Spleen deficiency can lead to various abnormal physiological functions of the spleen. Atractylodis Macrocephalae Rhizoma (AMR) is a traditional Chinese medicine used to invigorate the spleen and tonify qi. The study aimed to identify the primary active components influencing the efficacy of AMR in strengthening the spleen and replenishing qi through spectrum-effect relationship and chemometrics. Network pharmacology was used to investigate the mechanism by which AMR strengthens the spleen and replenishes qi, with molecular docking utilized for validation purposes. The findings indicated that bran-fried AMR exhibited superior efficacy, with atractylenolides and atractylone identified as the primary active constituents. Atractylenolide II emerged as the most influential component impacting the effectiveness of AMR, while the key target was androgen receptor. Furthermore, crucial pathways implicated included the mitogen-activated protein cascade (MAPK) cascade, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding, and RNA polymerase II sequence-specific DNA-binding transcription factor binding. In summary, our study has identified the primary active components associated with the efficacy of AMR and has provided an initial exploration of its mechanism of action. This offers a theoretical foundation for future investigations into the material basis and molecular mechanisms underlying the pharmacodynamics of AMR.

Ethnopharmacological relevanceThe quality requirements of Corydalis Rhizoma (CR) in different producing areas are uniform, resulting in uneven efficacy. As a genuine producing area, the effective quality control of CR in Zhejiang Province (ZJ) could provide a theoretical basis for the rational application of medicinal materials.Aim of the studyThe purpose of this study was to effectively distinguish the CR inside and outside ZJ, and provided a theoretical basis for the quality control and material basis research of ZJ CR.Materials and methodsThe core components of ZJ CR could be identified by HPLC combined with chemometrics screening, and the quality of CR from different producing areas was evaluated by a genetic algorithm-back propagation (GA-BP) neural network. Chromaticity and near-infrared (NIR) spectroscopy were used to identify CR inside and outside ZJ, and rapid content prediction was realized. The analgesic effect of CR in different regions was compared by a zebrafish analgesic experiment. Analgesic experiments in rats and analysis of the research status of quality components were used to screen the quality control components of ZJ CR.ResultsThe contents of palmatine hydrochloride (YSBMT), dehydrocorydaline (TQZJJ), tetrahydropalmatine (YHSYS), tetrahydroberberine (SQXBJ), corydaline (YHSJS), stylopine (SQHLJ), and isoimperatorin (YOQHS) in ZJ CR were higher than those in CR from outside ZJ, but the content of protopine (YAPJ) and berberine hydrochloride (YSXBJ) was lower than that in CR from outside ZJ. YHSJS and SQHLJ could be used as the core components to identify ZJ CR. The GA-BP neural network showed that the relative importance of ZJ CR was the strongest. Chroma-content correlation analysis and the NIR qualitative model could effectively distinguish CR from inside and outside of ZJ, and the NIR quantitative model could quickly predict the content of CR from inside and outside of ZJ. Zebrafish experiments showed that ZJ, Shaanxi (SX), Henan (HN), and Sichuan (SC) CR had significant analgesic effects, while Hebei (HB) CR had no significant analgesic effect. Overall comparison, the analgesic effect of ZJ CR was better than that of CR outside ZJ. The comprehensive score of the grey correlation degree between YAPJ, YSBMT, YSXBJ, TQZJJ, YHSYS, YHSJS, SQXBJ, and SQHLJ were higher than 0.9, and the research frequency were extremely high.ConclusionsThe relative importance of the content and origin of most components of ZJ CR was higher than that of CR outside ZJ. The holistic analgesic effect of ZJ CR was better than that of CR outside ZJ, but slightly lower than that of SX CR. YHSJS and SQHLJ could be used as the core components to identify ZJ CR. YAPJ, YSBMT, YSXBJ, TQZJJ, YHSYS, SQXBJ, YHSJS, and SQHLJ could be used as the quality control components of ZJ CR. The multidimensional evaluation method used in this study provided a reference for the quality control and material basis research of ZJ CR.

