osteogenic differentiation induction, and western blotting. Intestinal permeability and transport mechanisms were investigated using Caco-2 cell models and single-pass intestinal perfusion (SPIP) in rats. RESULTS:SSA (5-50 µM) increased the viability and proliferation of DEX-injured MC3T3-E1 cells, enhanced alkaline phosphatase (ALP) activity, and promoted mineralized nodule formation. Western blot analysis suggested that SSA's effects may involve activation of the Wnt/β-catenin signaling pathway, characterized by upregulation of β-catenin and downregulation of GSK3β. In the Caco-2 assays, SSA showed moderate absorption (Papp 1.551-2.443 × 10-6 cm/s; ER 0.751-0.898) via passive transcellular transport. SPIP experiments further indicated efficient absorption across all intestinal segments (Peff > 2 × 10-5 cm/s), with the duodenum as the main absorption site. CONCLUSIONS:SSA mitigates DEX-induced osteogenic inhibition and exhibits favorable intestinal absorption, suggesting its potential as a promising oral candidate for glucocorticoid-induced osteoporosis (GIOP). These results underscore the therapeutic promise of Achyranthes-derived phytosterols for future drug development.

Introduction: Rhubarb is a frequently used and beneficial traditional Chinese medicine. Wild resources of these plants are constantly being depleted, meaning that rhubarb products have been subjected to an unparalleled level of adulteration. Consequentially, reliable technology is urgently required to verify the authenticity of rhubarb raw materials and commercial botanical drugs.Methods: In this study, the barcode-DNA high-resolution melting (Bar-HRM) method was applied to characterize 63 rhubarb samples (five Polygonaceae species: Rheum tanguticum, Rh. palmatum, Rh. officinale, Rumex japonicus and Ru. sp.) and distinguish the rhubarb contents of 24 traditional Chinese patent medicine (TCPM) samples. Three markers, namely ITS2, rbcL and psbA-trnH, were tested to assess the candidate DNA barcodes for their effectiveness in distinguishing rhubarb from its adulterants. A segment from ITS2 was selected as the most suitable mini-barcode to identify the botanical drug rhubarb in TCPMs. Then, rhubarbs and TCPM samples were subjected to HRM analysis based on the ITS2barcode.Results: Among the tested barcoding loci, ITS2 displayed abundant sites of variation and was effective in identifying Polygonaceae species and their botanical origins. HRM analysis based on the ITS2 mini-barcode region successfully distinguished the authenticity of five Polygonaceae species and eight batches of TCPMs. Of the 18 TCPM samples, 66.7 % (12 samples) were identified as containing Rh. tanguticum or Rh. officinale. However, 33.3 % were shown to consist of adulterants.Conclusions: These results demonstrated that DNA barcoding combined with HRM is a specific, suitable and powerful approach for identifying rhubarb species and TCPMs, which is crucial to guaranteeing the security of medicinal plants being traded internationally.

ETHNOPHARMACOLOGICAL RELEVANCE:Kai-Xin-San (KXS) is a classic herbal formula for the treatment and prevention of AD (Alzheimer's disease) with definite curative effect, but its mechanism, which involves multiple components, pathways, and targets, is not yet fully understood.AIM OF THE STUDY:To verify the effect of KXS on gut microbiota and explore its anti-AD mechanism related with gut microbiota.MATERIALS AND METHODS:AD rat model was established and evaluated by intraperitoneal injection of D-gal and bilateral hippocampal CA1 injections of Aβ25-35. The pharmacodynamics of KXS in vivo includes general behavior, Morris water maze test, ELISA, Nissl & HE staining and immunofluorescence. Systematic analysis of gut microbiota was conducted using 16S rRNA gene sequencing technology. The potential role of gut microbiota in the anti-AD effect of KXS was validated with fecal microbiota transplantation (FMT) experiments.RESULTS:KXS could significantly improve cognitive impairment, reduce neuronal damage and attenuate neuroinflammation and colonic inflammation in vivo in AD model rats. Nine differential intestinal bacteria associated with AD were screened, in which four bacteria (Lactobacillus murinus, Ligilactobacillus, Alloprevotella, Prevotellaceae_NK3B31_group) were very significant.CONCLUSION:KXS can maintain the ecological balance of intestinal microbiota and exert its anti-AD effect by regulating the composition and proportion of gut microbiota in AD rats through the microbiota-gut-brain axis.

