Ruitao Yu

Background: Hepatocellular carcinoma (HCC) is a highly lethal malignancy with limited therapeutic options. Arctigenin (ARC), a natural lignan derived from Saussurea medusa, exhibits anti-cancer activity, but its mechanism against HCC remain incompletely elucidated. Methods: This study integrated network pharmacology, molecular docking, molecular dynamics, in vitro, and in vivo experiments to investigate ARC’s anti-HCC effects. Results: Seventy-five potential targets shared between ARC and HCC were identified, with KEGG analysis highlighting the PI3K/AKT pathway as central. ARC showed strong binding to key proteins, and molecular dynamics indicated stable interactions with PIK3CA and GSK3B. In HepG2 cells, ARC inhibited proliferation in a dose- and time-dependent manner (IC50: 11.17 μM at 24 h, 4.888 μM at 48 h), induced apoptosis at high concentrations, suppressed PIK3CA phosphorylation, and increased GSK3B (Ser9) phosphorylation. In H22 tumor-bearing mice, ARC dose-dependently inhibited tumor growth (high dose: 50.6% vs. 63.0% for CTX) with minimal weight loss. Conclusions: These findings suggest ARC suppresses HCC by modulating the PI3K/AKT pathway, providing evidence for its development as a plant-derived therapeutic agent.

Saussurea medusa is a rare alpine plant with significant medicinal value. To better understand the changes in its habitat in the context of climate change, this study used an optimized MaxEnt model to predict the current and future habitat of S. medusa under four shared socioeconomic pathways (SSPs) across three time periods (current, mid-century, and end-century) based on three climate system models. The results showed that the suitable habitat of S. medusa is mainly located in the southern and eastern parts of the Qinghai-Xizang Plateau (QXP), exhibiting a fragmented distribution pattern. The future suitable area of S. medusa is projected to decrease significantly by 42.5% to 96.7%, accompanied by a southward shift in its centroid and an upward shift in altitude. The study found that the highest temperature in the warmest month is the most important environmental factor affecting the distribution of S. medusa. This species is highly sensitive to climate change and requires urgent protection measures. Priority should focus on strengthening habitat protection in the southeastern Qinghai-Xizang Plateau, where some stable habitats remain outside protected areas. Expanding population monitoring, promoting ex-situ conservation, enhancing public education, and encouraging community involvement are essential. Additionally, as a medicinal plant, alternative strategies are needed to curb overharvesting of wild resources.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a global prevalence of approximately 0.46%, causing significant impairments in patients’ quality of life and an economic burden. Saussurea involucrata (SI) has long been used in traditional medicine to treat RA, but its underlying mechanism remains unclear. This study utilized network pharmacology and molecular docking to explore the potential pharmacological effects of bioactive compounds in SI on RA. A total of 27 active compounds were identified, along with 665 corresponding targets. Additionally, 593 disease-related targets were obtained from multiple databases, with 119 common targets shared with SI. The high-ranking targets mainly belong to the MAPK family and NF-κB pathway, including MAPK14, MAPK1, RELA, TNF, and MAPK8, all of which are associated with inflammation and joint destruction in RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed significant pathways related to IL-17 signaling, Th17 cell differentiation, and osteoclast differentiation. Molecular docking and dynamic simulations demonstrated strong interactions between several flavonoids and RA-related targets. Xuelianlactone, Involucratin, and Flazin exhibit outstanding binding efficacy with targets such as MAPK1, MAPK8, and TNF. These findings provide valuable insights into the therapeutic potential of SI for RA and offer directions for further drug development.

Three pairs of novel enantiomeric 8-O-4′ type neolignans (1a/1b–3a/3b), together with seven known analogues (4–10), were isolated from the whole plants of Saussurea medusa. Their structures were elucidated by extensive spectroscopic data analysis and electric circular dichroism (ECD) calculations after chiral separations. All compounds were obtained from S. medusa for the first time, and compounds 1–3 and 5–10 had never been obtained from the genus Saussurea previously. The anti-inflammatory activities of the compounds were evaluated by determining their inhibitory activities on the production of NO and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated RAW 264.7 cells. Compounds (+)-1a, (−)-1b and 5–7 inhibited NO production and had IC₅₀ values ranging from 14.3 ± 1.6 to 41.4 ± 3.1 μM. Compound 7 induced a dose-dependent reduction in the expression of iNOS in LPS-treated RAW 264.7 cells. Molecular docking experiments showed that all active compounds exhibited excellent docking scores (<−7.0 kcal/mol) with iNOS. Therefore, compounds (+)-1a, (−)-1b and 5–7 isolated from the whole plants of S. medusa may have therapeutic potential in inflammatory diseases.

Objectives: An ethanol extract of the whole plants of Saussurea medusa had been investigated to find novel anti-inflammatory sesquiterpenoids. Methods: Extensive spectroscopic data and chemical methods were applied to elucidate the structures of the compounds. Results: One new megastigmane sesquiterpenoid (1), along with 11 known analogues (2–12), were obtained from S. medusa. All isolates, except compounds 3 and 6, were mentioned from the studied plant for the first time. Compounds 1, 2, 4, 5, 7, 8 and 12 were firstly isolated from the genus Saussurea. Compounds 2, 9 and 10 were found to inhibit the lipopolysaccharide (LPS)-induced release of NO by RAW264.7 cells with IC₅₀ values ranging from 21.1 ± 1.7 to 46.7 ± 1.9 μM. Furthermore, iNOS expression experiment was performed to examine the interactions between the active compounds and the iNOS enzyme. Graphical Abstract