BackgroundRenal fibrosis is a hallmark and the final outcome of chronic kidney disease (CKD). Jingtian Granule (JT), a traditional formula used in the clinical treatment of CKD for many years. However, the mechanism of action of JT against renal interstitial fibrosis remain unknown.ObjectiveThis study aimed to explore the potential effects and mechanisms of JT on adenine - diet - induced CKD in mice.MethodsRenal interstitial fibrosis was induced in mice by adenine - diet and treated with JT. Renal function was assessed by measuring blood urea nitrogen and serum creatinine levels. Masson’s staining and type I collagen expression were used to evaluate renal collagen deposition. RNA sequencing was used to analyze the expression levels of mRNA in mouse kidney samples after JT treatment. The levels of glutathione (GSH) and malondialdehyde (MDA) were measured to assess lipid peroxidation in the kidneys. Iron metabolism levels were detected by Prussian blue staining and measurement of iron content. The protein levels of SIRT3, P53, glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11) were detected by Western blot. Subsequently, under the premise of SIRT3 knockout, renal function, fibrosis level, iron metabolism level, and lipid peroxidation level were detected, and mitochondrial damage was observed by transmission electron microscope (TEM). In addition, human proximal tubule epithelial cells (HK - 2) were treated with Erastin to induce ferroptosis, followed by exposure to JT. The levels of reactive oxygen species (ROS) were detected.ResultsJT significantly reduced collagen deposition in the kidneys. RNA sequencing identified 20 mRNAs that were differentially expressed in response to JT treatment. Bioinformatics analysis revealed that SIRT3 was a key mRNA regulated by JT. JT activated SIRT3 in fibrotic kidneys to inhibit the acetylation of P53. Under the premise of SIRT3 knockout, JT did not show significant therapeutic effects in inhibiting ferroptosis and fibrosis. In vitro experiments also showed that JT promoted the downregulation of ROS.ConclusionSIRT3 is the key ferroptosis - related mRNA regulated by JT. The ability of JT to modulate the SIRT3/P53 signaling pathway may be a viable approach for the treatment of renal interstitial fibrosis.

Qing-fei-da-yuan granules (QFDYGs) had been proved to be an effective TCM prescription for treating coronavirus disease 2019 (COVID-19), which are composed of a variety of TCMs, and characterized by multiple components, multiple targets and overall regulation. It is meaningful to further study the chemical composition and pharmacology of QFDYGs for quality evaluation. However, due to the complexity of the components of QFDYGs, there are no reliable and simple analytical methods for current quality evaluation. In this work, antipyretic activity assessment of QFDYGs in the LPS-induced New Zealand rabbit model was carried out to verify the efficacy firstly. It was proved that QFDYGs can be used to relieve fever to help preventing or controlling the prevalence of influenza and pneumonia. Subsequently, UHPLC-ESI-QTOF-MS/MS combined with network pharmacology, quality markers and fingerprint analysis were used to establish the quality control condition. The chemical compositions were analyzed by UHPLC-ESI-QTOF-MS/MS, and 79 of them were identified, such as arecoline, mangiferin, paeoniflorin, etc. Then, the network pharmacology strategy based on 45 candidate components (CCs) in conjunction with influenza and pneumonia diseases was employed to screen the potential active ingredients. According to the drug-CCs-genes-diseases (D-CCs-G-D) networks, baicalein, honokiol, baicalin, paeoniflorin, saikosaponin A, glycyrrhizic acid and hesperidin were selected as quality markers. And a method for content determination of the 7 quality markers was established by optimizing extraction methods, chromatographic conditions and methodological verification. Finally, the quality of 15 batches of QFDYGs was evaluated by using the 7 quality markers combined with fingerprints and principal component analysis (PCA). The analyzed results showed that baicalin, paeoniflorin, glycyrrhizic acid and hesperidin were the high content and stable quality markers. QFDYGs were characterized by overall consistency and individual ingredient differences among the 15 batches. Our quality evaluation study will provide reference for the further development and research of QFDYGs.

