This study investigated the structural and anti-inflammatory properties of phenolic acids from Oreocome striata (DC.) Pimenov & Kljuykov. Phytochemical exploration yielded one undescribed ferulic acid ester - Oreocomeate A (1), along with eight known phenolic derivatives. Compound 1's 7'S,8'R configuration was assigned via combined spectroscopic analysis (HR-ESI-MS, NMR) and ECD calculations. Notably, compounds 2 and 4 were first reported as isolates from this plant family. In bioactivity evaluation, compound 1 exhibited the strongest NO inhibition with the IC50 value of 15.71 ± 1.1 μM. Molecular docking models suggested potential interactions between compounds 1-9 and MT-ND target, indicating a mechanistic basis for their modulation of inflammatory pathway. These findings collectively identify phenolic acids as key bioactive constituents underlying CX's traditional anti-inflammatory applications.

Two novel 5,5-spiroketal sesquiterpenoid isomers, duhuosesquid A (1) and duhuosesquid B (2) were isolated from the roots of Angelica biserrata (R. H. Shan & Yuan) C. Q. Yuan & R. H. Shan. Their structures were determined by extensive spectroscopic analyses, and the absolute configurations of 1 and 2 were assigned via NMR calculations and ECD calculations. Additionally, their anti-inflammatory activities were evaluated through in vitro assays, with IC50 values of 15.9 ± 1.2 μM and 14.2 ± 0.5 μM, respectively.

Background: Migraine is widely recognized as the third most prevalent medical condition globally. Tianshu capsule (TSC), derived from "Da Chuan Xiong Fang" of the Jin dynasty, is integral in the clinical treatment of migraine. However, the chemical properties and therapeutic mechanisms of TSC different portions remain unclear. Purpose: This study was designed to investigate the effects of TSC different portions (including small molecular TSCP-SM and polysaccharides TSC-P) on migraine and explore the underlying mechanisms. Study design and methods: First of all, migraine rats were established by nitroglycerin injection and treated with TSC, TSC-P, and TSC-SM. ELISA, qPCR, and immunofluorescence were used to evaluate the pharmacological effects on migraine rats. Secondly, UPLC-Q/TOF-MS and GC--MS were employed to detect the components of TSC-SM. PMP-HPLC, NMR, FT-IR, UV-Vis, AFM, and SEM were used for the chemical profiling of polysaccharides. Thirdly, the metabolic behavior profile of TSC-P was characterized by oral administrated fluorescence-labeled TSC-P and detected by NIRF imaging. Finally, the anti-migraine mechanisms were explored by determining the composition of gut microbiota, analyzing colonic short-chain fatty acids (SCFAs), and examining serum tryptophan-related metabolites. Results: Both small molecules (45 volatiles and 114 small molecules) and polysaccharides (including Glc, Ara, Gal, and Gal A) have exhibited effectiveness in alleviating migraine, and this efficacy is associated with reduced CGRP and iNOS levels, along with increased beta-EP expressions. Further mechanistic exploration revealed that small-molecules exhibited effectiveness in migraine treatment by exerting antioxidative actions, while polysaccharides demonstrated superior therapeutic effects in regulating 5-HT levels. By monitoring the metabolic behavior of polysaccharides with fluorescent labeling, it was observed that TSC-P exhibited poor absorption. Instead, TSC-P demonstrated its therapeutic effects by modulating the aberrations in gut microbiota (including Alloprevotella, Muribaculaceae_ge, and Ruminococcaceae_UCG-005), cecum short-chain fatty acids (such as isobutyric, isovaleric, and valeric acids), and serum tryptophan-related metabolites (including indole-3-acetamide, tryptophol, and indole-3-propionic acid). Conclusion: This research provides innovative insights into chemical composition, metabolic behavior, and proposed anti-migraine mechanisms of TSC from a polarity-based perspective, and pioneering an exploration focused on the polysaccharide components within TSC for the first time.

