Phytomedicine最新文献

Background: Colorectal cancer (CRC) is among the most prevalent malignancies globally, with its incidence continuing to rise in recent years. Sorafenib, a multi-kinase inhibitor, has shown therapeutic effects in advanced CRC. Usenamine A (UD32-3), a natural compound, is isolated from lichens. However, anti-tumor activity of UD32-3 in CRC and its biological functions in anti-CRC activity of sorafenib remain unknown.

Purpose: This study aims to elucidate the mechanism underlying anti-CRC effects of UD32-3 and its potential to enhance the therapeutic efficacy of sorafenib.

Study design and methods: Immunofluorescence assays were employed to investigate reactive oxygen species (ROS) and autophagy levels. Gene knockdown or overexpression was performed using Lipofectamine 3000 reagent, and relative gene and protein expression levels were evaluated by quantitative real-time PCR (qRT-PCR) and Western blot analyses. Molecular docking analysis was performed to investigate the interaction between UD32-3 and superoxide dismutase 2 (SOD2). Mouse xenograft models were employed to evaluate the effects of combination therapy with UD32-3 and sorafenib.

Results: UD32-3 exerts anti-CRC activity by inducing ROS-mediated autophagy and inhibiting YAP pathway through targeting SOD2. Knocking down SOD2 sufficiently induced ROS generation and autophagy, and inhibited the YAP pathway, thereby enhancing the anti-CRC activity of UD32-3. Conversely, overexpression of SOD2 yielded opposite results, attenuating these effects. Combined treatment with UD32-3 and sorafenib exerted synergistic anti-tumor activities by activating autophagy and inhibiting YAP signaling pathway. Additionally, YAP inhibitor strengthened anti-CRC activity of UD32-3 and sorafenib by inhibiting SOD2 expression, suggesting autophagy-mediated negative feedback loop between SOD2 and YAP.

Conclusions: UD32-3 has significant druggable potential, and combination treatment of UD32-3 and sorafenib may serve as an effective therapeutic strategy for patients with certain CRC.

Background: Tibial dyschondroplasia (TD), characterized by impaired angiogenesis and abnormal chondrocyte maturation in the tibial growth plate (TGP), is a common bone disorder in commercial broilers. Strontium (Sr), a trace element with osteogenic and angiogenic properties that plays a crucial role in bone health, exhibits low bioavailability. Achyranthes bidentata polysaccharides, a major extract from Achyranthes bidentata with the function of "guiding the medicine downward", has been used to enhance drug delivery to the lower extremity meridians.

Purpose: This study aimed to prepare a novel Achyranthes bidentata polysaccharides-strontium (ABPS-Sr) chelate to enhance Sr bioavailability and investigate its therapeutic effects on tibial damage in TD broilers from the perspective of the gut-bone axis.

Methods: The ABPS-Sr chelate was synthesized and optimized using response surface methodology, followed by structural characterization. A thiram-induced TD broiler model was established to evaluate the therapeutic efficacy of the ABPS-Sr chelate using qRT-PCR, Western blot, immunoprecipitation, micro-CT, histological staining, and biochemical assays. 16S rRNA sequencing and targeted and non-targeted metabolomics were employed to characterize alterations in gut microbiota, intestinal metabolites and plasma lipid metabolites. Experiments involving phosphatidylcholine (PC)-exposed broilers and fecal microbiota transplantation (FMT) in mice were performed to verify the mediate role of gut microbiota and tibia-damaging effects of PC.

Results: The one-pot synthesis of ABPS-Sr chelate was optimized to achieve a yield of 27.7 %, with structural characterization confirming Sr²⁺ coordination-induced conformational changes and porous architecture. Dietary supplementation with ABPS-Sr chelate significantly improved growth performance, restored tibial microstructure, and promoted vessel density in the TGP in TD broilers. Moreover, ABPS-Sr chelate promoted angiogenesis in the TGP by upregulating VEGF expression and restored osteogenic differentiation by activating the ITGB1/FAK/PI3K/AKT1 signaling pathway. Furthermore, ABPS-Sr chelate reshaped gut microbiota composition, restored intestinal barrier function, and corrected hepatic lipid metabolism disorders, particularly by reducing plasma glycerophospholipid (e.g., PC) accumulation that exerts negative effects on bone health.

Conclusion: This study demonstrated that ABPS-Sr chelate restores tibial injury in TD broilers by enhancing osteogenesis and angiogenesis via modulation of the gut-liver-bone axis, which provides a promising nutritional intervention strategy for improving poultry bone health.

Background: Myopia has emerged as a global public health concern. Current therapeutic strategies primarily target symptom management. Traditional Chinese Medicine (TCM) demonstrates potential in myopia prevention and control, yet its underlying mechanisms remain incompletely understood.