Radix Dipsaci (RD) is the dry root of the Dipsacus asper Wall. ex DC., which is commonly used for tonifying the kidney and strengthening bone. The purpose of this study was to analyze the difference between raw and salt-processed RD from the chemical composition comprehensively. The fingerprints of raw and salt-processed RD were established by HPLC-DAD to determine the contents of loganin (LN), asperosaponin VI (AVI), caffeic acid (CaA), dipsanoside A (DA), dipsanoside B (DB), chlorogenic acid (CA), loganic acid (LA), isochlorogenic acid A (IA), isochlorogenic acid B (IB), and isochlorogenic acid C (IC). The results showed that after processing with salt, the components with increased contents were LA, CaA, DA, and AVI, and the components with decreased contents were CA, LN, IB, IA, IC, and DB. Then, the chemometric methods such as principal component analysis (PCA) and fisher discriminant analysis (FDA) were used to evaluate the quality of raw and salt-processed RD. In the classification of raw and salt-processed RD, the order of importance of each chemical component was LA > DB > IA > IC > IB > LN > CA > DA > AVI > CaA. These integrated methods successfully assessed the quality of raw and salt-processed RD, which will provide guidance for the development of RD as a clinical medication.

Anxiety disorders, a prevalent mental health condition often stemming from chronic stress, are characterized by uncontrollable emotional responses, heightened psychological stress, and cognitive impairment. Ziziphi Spinosae Semen, a traditional Chinese medicine (TCM), is widely used for its calming effects. Among its flavonoid components, spinosin serves as a primary bioactive compound, playing a significant role in treating psychiatric disorders. However, the mechanisms underlying the anxiolytic effects of spinosin are not fully elucidated. This study explores the protective effects of spinosin against anxiety in mice subjected to chronic restraint stress (CRS). Male C57BL/6J mice were subjected to restraint stress modeling for 10 consecutive days, and the treatment groups were gavaged with spinosin at doses of 1.25 mg/kg, 2.5 mg/kg, and 5 mg/kg, respectively. Behavioral experiments including the elevated plus maze test (EPM), open field test (OFT), and novelty suppressed feeding test (NSF) were conducted to confirm the successful establishment of the CRS model and the anxiolytic effect of spinosin. Additionally, spinosin normalized neurotransmitter levels and mitigated inflammation and neuronal damage in the hippocampus (HPC) and prefrontal cortex (PFC). Mechanistically, spinosin treatment significantly modulated the extracellular signal-regulated kinase 1/2 (ERK1/2)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway, a key axis in anxiety regulation. The upregulation of ERK1/2, p-CREB, and BDNF proteins significantly alleviated anxiety, suggesting that spinosin plays a pivotal role in treating CRS-induced anxiety disorders. Our findings indicate that spinosin treatment can ameliorate anxiety and that it verifies a previously unrecognized mechanism, providing crucial evidence for future research on anti-anxiety medications.