Review The Application of Artificial Intelligence in the Research and Development of Traditional Chinese Medicine Zhipeng Ke 1,2, Minxuan Liu 1,2,3, Jing Liu 1,2, Zhenzhen Su 1,2, Lu Li 1,2, Mengyu Qian 1,2, Xinzhuang Zhang 1,2, Tuanjie Wang 1,2, Liang Cao 1,2, Zhenzhong Wang 1,2, and Wei Xiao 1,2, * 1 National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Lianyungang 222106, China 2 Jiangsu Kanion Pharmaceutical Co., Ltd, Lianyungang 222104, China 3 ‍School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210009, China * Correspondence: xw_kanion@163.com Received: 4 September 2023 Accepted: 4 November 2023 Published: 6 March 2024 Abstract: With the accumulation of data in the pharmaceutical industry and the development of artificial intelligence technology, various artificial intelligence methods have been successfully employed in the drug discovery process. The integration of artificial intelligence in Traditional Chinese medicine has also gained momentum, encompassing quality control of Chinese patent medicines, prescriptions optimization, discovery of effective substances, and prediction of side effects. However, artificial intelligence also faces challenges and limitations in Traditional Chinese medicine development, such as data scarcity and complexity, lack of interdisciplinary professionals, black-box models, etc. Therefore, more research and collaboration are needed to address these issues and explore the best ways to integrate artificial intelligence and Traditional Chinese medicine to improve human health.

One new butylphthalide ligusticumolide H (1), together with the known butylphthalides senkyunolide I (2), senkyunolide H (3), (3 R ,3'S)-3'-hydroxy-3-butylphthalide (4), (3 R)-4-hydrox y-3-butylphthalide (5) and senkyunolide C (6) was isolated from the rhizome of Ligusticum striatum DC. Their structures were deter-mined by extensive spectroscopic analyses including HR-ESI-MS, 1D and 2D NMR, and the absolute configuration of 1 was established by NMR and ECD calculations. Their effect on NO production in IL-1P-stimulated chondrocytes was also evaluated.

Three undescribed coumarins, 6-(3-hydroxy-3-methyl-2-oxobutyl)-7-methoxycoumarin (1), (R)-6-(1,3-dihydroxy-3-methyl-2-oxobutyl)-7-methoxycoumarin (2), angelol N (6), together with four known coumarins were isolated from the roots of Angelica pubescens. Their structures were determined by extensive spectroscopic analyses. The absolute configurations of compounds 2 and 6 were assigned via electronic circular dichroism (ECD). Their inhibitory effects on lipopoly-saccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells were evaluated. Compounds 1-4 exhibited moderate inhibitory activities.

The kidney-shaped, red-colord fruit from the plant, Schisandra chinensis (Turcz.) Baill, which belongs to the Schisandraceae family, is among the most popular remedies used in traditional Chinese medicine. The English name of the plant is "Chinese magnolia vine". It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. In some cases, these constituents affects the pharmacological efficacy of the plant. Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. However, because of the complex composition of Schisandra chinensis, the extraction yields of lignans are low. Thus, it is particularly important to study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine. Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. First, the effects of 12 adsorbents, including silica gel, acidic alumina, neutral alumina, alkaline alumina, Florisil, Diol, XAmide, Xion, and the inverse adsorbents, C18, C18-ME, C18-G1, and C18-HC, on the extraction yields of lignans were investigated. Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. Xion was chosen as an adsorbent for MSPD-HPLC analysis of lignans from Schisandra chinensis. Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. The limits of detection and quantification ranged from 0.0089 to 0.0294 μg/mL and 0.0267 to 0.0882 μg/mL, respectively. Lignans were tested at low, medium, and high levels. The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. Both intra-day and inter-day precisions were less than 3.6%. Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. Finally, the optimized method was successfully applied to analyze five lignans from Schisandra chinensis samples from 17 cultivation areas.

Mitochondria are critical for metabolic homeostasis of the liver, and their dysfunction is a major cause of liver diseases. Optic atrophy 1 (OPA1) is a mitochondrial fusion protein with a role in cristae shaping. Disruption of OPA1 causes mitochondrial dysfunction. However, the role of OPA1 in liver function is poorly understood. In this study, we delete OPA1 in the fully developed liver of male mice. Unexpectedly, OPA1 liver knockout (LKO) mice are healthy with unaffected mitochondrial respiration, despite disrupted cristae morphology. OPA1 LKO induces a stress response that establishes a new homeostatic state for sustained liver function. Our data show that OPA1 is required for proper complex V assembly and that OPA1 LKO protects the liver from drug toxicity. Mechanistically, OPA1 LKO decreases toxic drug metabolism and confers resistance to the mitochondrial permeability transition. This study demonstrates that OPA1 is dispensable in the liver, and that the mitohormesis induced by OPA1 LKO prevents liver injury and contributes to liver resiliency.

