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Two new steroidal saponins (1 and 2), along with four known ones (3 ∼ 6) were obtained from the roots and rhizomes of Maianthemum henryi, their structures were determined to be spirost-5, 25(27)-diene-lβ, 3β-diol 1-O-α-L-rhamnopyranosyl-(1 → 2)-4-O-acetyl-β-D-fucopyranoside (1), (23S, 24S)-spirost-5, 25(27)-diene-lβ, 3β, 23, 24-tetrol 1-O-α-L-rhamnopyranosyl-(1 → 2)-4-O-acetyl-β-D-fucopyranoside (2), spirost-5, 25(27)-diene-lβ, 3β-diol 1-O-α-L-rhamnopyranosyl-(1 → 2)-β-D-fucopyranoside (3), spirost-5, 25(27)-diene-lβ, 3β-diol 1-O-α-L-rhamnopyranosyl-(1 → 2)-β-D-xylopyranoside (4), Henryioside A (5)、Henryioside B (6), by physicochemical properties and spectroscopic methods. In addition, their cytotoxic activity against human HepG2 tumor cells was evaluated by MTT method and all of the compounds exhibited cytotoxicity with the cells. [ABSTRACT FROM AUTHOR]

Angiogenesis is crucial for cancer initiation, development and metastasis. Identifying natural botanicals targeting angiogenesis has been paid much attention for drug discovery in recent years, with the advantage of increased safety. Isoliquiritigenin (ISL) is a dietary chalcone-type flavonoid with various anti-cancer activities. However, little is known about the anti-angiogenic activity of isoliquiritigenin and its underlying mechanisms. Herein, we found that ISL significantly inhibited the VEGF-induced proliferation of human umbilical vein endothelial cells (HUVECs) at non-toxic concentration. A series of angiogenesis processes including tube formation, invasion and migration abilities of HUVECs were also interrupted by ISL in vitro. Furthermore, ISL suppressed sprout formation from VEGF-treated aortic rings in an ex-vivo model. Molecular mechanisms study demonstrated that ISL could significantly inhibit VEGF expression in breast cancer cells via promoting HIF-1α (Hypoxia inducible factor-1α) proteasome degradation and directly interacted with VEGFR-2 to block its kinase activity. In vivo studies further showed that ISL administration could inhibit breast cancer growth and neoangiogenesis accompanying with suppressed VEGF/VEGFR-2 signaling, elevated apoptosis ratio and little toxicity effects. Molecular docking simulation indicated that ISL could stably form hydrogen bonds and aromatic interactions within the ATP-binding region of VEGFR-2. Taken together, our study shed light on the potential application of ISL as a novel natural inhibitor for cancer angiogenesis via the VEGF/VEGFR-2 pathway. Future studies of ISL for chemoprevention or chemosensitization against breast cancer are thus warranted. [ABSTRACT FROM AUTHOR]

Objective: To systematically evaluate the anti-inflammatory potential of diterpene lactones from Chuanxinlian () (AP)., Methods: We firstly adopted zebrafish, a novel and ideal animal model for high-throughput drug screening, to investigate the anti-inflammatory activities of 17 diterpene lactones isolated from AP., Results: The results showed that most of diterpene lactones displayed significant anti-inflammatory effects in lipopolysaccharide microinjection-, copper sulfate exposure- or tail transection-induced zebrafish inflammation models. Moreover, diterpene lactone 3-deoxy-andrographoside (AP-5) was firstly found to attenuate inflammatory responses, which was closely associated with the myeloid differentiation primary response 88/nuclear factor-kappa B and signal transducer and activator of transcription 3 pathways., Conclusion: Our research sheds light on the inestimable roles of zebrafish in high-throughput drug screening, elucidates the potent inhibitory effects of diterpene lactones against inflammation and indicates that AP-5 may serve as a potential alternative agent for the treatment of inflammatory diseases.

Exosome, a membranous vesicle with biological activity, not only transmits active substances between cells but also transfers information between cells to participate in cell communication. Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells acquire migratory and invasive properties to become mesenchymal stem cells. EMT is essential for the development of a spectrum of diseases. Studies have shown that exosomes have dual effects on EMT to, on the one hand, promote EMT and tumor cell invasion and metastasis and accelerate angiogenesis and tumor growth; on the other hand, exosomes can suppress tumor cell invasion, inhibit fibrosis of the heart, liver and kidney, and improve myocardial infarction by inhibiting EMT. Exosomes modulate EMT-related signaling pathways by carrying EMT-related proteins or miRNA to exert their bi-directional regulatory effects.