ETHNOPHARMACOLOGICAL RELEVANCE:Kidney-Yang deficiency syndrome (KYDS) is one of the common diseases of the elderly and closely related to the ageing of the body, it has a major impact on the quality of life of the patient. Eucommiae Cortex (EC) is the dried bark of Eucommia ulmoides Oliv. Which has the effect of tonifying the liver and kidneys, strengthening the muscles and bones. In Traditional Chinese Medicine clinics, EC is commonly used in the treatment of KYDS, but the material basis for the improvement of its efficacy in treating KYDS after salt processing remains unclear.AIM OF THE STUDY:This study aimed to find the main active ingredients that could improve the treatment of KYDS efficacy of EC after salt processing.MATERIALS AND METHODS:Firstly, the fingerprints of raw and salt-processed EC were established to determine the common components by using HPLC, and then an experimental study on the treatment of KYDS efficacy was carried out to compare the difference in the efficacy between raw and salt-processed EC. Thirdly, the spectrum-effect relationship of chemical components and pharmacodynamic indexes was established by using Grey Relational Analysis and Entropy Method. Finally, the network pharmacology and molecular docking technique was used to verify the kidney tonifying effect of the active ingredients of EC.RESULTS:According to the results of the analysis of hormonal index levels on the hypothalamic-pituitary-target gland axis and the extent of renal lesions, the therapeutic effect of EC on KYDS was mainly reflected in the regulation of the Adrenocorticotropic hormone, Corticosterone in the hypothalamic-pituitary-adrenal axis and Tri-iodothyronine, Tetra-iodothyronine in the hypothalamic-pituitary-thyroid axis, moreover the therapeutic effect of salt-processed EC was stronger than that of raw EC. The pharmacologically active ingredients that improved its treatment of KYDS efficacy after salt processing were peak 1 (geniposidic acid), peak 2 (chlorogenic acid), peak 5 (geniposide), peak 6 (genipin), peak 7 (pinoresinol diglucoside) and peak 11 (hyperoside). Meanwhile, the results of network pharmacology and molecular docking showed that the 6 active ingredients could exert kidney tonic effects through multiple signaling pathways by acting on core targets such as AKT1 and PTGS2.CONCLUSION:As far as we known, this was the first time to establish and compare the spectrum-effect relationship between raw and salt-processed EC, which laid the foundation for the pharmacokinetics studies of EC and provided a reference for future EC studies.

Ethnopharmacological relevance: The quality control methods of different specifications of Corydalis Rhizoma in Zhejiang China (ZJ CR) are the same, so the quality of each specification couldnot be guaranteed. To clarify the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications could provide reference for the quality control of ZJ CR. Aim of the study: The purpose of this study was to establish a quality control method for ZJ CR with different specifications and to screen out the pharmacodynamic material basis of ZJ CR with different specifications. Materials and methods: Firstly, according to the existing grading standards, the medicinal materials were divided into specifications, and the character indexes of ZJ CR with different specifications were established. The quality indexes were established by HPLC, network pharmacology and literature retrieval. The correlation between the trait indexes and quality indexes of ZJ CR with different specifications was analyzed, and the best quality control method was established. Further combined with the pharmacodynamic indexes of ZJ CR with different specifications, the pharmacodynamic material basis of ZJ CR with different specifications was screened out by spectrum-effect analysis. The correlation between trait indexes and pharmacodynamic indexes was analyzed to verify the rationality of grade standard. Results: The three specifications of ZJ CR were CR (Diameter >= 1.1 cm), CR (Diameter <1.1 cm), and CR (No size distinction). Diameter, width, thickness, grain weight, volume and 50 g grain number could be used as the trait indexes of ZJ CR. Protopine (CR1), palmatine hydrochloride (CR2), berberine hydrochloride (CR3), dehydrocorydaline (CR4), tetrahydropalmatine (CR5), tetrahydroberberine (CR6), corydaline (CR7), stylopine (CR8) and isoimperatorin (CR9) were identified. Total components, core components (CR5, CR6, CR7 and CR8), alcohol-soluble extracts (ASE) could be used as quality indexes. The best quality control methods of the three specifications respectively were: the larger the diameter and grain weight, the smaller the number of 50 g grains; The larger the diameter, the smaller the volume, thickness, width and number of 50 g particles; The larger the grain weight and volume, the smaller the number of 50 g grains. The main analgesic components of the three specifications respectively were: CR1, CR2 and core components; CR2, CR4; CR8, CR9. The larger the diameter and the less the number of 50 g grains, the better the analgesic effect of ZJ CR, and the grade standard was reasonable. Conclusions: This study showed that the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications were different, which may be caused by the differences in traits and the contribution of main active ingredients. This study constructed an evaluation model combining external traits, internal quality and overall efficacy, and provided theoretical support for the rationality of ZJ CR grade standard.

