硫熏人参量-质/效/毒关联性研究

Ginseng has been sulfur-fumigated to prevent against insects and moulds, and preserve color and freshness. Our previous study (partially supported by NSFC small fund No. 30940093 and Youth fund No. 81202920) found that sulfur-fumigation can cause not only the residue of sulfur dioxide (SO2), but also the chemical transformation of ginsenosides in ginseng, and significantly alter the absorption and metabolism of ginseng components. The Chinese Pharmacopeia (2010 Edition) newly employed residual SO2 not more than 150 mg/kg as one of the quality control standard of some herbs potentially sulfur-fumigated including ginseng, but this standard is dictated concerning merely the safety dose of SO2, whether or not it objectively reflect the extent of sulfur-fumigation that induce chemical changes, and consequently impact the efficacy and safety of ginseng need to be further investigated. In this proposal, the association between the amount of sulfur burned/subsequent drying duration and residual SO2/chemical profiles/efficacies/toxicities of ginseng will be investigated, using the method documented in current edition of Chinese Pharmacopeia to determine the content of SO2, modern multidimentional chromatography and their hyphenated techniques UPLC-QTOF-MS/MS, HPLC-TQ-MS/MS, GC-FID and HPGPC-ELSD etc. to qualitatively and quantitatively analyze chemical profiles of polysaccharides and ginsenosides, and classical animal models to evaluate biological effects and toxicities of ginseng samples sulfur-fumigated with different amount of sulfur and different subsequent drying durations, as well as their corresponding Du-Shen-Tang samples (water decoction of single ginseng). From this study, the rules of sulfur-fumigation extent/subsequent drying duration affecting the content of residual SO2, chemical profiles, efficacies and safeties of ginseng will be revealed, which can provide scientific basis for revising the residual SO2 standard that can really assure the efficacy and safety of ginseng. The present proposal also offers a new research strategy for dictating the residual SO2 standard of other herbs.

人参常被硫熏防霉增色。前期参与项目（小额30940093和青年81202920）研究发现，硫熏可导致人参药材SO2残留、人参皂苷成分结构改变和吸收代谢变化，现版《中国药典》新增SO2残留量不超过150 mg/kg作为检控硫熏人参等药材的标准，但此标准的制定仅依据了SO2本身的安全剂量，能否客观反映硫熏人参成分变化对功效和毒性的影响亟待深入研究。本项目拟以人参药材及其水煎汤剂独参汤为研究对象，采用药典方法测定药材SO2残留量；采用现代多维色谱及联用技术表征药材和独参汤中人参皂苷等小分子成分和人参多糖的结构、组成和含量；采用经典动物模型研究独参汤的功效和毒性，验证如下假说：硫熏程度/后续晾晒程度与人参药材SO2残留量、内在质量以及独参汤品质、功效和毒性之间存在量变对应关系。通过该假说的验证，揭示硫熏人参量-质/效/毒的关联性，为客观评价和修订人参等药材SO2残留限量标准提供科学依据和研究范例。

人参常用硫熏来防霉增色。目前国内外通过限制SO2残留量来控制硫熏药材的质量。然而，这些标准不能反映硫熏导致的药材质量以及药效和毒性的变化。另外，户外晾晒也可导致硫熏药材中实际SO2残留量降低。因此，本项目旨在研究硫熏程度和后续晾晒对人参SO2残留量、内在质量、功效和毒性的影响，并探讨他们之间的关联性。研究分为五个部分进行：（一）硫熏程度和后续晾晒对人参SO2残留量的影响。随着硫熏程度的增加，人参中SO2残留量逐渐升高；后续晾晒减少了人参中SO2残留量。（二）硫熏程度和后续晾晒对人参药材及对应的独参汤中小分子和糖类成分的影响。结果发现硫熏导致人参药材中皂苷及其含硫衍生物增加，独参汤中皂苷和多糖含量降低、寡糖和单糖含量升高；随着硫熏程度增加，人参药材及独参汤中化学成分呈不规律性变化；晾晒一周后，人参药材中皂苷降低、其含硫衍生物升高，独参汤中皂苷和寡糖降低、皂苷含硫衍生物及多糖和单糖升高。（三）硫熏程度和后续晾晒对独参汤药效的影响。结果发现硫熏减弱了人参的抗应激、抗休克和抗炎作用；随着硫熏程度增加，人参的抗应激、抗休克作用呈波动性变化，而人参的抗炎作用逐渐减弱；晾晒后，人参的抗应激、抗休克和抗炎作用减弱。（四）硫熏程度和后续晾晒对独参汤毒性的影响。结果发现未硫熏和硫熏人参样品没有急性毒性。但未硫熏和硫熏人参表现出一定的长期毒性。随着硫熏程度的增加，人参的长期毒性呈波动性变化；晾晒后，人参的长期毒性增强。（五）硫熏人参量-质/效/毒关联性分析。综上分析，表明SO2残留量与硫熏人参的质量/药效/毒性没有必然关联性，即低SO2残留量不代表药材具有较高的质量、更好的药效和较低的毒性。因此，硫熏药材的检控不能只考察SO2残留量，还需要考察更加专属性指标，以弥补SO2残留量检测的不足。本项目的研究意义在于为客观评价和修订人参SO2残留限量标准提供科学依据，也为其它硫熏药材专属性检控方法的开发提供研究范例。本项目共发表论文17篇，其中SCI 11篇，学术交流3次，授权发明专利1项，培养研究生3名。