Yanbian University

Crataegus pinnatifida Bunge, a plant used traditionally in herbal medicine for digestive health, is known for its gut-protective properties. Orientin, a natural flavonoid compound abundant in this species, exhibits anti-inflammatory and gut-protective activities.

This study examined the therapeutic potential of orientin against ulcerative colitis (UC) and aimed to elucidate its underlying molecular mechanisms.

This study established a DSS-triggered UC mouse model. RNA sequencing was carried out to identify key signaling pathways implicated in orientin's therapeutic effects. Disease activity, intestinal barrier integrity, inflammatory responses, ferroptosis, were systematically evaluated. To validate the role of GLUT1 in the pathogenesis of UC, GLUT1-knockdown mice were utilized. Additionally, LPS-stimulated primary intestinal epithelial cells (IECs) were employed to further confirm the protective effects of orientin in vitro.

RNA sequencing revealed that orientin significantly modulated genes associated with inflammation, ferroptosis, and metabolic pathways. Orientin alleviated DSS-triggered colitis by boosting body weight, preserving colon length, reducing histological damage. GLUT1 deficiency exacerbated intestinal injury, whereas orientin treatment attenuated these effects by regulating the ROS/HIF-1α/GLUT1 signaling axis. Orientin also repressed pro-inflammatory cytokines, neutrophil infiltration, and oxidative stress, while inhibiting the ferroptosis pathway. Moreover, it normalized glycolytic reprogramming by targeting the ROS/HIF-1α/GLUT1 pathway. In vitro studies further confirmed orientin's protective effects on IECs by enhancing barrier function, reducing inflammation, and restoring metabolic homeostasis.

This study underscores the pivotal role of the ROS/HIF-1α/GLUT1 axis and demonstrates the therapeutic potential of orientin in UC.

Traditional Chinese medicine holds that pilose antler can strengthen kidney yang, replenish essence and blood, fortify bones and muscles, as well as enhance immune function and promote hematopoiesis. However, studies on its potential to treat myelosuppression remain limited, and the underlying mechanisms and active components still require further investigation.

This study aimed to evaluate the therapeutic potential of PAPs against myelosuppression and to elucidate the underlying protective mechanisms.

The protein composition of PAPs was identified by LC-MS/MS, and network pharmacology was then applied to predict the mechanisms that may underlie its effects. The protective effects of PAPs against the cytotoxic effects of CTX on bone marrow mesenchymal stem cells (BMSCs) were evaluated in terms of apoptosis, ROS level, cell cycle, cell senescence, and osteogenic differentiation in vitro. Meanwhile, the ameliorative effects of PAPs in myelosuppressed mice were observed by measuring peripheral blood routine parameters and bone marrow histopathology in vivo.

In vitro, PAPs dose-dependently inhibited CTX-induced excessive ROS accumulation, restored SOD activity and reduced MDA content, alleviated apoptosis and senescence, and enhanced the osteogenic differentiation capacity of injured BMSCs. Immunofluorescence analysis further revealed that CTX upregulated Bax (by approximately 9.4-fold) and caspase-3 (by approximately 14.8-fold), and downregulated Bcl-2 (to approximately 0.34-fold). PAPs treatment reversed these changes, with the high-dose group reducing Bax to 0.18-fold and caspase-3 to 0.12-fold, and increasing Bcl-2 to 2.21-fold. In vivo, PAPs significantly elevated WBC, RBC, and PLT counts, as well as HGB levels, restored serum levels of SCF, TPO, EPO, and GM-CSF (to 0.69-0.80-fold of the control), and ameliorated severe bone marrow histopathological damage induced by CTX exposure.

These findings suggest that PAPs alleviate chemotherapy-induced myelosuppression by activating the PI3K/AKT pathway, reducing BMSC injury and oxidative stress, improving peripheral blood parameters, and ameliorating bone marrow histopathological damage. This study not only provides modern scientific evidence supporting the traditional use of deer antler for "nourishing essence and replenishing marrow", but also provides a solid experimental basis for the further development and utilization of PAPs.

A series of chalcone hybrids including benzoylpiperazin (phenylacetylpiperazin)-thiophene were designed, synthesized and evaluated their inhibitory activities against cholinesterase (ChE). All compounds displayed good inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, compound 2e displayed the most inhibitory activity against AChE, BChE and β-amyloid (Aβ₄₂) with IC₅₀ values 7.01, 5.39 and 4.47 μM, respectively. Meanwhile, 2e was found anti-Alzheimer's disease (AD) effect by significantly alleviating lipopolysaccharide (LPS)/Aβ-induced neurotoxicity, reducing the levels of reactive oxygen species (ROS), pro-inflammatory cytokines, and exert anti-inflammatory effects by regulating the NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) pathway. Furthermore, the molecular modeling studies showed that 2e target both catalytic active site as well as peripheral anionic site of AChE, BChE and Aβ₄₂, and possess strong bind affinity. In addition, in silico ADMET and toxicity predictions demonstrated favorable oral absorption and potential blood-brain barrier (BBB) permeability for 2e. The rationale remains partly overstated. The novelty claim should more precisely distinguish this scaffold from previously reported chalcone, piperazine, thiophene, and multitarget ChE/Aβ inhibitors. The phrase "anti-Alzheimer's agents" should be softened, because the data are limited to enzyme assays, Aβ assays, BV-2 cellular models, docking, and computational predictions.