Rhubarb is a significant medicinal herb in China. Its adulteration or fabrication is common in the market. Consequently, it is necessary to establish a comprehensive identification method to accurately identify genuine rhubarb and its adulterants. In this study, the sequences of chloroplast genes rps3-rpl22 and rpl16 from three genuine rhubarbs (Rheum tanguticum, Rh. palmatum and Rh. officinale) and their adulterants (Rumex japonicus and Rumex spp.) were amplified, sequenced and subjected to genetic analyses. The genetic distances for rps3-rpl22 and rpl16 between genuine rhubarbs and their adulterants showed that there was an evident barcoding gap, which allowed the adulterants to be distinguished from the genuine rhubarbs, as demonstrated by a neighbor joining tree. Additionally, Rh. officinale could be distinguished from the other two genuine rhubarbs. The anthraquinone, sennoside, polysaccharide and protein contents were analyzed in seven rhubarbs using high-performance liquid chromatography and ultraviolet spectrophotometry. Cluster and principal component analyses results showed that Rh. tanguticum and Rh. palmatum could be effectively distinguished. The study suggests that DNA barcoding based on rps3-rpl22 and rpl16 sequences coupled with multiple-indicator quantification can be successfully applied to identify rhubarb species and distinguish among the three genuine rhubarbs, and this can provide a scientific foundation for rhubarb quality assurance.

Kai-Xin-San (KXS) is a classic formula for the treatment of Alzheimer’s disease (AD). KXS has been widely used to treat emotional diseases; however, its active components remain unknown. There have been some reports about the efficacy and metabolic analysis of KXS, which are mainly based on studying normal animals. The current work first established an AD rat model by injecting D-galactose into the abdominal cavity and injecting Aβ25–35 into the hippocampus on both sides, followed by intragastric administration of KXS for a consecutive week; then, the analytical method for ethanol extraction from the serum of normal and model rats was developed using UPLC-LTQ-Orbitrap-MS; finally, the transitional components in the blood were systematically compared and analyzed by multivariate statistical analysis. A total of 36 components of KXS were identified in the rat serum of the normal group, including 24 prototype components (including ginsenosides, triterpenoid acids of Poria cocos, polygala saponins, polygala xanthones and polygala ester) and 13 metabolites (including desugar, hydration and oxidation products of ginsenosides, triterpenoid acid hydroxylation, deoxygenation, demethylation, desaturation, and glycine-conjugated products of Poria cocos). Twenty KXS-relevant components were detected in the rat serum of the model group, including 11 prototypes and 9 metabolites. The normal group and the model group shared 12 common components, including 9 prototypes and 3 metabolites. The intestinal microecological balance of the model rats probably was destroyed, affecting the absorption/metabolism of saponins by the body, which resulted in fewer transitional components in the model group. This study reflected the drug-body interaction from an objective and accurate perspective, offering references and insights for elucidating the basis of active components and mechanism of action of KXS for treating AD.

目的:研究藏药尖突黄堇的解热、镇痛、抗炎作用.方法:昆明小鼠分为模型组,阳性药阿司匹林组,尖突黄堇醇提物低、中、高剂量组(生药 0.5、1.0、1.5 g/kg).通过皮下注射干酵母诱导小鼠发热模型探究其解热作用;通过冰醋酸致小鼠扭体法探究其镇痛作用;通过二甲苯诱导小鼠耳廓肿胀方法探究其抗炎作用.结果:尖突黄堇总醇提物可显著抑制干酵母所致发热小鼠的肛温上升;显著抑制冰醋酸所致小鼠疼痛,减少扭体次数;显著降低二甲苯致小鼠耳廓肿胀,减少肿胀度.结论:尖突黄堇具有明显的解热、镇痛、抗炎作用,但其具体的药效作用还有待进一步研究.