目的 基于核苷酸结合寡聚化结构域样受体蛋白3(NOD-like receptor family pyrin domain containing 3,NLRP3)/白细胞介素-1β(interleukin-1β,IL-1β)通路探讨筋骨止痛凝胶改善膝骨性关节炎大鼠膝关节炎症、疼痛的作用和机制.方法 70只雄性SD大鼠随机分为对照组,模型组,筋骨止痛凝胶高、中、低剂量(1.24、0.62、0.31 g/kg)组,扶他林(0.105g/kg)组和青鹏膏(0.105 g/kg)组,每组10只.对照组大鼠左膝关节腔注射50μL无菌生理盐水,其余各组注射40mg/mL单碘乙酸钠建立膝骨性关节炎大鼠模型,造模后1d开始给药,持续14d.测定各组大鼠机械痛阈值(paw withdrawal mechanical threshold,PWT)、热刺激缩足反射潜伏期(paw withdrawal thermal latency,PWTL)及足负重;采用苏木素-伊红(HE)染色观察膝关节滑膜组织病理情况;采用ELISA检测血清中IL-1β、前列腺素E2(prostaglandin E2,PGE2)及关节液中IL-1β水平;采用qRT-PCR检测滑膜组织中IL-1β、PGE2和NLRP3mRNA表达.结果 与模型组比较,各给药组大鼠PWT、PWTL和足负重均显著升高(P＜0.05、0.01);筋骨止痛凝胶低剂量组、扶他林组和青鹏膏组滑膜组织病理学评分显著降低(P＜0.01);筋骨止痛凝胶高剂量组血清和关节液中IL-1β水平均明显降低(P＜0.05、0.01),筋骨止痛凝胶低、中剂量组和青鹏膏组血清中PGE2水平明显降低(P＜0.05、0.01);筋骨止痛凝胶低剂量组和扶他林组滑膜组织中IL-1βmRNA表达水平均显著降低(P＜0.05、0.01),筋骨止痛凝胶低、中剂量组及扶他林组和青鹏膏组PGE2和NLRP3mRNA表达水平均显著降低(P＜0.05、0.01).结论 筋骨止痛凝胶可能通过调控IL-1β、PGE2、NLRP3炎症因子的表达,抑制滑膜炎进展,从而发挥抗膝骨性关节炎的作用.

目的 建立小儿健脾颗粒(Xiao'er Jianpi Granules,XJG)的定性、定量分析方法.方法 采用TLC法,以"整体鉴别"新模式为基础,建立了一样多测(炒莱菔子、甘草及陈皮)及一板多鉴(炒莱菔子、甘草)的鉴别方法.采用HPLC法,采用Kromasil C18色谱柱(150mm×4.6mm,3.5 μm),以0.1％三氟乙酸-乙腈为流动相进行梯度洗脱,进样量5μL,柱温30 ℃,体积流量1 mL/min,检测波长252nm(甘草酸)、275nm(甘草苷)、283nm(芸香柚皮苷、橙皮苷)、326nm(3,6'-二芥子酰基蔗糖、芥子碱硫氰酸盐).结果 建立的TLC鉴别方法,斑点清晰,能专属的鉴别处方中白术、陈皮、山药、炒莱菔子、焦山楂、甘草;建立了芥子碱硫氰酸盐、3,6'-二芥子酰基蔗糖、橙皮苷、芸香柚皮苷、甘草苷、甘草酸含量测定方法,6个成分在各自质量浓度范围内线性关系良好(r≥0.9999),精密度、稳定性及重复性良好,加样回收率为97.8％～101.6％;4批样品中芥子碱硫氰酸盐、3,6'-二芥子酰基蔗糖、橙皮苷、芸香柚皮苷、甘草苷、甘草酸的质量浓度分别为0.57～0.80、0.44～0.64、3.81～4.93、1.45～2.72、0.56～1.14、1.20～1.58mg/mL.结论 建立了 6 个药味的 TLC 鉴别方法,斑点清晰且专属性强.建立了 HPLC同时测定的6个成分含量测定方法,建立的方法快速、准确、专属性强,为其质量标准建立提供参考依据.

