EnkiLife 2H Rapid WB Kit Supports CV@PA-gel Synergistic Platform for Dual-Target Therapy of Intestinal and Neuroimmune Dysfunction in Inflammatory Bowel Disease

   Published in *Advanced Science*, this research was completed by the teams of Min Zhou and Danni Zhong from the First Affiliated Hospital, Zhejiang University School of Medicine. They constructed a colon-targeted CV@PA-gel synergistic platform and clarified its mechanism for intervening IBD gut-brain comorbidity: CV@PA-gel treatment, a novel, safe and effective intervention, can maintain intestinal barrier integrity and reduce gut microbiota translocation, further block microglia-induced A1 astrocyte transformation, and ultimately alleviate DSS-induced depressive-like behaviors and cognitive dysfunction.

   Inflammatory Bowel Disease (IBD) is a chronic inflammatory intestinal disorder. 47% of active patients suffer from depression, 58% experience anxiety, accompanied by cognitive impairment, forming a vicious cycle of "intestinal inflammation → psychiatric symptoms → aggravated intestinal inflammation". Current clinical treatment is highly fragmented; only 2% of adult IBD patients receive standardized psychological intervention, antidepressant administration duration is generally insufficient, and integrated therapeutic strategies targeting both intestinal and central nervous systems are lacking.

  The gut microbiota-gut-brain axis serves as the core pathway through which peripheral inflammation affects the central nervous system: increased barrier permeability leads to translocation of endotoxins such as lipopolysaccharide (LPS) into the bloodstream, triggering systemic inflammation and subsequent central nervous system impairment. However, the molecular mechanism by which peripheral immune activation specifically mediates IBD-associated neuropathology remains unclear. Existing studies suggest complement component C3 participates in pathological synaptic pruning during depression, and IBD patients exhibit elevated C3 levels; meanwhile, neurotoxic A1 astrocytes are induced by activated microglia and involved in multiple neurodegenerative diseases. This study proposes a core hypothesis: gut inflammation-driven systemic endotoxemia activates hippocampal complement C3 signaling, which may drive microglia-dependent polarization of neurotoxic A1 astrocytes, thereby providing a mechanistic basis for comorbid cognitive and emotional disorders.

  Paeoniflorin (PA), a natural monoterpene glycoside, possesses anti-inflammatory and neuroprotective activities, inhibits macrophage secretion of complement C1q, alleviates intestinal inflammation, and exerts therapeutic effects in depression models. Nevertheless, its low oral bioavailability and rapid in vivo clearance severely restrict clinical translation, highlighting an urgent demand for targeted delivery systems to overcome pharmacokinetic bottlenecks.

[Synthesis and Characterization of CV@PA-gel]

[Tissue Distribution and Biodegradation of CV@PA-gel]

[In Vitro Cellular Compatibility and Oral Safety Assessment of CV@PA-Gel]

Active IBD patients and healthy controls were enrolled to verify clinical relevance:

Mice received two cycles of DSS treatment (1 week of 2% DSS drinking water followed by 1 week of normal drinking water per cycle) to construct a chronic colitis mouse model, successfully recapitulating:

[General and Cytokine Profiles of Human Subjects and Chronic Colitis Mice with DSS-Induced Anxiety/Depressive-Like Behaviors]

A conditioned medium co-culture system was utilized to clarify cellular mechanisms:

[PA Targets Suppressing A1 Reactive Astrocytes and Three Forms of Neurogenesis]

In chronic DSS models, CV@PA-gel comprehensively reverses:

[CV@PA-gel Alleviates DSS-Induced Depressive, Anxious and Cognitive Impairments as well as Intestinal Barrier Inflammation]

[Figure: Effects of CV@PA-gel on Neuroinflammatory Responses Mediated by Cytokines and Related Molecules]

[Hippocampal Repair Effects of CV@PA-gel]

To eliminate confounding factors of indirect psychiatric relief via intestinal improvement, a chronic low-dose intraperitoneal LPS injection model was established to directly simulate endotoxemia:

[Systemic Endotoxemia Triggers Complement-Mediated Two Types of Neuropsychiatric Dysfunction]

Regulation of intestinal microecology by CV@PA-gel constitutes another critical synergistic mechanism:

[Metagenomic Bioinformatic Analysis and Fecal Metabolite Changes Across Groups]

  Colitis-induced intestinal barrier dysfunction and gut microbiota translocation may trigger complement system damage and excessive proliferation of reactive astrocytes, thereby promoting the onset of anxiety and depression. This study provides evidence supporting CV@PA-gel treatment as a novel, safe and effective intervention capable of maintaining intestinal barrier integrity, reducing gut microbiota translocation, further blocking microglia-induced A1 astrocyte transformation, and ultimately ameliorating DSS-induced depressive-like behaviors and cognitive impairment. These findings further suggest that oral CV@PA-gel may serve as a promising therapeutic strategy targeting the microbiota-gut-brain axis for IBD and its comorbid psychiatric disorders, representing a valuable therapeutic target.

    We are honored that EnkiLife’s 2H Rapid WB Ready-to-Use Full-Kit assisted the protein WB detection in this research.

  EnkiLife focuses on research reagent R&D and delivers comprehensive Western Blot solutions. From sample preparation to signal development, all product lines undergo comprehensive optimization for safety and efficiency. Our flagship 2H Rapid WB Ready-to-Use Full-Kit compresses traditional 1–2 day experiments into 2 hours with an out-of-the-box design, greatly facilitating researchers and accelerating scientific output.