Ethnopharmacology relevance: Duhuo Jisheng decoction (DHJSD) is a traditional Chinese formula that has been widely used in clinical practice to treat osteoarthritis (OA), which has the effects of removing invaded cold and dampness, relieving joint pain. However, it is difficult to determine the effective substances and mechanisms due to assorted herbs and components, and further research is needed.Aim of the study: This study was designed to explore and verify the mechanism and targets of DHJSD in the treatment of OA via network analysis and experiments.Method: In this study, the active ingredients of DHJSD were qualitatively by UPLC-QDA. Network analysis is used to get the common target and pathways. After that, we explored the therapeutic mechanism of DHJSD through the rat model of knee osteoarthritis (KOA). HE staining is used to judge the establishment of animal model. ELISA and Western blotting were used to verify the expression of key pathway proteins.Conclusion: In this study, seventeen chemical constituents in DHJSD were identified. According to the network analysis, we get the potential associated pathways of action. Then, the molecular docking and SPR experiment showed that the sixteen identified components with high binding energy to IL-6. HE staining showed that the high-dose group of DHJSD had an obvious therapeutic effect on model rats. Compared with the model group, the levels of IL-1β, TNF-α, MMP3, MMP13, ADAMTS4 and ADAMTS5 in serum, and the expression of STAT3 and p-STAT3 protein in administration groups were significantly decreased. It indicated that the IL-6/STAT3 signaling pathway was one of the important pathways regulated by DHJSD to improve the OA.

Lonicerae japonicae Flos (LF) is a kind of healthcare food with hepatoprotective function. This study was designed to explore the spectrum-effect relationships between UPLC fingerprints and the hepatoprotective effects of LF. Fingerprints of ten batches of LF were established by UPLC-PDA. The inhibitory levels of AST and ALT were used as pharmacological indexes, and secoxyloganin, isochlorogenic acid A and isochlorogenic acid C were screened as hepatoprotective active compounds by grey relational analysis (GRA) and partial least squares regression analysis (PLSR). Caspase-3 was obtained by network pharmacology as a key target of hepatoprotective active compounds. Molecular docking is used to explore the interaction between small molecules and proteins. This work provided a general model of the combination of UPLC-PDA and hepatoprotective effect to study the spectrum-effect relationship of LF, which can be used to considerable methods and insight for the fundamental research of the material basis of similar healthcare food.

Ethnopharmacology relevance: Duhuo Jisheng decoction is a traditional Chinese formula that has been widely used in clinical practice to treat osteoarthritis, which has the effects of removing invaded cold and dampness, relieving joint pain. However, it is difficult to determine the effective substances and mechanisms due to assorted herbs and components, and further research is needed. Aim of the study: This study was designed to explore and verify the mechanism and targets of DHJSD in the treatment of OA via network analysis and experiments.Method: In this study, the active ingredients of DHJSD were qualitatively analyzed by UPLC-QDA. Network analysis was used to identify common targets and pathways. Next, we explored the therapeutic mechanism of DHJSD through a rat model of knee osteoarthritis. HE staining was used to judge the establishment of the animal model. ELISA and Western blotting were used to verify the expression of key pathway proteins.Conclusion: In this study, seventeen chemical constituents in DHJSD were identified. According to the network analysis, we obtained the potential associated pathways of action. Then, molecular docking and SPR experiments showed that the sixteen identified components had high binding energies to IL-6. HE staining showed that the high-dose group of DHJSD had an obvious therapeutic effect on model rats. Compared with the model group, the levels of IL-1 & beta;, TNF-& alpha;, IL-6, MMP3, MMP13, ADAMTS4 and ADAMTS5 in serum and the expression of STAT3 and p-STAT3 protein in administration groups were significantly decreased. This result indicated that the IL-6/STAT3 signaling pathway was one of the important pathways regulated by DHJSD to improve OA.

目的:建立以去氢吴茱萸碱、吴茱萸次碱和吴茱萸碱为指标成分的吴茱萸含量测定标准.方法:基于文献与前期基础,确定去氢吴茱萸碱、吴茱萸次碱和吴茱萸碱为吴茱萸的质控指标.对去氢吴茱萸碱的化学结构与存在型体进行系统分析,优选盐酸作为流动相添加剂,改善其色谱峰的对称性.优化流动相pH值、组成及梯度条件,建立并验证基于上述3个指标成分的HPLC分析方法.对主产区主流品种的吴茱萸进行含量分析,初步拟定其含量限度值.结果:流动相pH=1时,去氢吴茱萸碱色谱峰的对称性符合药典要求.优化的色谱条件下,各化合物分离良好,色谱峰对称因子均在0.95～1.05,柱分离效能与分析时间均优于现行药典方法.经25批次样品的分析验证,本法与药典方法无显著性差异.初步拟定含量限度值为:吴茱萸碱和吴茱萸次碱的总量不低于0.15％,去氢吴茱萸碱0.30％.结论:解决了去氢吴茱萸碱的色谱峰拖尾问题;所建立的含量测定方法简单、快速、准确、可靠;建议的含量测定标准具有更好的专属性、可测性与可行性,可为新版药典中吴茱萸质量标准的提升提供依据与参考.