The 5-year survival rate of non-small cell lung cancer (NSCLC) patients is very low. MicroRNAs (miRNAs) are involved in the occurrence of NSCLC. miR-122-5p interacts with wild-type p53 (wtp53), and wtp53 affects tumor growth by inhibiting the mevalonate (MVA) pathway. Therefore, this study aimed to evaluate the role of these factors in NSCLC. The role of miR-122-5p and p53 was established in samples from NSCLC patients, and human NSCLC cells A549 using the miR-122-5p inhibitor, miR-122-5p mimic, and si-p53. Our results showed that inhibiting miR-122-5p expression led to the activation of p53. This inhibited the progression of the MVA pathway in the NSCLC cells A549, hindered cell proliferation and migration, and promoted apoptosis. miR-122-5p was negatively correlated with p53 expression in p53 wild-type NSCLC patients. The expression of key genes in the MVA pathway in tumors of p53 wild-type NSCLC patients was not always higher than the corresponding normal tissues. The malignancy of NSCLC was positively correlated with the high expression of the key genes in the MVA pathway. Therefore, miR-122-5p regulated NSCLC by targeting p53, providing potential molecular targets for developing targeted drugs.

OBJECTIVE To study the anti-inflammatory and anti-tussive effects of Qingfei Dayuan granules (, QFDY), and to evaluate the acute and sub-chronic toxicity of QFDY. METHODS Anti-inflammatory effects were evaluated by murine model of xylene induced ear edema in mice. Ear swelling degree was calculated and tumor necrosis factor-α, interleukin-1β and interleukin-6 were determined. Anti-tussive evaluations were carried out in the mouse cough model induced by ammonia liquor. Latent period cough and number of cough within 3 min were counted. In acute toxicity study, the rats were randomly divided into test group and solvent control group. Body weighs, food intakes and general clinical signs were monitored. In the sub-chronic toxicity study, QFDY was administered to rats at 0, 4, 8 and 16 g/kg per day for 28 and 30 d of post treatment was conducted. Mortalities, clinical signs, body weight changes, food intakes, ophthalmological examinations, hematological parameters, biochemical indicators, electrolyte indicators, urinalyses and histopathological examinations were monitored. RESULTS QFDY significantly inhibited the development of ear edema in anti-inflammatory assay and decreased cough frequency caused by ammonia liquor. The results presented a dose-effect relationship. In acute toxicity study, no abnormality exhibited at dose of 24.0 g/kg per day during the 14-d observation period. In the sub-chronic toxicity study, higher reticulocyte count, lymphocyte and lower Cl-, blood urea nitrogen were analyzed compared with the solvent control group. But the differences were considered to be incidental and not clinically toxic. Obvious dose-effect relationship of urine color was observed, and the three test groups at the end of the experiments resulted in significant increase in urobilinogen, bilirubin, ketone body and urine leukocyte. However, all the positive indicators returned to normal in the recovery period. Therefore, no toxicological changes were found during the study period. CONCLUSION QFDY showed significant anti-inflammatory and anti-tussive effects in mice. The lethal dose (LD50) of per oral QFDY in rats was estimated to be more than 24.0 g/kg per day and the no observed adverse effect level was over 16 g/kg per day, which suggested that QFDY is relatively safe for oral medication at the present dose on rats. Our experimental results provide a reference for the further development and research of QFDY.

