川续断是川续断科植物川续断的干燥根，具有抗菌、消炎、抗氧化、抗肿瘤、神经保护等药理活性。川续断皂苷VI是川续断的主要活性成分，也是《中国药典》（2020版）规定的川续断的指标成分。自2007年以来，川续断皂苷VI的药理活性和临床用途吸引了国内外众多医药工作者的关注，据不完全统计，迄今已有相关专利20余项，研究论文近百篇。
本期我们来一起认识川续断皂苷VI这个明星天然化合物吧！
The traditional Chinese medicine Chuan-Xu-Duan, possesses pharmacological activities of antibacterial, anti-inflammatory, antioxidant, anticancer, and neuroprotective effects, is the dried root of the plant Dipsacus asper Wall. exHenry belonging to the Dipsacus family. Dipsacus asperoside VI is the principal active constituent of Chuan-Xu-Duan, and it is also the designated marker compound for Chuan-Xu-Duan as specified in the Pharmacopoeia of the People's Republic of China (2020 edition).
Since 2007, the pharmacological activities and clinical applications of dipsacus asperoside VI have garnered significant attention from numerous domestic and international pharmaceutical researchers. According to incomplete statistics, there have been more than 20 related patents and nearly one hundred research papers published to date.
川续断皂苷VI的化学结构
结构与命名
如图所示，川续断皂苷VI，又称木通皂苷D，英文名为akebia saponin D，其骨架为齐墩果烷型五环三萜，在齐墩果烷母核的C-3位连接1个阿拉伯糖，C-28位连接1个龙胆二糖。
1. Name and Structure
Dipsacus asperoside VI, as shown in above figure, is also named as akebia saponin D, belonging to the oleanane-type pentacyclic triterpenoid saponins. It features an arabinose moiety linked to the C-3 position of the oleanane nucleus and a gentiobiose moiety linked to the C-28 position.
理化性质
川续断皂苷VI为白色粉末，可用氯仿/甲醇结晶。其分子式为C47H76O18，分子量为928.50，熔点为234-235℃，CAS号为39524-08-8。
川续断皂苷VI可发生Liebermann-Burchard反应、Kahlenberg反应和Tschugaeff反应，其酸水解产物为三萜母核和阿拉伯糖、葡萄糖。
2. Physical and Chemical Properties
Dipsacus asperoside VI presents as a white powder that can be crystallized using chloroform/methanol. Its molecular formula is C47H76O18, with a molecular weight of 928.50. It exhibits a melting point of 234-235℃ and is identified with CAS number 39524-08-8.
Dipsacus asperoside VI can be identified by the Liebermann-Burchard reaction, Kahlenberg reaction, and Tschugaeff reaction. Upon acid hydrolysis, it yields triterpenoid nucleus, arabinose, and glucose as products.
药理活性
现代药理学研究表明，作为续断的主要活性成分，川续断皂苷VI能有效透过血脑屏障，具有显著的抗骨质疏松、抗炎及神经保护等活性。
3. Pharmacological Activities
Dipsacus asperoside VI, as the primary active compound of Chuan-Xu-Duan, exhibits the capability to effectively penetrate the blood-brain barrier, and show significant activities in terms of anti-osteoporosis, anti-inflammatory, and neuroprotective effects, which has been revealed by modern pharmacological studies.
