The traditional Chinese medicine Psoralea corylifolia L. (PCL) has been clinically used to treat diarrhea and gastrointestinal inflammatory disorders. G protein-coupled receptor 84 (GPR84) is emerging as a potential target for inflammatory bowel disease (IBD). Pharmacological investigations confirm the efficacy of PCL against IBD, but its active components targeting GPR84 and their mechanisms remain unclear.

AIM OF THE STUDY:

We aimed to identify active components from PCL against GPR84, evaluate their therapeutic effects and elucidate their mechanisms of action in IBD treatment.

MATERIALS AND METHODS:

The GPR84 screening model was established using dynamic mass redistribution (DMR) assays, with isobavachalcone identified as an antagonist. Its activity was confirmed by fluorescence imaging plate reader and cellular thermal shift assays. The binding interactions were analyzed through DMR co-stimulation assay, molecular docking and molecular dynamics simulations. The efficacy of isobavachalcone was assessed in lipopolysaccharide-stimulated RAW264.7 macrophages and 2,4,6-trinitrobenzene sulfonic acid-induced Crohn's disease-like colitis mice model. RNA sequencing, siRNA knockdown and western blotting were used to elucidate its molecular mechanism.

RESULTS:

Isobavachalcone was identified as a selective GPR84 antagonist. It stably bound to GPR84 via π-cation, π-π stacking and hydrogen bonding interactions. In vitro, isobavachalcone demonstrated potent anti-inflammatory activity. In vivo, isobavachalcone markedly alleviated body weight loss, colonic shortening, colonic damage and macrophage infiltration. Moreover, isobavachalcone protected intestinal barrier integrity and inhibited proinflammatory cytokines, especially macrophage-produced Tnf-α, Il-6, Il-1α/β and Il-23. Mechanistically, isobavachalcone inhibited the GPR84-PI3K-AKT axis.

CONCLUSIONS:

This study reveals the underlying mechanisms of PCL and identifies isobavachalcone as a potential candidate for Crohn's disease treatment, providing scientific basis for its clinical efficacy.

2026-01-01·COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY

Inhibitory effects of isobavachalcone against Tetrahymena thermophila: Mechanistic insights

Article

作者: Liu, Yuxiao ; Liu, Juan ; Yu, Qinghua ; Wang, Wei ; Ye, Shigen ; Sheng, Dong ; Wu, Yunpeng ; Xiao, Yuehan ; Guo, Zhixin ; Zhou, Weijia ; Tang, Hongming ; Ren, Xu

Isobavachalcone (IBC), a bioactive flavonoid derived from Psoralea corylifolia, exhibits potent anti-ciliate activity, but its underlying mechanism remains unclear. Utilizing Tetrahymena thermophila as a model organism, we demonstrated that IBC induces dose-dependent mortality (12 h-IC₅₀: 1.39 mg/L) and inhibits growth. Mechanistically, IBC triggers oxidative stress by elevating reactive oxygen species (ROS) and disrupting antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH). This disruption leads to membrane damage, as evidenced by lactate dehydrogenase (LDH) leakage and ATPase inhibition, as well as mitochondrial dysfunction. Microscopic examination and staining confirmed that cell death occurs via necrotic cell death rather than apoptosis. Transcriptome analysis revealed key pathways, including peroxisome-mediated oxidation, glutathione metabolism, and ATP-binding cassette (ABC) transporters, further supporting the role of IBC in oxidative and structural disruption. These findings elucidate the anti-ciliate mechanism of IBC, providing valuable insights for developing targeted anti-parasitic agents.

2025-12-31·Virulence

Combination of isobavachalcone and amphotericin B has antifungal effect against Cryptococcus neoformans and protects host tissue damage by inhibiting ferroptosis

Article

作者: Qian, Weidong ; Liu, Qiming ; Lu, Jiaxing ; Chen, Si ; Liu, Na ; Wang, Ting

Despite recent advancements in antifungal therapy, the antifungal armamentarium remains limited compared to antibiotics available for bacterial infections. Developing novel and effective therapeutic strategies is imperative but challenging. One promising approach involves synergizing existing antifungals with complementary agents to enhance efficacy and reduce the required dosages. This study investigates the synergistic effect of isobavachalcone (IBC) and amphotericin B (AmB) against Cryptococcus neoformans in vitro and in vivo, focusing on ferroptosis modulation. Ferroptosis-related markers, including glutathione (GSH), malondialdehyde (MDA), ferrous ions, and reactive oxygen species (ROS), were analyzed in Caenorhabditis elegans model infected with C. neoformans. IBC (4 μg/mL) significantly lowered AmB's MIC from 1 μg/mL to 0.25 μg/mL, indicating a fourfold enhancement in potency. The IBC-AmB combination caused structural damage to C. neoformans, compromising membrane permeability and cell wall integrity. The combination elevated host GSH levels while reducing ferrous ions, MDA, and ROS in the infected C. elegans model. Mechanistically, the treatment upregulated antioxidant/stress response genes (SKN-1, GST-4, GST-5, GPX-1, DAF-16, CNC-11) and antimicrobial peptides (NLP-29). Conversely, the pro-inflammatory pathway gene PMK-1 was downregulated. The IBC-AmB combination not only reduces the MIC of AmB by fourfold but also enhances antifungal efficacy through a multifaceted mechanism that directly targets the fungal pathogen and modulates the host response. This dual action has the potential to reduce the adverse effects of AmB and improve therapeutic outcomes in the treatment of cryptococcal infections.

100 项与 isobavachalcone 相关的药物交易

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