清热类中药的抗补体活性多糖及其构效关系

Polysaccharides are very important constituents of traditional Chinese medicines (TCMs) because of their various biological activities including immuno-modulating and anti-tumor effects. The extreme complexity of polysaccharide structures leads to the high difficulty for the chemical and pharmacological research. The polysaccharides from the tonic TCMs have been well demonstrated for their immune-enhancing activity. However, according to our previous studies, the polysaccharides from the heat-clearing TCMs had anticomplement activity and their structures were significantly different from those in the tonic TCMs. The animal studies also indicated that the anti-complementary polysaccharides had obvious antipyretic and anti-inflammatory effects. Therefore, this proposal is to continue the comparative study with the polysaccharides obtained from the heat-clearing TCMs and the tonic TCMs. The homogeneous polysaccharides in the 4 heat-clearing TCMS, including Stellaria nipponica Ohwi, Artemisia annua Linn, Commelina communis Linn and Fagopyrum dibotrys (D. Don) Hara, will be purified and chemically characterized. The homogeneous polysaccharides will be evaluated for their anticomplement activities and the structure-activity relationships will be summarized. Meanwhile, 2-3 homogeneous polysaccharides with potent in vitro anticomplement activity will be investigated using the mice with acute lung injury induced by lipopolysaccharide to confirm their beneficial pharmacological effects. This study will provide the important scientific base to understand the structures and effects of polysaccharides in the heat-clearing TCMs for further research and development as therapeutic agents.

多糖具有免疫调节、抗肿瘤等多种生物活性，是中药的重要活性物质，但结构的复杂性导致其研究难度大、质量难控、药效不稳。补益类中药多糖的免疫增强活性已为人们熟知，而我们的前期研究发现，清热类中药的多糖普遍具有补体抑制活性，其结构与补益类中药多糖差异明显，且动物实验证实抗补体活性粗多糖多具有显著的解热抗炎作用。因此，本项目拟在比较研究清热类与补益类中药多糖的基础上，选择白花蛇舌草、青蒿、金荞麦、鸭跖草等4种代表性清热类中药进行系统的均一多糖分离纯化、结构表征与抗补体活性评价，通过分析活性不同的均一多糖结构差异，结合前期对抗补体均一多糖的研究成果，明确清热类中药抗补体活性多糖的结构特点与构效关系，并选择2-3个活性显著的代表性均一多糖采用小鼠急性肺损伤模型评价其体内药效作用。研究结果将为深入研究中药来源的补体抑制活性多糖指明方向，并为清热类中药的药效物质基础与质量控制研究提供重要科学依据。

多糖具有免疫调节、抗肿瘤等多种生物活性，是中药的重要活性物质，但结构的复杂性导致其研究难度大、质量难控、药效不稳。补益类中药多糖的免疫增强活性已为人们熟知，而我们研究发现，清热类中药的多糖普遍具有补体抑制活性，其结构与补益类中药多糖差异明显，且动物实验证实抗补体活性粗多糖多具有显著的解热抗炎作用。因此，本项目在比较研究清热类与补益类中药多糖的基础上，从白花蛇舌草、青蒿、鸭跖草、金荞麦、金钱草、满山红等6种代表性清热类中药中分离表征到39个均一多糖，并进行了系统的抗补体活性评价与构效关系分析，结合前期对抗补体均一多糖的研究成果，发现清热类中药抗补体活性多糖普遍具有单糖组成多样、多分支的结构特点；其中酸性多糖的较高的糖醛酸含量对抗补体活性有重要作用；从鸭跖草中还发现了特别的抗补体活性糖蛋白，其活性与蛋白组分密切相关；金荞麦粗多糖无抗补体活性，其组成较为单一，葡萄糖占比超过75%，也反向验证了前述构效关系。最后选择2个活性显著、结构有代表性的均一多糖采用小鼠急性肺损伤模型证实了其体内抗补体及抗炎药效作用，同时发现抗补体多糖减少NETs形成的作用机制。研究结果为深入研究中药来源的补体抑制活性多糖指明了方向，并为清热类中药的药效物质基础与质量控制研究提供了重要科学依据。