Objective:To study the differences in volatile oil content of bran-processed Atractylodes lancea and its standard decoction concentrate and freeze-dried powder,as well as the differences in the types and contents of chemical components in volatile oil,and to clarify the quality value transmitting.Method:Ten batches of A.lancea rhizoma were collected and prepared into raw products and bran-processed products of A.lancea,standard decoction concentrate and freeze-dried powder of bran-processed A.lancea in order to extract the volatile oil,and the transfer rate of volatile oil in each sample was calculated.Quantitative analysis of the main chemical components（β-eudesmol,atractylon,atractylodin） in each volatile oil was performed by gas chromatography（GC） on the HP-5 quartz capillary column（0.32 mm×30 m,0.25μm） with a flame ionization detector（FID）,a split ratio of 10∶1 and a temperature program(initial temperature at 80℃，hold for 1 min,rise to 150℃ at 10℃·min -1 ,hold for 10 min,rise to 155℃at 0.5℃·min -1 ,hold for 5 min,rise to 240℃at 8.5℃·min -1 ,hold for 8 min).Cluster analysis and principal component analysis（PCA） were used to explore the overall differences in types and contents of chemical components between the standard decoction concentrate and freeze-dried powder.Result:The transfer rates of volatile oil in the bran-processed products,standard decoction concentrate and freeze-dried powder were 70.51%,1.57%and 40.90%,respectively.The average transfer rates of β-eudesmol,atractylon and atractylodin in the volatile oil of bran-processed A.lancea were 58.45%,48.49%and 55.64%,respectively.In the standard decoction concentrate,only β-eudesmol and atractylodin were detected,and their average transfer rates were 0.22%and 0.10%,respectively.And only β-eudesmol was detected in the freeze-dried powder with the average transfer rate of 8.37%.The results of cluster analysis and PCA showed that there are obvious differences in the types and contents of chemical components between the standard decoction concentrate and freeze-dried powder.Conclusion:The quality value transmitting between bran-processed A.lancea and its standard decoction concentrate and freeze-dried powder is stable,and if the freeze-dried powder is selected as the reference material of dispensing granules,appropriate amount of volatile oil should be added back to make it consistent with the quality of the standard decoction concentrate.

目的:优选保元颗粒的制备工艺.方法:建立超高效液相-蒸发光散射检测(UPLC-ELSD)法同步测定人参皂苷Rb1与黄芪甲苷含量.以人参皂苷Rb1与黄芪甲苷转移率为评价指标,正交试验考察提取时间、提取次数、溶剂倍数对保元汤提取工艺的影响,观察浸膏相对密度对干燥工艺的影响.选用湿法制粒,以成型率、休止角、吸湿率、堆密度、溶化性为评价指标,考察辅料、润湿剂等对制粒的影响,优化保元颗粒的成型工艺.结果:优选的最佳提取工艺为加水量10倍,提取2次,每次1h.喷雾干燥时浸膏的相对密度确定为1.05～ 1.15.最佳成型工艺以麦芽糊精为辅料,麦芽糊精与干膏粉用量比例为1∶1,以90％乙醇为湿润剂进行湿法制粒.结论:优化的保元颗粒制备工艺稳定、可行,可为保元颗粒的生产提供参考.

The present study explored the differences in active ingredients and in vitro anti-inflammatory effects of the decoction pieces by integrated processing(IPDP) and traditional processing(TPDP) of Polygoni Cuspidati Rhizoma et Radix(PCRER).The content of polydatin, resveratrol, emodin-8-O-β-D-glucoside, emodin, and physcion in IPDP and TPDP was determined by high-performance liquid chromatography(HPLC).The inflammation model was induced by lipopolysaccharide(LPS) in RAW264.7 cells.The mRNA levels of inflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β) in 60% ethanol extracts of IPDP and TPDP of different concentrations(5 and 10 μg·mL~(-1)) were determined by PCR.The results showed that the content of polydatin and emodin-8-O-β-D-glucoside in IPDP was significantly higher than that in TPDP, while the content of resveratrol, emodin, and physcion was higher in TPDP.The anti-inflammatory results showed that ethanol extracts of IPDP of different concentrations(5 and 10 μg·mL~(-1)) significantly inhibited the increase in the mRNA levels of IL-1β and TNF-α induced by LPS, whereas TPDP only had a significant inhibitory effect on IL-1β.This study preliminarily showed that the total content of five active ingredients in IPDP was higher than that in TPDP, and IPDP was superior to TPDP in anti-inflammatory activity in vitro, which provided an experimental basis for the production and application of IPDP.