Objective To explore a method to evaluate the quality of Guizhi Fuling Capsules(桂枝茯苓胶囊,GZFLC)through its biological activity,which inhibits the contractile activity of uterine smooth muscle based on clinical anti-dysmenorrhea effect of GZFLC.Methods Uterine sensitivity in mice was increased by estrogen injection,and a contraction model of ex vivo uterine smooth muscle contraction in mice induced by oxytocin was established.The contraction frequency,amplitude and peak area of uterine smooth muscle before and after administration were recorded.Peak area was used as an indicator for normalized efficacy.The main influencing factors of the contraction model such as estrogen injection method and injection days,oxytocin concentration,animal age and GZFLC pretreatment methods were investigated.After the biological activity evaluation method of GZFLC was established,the methodology was investigated.A total of 10 batches of GZFLC qualified samples and two GZFLC high-temperature destruction samples were detected for biological activity.Results After ip 10 mg/(kg·d)estrogen for three consecutive days,the contraction peak area of smooth muscle was higher and the contraction rhythm was better;The optimal induction concentration of oxytocin was 0.050 μg/mL;The GZFLC was configured to a concentration of 0.125 g/mL and then dissolved ultrasonically for 60 min,which was conducive to the efficacy;The repeatability RSD was 11.298％,the intraday precision RSD was 12.452％,and the interday precision RSD was 10.43 8％;The half inhibitory concentration(IC50)of 10 batches of GZFLC was 1.526-1.631 mg/mL,and the IC50 of GZFLC was significantly increased after high temperature destruction.Conclusion The quality evaluation method of GZFLC based on anti-contractive activity of uterine smooth muscle is reproducible and precise,which provides a scientific basis for the establishment of comprehensive quality evaluation criteria for GZFLC.

目的 研究银杏二萜内酯K(ginkgolide K,GK)对D-半乳糖诱导的小鼠原代星形胶质细胞抗衰老作用及可能机制.方法 以小鼠原代星形胶质细胞为研究对象,建立D-半乳糖诱导的衰老模型,设置对照组、模型组和GK组,GK(50μg/mL)预处理3 h后,以150 mmol/LD-半乳糖造模6d,采用β-半乳糖苷酶染色法检测衰老星形胶质细胞;Western blotting法测定衰老标志蛋白(p21、p53和Lamin B1)、沉默信息调节因子1(silent information regulator 1,SIRT1)、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF、自噬标志蛋白微管相关蛋白 1 轻链 3-Ⅱ/Ⅰ(microtubule associated protein 1 light chain 3-Ⅱ/Ⅰ,LC3-Ⅱ/Ⅰ)和自噬选择性底物p62表达;ELISA检测衰老相关分泌表型[白细胞介素-6(interleukin-6,IL-6)、IL-1β、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)];免疫荧光检测增殖标志分子Ki67表达.结果 与对照组比较,D-半乳糖显著诱导原代星形胶质细胞β-半乳糖苷酶阳性表达(P＜0.001),促进衰老标志蛋白p21、p53的上调和Lamin B1的下调(P＜0.05、0.01),减少增殖标志分子Ki67的表达(P＜0.01),表明成功构建了公认的细胞衰老模型.与模型组比较,GK显著减少β-半乳糖苷酶阳性表达(P＜0.001),下调p21、p53和上调LaminB1蛋白的表达(P＜0.05、0.01),增加Ki67的表达(P＜0.01),表明GK具有抗衰老作用.此外,GK显著促进BDNF蛋白表达.(P＜0.05),减少TNF-α的分泌(P＜0.05),上调SIRT1和自噬标志蛋白LC3-Ⅱ/Ⅰ表达(P＜0.05、0.01),减少p62蛋白表达(P＜0.01).结论 GK可有效抑制原代星形胶质细胞的衰老,其作用机制可能与上调SIRT1、BDNF表达和促进细胞自噬有关,从而多维度协同达到抗细胞衰老的效应.

