党参属植物具有重要的药用和食用价值，应用历史悠久。其中，党参为桔梗科植物党参Codonopsis pilosula (Franch.) Nannf.、素花党参Codonopsis pilosula Nannf. var. modesta (Nannf.) L.T.Shen或川党参Codonopsis tangshen Oliv.的干燥根。党参正式得名并作药用始于清代吴仪洛所著的《本草从新》，具有健脾益肺、养血生津的功效，可用于治疗脾肺气虚、气血不足、津伤口渴等症。目前，《中国药典》（2015版）中尚未规定党参药材的指标性成分，仅在鉴别项中规定党参炔苷为对照品。为寻找体现党参药材药效差异的生物活性标志物，完善党参药材的质量标准，在系统总结前期研究报道的基础上，对党参属药用植物的传统应用、化学成分、药理毒理等内容进行综述，并从化学成分分析（指纹图谱、含量测定）、化合物分离鉴定、提取物体内实验、潜在活性成分体外验证、生物信息学分析等多个方面开展系统研究，评价党参药材的化学质量，阐明党参药材免疫调节和造血改善的药效物质基础。具体的研究内容及结果如下： 1. 采用HPLC-DAD法建立了党参药材的化学指纹图谱及党参炔苷的含量测定方法，采用UV-vis法建立了党参多糖的含量测定方法，采用HPLC-ELSD法建立了游离态糖类成分蔗糖、葡萄糖和果糖的含量测定方法，从多个维度建立了党参药材的化学质量评价方法。在此基础上，分析了不同栽培措施、初加工方法及储藏方法对党参药材化学质量的影响，评价了党参饮片的化学质量。 对于不同栽培措施种植的党参药材，以党参炔苷和党参多糖的含量为指标，不施用壮根灵、不打尖、搭架是种植党参药材较佳的栽培措施。对于不同初加工方法处理的党参药材，建议采用晒干或阴干的方法，避免采用硫熏的方法。根据企业对党参药材规模化初加工的需求，可采用40-50 ℃烘干的方法进行处理。另外，揉搓有利于党参多糖、葡萄糖和果糖含量的提高，而不利于党参炔苷和蔗糖含量的积累。对于不同储藏方法处理的党参药材，在6个月内，党参炔苷的含量在不同温度和湿度下呈现下降趋势，而党参多糖、蔗糖、葡萄糖和果糖的含量均呈现先升高再降低的趋势。其中，常温或常湿条件下党参炔苷的下降幅度最快，各糖类成分的上升和下降幅度也最大，-20 ℃或5 %湿度下党参炔苷及各糖类成分的稳定性最好。因此，低温低湿条件有利于党参药材化学质量的稳定性。对于党参饮片的化学质量，甘肃岷县药材基地的党参饮片内部的化学质量一致性较好，而河北安国药材市场及北京药店的党参饮片内部的化学质量一致性较差。 2. 采用谱效关系研究的方法探讨了党参药材中化学成分与药理作用之间的内在联系，寻找反映党参药材免疫调节和造血改善功能的活性化合物。一方面，采用UPLC-ESI-Q-TOF-MS/MS的方法对党参药材的化学成分进行定性鉴别，共推断出30个化合物。建立不同初加工方法处理的党参药材的UPLC指纹图谱，共31个共有峰，指认出其中13个共有峰。相似度分析和热图分析表明，不同初加工方法处理的党参药材之间的化学成分具有一定的差异性。其中，阴干处理的党参药材中各化学成分含量高于晒干和烘干处理的党参药材。另一方面，基于党参药材健脾益肺、养血生津的传统功效，选取免疫调节和造血改善两个方面开展现代药效学研究。结果表明，党参药材醇提物对环磷酰胺诱导的小鼠免疫和造血功能抑制具有显著的改善功能。其中，阴干处理的党参药材醇提物的功效强于晒干和烘干处理的党参药材醇提物。之后，将UPLC指纹图谱与药效学研究结果相结合，进行谱效关系研究。根据典型相关分析结果，发现共有峰4（色氨酸）、6（丁香苷）、7（未知）、8（党参苷I）、10（党参吡咯酯A）、11（未知）和17（党参炔苷）等7个化合物与党参药材的免疫调节和造血改善功能具有较强相关性，可作为党参药材的潜在生物活性标志物。进一步利用多种色谱分离技术对共有峰7和11进行分离，获得单体化合物，并采用波谱学技术对其进行结构鉴定。其中，心叶山梗菜炔苷A（共有峰7）首次在党参植物中发现，大花红景天IV（共有峰11）首次在党参属中发现。最后，采用UPLC-DAD法对不同初加工方法处理的党参药材中7个潜在活性化合物进行了定量分析。 采用网络药理学的研究方法，探讨了党参药材中7个潜在活性化合物治疗白细胞减少症的作用机制。通过对化合物及疾病进行靶点预测、生物分子功能分析、通路分析和分子对接分析，构建“活性成分-靶点-通路”网络关系图。结果表明，党参药材中7个潜在活性化合物作用于70个靶点和56条通路发挥治疗白细胞减少症的作用。 3. 采用体外细胞模型，从免疫调节功能的角度验证了党参药材醇提物及7个潜在活性化合物的药理活性。结果表明，党参药材醇提物及4个化合物可以促进LPS诱导的RAW264.7细胞的增殖，并抑制IL6、TNFα及IFN-γ等炎症因子的分泌，其作用呈浓度依赖性。另外，党参药材醇提物及7个化合物可以促进5-Fu诱导的JURKAT E6-1细胞的增殖，并促进IL6、TNFα及IFN-γ等炎症因子的分泌，其作用呈浓度依赖性。因此，党参药材醇提物及潜在活性化合物可促进免疫相关细胞的增殖，并调节炎症因子的分泌，从而发挥免疫调节功能。 4. 采用体外细胞模型，从造血改善功能的角度验证了党参药材醇提物及7个潜在活性化合物的药理活性。结果表明，党参药材醇提物及7个化合物可以促进CFU-E、BFU-E、CFU-GM、CFU-GEMM等集落的形成，并促进造血干（祖）细胞表面CD34+分子的表达，抑制CD45+、CD14+、CD3+、CD19+及CD71+分子的表达。ATRA诱导分化后，造血干（祖）细胞表面CD34+、CD3+、CD19+及CD71+分子的表达下调，CD45+及CD14+分子的表达上调，形态上出现明显分化。党参药材醇提物及7个化合物作用后可促进CD34+、CD3+、CD19+及CD71+分子的表达上调，CD45+及CD14+分子的表达下调，且形态上分化程度明显下降。因此，党参药材醇提物及潜在活性化合物可促进造血干（祖）细胞的增殖，维持造血干（祖）细胞的干性，从而发挥造血改善功能。 综上，本研究从多个维度建立了党参药材的化学质量评价方法，并分析了不同栽培、初加工及储藏方法对党参药材化学质量的影响，评价了党参饮片的化学质量。采用谱效关系研究的方法探究了与党参药材免疫调节和造血改善功能相关的活性化合物：色氨酸、丁香苷、心叶山梗菜炔苷A、党参苷I、党参吡咯酯A、大花红景天IV、党参炔苷等，可作为党参药材的潜在生物活性标志物。采用网络药理学的研究方法探讨了党参药材潜在活性化合物治疗白细胞减少症的作用机制，体现了中药多成分、多靶点、多通路的特点。采用体外细胞模型对党参药材醇提物及潜在活性化合物的免疫调节和造血改善功能进行了验证。因此，本研究阐释了党参药材免疫调节和造血改善的药效物质基础，为党参药材质量标准的提升奠定了基础。