目的 比较虎杖产地加工与炮制一体化(简称"一体化")制备的饮片与传统饮片的指纹图谱及体外抗氧化活性差异.方法 根据一体化工艺和传统工艺分别制备10批虎杖一体化饮片和10批传统饮片.采用高效液相色谱法建立虎杖两种饮片的指纹图谱,并进行比较;检测虎杖两种饮片对1,l-二苯基-2-三硝基苯肼(DPPH)自由基、ABTS自由基、超氧自由基、羟自由基的清除率以及对Fe3+的还原能力,比较这两种饮片的体外抗氧化活性.结果 虎杖两种饮片共有11个共有峰,其中一体化饮片共有17个共有峰,传统饮片共有13个共有峰;虎杖一体化饮片中6号峰(虎杖苷)和15号峰(大黄素-8-O-β-D-葡萄糖苷)的峰高明显高于传统饮片,传统饮片中13号峰(白藜芦醇)、17号峰(大黄素)和19号峰(大黄素甲醚)的峰高明显高于一体化饮片.体外抗氧化活性结果显示,虎杖一体化饮片和传统饮片对DPPH自由基、ABTS自由基、超氧自由基和羟基自由基均具有清除能力,对Fe3+也均具有还原能力.结论 虎杖一体化炮制工艺较传统炮制工艺可更好地保留虎杖的有效成分,且虎杖一体化饮片的体外抗氧化活性强于传统饮片.

Ethnopharmacological relevance: Coptis chinensis Franch (CC) and Zingiber officinale Roscoe (dried ginger; DG) are traditional Chinese medicines. CC can dry dampness, relieve fire and detoxify, and is used to treat gastritis, gastric ulcer, colitis. DG can warm spleen and stomach for dispelling cold, used for the treatment of spleen and stomach deficiency. Both CC and DG are widely used to treat gastrointestinal diseases. CC-DG herb medicine combination originates from Huanglian decoction and Pinellia xiexin decoction in "Shanghan Lun" to comfort the stomach and intestines. CC and DG are used for the treatment of nausea and choking diaphragm which highly associated with gastric cancer clinically in ancient time. Aim of the study: This study aimed to investigate the effects and underlying molecular mechanisms of CC-DG combination on gastric cancer. Materials and methods: The CC-DG extract was subjected to HPLC analysis. Viability (MTT) and cytotoxicity (CCK8) assays were performed using the SGC7901 and MFC cells. Cell cycle and apoptosis were measured by flow cytometry. The mRNA expression levels were measured by RT-PCR. In vivo anti-tumor activity of CC-DG was assessed in a tumor xenograft model. Results: Twelve different proportions of CC-DG were tested for inhibitory effects on gastric cancer cells; CC-DG ratio 1:1 was found most effective. CC-DG administration significantly reduced the cell proliferation, migration, and colony formation, while increased cell apoptosis compared with the control group. CC-DG regulated differentially expressed genes in SGC7901 cells were subjected to pathway enrichment analysis. CC-DG significantly inhibited the cell glucose metabolism, downregulated the expression of LDHA and SLC2A1 genes, and changed the expression of other related genes including ME2, LDHD, LDHB, HIF1A, PKM, Pcx, and Got1. In addition, CC-DG suppressed tumorigenesis and inhibited MKI67 expression in the tumor xenograft model. Conclusions: CC-DG inhibited the proliferation, migration, invasion of SGC7901/MFC gastric cells, and in turn, suppressed tumorigenesis by regulating glucose metabolism through regulation of LDHA and SLC2A1 genes.