Aim: The purpose of this study was to explore the application status of natural products in osteoporosis research and explore its research hotspots and future research directions by analyzing the literature in the field Aim: The purpose of this study was to explore the application statu of natural products in osteoporosis of natural products therapy for osteoporosis from 2000 to 2021. Method: Publications on natural products re earch and explor its research hotspots and future research directions by analyzing the literature in the field of naural product therapy fo osteoporosis fom 2000 to 2021 Method: Publcatons on natura product in osteoporosis res earch were extracted from the Web of Science core collection database. Bibliometrics in osteoporos s reserch were extracted from the Web of Scienc core cllection dabase Bibliomtrics package in R language, VOSviewer and CiteSpace software were used for visualization analysis. Result: package in R langu ge VOSviewer and CiteSpace software were used for visualization anaysis. Result: From 2000 to 2021, the number of articles on natural products in osteoporosis research was 1 596, and the From 2000 to 2021 the number of articles on natural products in osteoporos s research was 1 596 and the total number of articles increased rapidly. China was the driving force in this field, and the top-contributing institution was Guangzhou University of Chinese Medicine. Most publications were published in the Journal total number of articles increased rapidly China was the driving force in this field and the top-contributing of Ehnpharmacology. While J.K. Xu and Y. Zhang were the most cited and co-cited author. Countries, in titution was Guangzh u University of Chinese Medicine Most publcations were publi hed in he Journal of Ethnopharmacology. While JK Xu and Y. Zhang were the most cited and co-c ted author. Countries, research institutions and authors in different regions cooperate closely. The hot topics included osteoporosis, diffeentation, expression, in vitro, cell, oseoeneis and osteogenesis wre the research frontiers in recent research institutions and authors in different regions cooperate closely The hot topics included osteoporosis differentiation expression in vitro ell osteogenesis and osteogenesis were the rsearch fronier n rcent years. Conclusion: This study conducted a bibliometric visualization analysis on the research status , research hotspots and development trend of natural prducts in osteoprosis for the first time. In ddition, this years Conclusion: This study conducted a bibliometric vi ualization analysis on the esearch status research paper also puts forward suggestions and prospects for the future development of this field, which will help hotspots and development trend of natural products in osteoporosis for the first t me. In addition this reseachers to open up new dirctions for future research in this fil. paper also puts forward suggestions and prospects for the future de 2022 Beijing Academy of Food Scences Pushng services by Elsevier B on eaf of e (c) 2022 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V . on behalf of KeAi Communications Co Ltd This is an open access article under the CC BYNC ND license Communications Co Ltd This is an open access article under the CC BY NC ND license Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

目的:建立枳壳色谱指纹图谱定性、多组分定量与化学计量学的整合分析方法,评价不同产区、不同基原枳壳药材的质量属性与差异.方法:采用COSMOSIL 5C18-MS-Ⅱ色谱柱(4.6 mm×250 mm,5μm),流动相乙腈-0.2％磷酸水溶液梯度洗脱(0～4 min,19％A;4～5 min,19％～21％A;5～18 min,21％A;18～19 min,21％～28％A;19～27 min,28％A;27～28 min,28％～40％A;28～36 min,40％A;36～37 min,40％～50％A;37～42 min,50％～60％A;42～46 min,60％～95％A;46～55 min,95％～100％A),流速1 mL· min-1,柱温30 ℃,检测波长320 nm,进样量10 μL.建立不同产地、不同基原枳壳的高效液相色谱法(HPLC)指纹图谱,结合聚类分析(CA),主成分分析(PCA)和正交偏最小二乘法-判别分析(OPLS-DA)对26批枳壳进行质量评价.开发并验证了12个组分的含量测定分析方法,并基于样品含量差异对不同产地、不同基原的枳壳进行热图聚类分析.结果:指纹图谱及含量测定的方法学验证均良好,12批枳壳的指纹图谱相似度处于0.85～0.996,标定了20个共有峰,并归属了其中14个色谱峰;定量分析的12个成分分离度、线性关系均良好,加样回收率99.2％～101.0％,RSD均≤2.0％;CA,PCA与OPLS-DA显示,不同产地枳壳的区分度较大,不同品种间也存在差异.结论:基于同一色谱条件的指纹图谱定性与多指标成分定量分析操作方便、准确可靠,结合化学计量学手段可实现对不同产地、不同基原枳壳的判别归属与质量分析,可为其整体质量控制和评价提供参考.