3.1 治疗筋伤骨折
张玮、Ishida K，Haudenschild D.R.等人在独立动物实验中均发现川续断皂苷VI能上调小鼠成肌细胞C2C12中Ocn、Runx2和Col1α1的mRNA和蛋白质水平；Oury J等研究发现川续断皂苷VI可以通过PI3K/AKT信号通路诱导骨髓基质细胞成骨分化，还可以通过BMP-2/MAPK/SMAD依赖的Runx2信号通路诱导成骨细胞分化。此外临床实验证明川续断皂苷VI能够抑制破骨细胞的形成，促进成骨细胞分化，提高成骨细胞的活性和数量，进而促进基质钙化、骨痂生长，从而防止骨质疏松、促进骨折的愈合，发挥川续断“强筋骨、续折伤”的功效。
3.1 Activity on Treatment of Tendon Injury and Bone Fractures
Professors Zhang Wei, Ishida K, Haudenschild D.R. etc observed that dipsacus asperoside VI upregulates the mRNA and protein levels of Ocn, Runx2, and Col1α1 in murine myoblasts C2C12 in individual animal experiments. Professor Oury J discovered that dipsacus asperoside VI induces osteogenic differentiation in bone marrow stromal cells through the PI3K/AKT signaling pathway and further stimulates osteoblast differentiation via the BMP-2/MAPK/SMAD-dependent Runx2 signaling pathway. Clinical trials have demonstrated that dipsacus asperoside VI inhibit osteoclastogenesis, promote osteoblast differentiation, enhance osteoblast activity and quantity, thereby facilitating extracellular matrix calcification and bone callus growth. Consequently, this compound prevents osteoporosis, accelerates fracture healing, and manifests the therapeutic effects of Chuan-Xu-Duan in the context of "strengthening tendons and bones, promoting fracture recovery."
3.2 抗炎活性
在LPS诱导的RAW264.7细胞模型中，川续断皂苷Ⅵ被证实能通过抑制炎性细胞因子1L-1β、TNF-α和IL-6的蛋白或基因表达水平，同时增加HO-1基因表达，抑制一氧化氮合酶的活性，降低一氧化氮的生成量，还可以通过调节M1/M2型巨噬细胞极化，从而发挥抗炎、免疫调节作用。
3.2 Anti-inflammatory Activity
In the LPS-induced RAW264.7 cell model, dipsacus asperoside VI has been demonstrated to exhibit anti-inflammatory and immunomodulatory effects by inhibiting the protein or gene expression levels of inflammatory cytokines such as IL-1β, TNF-α, and IL-6, while concurrently increasing the expression of the HO-1 gene. Furthermore, it suppresses the activity of nitric oxide synthase, thereby reducing nitric oxide production. Dipsacus asperoside VI also regulates the polarization of M1/M2 macrophages, thereby exerting its anti-inflammatory and immunomodulatory activities.
3.3 神经保护活性
此外，川续断皂苷VI还具有抗肿瘤、抗氧化等生物活性。
Research conducted by international scholars has revealed that dipsacus asperoside VI exhibit a protective effect against amyloid-β-induced cytotoxicity in PC12 neuronal cells. This compound has the potential to ameliorate Alzheimer's disease-related inflammation and improve memory impairments. On a domestic front, scholars have demonstrated through a mouse sleep deprivation model that dipsacus asperoside VI can modulate the phenotype of microglial cells in the hippocampal region of mice. This modulation enhances the expression of the neurotrophic factor BDNF, activates the PI3K and Akt signaling pathways, stimulates neurogenesis in the adult hippocampus, and consequently enhances cognitive function. As a result, dipsacus asperoside VI exhibits promising applications in the fields of antidepressant and anti-age-related cognitive decline therapies.
Moreover, dipsacus asperoside VI also have been discovered its biological activities such as anticancer and antioxidant properties.
综上，作为源自中药的天然活性分子，川续断皂苷VI吸引了国内外众多学者的关注，其抑制破骨细胞生长并促进成骨细胞分化的活性可用于开发防治骨质疏松、骨折等骨科疾病的相关药物；其较强的抗炎活性，可用于开发炎症以及与炎症相关的动脉粥样硬化等心脑血管疾病治疗药物；其神经保护活性在抑郁症、老年痴呆等精神疾病的治疗领域具有较高的开发潜力。
In conclusion, as a natural bioactive molecule originating from traditional Chinese medicine, dipsacus asperoside VI has garnered significant attention from scholars both domestically and internationally. Its dual activity of inhibiting osteoclast proliferation while promoting osteoblast differentiation holds promise for the development of therapeutic agents targeting bone-related disorders such as osteoporosis and fractures. Its robust anti-inflammatory activity can be harnessed for the development of drugs targeting inflammation and conditions related to inflammation, including atherosclerosis, in the cardiovascular and cerebrovascular disease context. Moreover, its neuroprotective activity exhibits substantial potential for the treatment of psychological disorders such as depression and neurodegenerative diseases, highlighting its promising development prospects.