Objective To explore the protective effect and mechanism of ginkgo diterpene lactone（GDL）on cell senescence induced by oxidative stress. Methods The cell model of PC12 neuron aging induced by H 2 O 2 was established, and platelet activating factor antagonist WEB-2086 or GDL was pretreated respectively, cell activity was detected by CCK-8 kit; β-Galactosidase staining was used to detect the aging cell rate; The average nuclear volume of cells was observed by DAPI staining; p21, p53, Lamin B1, platelet activating factor receptor（PAFR）, Sirtuin 1（SIRT1）, phosphorylated signal transducer and activator of transcription 3（p-STAT3）,brain-derived neurotrophic factor（BDNF）and neurotrophic factor 3（NT3）and nerve growth factor（NGF）protein expressions were detected by Western blotting; Apoptosis was observed by TUNEL staining. Results Compared with control group, the activity of cells in model group was significantly decreased（P ＜ 0.05）, the number of aging cells was significantly increased（P ＜ 0.01）and the expression of PAFR was significantly increased（P ＜ 0.001）. Compared with model group, WEB-2086 significantly inhibited the expression of PAFR（P ＜ 0.001）, significantly increased the expression of SIRT1 protein（P ＜ 0.05）, and significantly reduced the aging cell rate of β-galactosidase（P ＜ 0.05）. GDL significantly increased the cell viability（P ＜ 0.05）, significantly increased the expressions of Lamin B1, SIRT1, BDNF and NT3（P ＜ 0.05, 0.01）, and significantly decreased the expressions of PAFR, p-STAT3, p21 and p53（P ＜ 0.05, 0.01）. Conclusion GDL can protect neurons, inhibit apoptosis and delay the aging of PC12 neurons induced by oxidative stress represented by H 2 O 2 , and its mechanism may be related to antagonizing PAFR and regulating SIRT1/STAT3 signaling pathway.

目的 通过HPLC-Q-TOF-MS/MS分析小儿佛芍和中颗粒(XFHG)中的化学成分,依据解析的化学成分结合网络药理学预测其治疗功能性腹痛的药效物质基础,筛选出潜在功效成分,预测作用机制.方法 采用HPLC-Q-TOF-MS/MS对XFHG进行化学成分分析,分别在正、负离子模式下扫描,结合对照品与中药系统药理学数据库与分析平台(TCMSP)、文献中的碎片离子信息、保留时间进行匹配,确认化学成分.筛选质谱解析得到的化学成分中口服生物利用度≥20％、类药性≥0.5的成分,同时纳入《中国药典》2020年版中规定的指标成分以及SwissADME数据库筛选得到的成分作为活性成分;通过TCMSP、Massbank、本草组鉴数据库、Genecards数据库及文献筛选,分别建立XFHG活性成分靶点数据库、功能性腹痛相关疾病的靶点数据库,筛选出共同靶点,导入网络可视化软件Cytoscape 3.9.1中,构建"XFHG-成分-功能性腹痛"靶点相互作用网络图,筛选出核心成分;共有靶点导入STRING11.5数据库中,构建蛋白质-蛋白质相互作用(PPI)网络图,并将得到的数据导入Cytoscape 3.9.1中,筛选出核心作用的靶点;将核心靶点导入DAVID数据库进行京都基因与基因组百科全书(KEGG)通路和基因本体(GO)富集分析.结果 XFHG定性分析中共解析出96个化学成分,包括26个黄酮类、17个有机酸类、13个萜类、11个生物碱类、6个柠檬苦素类、8个苯丙素类、4个苯乙醇苷类及11个其他类;筛选出发挥治疗功能性腹痛作用的核心成分15个,来源于6味药材,包括小檗碱、芍药苷、连翘酯苷A、连翘苷、吴茱萸碱、吴茱萸次碱等;XFHG 治疗功能性腹痛的核心靶点有 TNF、AKT1、IL6、IL-1β、VEGFA、TP53、CASP3、PTGS2、CAT、MAPK3;KEGG通路分析共得到109条通路,免疫应答、炎症反应相关的信号通路排名靠前;GO富集分析得到生物过程(BP)条目145个、细胞组分(CC)条目10个、分子功能(MF)条目9个,富集值排名靠前的条目涉及脂多糖介导的信号通路、糖皮质激素反应、一氧化氮生物合成过程的正向调控等与炎症反应相关的生物过程.结论 根据HPLC-Q-TOF-MS/MS解析的化学成分结合网络药理学预测了XFHG治疗功能性腹痛的潜在功效成分,预测其作用机制与免疫调节、抗炎相关.