The aim of this study was to establish an ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry method with positive and negative ion exchange scanning mode for simultaneous quantification of two different skeleton components to reveal the differences among raw and processed Angelicae Pubescentis Radix. The results of methodology showed that each compound had good linearity and recovery rates. And the chemometrics results indicate that there were differences not only in Angelicae Pubescentis Radix samples from different sources but also in raw and processed Angelicae Pubescentis Radix. The results of this study confirm that the method has been successfully applied in simultaneous determination and discovering the difference of two different skeleton components between raw and processed Angelicae Pubescentis Radix for the first time. In short, the method could be an effective tool for detecting the quality of traditional Chinese medicine, and can better reveal the difference between raw and processed Chinese medicine from different sources.

目的 验证枳壳理气质量标志物(Q-marker)的有效性.方法 采用离体肠肌实验,应用BL-420N信息化生物信号采集与分析系统,观察记录枳壳醇提物、水提物和Q-marker混合溶液对正常小鼠离体小肠平滑肌收缩活动的影响.在体实验将KM小鼠50只随机分为5组,即空白组、阳性药组、枳壳醇提物组、枳壳水提物组、Q-marker混合溶液组,分别按25 mL·kg-1灌胃给药,连续7 d,采用炭末推进法,测定小肠推进率和胃排空率来评价各组的药效.结果 离体实验中,枳壳醇提物组、枳壳水提物组和Q-marker混合溶液组在累积给药体积为50μL和150μL时,对正常小鼠离体小肠平滑肌收缩活动均呈现促进作用,而在累积给药体积350μL时,则呈现抑制作用.在体实验中,枳壳醇提物组、枳壳水提物组与Q-marker混合溶液组对正常小鼠胃排空和小肠推进均具有显著的促进作用(P＜0.01),且枳壳醇提物组、枳壳水提物组与Q-marker混合溶液组之间无显著性差异.结论 枳壳Q-marker混合溶液与提取物的理气作用无显著性差异,提示该研究确定的15个枳壳理气质量标志物能够整体上代表枳壳的质量属性.

Traditional Chinese medicine considers Lonicerae japonicae flos to have antibacterial detoxification, liver protection, and gallbladder protection. At present, studies have proven that Lonicerae japonicae flos has a good therapeutic effect on liver injury. Therefore, to confirm the clinical applicability of Lonicerae japonicae flos in the treatment of liver injury, we were the first to compare the pharmacokinetics of an oral ethanol extract of Lonicerae japonicae flos in normal rats and carbon tetrachloride-induced liver injury model rats. A method was developed for the simultaneous determination of 3-caffeoylquinic acid, 4-caffeoylquinic acid, 5-caffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, protocatechuic acid, Sweroside, and Secoxyloganin in rat plasma by ultra-performance liquid chromatography tandem mass spectrometry. The results show that the method is reliable and reproducible and can be used for quantitative determination of biological samples. The pharmacokinetic parameters showed that the area under the concentration–time curve of eight compounds in the model group was significantly increased. The results showed that the total absorption of the active components of Lonicerae japonicae flos in the blood increased, the clearance rate slowed down, and the bioavailability of Lonicerae japonicae flos increased in liver injury diseases.

Background: Indirubin is the main bioactive component of the traditional Chinese medicine Indigo naturalis and is a bisindole alkaloid. Multiple studies have shown that indirubin exhibits good anticancer, anti-inflammatory and neuroprotective properties. Methods: The purpose of this review is to provide a summary of the pharmacological mechanisms of indirubin and its derivatives. Results: Indirubin and its derivatives exert anticancer effects by regulating the expression of cyclin-dependent kinases (CDKs), GSK-3β, Bax, Bcl-2, C-MYC, matrix metalloproteinases (MMPs), and focal adhesion kinase (FAK) through the PI3K/AKT/mTOR, nuclear factor (NF)-κB, mitogen-activated protein kinase (MAPK), JAK/signal transducer and activator of transcription 3 (STAT3) pathways and other signaling pathways. We also reviewed the anti-inflammatory and neuroprotective properties of indirubin and its derivatives. Conclusion: The findings of recent studies assessing indirubin and its derivatives suggest that these compounds can be used as potential drugs to treat tumors, inflammation, neuropathy and bacterial infection.

