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.
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.
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.
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.
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 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.
此外，川续断皂苷VI还具有抗肿瘤、抗氧化等生物活性。3.3 Neuroprotective Activity
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.
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.