Zuoguiyin (ZGY), a traditional Chinese medicine formula used to nourish Yin and replenish vital essence, possesses tonifying properties that are conceptually aligned with modern strategies aiming to modulate the immunosuppressive tumor microenvironment (TME). In esophageal squamous cell carcinoma (ESCC), M2 macrophages are pivotal components that drive tumor progression. Therefore, therapeutic strategies targeting M2 macrophages may offer a beneficial approach.

AIM OF THE STUDY:

This study aimed to explore whether ZGY suppresses ESCC by disrupting the pro-tumorigenic interactions between M2 macrophages and cancer cells, with a specific focus on the immunometabolic axis.

MATERIALS AND METHODS:

A co-culture system of ESCC cells and macrophages was employed to investigate cellular interactions. An in vivo ESCC mouse model induced by a 4-nitroquinoline-1-oxide (4-NQO) was employed for validation. Proteomic analysis, Seahorse metabolic analysis, flow cytometry, Western blotting, molecular docking, and molecular dynamics simulations were conducted to elucidate the underlying mechanisms and identify active components.

RESULTS:

IL-4 secreted by ESCC cells bound to the IL-4 receptor on macrophages, activating the JAK/STAT6 signaling pathway and driving M2 polarization. These M2 macrophages, in turn, enhanced glycolytic metabolism in ESCC cells. ZGY treatment did not directly affect the cancer cells but effectively inhibited M2 polarization by blocking JAK2/STAT6 phosphorylation. This led to a reversal of the M2-driven enhancement of tumor glycolysis and a reduction in tumor growth in vivo. Isoferulic acid and norharman, key bioactive components of ZGY, were identified as stable binders of JAK2.

CONCLUSIONS:

This study elucidates the mechanism through which IL-4/JAK2/STAT6-mediated M2 macrophages promote glycolysis in ESCC and demonstrates that ZGY disrupts this pathway by targeting JAK2 in macrophages. These findings provide a mechanistic foundation for developing ZGY as a promising tumor microenvironment-modifying therapy for ESCC.

2026-05-01·CHEMISTRY & BIODIVERSITY

Comprehensive Profiling of Acetylcholinesterase Inhibitors From Cimicifuga foetida Using Activity‐Oriented Offline Preparation Technology

Article

作者: Li, Sainan ; Liu, Xuanlin ; Liu, Qiang ; Zhang, Yuchi ; Zhou, Yang ; Shi, Dongfang

ABSTRACT:

Owing to the complexity and diversity of chemical constituents in natural food ingredients, functional food research has long faced two major technical challenges: the rapid and accurate screening of bioactive compounds, and their targeted preparation. This study aimed to establish an efficient strategy for screening and preparing acetylcholinesterase inhibitors (AChEIs) from Cimicifuga foetida ( C. foetida ) to improve the efficiency of fungal food preparation. First, the extraction process of C. foetida was optimized using the Non‐dominated Sorting Genetic Algorithm II (NSGA‐II) regression model. Next, the potential anti‐Alzheimer's effects of the extracted active compounds were evaluated by affinity‐ultrafiltration mass spectrometry (AUF‐MS), molecular docking, enzyme kinetics, and network pharmacology analyses. Five compounds, namely cimifugin, cimifugoside, caffeic acid, ferulic acid, and isoferulic acid, exhibited strong binding affinity to the active site of AChEIs. These findings highlight the potential of C. foetida as a valuable source for the discovery and development of novel therapeutic agents from natural food resources.

2026-03-18·JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

Plant-Derived Isoferulic Acid and RNAi Synergize to Overcome Detoxification Defenses in the Bird Cherry–Oat Aphid ( Rhopalosiphum padi )

Article

作者: Xia, Linhai ; Wang, Ni ; Peng, Xiong ; Piñero, Jaime C. ; Tang, Hongcheng ; Yuan, Xiaoxiao ; Chen, Maohua ; Zhu, Zhenyin ; Hou, Wenhua

Sustainable management of insect pests is threatened by insecticide resistance, driving demand for effective, environmentally safe tools. The bird cherry-oat aphid (Rhopalosiphum padi), a major cereal pest, shows resistance to pyrethroids, neonicotinoids, and other insecticide classes. We identified isoferulic acid, a phenolic compound from Prunus padus, as a potent aphicide with lethal and sublethal impacts. Bioassays showed dose-dependent lethality (LC₅₀ = 1.74 mg/L at 48 h), while sublethal exposure shortened adult longevity (17.7 to 10.2 d) and reduced fecundity (81 to 53 nymphs/female). Transcriptomic and enzymatic analyses revealed broad induction of detoxification pathways, with RpLipase consistently upregulated. RNAi-mediated knockdown of RpLipase enhanced susceptibility, lowering the LC₅₀ to 0.85 mg/L and confirming its role in tolerance. Nontarget assays with the predator Harmonia axyridis revealed no acute toxicity. Collectively, isoferulic acid is a promising plant-derived insecticide, and silencing induced detoxification genes enhances its potency, providing a foundation for developing novel resistance-breaking strategies.

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适应症	最高研发状态	国家/地区	公司	日期
帕金森病	临床前	中国	中国科学院大学	2025-10-01
帕金森病	临床前	中国	云南大学	2025-10-01
帕金森病	临床前	中国	中国科学院昆明植物研究所	2025-10-01