苓桂术甘汤出自《金匮要略》,是温阳化饮法治疗"痰饮病"的代表方,由茯苓、桂枝、白术、甘草组成,具有温阳化饮、健脾利湿之功效,用于中阳不足之痰饮,证见胸胁支满、目眩心悸、短气而咳、舌苔白滑、脉弦滑,为国家中医药管理局发布的《古代经典名方目录(第一批)》之第 19 首,《古代经典名方关键信息表(7 首方剂)》之第 1 首.为了满足临床需要,课题组前期依据《按古代经典名方目录管理的中药复方制剂药学研究技术指导原则(试行)》和《中药注册分类及申报资料要求》的要求,将苓桂术甘汤开发为现代制剂苓桂术甘颗粒,是首个按照中药注册分类3.1 类按古代经典名方目录管理的中药复方制剂申请上市的品种,于2022 年12 月27 日首个获批.本研究探讨苓桂术甘颗粒研发过程关键环节的技术要点,以期为其他经典名方复方制剂的相关研究提供思路与参考.

目的 为加快实现中药生产过程中对中药配方颗粒的质量控制,从粉体物料属性出发,探究其对水提工艺下干法制粒的中药配方颗粒溶化性影响机制.方法 以60种中药配方颗粒及中间体混合粉为研究对象,通过对各品种混合粉粉体属性进行测定,建立粉体物性参数与颗粒溶化性关联模型.采用二维矩阵热点图对各品种间及物性指标间相似性进行分析,结合系统聚类分析对其进行归类,并运用多元统计方法初步筛选影响水提工艺下中药配方颗粒溶化性的关键因素.结果 各品种间粉体物性参数相关系数在-0.951～1.000,并按照各品种物理属性大致可以分为5类,结合变量投影响应值(variable importance for the projection,VIP)、自变量回归系数与方差膨胀因子(variance inflation factor,VIF)分析,最终筛选出其休止角(a)、含水量(HR)、吸湿性(H)与比表面积(SSA)4个指标为影响中药配方颗粒溶化性的关键物料属性(critical material attributes,CMAs).结论 基于中药粉体物料属性与数据分析初步探寻影响水提条件下干法制粒的中药配方颗粒的溶化性机制,为后期工艺改进提供参考.

目的 探究水-醇双提工艺下中药复方粉末影响颗粒流动性的关键物性参数.方法 以水-醇双提工艺下杏贝止咳颗粒(Xingbei Zhike Keli,XZK)、桂枝茯苓胶囊(Guizhi Fuling Jiaonang,GFJ)以及参乌益肾片(Shenwu Yishen Pian,SYP)3个中药复方品种的制粒前粉末与制粒后颗粒为研究对象,采用多元统计分析方法,绘制粉末物理指纹图谱,结合Pearson相关系数评价粉末质量一致性;采用主成分分析(principal component analysis,PCA)结合因子分析评价颗粒流动性;并构建以松装密度(Da)、振实密度(Dc)、休止角(a)、豪斯纳比(IH)、粒径＜50 μm百分比(Pf)、均匀性(HG)、均齐度(UN)、粒径(D10、D50、D60、D90)、分布宽度(span)、分布范围(width)、比表面积(SSA)、孔隙率(Ie)、卡尔指数(IC)、含水量(HR)、吸湿率(H)为自变量、以颗粒流动性总因子得分(TFS)为因变量的正交偏最小二乘法-判别分析(orthogonal partial least-squares discrimination analysis,OPLS-DA)模型,用以辨识粉末关键物性参数.结果 分别构建了 3个品种各15批粉末的物理指纹图谱,结合Pearson相关系数结果显示3个品种粉末质量一致性良好,其中SYP颗粒优于XZK颗粒再优于GFJ颗粒;计算得颗粒流动性TFS,整体来看流动性XZK颗粒优于SYP颗粒再优于GFJ颗粒;OPLS-DA模型优化后辨识出H、UN、SSA、HR为影响颗粒流动性的关键物性参数,置换检验结果表明模型有效可靠.结论 基于OPLS-DA模型辨识出影响水-醇双提工艺下中药复方粉末影响颗粒流动性的关键物性参数为H、UN、SSA、HR.

