Jianpi Huayu Decoction suppresses cellular senescence in colorectal cancer via p53-p21-Rb pathway: Network pharmacology and in vivo validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianpi Huayu Decoction (JHD) is an herbal prescription in traditional Chinese medicine based on Sijunzi Decoction to treat patients with colorectal cancer (CRC). Its effects on the inhibition of CRC cell proliferation and tumor growth are promising; however, its multicomponent nature makes a complete understanding of its mechanism challenging. AIM OF THE STUDY: To explore the therapeutic targets and underlying molecular pathways of JHD in CRC treatment using network pharmacology techniques and in vivo validation. MATERIALS AND METHODS: The active ingredients and targets of JHD were identified, compound-target interactions were mapped, and enrichment analyses were conducted. We identified the hub targets of JHD-induced cellular senescence in CRC. The binding affinities between compounds and targets were evaluated through molecular docking. Subsequently, we conducted bioinformatic analyses to compare the expression of hub targets between colorectal tissue and normal tissue. Finally, in vivo experiments were carried out utilizing a xenograft model to assess the effects of JHD on cellular senescence biomarkers. RESULTS: Network pharmacology revealed 129 active ingredients in JHD that were associated with 678 targets, leading to the construction of compound-target and target-pathway networks. Enrichment analyses highlighted key pathways including cellular senescence. Based on this, hub targets associated with cellular senescence were determined and validated. Molecular docking indicated favorable interactions between the active components and hub targets. Gene expression and survival analysis in CRC tissue were consistent with the potential roles of hub genes. Animal experiments showed that JHD triggered cellular senescence and suppressed the growth of CRC by regulating the p53-p21-Rb signaling pathway. CONCLUSIONS: This research adopted network pharmacology, bioinformatics, and animal experiments to unveil that JHD induces cellular senescence in CRC by influencing the p53-p21-Rb pathway and senescence-associated secretory phenotypes, highlighting its potential as a CRC treatment.

Molecular bases for the stronger plastic response to high nitrate in the invasive plant Xanthium strumarium compared with its native congener.

MAIN CONCLUSION: High expressions of nitrate use and photosynthesis-related transcripts contribute to the stronger plasticity to high nitrate for the invader relative to its native congener, which may be driven by hormones. Strong phenotypic plasticity is often considered as one of the main mechanisms underlying exotic plant invasions. However, few studies have been conducted to investigate the related molecular mechanisms. Here, we determined the differences in the plastic responses to high nitrate between the invasive plant X. strumarium and its native congener, and the molecular bases by transcriptome analysis and quantitative real-time PCR validation. Our results showed that the invader had higher plasticity of growth, nitrogen accumulation and photosynthesis in responses to high nitrate than its native congener. Compared with its congener, more N utilization-related transcripts, including nitrate transporter 1/peptide transporter family 6.2 and nitrate reductase 1, were induced by high nitrate in the root of X. strumarium, improving its N utilization ability. More transcripts coding for photosynthetic antenna proteins were also induced by high nitrate in the shoot of X. strumarium, enhancing its photosynthesis. Hormones may be involved in the regulation of the plastic responses to high nitrate in the two species. Our study contributes to understanding the molecular mechanisms underlying the stronger plasticity of the invader in responses to high nitrate, and the potential function of plant hormones in these processes, providing bases for precise control of invasive plants using modern molecular techniques.

Identification of alkaloidal compounds from leaves and roots of Stephania succifera by HPLC-QTOF-MS and prediction of potential bioactivity with PharmMapper.

INTRODUCTION: The roots of Stephania succifera are used in traditional medicine for the treatment of several diseases. Research on this plant has mainly focused on bioactive alkaloids from the roots, and no previous work on compounds from the abundant leaves has yet been reported. OBJECTIVE: To identify and compare alkaloidal compounds in S. succifera roots and leaves and to predict the potential bioactivity of some alkaloids. METHODS: High-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF-MS/MS) was employed to identify alkaloidal compounds from S. succifera. The potential targets and bioactivities of most alkaloids were predicted using the PharmMapper server. RESULTS: Fifty-six alkaloidal compounds, including protoberberine-, aporphine-, proaporphine-, benzylisoquinoline-, and lactam-type alkaloids, were identified or tentatively identified in S. succifera roots and leaves based on the HPLC-MS data. Forty-one compounds have not been previously reported in S. succifera and eight of them have not been previously reported in the literature. Twenty-four alkaloidal compounds were found in both roots and leaves. Twelve potential targets with different indications were predicted for some alkaloids. CONCLUSION: Comparison of chemical constituents and their potential bioactivities for S. succifera roots and leaves indicated that diverse bioactive alkaloids were present in the leaves as well as the roots. PharmMapper provided new directions for bioactivity screening. This study will be helpful for further understanding the medicinal components of S. succifera and the rational utilisation of plant resources.