Genus Codonopsis Wall. (Campanulaceae) has important medicinal and edible value with a long history. Codonopsis Radix, the dried root of Codonopsis pilosula (Franch.) Nannf., Codonopsis pilosula Nannf. var. modesta (Nannf.) L.T.Shen or Codonopsis tangshen Oliv., is definitely recorded as traditional Chinese medicine dating back to Qing Dynasty in Ben Cao Cong Xin, with indications for strengthening spleen and tonifying lung, as well as nourishing blood and engendering liquid. At present, no index component of Codonopsis Radix was stipulated in Chinese pharmacopoeia (2015 edition), with only lobetyolin specified as the reference substance in the TLC identification item. In order to explore the bioactive markers reflecting the traditional efficacy and improve the quality standard of Codonopsis Radix, traditional uses, phytochemistry, pharmacology and toxicology of Codonopsis were reviewed on the basis of systematic summary of literatures and studies. Systematic study on chemical constituent analysis (fingerprint chromatography and content determination), isolation and identification of compound, in vivo experiment of extract, in vitro validation of potential bioactive compound, bioinformatics analysis, etc. was conducted. Thus, the quality of Codonopsis Radix was evaluated and the efficacious material basis on immune regulation and hematopoietic improvement of Codonopsis Radix was elucidated. The specific research content and result were as follows: 1. The fingerprint of Codonopsis Radix and the determination of lobetyolin were established based on HPLC-DAD method. The determination of polysaccharide was adopted by UV-vis method. The determination of sucrose, glucose and fructose was set using HPLC-ELSD method. The chemical quality evaluation system was established based on above methods to evaluate the effect of different cultivation measures, processing methods and storage methods of Codonopsis Radix and evaluate the chemical quality of Codonopsis Radix slices. For the cultivation measures, the appropriate measure was not using Zhuanggenling, not pinching and shelving based on the content of lobetyolin and polysaccharide. For the processing methods, sun-drying or shade-drying was recommended, and sulfur fumigation should be avoided. And dryer-drying at 40-50 C was suggested to meet the requirement of large scale processing. In addition, based on the content of polysaccharide, glucose and fructose, kneading was advised. As for lobetyolin and sucrose, kneading should be avoided. For the storage methods, the content of lobetyolin showed a decrease tendency, while that of polysaccharide, sucrose, glucose and fructose showed a tendency of first rise then fall during 6 months at different storage methods. Low temperature and humidity were beneficial for the quality stability of Codonopsis Radix. For Codonopsis Radix slices, the consistency of chemical quality of Codonopsis Radix slices from the production base in Min county, Gansu province was