目的 探究水-醇双提物的中药物料粉体性质对颗粒吸湿性的影响,筛选潜在关键影响因素.方法 以5个品种共计175批中间体粉末的18个粉体参数为自变量,颗粒吸湿性为因变量,进行原始数值描述、变量相关性分析、主成分分析(principal component analysis,PCA)和偏最小二乘法(partial least squares,PLS)预测模型分析,研究水-醇双提物的中药物料粉体性质对颗粒吸湿性的影响.结果 原始数值描述发现中间体粉末及颗粒均存在强吸湿性,但相对于粉末,颗粒吸湿性较低,表明制粒工艺一定程度上可改善粉末吸湿性;相关性分析结果显示中间体粉末的粒度分布宽度、均匀性、吸湿性、含水量与颗粒吸湿性呈强相关;PCA确定2个关键主成分,其方差贡献率分别为57.13和19.82;PLS预测模型在2个关键主成分前提下,以变量投影重要性(variable importance in the projection,VIP)、回归系数、方差膨胀因子(variance inflation factor,VIF)及平均相对预测误差为判定指标,确定粉末含水量、吸湿性、振实密度和D50是影响颗粒吸湿性的潜在关键物性指标.结论 采用相关性分析、PCA和PLS预测模型探究中药粉体物料性质对颗粒吸湿性的影响,为中药粉体物料性质影响颗粒吸湿性的共性技术研究提供数据依据和理论参考.

目的 基于UPLC-Q-TOF-MS/MS技术和网络药理学探讨麻杏止哮颗粒治疗哮喘的有效成分和作用机制.方法 通过UPLC-Q-TOF-MS/MS技术及中药系统药理学数据库与分析平台(TCMSP)数据库筛选麻杏止哮颗粒的活性成分和相关靶点;利用Disgenet、Genecards数据库检索哮喘疾病靶点,利用韦恩图绘制平台获取共有靶点,并将信息导入Cytoscope3.9.1软件和STRING在线分析平台,进行网络拓扑学分析,构建药物关键活性成分-关键靶点网络和药物-有效成分-核心靶点网络;基于核心靶点通过DAVID数据库进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析.结果 结合质谱分析与数据库筛选得到药物活性成分24个,药物靶点147个,疾病靶点1483个,共同靶点106个,关键活性成分23个;经蛋白质相互作用分析及网络拓扑分析后,获取核心靶点10个,分别是肿瘤坏死因子、白细胞介素-6、细胞肿瘤抗原p53、白细胞介素-1β、血管内皮生长因子A、表皮生长因子受体、分裂原活化蛋白激酶3、半胱氨酸蛋白酶3、基质金属蛋白酶9、纤连蛋白1,药物有效成分5个,包括槲皮素、异鼠李素、汉黄芩素、柚皮素、儿茶素;GO富集到基因功能69个,KEGG富集到基因通路70条,分析结果表明,麻杏止哮颗粒治疗哮喘的作用机制是通过调节晚期糖基化终末化产物-晚期糖基化终末产物受体信号通路在糖尿病并发症中的作用、分裂原活化蛋白激酶信号通路、白细胞介素-17信号通路、磷脂酰肌醇3激酶-蛋白激酶B信号通路、人类巨细胞病毒感染通路等来发挥治疗哮喘的作用.结论 初步揭示了麻杏止哮颗粒治疗哮喘的有效成分和作用机制,为麻杏止哮颗粒药效物质基础研究奠定基础,为质量控制提供参考依据.

Focusing on the development and quality improvement strategy of the traditional Chinese medicine(TCM) industry, the scientific and technological innovation of the new engineering of TCM should be paid attention to solve the "stuck neck" dilemma. Under the background of the ecological and industrial revolution of the scientific and technological innovation system, the super-scale information interaction and multi-dimensional integration will inevitably lead to profound changes in the manufacturing mode of TCM. Manufacturing measurement of TCM is formed on the basis of the reliability engineering theory of process control of TCM production. It is the development extension of system theory and system science ideas and a cross-fertilization discipline that combines theory with practice and adheres to the "four-oriented" re-epistemology improvement of the TCM discipline. In response to the problems of complex raw material sources, coarse process technology, unclear material basis, and poor applicability of equipment and technology in the manufacture of TCM, the transformation research mode of "aiming at the integration of pharmaceutical industry-developing intelligent production line-enabling industrial transformation" has been developed. This paper proposed the four key engineering technical problems, i.e., the identification of critical quality attributes(CQA) in the manufacture of TCM, the quality by design(QbD) and product development of the manufacturing process of TCM, the quality transfer principle and multivariate process capability index of TCM manufacturing, and the development of measurement technology and equipment of the manufacturing measurement of TCM, to achieve the systematization of quality control indicators, real-time process control, digitalization of manufacturing process, transparency of quality transfer, and intelligent whole-process control. In this paper, the new concepts, new theories, and new technologies provide a reference for the industrialization of TCM.