目的 分析并评价不同厂家浙贝母配方颗粒的质量.方法 收集10批不同厂家浙贝母配方颗粒样品,1批浙贝母饮片,根据2020年版《中国药典》中收载的颗粒剂质量检测方法,结合浙贝母饮片检测指标对11批样品进行质量比较分析,比较不同厂家浙贝母配方颗粒的粒度、干燥失重、溶化性、浸出物、贝母素甲和贝母素乙含量等指标,建立不同厂家浙贝母配方颗粒的指纹图谱及相似度评价,采用PCA、OPLS-DA分析不同厂家浙贝母配方颗粒差异性.结果 不同厂家浙贝母配方颗粒的质量存在较大差异,各批次样品粒度检查、薄层色谱鉴别、浸出物测定均符合药典规定标准,干燥失重检查均符不合药典规定,H样品的溶化性最优.综合各项指标分析可知:E样品总体质量分析结果相对较好,溶化性、粒度、总灰分、浸出物等各项指标均符合药典规定,且贝母素甲、贝母素乙的含量较高.结论 不同厂家浙贝母配方颗粒的质量差异较大,有必要统一规范浙贝母配方颗粒的制备工艺.

目的 研究醋延胡索炮制过程中原阿片碱、盐酸巴马汀、盐酸小檗碱、去氢紫堇碱、延胡索乙素、四氢小檗碱、延胡索甲素含量与色度值的相关性.方法 该药物分析采用 Agilent ZORBAX-Extend-C18 色谱柱(4.6 mm×250 mm,5 μm);流动相 0.6%乙酸-乙腈,梯度洗脱;体积流量 1.0 mL/min;柱温 25℃;检测波长 280 nm.以不同炮制时间点醋延胡索为研究对象,比较色度值(L*、a*、b*、E*ab)与生物碱含量的相关性.结果 7 种生物碱在各自范围内线性关系良好(R2≥0.998 1),平均加样回收率 98.35%～101.24%,RSD小于 2%.炮制时间为 0～15 min时,L*、b*、E*ab与生物碱含量呈显著负相关,a*与生物碱含量呈显著正相关;炮制时间为 15～30 min时,L*、b*、E*ab与生物碱含量呈显著正相关,a*与生物碱含量呈显著负相关.醋延胡索在炮制过程中颜色由黄转黑时,生物碱含量升高;由黑转红时,生物碱含量降低,炮制时间为 15 min时最高.结论 该方法准确可行,可快速实现不同炮制时间点醋延胡索质量客观评判.

Ethnopharmacological relevance: Dipsaci Radix (DR) is the dry root of Dipsacus asper Wall. ex DC. Aim of the study: The purpose of this study was to compare the effects of DR on rats before and after salt-processed with kidney yang deficiency syndrome (KYDS), and we selected the BMP-Smad signaling pathway to explore the mechanism of DR.Materials and methods: The model of KYDS was established by subcutaneous injection of hydrocortisone, the crude DR (CDR) and salt-processed DR (SDR) were given the corresponding dose (2 g/kg, 4 g/kg, and 6 g/kg). The organ index and the contents of adrenocorticotropic hormone (ACTH), cortistatin (CORT), thyroid hormone (T4), tumor necrosis factor-alpha (TNF-alpha), testosterone (T), estradiol (E2), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), Na+-K+-ATPase, and growth hormone (GH) in serum were measured to evaluate the intervention effect of DR on KYDS rats. The expression of Smad 1, Smad 4, Smad 5, Smad 8, and BMP 7 protein in kidney was determined by immunohistochemistry, quantitative PCR (qPCR) and Western blot analysis. The effects of DR on 5 expression factors in the BMP-Smad signaling pathway were studied. Constituents absorbed into blood were identified by UPLC-Q-TOF/MS.Results: The results showed that compared with the model group, the thymus and kidney index, as well as the contents of ACTH, CORT, cAMP, GH, Na+-K+-ATPase, T, T4, and E2 were significantly increased in the CDR and SDR groups, and the contents of cGMP and TNF-alpha were significantly decreased. Compared with the CDR high dose group, ACTH, Na+-K+-ATPase, T, and T4 were significantly increased in the SDR high dose group. The results of immunohistochemistry, qPCR, and Western blot analysis showed that compared with the model group, the expression levels of Smad 1, Smad 4, Smad 5, Smad 8 and BMP 7 proteins in the kidney of DR groups were significantly increased. And SDR groups tended to be better than CDR groups. 8 constituents migrating to blood were identified.Conclusion: This study showed that both CDR and SDR could have a good therapeutic effect on KYDS, and SDR was better than CDR. This study chose the BMP-Smad signaling pathway to study the mechanism of DR in the treatment of KYDS and provided a scientific basis for the processing mechanism of salt-processed.