Purpose: This study aimed to investigate the preventive and therapeutic effects of Yiqi Congming Decoction (YQCM) on lens-induced myopia (LIM) in rats and to elucidate whether its efficacy involves the inhibition of the cAMP/PKA/HIF-1α signaling pathway to intervene in scleral remodeling, thereby delaying myopia progression.

Methods: The chemical composition of YQCM was identified using high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS). A LIM rat model was established and divided into preventive-administration and therapeutic-administration groups. Axial length measurement, histological analysis, and molecular biological techniques were employed to systematically evaluate the effects of YQCM on ocular axial growth, scleral ultrastructure, and the expression of key factors within the cAMP/PKA/HIF-1α pathway.

Results: YQCM significantly suppressed axial elongation. The high-dose YQCM regimen reduced the axial elongation rate by 30.3% in the prevention group and 25.8% in the treatment group, respectively. Histological analysis revealed that YQCM effectively alleviated pathological scleral thinning and promoted a more regular collagen fiber arrangement. Mechanistic studies demonstrated that YQCM markedly downregulated the expression of cAMP, PKA, and HIF-1α in the sclera, while simultaneously upregulating the levels of growth factors TGF-β1 and bFGF. This coordinated action ultimately inhibited scleral extracellular matrix degradation, promoted collagen synthesis, and delayed myopia progression.

Conclusion: This study demonstrates for the first time that YQCM can inhibit LIM progression in rats by modulating the cAMP/PKA/HIF-1α signaling axis and stimulating growth factor expression, thereby intervening in the scleral remodeling process. These findings indicate that YQCM represents a multi-targeted therapeutic strategy, showing promise as a potential drug candidate for myopia control.

Background: Huang-Qi-Long-Dan Granule (HQLDG) is an herbal formula that is commonly used to treat ischemic stroke (IS) in clinical practice. Comprehension of the underlying mechanism is conductive to an improved understanding of the use of this formula.

Purpose: The anti-IS effect and the underlying mechanism of HQLDG were explored in this study.

Methods: A zebrafish cerebral thrombosis model and a mouse transient middle cerebral artery occlusion (tMCAO) model were used in this study.

Results: HQLDG significantly decreased brain thrombosis; increased blood vessel diameter and blood flow velocity; ameliorated motor activity, including velocity, acceleration, sinuosity, etc.; and regulated expression of the coagulation cascade genes vWF, proca and tfpia in zebrafish model. Ameliorated motor activity and improved brain pathology were also observed in tMCAO mice. Furthermore, HQLDG decreased oxidative stress-, inflammation- and apoptosis- related indicators in zebrafish, which were also confirmed in tMCAO mice. Moreover, HQLDG could increase the translocation of Nrf2 into the nucleus in brain tissue. However, the protective effects of HQLDG on cerebral thrombosis zebrafish were decreased after the inhibition of Nrf2 with ML385 or CRISPR/Cas9 gene-editing technology in zebrafish. Moreover, inhibition of Nrf2 significantly attenuated the effect of HQLDG on NF-κB. The protective effect of HQLDG on motor activity was significantly decreased in NF-κB inhibited gene-edited zebrafish.

Conclusions: These findings underscore the potential of HQLDG as a promising therapeutic agent for IS, while further confirming the reliability of zebrafish as an IS model and expanding the visualization indicators of IS to complement mammalian indicators.

Background: The Qingjin Pingchuan Formula (QJPC), a multi-herb traditional Chinese medicine prescription, is clinically employed for severe community-acquired pneumonia (SCAP), though its underlying molecular mechanisms remain incompletely understood.

Purpose: This study aimed to elucidate the anti-inflammatory effects of QJPC and its impact on neutrophil-mediated signaling pathways.

Methods: An integrative strategy combining network pharmacology, single-cell RNA sequencing (scRNA-seq), and experimental validation was applied. Chemical profiling of QJPC and drug-containing human serum was conducted using UPLC-MS. Network pharmacology and molecular docking analyses predicted and verified potential targets. A murine lipopolysaccharide (LPS)-induced acute lung injury model was established for in vivo studies. Functional assays were performed on primary neutrophils, and neutrophil-depleted mice were used to confirm neutrophil-dependent effects. The SHP1 agonist SC43 was co-administered to further assess SHP1-mediated mechanisms.

