Potential mechanisms of Pyrrosiae Folium in treating prostate cancer based on network pharmacology and molecular docking.

OBJECTIVE: The network pharmacology approach and molecular docking were employed to explore the mechanism of Pyrrosiae Folium (PF) against prostate cancer (PCa). METHODS: The active compounds and their corresponding putative targets of PF were identified by the Traditional Chinese Medicine Systems Pharmacology (TCMSP), the gene names of the targets were obtained from the UniProt database. The collection of genes associated with PCa was obtained from GeneCards and DisGeNET database. We merged the drug targets and disease targets by online software, Draw Venn Diagram. The resulting gene list was imported into R software (v3.6.3) for GO and KEGG function enrichment analysis. The STRING database was utilized for protein-protein interaction (PPI) network construction. The cytoHubba plugin of Cytoscape was used to identify core genes. Further, molecular docking analysis of the hub targets was carried out using AutoDock Vina software (v1.5.6). RESULTS: A total of six active components were screened by PF, with 167 corresponding putative targets, 1395 related targets for PCa, and 113 targets for drugs and diseases. The 'drug-component-disease-target' network was constructed by Cytoscape software and the target genes mainly involved in the complex treating effects associated with response to oxidative stress, cytokine activity, pathways in cancer, PCa pathway, and tumor necrosis factor (TNF) signaling pathway. Core genes in the PPI network were TNF, JUN, IL6, IL1B, CXCL8, RELA, CCL2, TP53, IL10, and FOS. The molecular docking results reveal the better binding affinity of six active components to the core targets. CONCLUSION: The results of this study indicated that PF may be have a certain anti-PCa effect by regulating related target genes, affecting pathways in cancer, TNF signaling pathway, and hepatitis B signaling pathway.

Nigegladines A-C, Three Thymoquinone Dimers from Nigella glandulifera.

Nigegladines A-C (1-3), three thymoquinone dimers, were isolated from the seeds of Nigella glandulifera. Racemic 1 possesses a unique tricyclo[5.4.0.12,6]dodecane carbon skeleton, and compounds 2 and 3 are two unusual diterpenoid alkaloids with indole cores. Their structures were determined by extensive spectroscopic analyses, and that of 1 was confirmed by single-crystal X-ray diffraction. Both (+)-1 and (-)-1 exhibited significant protective effects against hypoxia/reoxygenation-induced H9c2 myocardial cell injury.

Three new alkaloids from the seeds of Nigella glandulifera.

Three new alkaloids namely 8-(4-hydroxyphenyl)-6-methoxy-3,4-dihydroisoquinolin-1(2H)-one (1), 4-aminonigellidine (2), and N-[(4-hydroxy-2-isopropyl-5-methyl)]phenylurea (3), along with six known ones (4-9), were isolated from the seeds of Nigella glandulifera. The structures of 1-3 were determined through spectroscopic analyses (HRESIMS, 1D/2D NMR). Compound 1 was a rare isoquinolinone alkaloid with phenyl substituted at C-8.

Suppressive effects of total alkaloids of Lycopodiastrum casuarinoides on adjuvant-induced arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Lycopodiastrum casuarinoides is a folk medicine used to treat inflammation-associated diseases including rheumatoid arthritis in South China. Since the major secondary metabolites in Lycopodiastrum casuarinoides are alkaloids, the present study aims to investigate the suppressive effects of total alkaloids of Lycopodiastrum casuarinoides (ALC) on adjuvant-induced arthritis (AA) in rats. MATERIALS AND METHODS: AA was induced (day 0) in male Sprague-Dawley rats by intradermal injection of complete Freund׳s adjuvant (CFA) in right hind footpad. Diclofenac sodium (SD) was chosen as the positive drug. SD (10mg/kg) and ALC (20 and 40 mg/kg) administration started from day 1 and continued for 28 days. Paw swelling, arthritis scores, and histopathological changes were evaluated. In addition, the serum levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), as well as cyclooxygenase-2 (COX-2) and nuclear factor (NF)-κB expressions in joint synovial tissues were detected. RESULTS: ALC administration significantly suppressed the inflammatory responses in the joints of AA rats. It also decreased the serum levels of TNF-α, IL-6 and PGE2. Moreover, Western blot analysis showed that COX-2 and NF-κB expressions in synovial tissues of AA rats were significantly reduced. CONCLUSION: These results indicated that ALC prevented the pathological development of AA in rats. ALC may be a potential candidate for the treatment of inflammation and arthritis.