Objective:A HPLC-MS method was established for the determination of pharmacokinetics of two main com-ponents in plasma of rats in crude and sweated Dipsaci Radix,to study the pharmacokinetic characteristics.Methods:The rats were orally administered with water extract of crude and sweated Dipsaci Radix.Orbital sinus blood was taken at the specified time before and after administration.HPLC-MS was used to determine the concentration of loga-nin and asperosaponin Ⅵ in rat plasma of crude and sweated Dipsaci Radix.Results:Loganin and asperosaponin Ⅵ could be detected in the blood of rats after oral administration for 5 min.Crude Dipsaci Radix:the half-life t1/2 of loga-nin was 93.79 min,and that of asperosaponin Ⅵ was 86.51 min.Sweated Dipsaci Radix:loganin t1/2 was 69.71 min,asperosaponin Ⅵ t1/2 was 85.78 min;the Cmax and AUC of loganin and asperosaponin Ⅵ of crude Dipsaci Radix were larger,indicating that loganin and asperosaponin Ⅵ of crude Dipsaci Radix were more conducive to the efficacy.Con-clusion:This method is suitable for the determination of plasma concentration and pharmacokinetic study of loganin and asperosaponin Ⅵ in rats of crude and sweated Dipsaci Radix.The experimental results showed that loganin and asper-osaponin Ⅵ in crude Dipsaci Radix are more conducive to the efficacy.

In order to quickly determine the processing degree and quality of Polygonati Rhizome (PR), the rapid qualitative and quantitative model for the whole steaming process was established in this study. Firstly, the contents and the chromaticity value of polysaccharide, saponin, 5-hydroxymethyl furfural (5-HMF), 5-hydroxymaltol, polygonatine A, fructose, glucose, sucrose, and the chromaticity value in 98 batches of PR during the whole processing were determined. The chromaticity value was used to establish the qualitative discrimination model of the whole steaming process by partial least squares-discriminant analysis (PLS-DA). Then, the near-infrared (NIR) spectra of all samples were collected to establish the NIR qualitative discriminant model. The samples of four different processing stages, raw products, less processed products, finished processed products, and over processed products, were well distinguished in two qualitative models, and the model validation results were good. Finally, the chromaticity value, the content, and NIR spectra were imported into TQ Analyst software. After screening the pretreatment methods, the optimal pretreatment method combined with partial least squares (PLS) was selected to establish the NIR quantitative model of 11 indicators. The correlation coefficient of models was above 0.9, indicating that the model had high prediction accuracy. Through the establishment of the qualitative discriminant model, the different processing degrees of PR could be accurately distinguished, and the NIR quantitative prediction model could accurately predict the content and the chromaticity value, which provided a scientific basis for the quality identification of PR in the whole process of processing.

目的 评价不同产地浙贝母质量.方法 采用UV-Vis、HPLC-ELSD、HPLC-DAD法测定总生物碱含量,贝母素甲、贝母素乙总含量,水溶性成分(尿嘧啶、胞苷、尿苷、2-脱氧尿苷、肌苷、腺嘌呤、胸苷、腺苷、2-脱氧腺苷)总含量,主成分分析(PCA)、偏最小二乘法-判别分析(OPLS-DA)评价质量.结果 浙江产浙贝母中总生物碱含量,贝母素甲、贝母素乙总含量,9 种水溶性成分总含量均高于湖南安化、湖北宜昌产,其中舟山产样品中 9 种水溶性成分总含量、总生物碱含量,象山产样品中贝母素甲、贝母素乙总含量显著高于其他浙江产地样品中.结论 浙江产浙贝母质量较好,以舟山、象山产更明显.本实验可为该药材采购产地选择及优良新品种选育提供参考.