目的 建立保元汤标准汤剂的超高效液相色谱法(Ultra Performance Liquid Chromatography,UPLC)特征图谱,并建立同时测定人参皂苷Rb1和甘草酸2种指标成分含量的方法,为该经典名方的质量控制及评价提供参考.方法 采用ACQUITY BEH Shied C18 column(2.1×100 mm,1.7μm)色谱柱,以0.01％甲酸水(A)-0.05％甲酸乙腈(B)为流动相梯度洗脱,柱温30℃,流速0.4 mL min-1,检测波长203 nm、237 nm.建立15批保元汤标准汤剂的UPLC特征图谱,应用"中药色谱指纹图谱相似度评价系统"软件(2012版)进行相似度分析,归属共有峰.采用层次聚类分析(HCA),主成分分析(PCA)等对特征图谱数据进行评价.利用UPLC特征图谱方法测定2种成分含量.结果 建立了15批保元汤标准汤剂的特征图谱,相似度均大于0.85,并确认了21个共有峰,指认出毛蕊异黄酮葡萄糖苷、甘草苷、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1、甘草酸6个峰.15批保元汤聚为4类,载荷散点图显示毛蕊异黄酮葡萄糖苷、人参皂苷Rg1等7个成分含量对保元汤质量有较大影响.含量测定显示,在一定范围内人参皂苷Rb1、甘草酸线性关系良好(r≥0.997).标准汤剂中含量测定结果分别在12.62-30.33μg·mL-1、63.80-106.67μg·mL-1,转移率分别在51.04％-70.06％、54.89％-74.38％;对应实物中含量测定结果分别在0.98-2.27 mg·g-1、4.42-8.74 mg·g-1,转移率分别在78.14％-101.19％、89.99％-99.88％.结论 建立的保元汤UPLC特征图谱及双指标成分含量测定方法专属性强、灵敏度高,可为该方剂复方制剂的质量控制与评价提供参考.

目的:建立保元汤物质基准的指纹图谱并对其共有峰进行成分指认.方法:制备15批保元汤物质基准,采用超高效液相色谱-二极管阵列检测器法(UPLC-PDA)测定15批保元汤物质基准的指纹图谱,并开展方法学研究;使用ACQUITY UPLC BEH Shield C18色谱柱(2.1 mm×100 mm,1.7 μm),流动相0.05％甲酸水溶液(A)-0.05％甲酸乙腈溶液(B)梯度洗脱(0～0.5 min, 5％～19％B;0.5～6 min, 19％B;6～10 min, 19％～27％B;10～20 min, 27％～45％B;20～20.1 min, 45％～95％B;20.1～23 min,95％B),流速0.4 mL· min-1,检测波长203 nm和260 nm,柱温30℃C,进样量2μL;采用“中药指纹图谱相似度评价系统”(2012版)建立指纹图谱,并生成对照指纹图谱;采用超高效液相色谱-电喷雾串联质谱法(UPLC-ESI-MS/MS)和对照品比对等方式进行保元汤物质基准的成分指认,质谱条件为全信息串联质谱(MSE)扫描模式检测,质量扫描范围m/z 50～1 200.结果:15批保元汤物质基准与对照指纹图谱的相似度均＞0.90,共有37个共有峰,通过UPLC-ESI-MS/MS指认了其中22个,分别为甘草苷,人参皂苷Rg1,人参皂苷Rb1,人参皂苷Re等,均来源于人参、黄芪、甘草、生姜4味药材.结论:该方法精密度、重复性、稳定性良好,表征了保元汤组分整体特征,为该经典名方的颗粒剂开发提供了实验依据.

保元汤是《古代经典名方目录(第一批)》收载的经典名方之一,已具有500多年应用历史,现代广泛用于治疗元气不足、虚损劳怯等.通过分析明、清两代具有代表性的中医古籍结合现代研究,分析、总结了保元汤来源、组成、药效等,综述保元汤的古代和现代文献研究概况,为建立保元汤物质基准质量标准提供了参考.通过研究发现,保元汤早期用以治疗小儿痘疹类疾病,随着社会发展,历代医家通过在临床实践中不断摸索,赋予了保元汤新的内涵,使其临床治疗疾病的范围得到扩充.现代医家将保元汤及其加减方临床用于冠心病、再生障碍性贫血、慢性肾功能衰竭、慢性肾炎、白细胞减少等多种疾病,充分说明保元汤临床效果显著,具有潜在开发价值.