Results: QJPC alleviated pulmonary inflammation by modulating the SHP1-JAK2/SRC-STAT3 axis in neutrophils. UPLC-MS identified 17 systemically absorbed constituents. Network pharmacology predicted JAK2, SRC, and STAT3 as key targets, which were supported by molecular docking. In LPS-injured mice, QJPC improved histopathology, reduced IL-6, and elevated IL-10 levels. scRNA-seq demonstrated that QJPC reshaped neutrophil heterogeneity and upregulated Ptpn6, encoding the phosphatase SHP1. Functional assays confirmed that QJPC enhanced SHP1 protein expression, suppressed STAT3 phosphorylation and nuclear translocation, and attenuated JAK2 and SRC activation in primary neutrophils. In vivo, QJPC's anti-inflammatory effects were diminished in neutrophil-depleted mice and modulated by SC43 co-treatment. Together, these findings indicate that QJPC exerts lung-protective effects, at least partly, through SHP1 upregulation and subsequent inhibition of the JAK2/SRC-STAT3 pathway in neutrophils. This study provides mechanistic insight into the anti-inflammatory action of QJPC and supports its therapeutic potential in neutrophil-driven pulmonary inflammatory diseases.

Background: Hyperactive de novo nucleotide synthesis is a metabolic hallmark of pulmonary metastatic triple-negative breast cancer (TNBC), largely driven by upregulation of phosphoribosyl pyrophosphate synthetase 2 (PRPS2). No specific PRPS2 inhibitors are available for clinical intervention of metastasis.

Purpose: This study aimed to identify novel natural compounds targeting PRPS2 transcription and investigate their therapeutic potential against TNBC stemness and metastasis.

Methods: A cell‑based high‑throughput screening of traditional Chinese medicine‑derived compounds was performed, followed by functional validation in vitro and in vivo. A PRPS2‑promoter‑driven luciferase reporter assay screened 312 natural compounds; the lead compound was assessed in TNBC cell lines and a murine pulmonary metastasis model. Mechanistic studies included biotin‑conjugated pull‑down, chromatin immunoprecipitation (ChIP), and reporter assays.

Results: Pseudoginsenoside F11 (PF11) was identified as an effective inhibitor of PRPS2 transcription. PF11 treatment at 20 μM for 72 h significantly suppressed PRPS2 expression by >60%, cancer cell stemnessas evidenced by ∼70% decrease in mammosphere formation and ∼50% reduction in ALDH⁺ population, and pulmonary metastasis in murine models by approximately 80%. The transcription factor YBX1 was identified as the direct binding target of PF11. PF11 binding enhanced YBX1's affinity for the PRPS2 promoter, enabling it to compete with and displace the transcriptional activator c-Myc. YBX1 recruited the NuRD corepressor complex to the promoter, leading to transcriptional repression of PRPS2.

Conclusion: These findings unveil a novel mechanism by which PF11 activates a YBX1-NuRD corepressor complex to downregulate PRPS2, thereby attenuating TNBC stemness and metastasis. PF11 is identified as the first natural inhibitor of PRPS2 transcription, and demonstrates that plant-derived compounds can induce transcription factor reprogramming of YBX1 to reveal new metabolic‑epigenetic‑stemness regulatory axes, aligning with the journal's focus on mechanistic phytomedicine research.

Background: Ovarian cancer remains a leading cause of gynecologic cancer-related mortality, primarily driven by the development of multidrug resistance. Plant-derived natural products have gained attention as promising adjuncts to conventional treatments due to their multifaceted mechanisms and low systemic toxicity.

Purpose: This review summarizes recent advances in plant-derived compounds that counteract ovarian cancer resistance and explores their underlying molecular mechanisms.

Methods: A comprehensive literature search was performed in the PubMed and Web of Science databases to identify English-language articles published up to September 2025. The search terms included "ovarian cancer", "drug resistance", "aging", "plant nanotechnology", "Chinese herbal medicine", and "natural products", which were combined using Boolean operators "AND/OR". Studies were eligible for inclusion if they addressed the pharmacological effects, molecular mechanisms, and therapeutic potential of plant-derived compounds in overcoming drug resistance in ovarian cancer. Basic research studies, in vitro and in vivo experiments, preclinical investigations, and relevant reviews were included, whereas duplicate articles were excluded.

Results: Various resistance mechanisms, including altered drug transport, enhanced DNA repair, immunosuppressive microenvironment remodeling, and senescence-associated phenotypes, are modulated by flavonoids, alkaloids, saponins, terpenes, and polysaccharides. These compounds target critical signaling pathways, such as PI3K/Akt/mTOR, STAT3, NF-κB, and VEGFR2/FAK. Advances in nanoparticle delivery and senescence regulation further enhance their therapeutic efficacy.

Conclusions: The integration of natural products with standard therapies may offer a viable strategy to overcome chemoresistance in ovarian cancer, highlighting the need for further translational and clinical investigations.