ETHNOPHARMACOLOGICAL RELEVANCE:Dipsaci Radix (DR) is the dry root of the Dipsacus asper Wall. ex DC., which has the function of tonifying the liver and kidney, continuing tendons and bones, and regulating blood vessels. However, there are few reports on the main active ingredients.AIM OF THE STUDY:This study aimed to find the main active components of DR in the treatment of osteoarthritis (OA) by spectrum-effect relationship and compare the differences between RDR and WDR.MATERIALS AND METHODS:Firstly, the high-performance liquid chromatography (HPLC) method was used to establish the fingerprint of DR, and 10 peaks of them were determined by UPLC-Q-TOF/MS. Then, the OA rat model was established by injecting sodium iodoacetate to study the effect of DR on OA. The spectrum-effect relationship was analyzed by grey relational analysis (GRA) and Pearson correlation analysis.RESULTS:According to the pharmacological results, compared with the model group, the cartilage score, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), and Mankin score of rats in low, medium and high dose groups were decreased, and the therapeutic effect of wine-processed DR tended to be better than raw DR at the same dose. Finally, the active components of DR were preliminarily determined as 4 (loganic acid), 6 (chlorogenic acid), 8 (caffeic acid), 14 (dipsanoside B), 16, and 17 (asperosaponin VI) which had a large correlation in GRA and Pearson correlation analysis.CONCLUSION:This study established the spectrum-effect relationship between the raw and wine-processed DR for the first time, which provided a theoretical basis for the study of the pharmacodynamic substance basis of DR before and after processing. This research provided a reference for the subsequent study of DR.

目的 建立麸炒白术Atractylodis Macrocephalae Rhizoma炮制全过程的定性判别模型,筛选出可以表征麸炒白术不同炮制程度的气味成分.方法 制备麸炒白术饮片,不同时间点取样进行分析.采用Heracles NEO超快速气相电子鼻采集气味图谱,与Arochembase数据库对比得到气味成分信息,结合峰面积分析气味成分的变化规律并进行化学计量学分析.结果 通过判别因子分析(discriminant factor analysis,DFA)、正交偏最小二乘-判别分析(orthogonal partial least squares-discriminant analysis,OPLS-DA)、层次聚类分析(hierarchical cluster analysis,HCA)等将麸炒白术炮制全过程样品成功分为4类:生品、炮制不及、炮制成品和炮制太过.在炮制过程中,3-甲基十五烷、十二烷基丙酸酯、正辛基环已烷、1,3-二硝基苯、8-甲基十五烷5个气味成分的峰面积占比较高,其中1,3-二硝基苯在炮制全过程中峰面积呈降低趋势;3-甲基十五烷从炮制不及到炮制成品的过程中峰面积呈增加的趋势,从炮制成品到炮制太过的过程中峰面积呈降低趋势;十二烷基丙酸酯从生品到炮制不及和炮制成品到炮制太过的过程中峰面积呈降低趋势;正辛基环已烷、8-甲基十五烷从生品到炮制不及的过程中峰面积呈降低趋势,从炮制不及到炮制成品的过程中峰面积呈增加趋势,从炮制成品到炮制太过的过程中峰面积呈降低趋势,且上述5个气味成分的变量重要性投影值均大于1.结论 Heracles NEO超快速气相电子鼻能通过气味对麸炒白术不同炮制程度样品进行定性判别,3-甲基十五烷、十二烷基丙酸酯、正辛基环已烷、1,3-二硝基苯及8-甲基十五烷5个气味成分的变化可作为麸炒白术不同炮制程度的判断依据.