目的:比较桑不同药用部位(桑叶、桑枝、桑白皮)总生物碱对α-葡萄糖苷酶活性的抑制作用.方法:采用采用蒸发光散射检测器(ELSD)-高效液相色谱法(HPLC)测定桑不同药用部位总生物碱中1-脱氧野尻霉素(DNJ)含量;以半数抑制浓度(IC50)为评价指标,以阿卡波糖为阳性对照,以对-硝基苯基-α-D-吡喃葡萄糖苷为底物,采用体外抑制模型评价桑不同部位总生物碱对α-葡萄糖苷酶活性的抑制作用.结果:桑不同药用部位总生物碱中DNJ质量分数为桑白皮生物碱(30.1％)>桑枝生物碱(25.8％)>桑叶生物碱(21.4％).桑不同药用部位总生物碱对α-葡萄糖苷酶抑制作用强度为桑枝生物碱>桑叶生物碱>桑白皮生物碱>阿卡波糖.结论:在桑枝、桑叶、桑白皮总生物碱中,以桑枝总生物碱对α-葡萄糖苷酶活性抑制作用最强,为桑资源开发辅助降血糖的药品和保健食品提供依据.

目的 建立黄连样品的HPLC特征图谱,阐述其量质传递规律.方法 采用相同色谱条件分别建立23批黄连药材、饮片、提取液、浓缩液、标准汤剂冻干粉、喷雾干膏粉和配方颗粒成品的HPLC特征图谱,比较其相似度;再对其进行定性、定量的量质传递分析,通过K值、损失率的大小和波动性来评价定量传递关系.结果 黄连特征图谱均含有8个色谱峰,其中,峰1为木兰花碱、峰3为非洲防己碱、峰4为药根碱、峰5为表小檗碱、峰6为黄连碱、峰7为巴马汀、峰8为小檗碱;23批样品的相似度均≥0.990,呈现良好的相关性;各过程中K值的波动稳定,实现了稳定的量质传递,损失率≤10％.结论 所用方法准确、稳定、可靠,通过HPLC特征图谱阐述了黄连配方颗粒的量质传递规律.

棕色是间于黄色和红色之间的一种复合颜色,棕色素则为色素中的黄色物质与红色物质混合而成的复合色素.天然棕色素常提取于植物成熟的果实、种子、果壳或果核中,用于着色棕色食品,如可可色素用于巧克力着色、板栗壳色素用于配制酒调色等.本文综述了国内外常见天然棕色素的研究概况,包括来源、提取方法、主要化学成分类型、药理活性、稳定性、应用情况等方面.

Polygonum perfoliatum L.is a kind of traditional Chinese medicine with widely application in recent years.The chemical composition is very complex,it also contains wide pharmacological effects,such as anti-inflammatory,anti-virus,anti-tumor and so on.This article presents an overview about domestic and oversea researches on main chemical constituents and pharmacological effects of Polygonum perfoliatum L.to provide a scientific basis for its development,utilization and further research.

OBJECTIVE:To study the chemical constituents of Polygonum perfoliatum.METHODS:The chemical constituents of Polygonum perfoliatum were isolated and purified by chromatography on silica gel, Sephadex LH-20 and Semi-preparative HPLC. The structures of compounds were elucidated and identified by physicochemical properties, H-NMR, 13C-NMR and ESI-MS.RESULTS:Ten compounds were isolated and identified as 5-hydroxymethyl-2-furaldEhyde (1), methyl caffeoate (2), protocatechuic aldehyde (3), quercetin (4), pinocernbrin (5), catechin (6), taxifolin (7), taxifolin-3-O-beta-D-xylopyranoside (8), 13-epitorulosal (9), coumarin-7-O-beta-D-glucose glycosidic (10).CONCLUSION:[corrected] Compounds 6-9 are isolated from this plant for the first time.