从中药(TCM)中分离具有活性的天然产物分子(NPMs)单体已成为传统医学现代化的研究热点。然而，这些NPMs往往存在各种缺陷，使应用领域及效能发挥受限。为了打破其固有的局限性，更充分地挖掘NPMs的应用潜能，目前已借助纳米技术、结构修饰、靶向递送等方式对其进行改良并取得了显著成效，但这些改良技术所涉及的载体相关毒性的限制以及复杂的配方技术无疑为NPMs的进一步应用增加了额外的难度。与上述被动增强的策略不同，我们认为中药中的NPMs可以凭借其独特的结构特点赋予其组装特性，实现“自我增效”。

我们从药用植物金佛山雪胆(Hemsleya penxianensis)中分离鉴定了β-谷甾醇和23个葫芦烷型三萜衍生物，其中化合物hemsleyacins P-R (6, 7, 13)，hemsleyaosides L-N (15–17)为新化合物。深入研究发现，主成分雪胆甲素（HA）和β-谷甾醇（Sito）具有共组装特性，这可能是雪胆发挥药效的另外一种作用模式。因此，课题组首次运用化学表征和计算机模拟，探讨了共组装的Sito-HA的形貌、性能和驱动力的变化及其共组装的机理。此外，Sito-HA表现出显著增强的协同抗胃癌功效，原因可能是它们相互作用后形态和亲水性得到改善，从而使共组装体更容易附着在细胞上发挥作用。本研究不仅拓展了天然产物的应用潜力，而且为中药内在物质通过共组装发挥治疗效果提供了新的视角。

另外，大苞荆芥（Nepeta bracteata Benth.）为唇形科荆芥属植物，具有温肺、止咳、化痰、抗炎、消肿等功效。通过化学成分分离研究，共获得6个二萜类化合物，其中包括一个新颖的labdane（半日花烷）型二萜：nepebracteatalic Acid (NA)。进一步研究发现该二萜分子NA具有组装纳米特性，其通过非共价相互作用，包括分子间氢键、疏水相互作用和静电相互作用，即可自组装形成纳米颗粒（NA NPs）。基于这一自组装特性， NA NPs在氢键的作用下表现出缓释性能，且与临床抗炎药物吲哚美辛相比，更是显著降低了IL-6和TNF-α炎症因子的表达水平，量化NA NPs对核因子-κB (NFκB)信号通路的影响证实了其相对于游离NA显著增强的抗炎特性。结合N. bracteata的临床应用，NA NPs表现出了更显著的炎症抑制、促进胶原沉积、血管生成及创面闭合的能力。

综上所述，本研究以天然产物结构组装特性为视角，在对金佛山雪胆和大苞荆芥二种药用植物开展化学成分研究的基础上，深入挖掘雪胆三萜HA及β-谷甾醇、二萜NA的组装功能特性，为阐明中药或民族药的药用价值提供新的研究思路，也为天然产物的应用和发展提供了新的方向。

    The isolation of single pharmacologically active natural product molecules (NPMs) from traditional Chinese medicine (TCM) has become the focus of traditional medicine modernization. However, these NPMs always have various defects which limited in application field and efficacy aspects. In recent years, NPMs have been improved through nanotechnology, structural modification and targeted delivery, etc. for breaking the inherent limitations of NPMs and fully exploiting the potential of their application. Despite the effect, the limitation of carrier-related toxicity and the complex formulation technology involved in these modified techniques undoubtedly add additional difficulty to putting into use for NPMs. Unlike the strategies of passive enhancement, we propose that NPMs in TCM have potential to achieve the enhancement of “self-efficiency” by virtue of the self-assembled characteristic conferred by unique structural features.

   β-sitosterol and 23 cucurbitane type triterpenoid analogues, including new compounds hemsleyacins P-R (6, 7, 13) and hemsleyaosides L-N (15-17), are isolated and identified from medicinal plant Hemsleya penxianensis. Digging further, hemslecin A (HA) and β-sitosterol (Sito), the principal components of H. penxianensis possess co-assembly properties which is another possible functioning mode of therapeutic effect for H. penxianensis. Therefore, the group explores the changes of morphology, properties and driving force as well as the mechanism of co-assembled Sito-HA by chemical characterization and computer simulation for the first time. Furthermore, the Sito-HA exhibit a remarkably enhanced, synergistic efficacy against gastric cancer. The reasons could be that morphology and hydrophilicity are improved after their interaction, thus making co-assembly adhere to the cells more easily to exert its effects. This research not only expands the potential application of NPMs, but also provides the new sight of TCM (H. penxianensis) in therapeutic effect with their inner substance co-assemblies.

    Moreover, Nepeta bracteata Benth.，belonging to the genus Nepeta in the labiaceae family, functions on warming the lungs, relieving cough, removing phlegm, anti-inflammation and reducing swelling. Six diterpenoids are obtained through chemical separation, including nepebracteatalic Acid (NA), a novel labdane diterpenoid. Further study revealed that the diterpenoid molecule NA has the property of assembly, which can self-assemble into nanoparticles (NA NPs) through non-covalent interactions, including intermolecular hydrogen bonding, hydrophobic interaction and electrostatic interaction. Based on this self-assemble characteristic, NA NPs possesses a certain sustained release performance under the role of hydrogen bonds, lower inflammatory expression levels for IL-6 and TNF-α than clinical anti-inflammatory drug Indometacin. And the effect of NA NPs on nuclear factor-κB (NFκB) signaling pathway is quantified to confirm the significantly enhanced anti-inflammatory property relative to free NA. Meanwhile, NA self-assembly performs outstanding inflammation inhibition, collagen deposition, angiogenesis and wound closure during wound healing which is consistent with the clinical application of N. bracteate.

    In conclusion, from the perspective of structural assembly characteristics of NPMs, further exploration of the assembly functions of triterpene HA and β-sitosterol as well as diterpene NA based on the study of chemical constituents of two medicinal plants, N. bracteata Benth. and H. penxianensis, provides a new research sight for clarifying the medicinal value of TCM or ethnic medicine, and also points out a new direction for the application and development of NPMs.