consistent, while consistency of chemical quality of slices from the Anguo medicine market in Hebei province and pharmacy in Beijing was poor. 2. The bioactive compounds reflecting the immune regulation and hematopoietic improvement activities of Codonopsis Radix were explored by spectrum-effect relationship analysis. Firstly, UPLC-ESI-Q-TOF-MS/MS analysis was conducted to identify the chemical constituents in Codonopsis Radix and 30 compounds were deduced. UPLC fingerprint of Codonopsis Radix prossessed with different methods was established. There were 31 common peaks in total and 13 of them were pointed out. Similarity analysis and heatmap analysis indicated that chemical constituents in Codonopsis Radix prossessed with shade-drying were higher than those prossessed with sun-drying or dryer-drying. Secondly, immune and hematopoietic function of Codonopsis Radix was investigated based on traditional efficacy. The results indicated that Codonopsis Radix methanol extract could ameliorate the immune and hematopoietic function inhibited by cyclophosphamide in mice. And the function of Codonopsis Radix methanol extract prossessed with shade-drying was better than that prossessed with sun-drying or dryer-drying. Then, the spectrum-effect relationship analysis between UPLC fingerprint and pharmacological effect was carried out. According to the results of canonical correlation analysis, common peak 4 (Tryptophan), 6 (Syringin), 7 (Unknown), 8 (Tangshenoside I), 10 (Codonopyrrolidium A), 11 (Unknown), 17 (Lobetyolin) might be the potential bioactive compounds related to the immune regulation and hematopoietic improvement function of Codonopsis Radix. The two unknown compounds were further isolated by chromatographic separation techniques and their structures were identified by spectroscopic techniques. It turned out that Cordifolioidyne A (common peak 7) was isolated firstly in Codonopsis Radix, and Creoside IV (common peak 11) was isolated firstly in Codonopsis. Finally, UPLC-DAD method was applied for the quantitative analysis of 7 potential bioactive compounds in Codonopsis Radix prossessed with different methods. The mechanism of 7 potential bioactive compounds of Codonopsis Radix in treating leukopenia was studied by network pharmacology. Target prediction, biomolecular function analysis, pathway analysis and molecular docking analysis were conducted for compounds and disease, and the network diagram of “bioactive compound-target-pathway” was constructed. The results indicated that 7 compounds in Codonopsis Radix acted on 70 targets and 56 pathways in the treatment of leukopenia. 