Mechanistic insights into xanthomicrol as the active anti-HCC ingredient of Phytolacca acinosa Roxb.: A network pharmacology analysis and transcriptomics integrated experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Phytolacca acinosa Roxb. (PAR) is a Traditional Chinese Medicinal (TCM) plant with a broad global distribution encompassing 35 species, four of which are found in the People's Republic of China. It occupies a significant role in both Oriental and American traditional medicine, employed in treating a range of conditions such as edema, inflammation, dermatitis, and rheumatism. PAR is also used as a molluscicide and for addressing tumors and bronchitis. The plant is documented in the Chinese Pharmacopoeia and has a longstanding history in TCM, particularly for its diuretic properties and in treating ailments such as edema, swelling, and ulcers. Notably, PAR has demonstrated potent inhibitory effects against the A549 human lung cancer cell line, underscoring its potential in contributing to the development of novel cancer therapeutics. AIM OF THE STUDY: The research aims to elucidate the active components of PAR and their mechanisms in treating hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Employing network pharmacology, this study predicted the principal active compounds and key targets of PAR. A holistic methodology incorporating biological network analysis, transcriptomics sequencing, molecular docking, and molecular dynamics (MD) simulations was utilized to forecast the effects of PAR on HCC, with empirical evidence supporting these findings. RESULTS: Network pharmacology identified xanthomicrol as the foremost active compound in PAR. The tumor-suppressive functions of PAR, as indicated by KEGG pathway analysis and transcriptomics sequencing, predominantly occur via the PI3K/AKT pathway. Molecular docking and dynamics simulations demonstrated the high affinity of xanthomicrol towards TNF, MMP9, PPARG, KDR, and MMP2. In vivo experiments verified the efficacy of xanthomicrol in curtailing HCC tumor growth, while in vitro assessments revealed its substantial impact on the proliferation and apoptosis of HepG2 and HCCLM3 cells. Moreover, the study indicates that xanthomicrol may modulate the expression of TNF, MMP9, PPARG, KDR, and MMP2 in HCC cells and inhibit the activation of the PI3K/AKT pathway. CONCLUSIONS: Xanthomicrol, a principal active component of PAR, has been identified to impede the growth of HCC by targeting the PI3K/Akt/MMP9 pathway. This insight could enhance therapeutic approaches for HCC.

Effects of matrix modification and bacteria amendment on the treatment efficiency of municipal tailwater pollutants by modified vertical flow constructed wetland.

Although vertical flow constructed wetland (VFCW) has great potentials for degradation of water contaminants, traditional VFCW has limited removal efficiencies for pollutants. This study constructed three sets of modified VFCW systems, including VFCW-A with matrix-modification using mixture of biochar and activated carbon, VFCW-B with microbial amendment using denitrifying bacteria, and VFCW-C with combined treatments of both. Their removal efficiencies for various pollutants in synthetic municipal tailwater were investigated. Results showed that the removal efficiencies for NH4-N, NO3-N, total nitrogen (TN), total phosphorus (TP), and chemical oxygen demand (COD) by VFCW-C were higher than VFCW-B throughout the experimental period, indicating that matrix-modification could improve the VFCW performance. The higher removal efficiencies for TN, TP, and COD by VFCW-C than VFCW-A also suggested the effectiveness of microbial amendment in VFCW. However, the improved removal for NO3-N by VFCW-C over VFCW-A became less obvious at later operation stage due to insufficient carbon source. All three VFCWs achieved their best removal efficiency when carbon source was supplemented at CH3COO-/TN ratio of 0.5. Our study suggested that the combined treatment of matrix-modification using biochar/activated carbon mixture and microbial amendment using denitrifying bacteria could effectively enhance the treatment efficiency of VFCW systems for tailwater pollutants from sewage plant.