Ethnopharmacological relevance: Nowadays, gastrointestinal motility disorders (GMD) have reduced the quality of people's daily life worldwide, but there is still a lack of effective western medicine treatment. Fructus aurantii (FA), a representative regulating-qi herbal medicine, has been widely used to treat GMD in China for thousands of years, but it is not clear that which specific components contribute to the efficacy. Aim of the study: The efficacy differences of various fractions of FA on normal mice and GMD rats were compared, so as to find out the main effective fraction of FA, and to screen the main regulating-qi components based on spectrum-effect relationship and multivariate statistical analysis. Materials and methods: The fingerprints of different fractions of FA were established and main compounds were identified with UHPLC-Q-TOF/MS technique. The promoting gastrointestinal motility activities of FA were evaluated by defecation test, gastric emptying and intestinal propulsion test in mice, and further investigated according to the biochemical analysis of 5-HT, SP, MLT, GAS and VIP in GMD rats' plasma. One-way ANOVA was used to find out the difference of efficacy. The active components were screened through spectrum-effect relationship with PCA-X, Pearson bivariate correlation analysis and OPLS analysis. Conclusions: Ethyl acetate fraction is the main active fraction, and nine compounds are the major regulating-qi components. The developed spectrum-effect analysis can be used for the screening of bioactive components in natural products with high accuracy and reliability.

Aurantii Fructus is a commonly used qi-regulating medicinal herb in China. Both traditional Chinese medicine theory and modern experimental research demonstrate that Aurantii Fructus has dryness effect, the material basis of which remains unclear. In recent years, spectrum-effect relationship has been widely employed in the study of active ingredients in Chinese medicinal herbs, the research ideas and methods of which have been constantly improved. Based on the idea of spectrum-effect study, the ultra-high perfor-mance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) fingerprints of different fractions of Aurantii Fructus extract were established for the identification of total components. Then, the dryness effects of the fractions on normal mice and gastrointestinal motility disorder(GMD) rats were systematically compared. Finally, principal component analysis(PCA), Pearson bivariate correlation analysis and orthogonal partial least squares analysis(OPLS) were integrated to identify the dryness components of Aurantii Fructusextract. The results showed that narirutin, naringin, naringenin, poncirin, oxypeucedanin, and eriodictyol-7-O-glucoside had significant correlations with and contributed to the expression of AQP2 in kidney, AQP3 in colon, and AQP5 in submandibular gland, which were the main dryness components in Aurantii Fructus.

In recent years, drug-induced liver injury (DILI) has become an important issue of public health. Euodiae Fructus (EF) is a commonly used herb with mild toxicity in clinic, and large doses of EF can cause significant liver damage. Licorice processing might reduce the hepatotoxicity of CEF (crude EF), but up to now, studies on the hepatotoxicity of EF have been hardly reported, let alone its material basis and mechanism of detoxification by licorice processing. This work firstly established a stomach excess-cold syndrome animal model induced by intragastric administration of cold Zhimu ( Anemarrhena asphodeloides Bge). Secondly, multiple approaches and indexes were used to evaluate the hepatotoxicity of the drugs in the rats including general behavior, biochemical analysis, protein expressions, and histopathological examination. Thirdly, the hepatotoxicity of three doses of three CEF and LPEF (licorice-processed EF) extracts was systematically investigated, and the hepatotoxicity differences were analyzed and compared comprehensively among the three extracts, three doses, and CEF and LPEF. Finally, the connotation of detoxification of EF by licorice processing was preliminarily discussed according to the changes in toxic components after processing, toxicological characteristics, and TCM (traditional Chinese medicine) theory. All extracts of EF were found to have dose-dependent hepatotoxicity, and the toxicity was in the descending order of water extract, ethanol extract, and volatile oil. The hepatotoxic mechanism of EF may be related to peroxidation damage, inflammatory factor, and mitochondrial injury. The CEF hepatotoxicity can be significantly reduced by licorice processing. EF should be safe for short-term use at pharmacopeial dose under the guidance of the TCM theory. The detoxification mechanism is probably related to the reduction of toxic components and antagonistic action of licorice.