Chemical investigation of secondary metabolites from the marine-derived fungus Aspergillus austroafricanus Y32-2 resulted in the isolation of two new prenylated indole alkaloid homodimers, di-6-hydroxydeoxybrevianamide E (1) and dinotoamide J (2), one new pteridine alkaloid asperpteridinate A (3), with eleven known compounds (4–14). Their structures were elucidated by various spectroscopic methods including HRESIMS and NMR, while their absolute configurations were determined by ECD calculations. Each compound was evaluated for pro-angiogenic, anti-inflammatory effects in zebrafish models and cytotoxicity for HepG2 human liver carcinoma cells. As a result, compounds 2, 4, 5, 7, 10 exhibited pro-angiogenic activity in a PTK787-induced vascular injury zebrafish model in a dose-dependent manner, compounds 7, 8, 10, 11 displayed anti-inflammatory activity in a CuSO₄-induced zebrafish inflammation model, and compound 6 showed significant cytotoxicity against HepG2 cells with an IC₅₀ value of 30 µg/mL.

Danggui–Chuanxiong (DC) is a commonly used nourishing and activating blood medicine pair in many gynecological prescriptions and modern Chinese medicine. However, its activating blood mechanism has not been clearly elucidated. Our research aimed at investigating the activating blood mechanisms of DC using network pharmacology and zebrafish experiments. Network pharmacology was used to excavate the potential targets and mechanisms of DC in treating thrombus. The antithrombotic, anti-inflammatory, antioxidant, and vasculogenesis activities of DC and the main components of DC, ferulic acid (DC2), ligustilide (DC7), and levistilide A (DC17), were evaluated by zebrafish models in vivo. A total of 24 compounds were selected as the active ingredients with favorable pharmacological parameters for this herb pair. A total of 89 targets and 18 pathways related to the thrombus process were gathered for active compounds. The genes, TNF, CXCR4, IL2, ESR1, FGF2, HIF1A, CXCL8, AR, FOS, MMP2, MMP9, STAT3, and RHOA, might be the main targets for this herb pair to exert cardiovascular activity from the analysis of protein–protein interaction and KEGG pathway results, which were mainly related to inflammation, vasculogenesis, immunity, hormones, and so forth. The zebrafish experiment results showed that DC had antithrombotic, anti-inflammatory, antioxidant, and vasculogenesis activities. The main compounds had different effects of zebrafish activities. Especially, the antithrombotic activity of the DC17H group, anti-inflammatory activities of DCH and DC2H groups, antioxidant activities of DCM, DCH, DC2, DC7, and DC17 groups, and vasculogenesis activities of DCM, DCH, and DC2 groups were stronger than those of the positive group. The integrated method coupled zebrafish models with network pharmacology provided the insights into the mechanisms of DC in treating thrombus.

Osteoarthritis (OA), defined as a long-term progressive joint disease, is characterized by cartilage impairment and erosion. In recent decades, magnolol, as a type of lignin extracted from Magnolia officinalis, has been proved to play a potent anti-inflammatory role in various diseases. The current research sought to examine the latent mechanism of magnolol and its protective role in alleviating the progress of OA in vivo as well as in vitro experimentations. In vitro, the over-production of Nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6), induced by interleukin-1 beta (IL-1β), were all inhibited notably by magnolol in a concentration-dependent manner. Moreover, magnolol could also downregulate the expression of metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5). All these changes ultimately led to the deterioration of the extracellular matrix (ECM) induced by IL-1β. Mechanistically, magnolol suppressed the activation of PI3K/Akt/NF-κB pathway. Furthermore, a powerful binding capacity between magnolol and PI3K was also revealed in our molecular docking research. In addition, magnolol-induced protective effects in OA development were also detected in a mouse model. In summary, this research suggested that magnolol possessed a new therapeutic potential for the development of OA.