3. Cell model was used to verify the immune regulation function of Codonopsis Radix methanol extract and 7 potential bioactive compounds in vitro. The results indicated that Codonopsis Radix methanol extract and 4 compounds could promote the proliferation of RAW264.7 cells and inhibit the secretion of IL6, TNFα and IFN-γ induced by LPS in a dose-dependent manner. In addition, Codonopsis Radix methanol extract and 7 compounds could promote the proliferation of JURKAT E6-1 cells and improve the secretion of IL6, TNFα and IFN-γ induced by 5-Fu in a dose-dependent manner. The findings showed that Codonopsis Radix methanol extract and compounds could promote the proliferation of immune-related cells, and regulate the secretion of inflammatory factors, thus playing a role in immune regulation. 4. Cell model was used to verify the hematopoietic improvement function of Codonopsis Radix methanol extract and 7 potential bioactive compounds in vitro. The results indicated that Codonopsis Radix methanol extract and 7 compounds could promote the formation of CFU-E, BFU-E, CFU-GM and CFU-GEMM and promote the expression of CD34+ of hematopoietic stem/progenitor cells, while inhibit the expression of CD45+, CD14+, CD19+ and CD71+. In addition, after all-trans retinoic acid (ATRA) treatment, the expression of CD34+, CD3+, CD19+ and CD71+ was down-regulated, while the expression of CD45+ and CD14+ was up-regulated, and the cells showed significant differentiation morphologically. Codonopsis Radix methanol extract and 7 compounds could increase the expression of CD34+, CD3+, CD19+ and CD71+, while decrease the expression of CD45+ and CD14+, and the differentiation degree of cells was slowed obviously in morphology. In conclusion, Codonopsis Radix methanol extract and compounds could promote the proliferation and maintain the differentiation function of hematopoietic stem/progenitor cells, thus improving the hematopoietic function. To sum up, the quality evaluation system of Codonopsis Radix was established from multiple dimensions, and the effect of different cultivation measures, processing methods, storage methods and different Codonopsis Radix slices were analyzed by the developed quality evaluation system. The spectrum-effect relationship analysis was conducted to explore the bioactive compounds reflecting the traditional efficacy of Codonopsis Radix. The results showed that Tryptophan, Syringin, Cordifolioidyne A, Tangshenoside I, Codonopyrrolidium A, Creoside IV and Lobetyolin might be the potential bioactive compounds related to the immune regulation and hematopoietic improvement function of Codonopsis Radix. Network pharmacology was applied to explore the mechanism of 7 potential bioactive compounds in treating leukopenia, and the results reflected the characteristics of multi-component, multi-target and multi-pathway. The function of Codonopsis Radix methanol extract and 7 potential bioactive compounds on immune regulation and hematopoietic improvement function was verified by cell model in vitro. In conclusion, the study clarified the effective substances on immune regulation and hematopoietic improvement and laid a foundation for the improvement of quality standard of Codonopsis Radix.